Synthetic methods for lactones and cerium-catalyzed lactones.

Abstract

This invention discloses a method for synthesizing lactone compounds and cerium-catalyzed lactone compounds. The synthesis method comprises the following steps: under visible light irradiation, in an oxygen atmosphere, and in the presence of a photocatalyst and a cerium catalyst, a cyclic ketone compound containing a structural fragment as shown in Formula II is subjected to a cyclization reaction in a solvent to obtain a lactone compound containing a structural fragment as shown in Formula I. This method uses readily available raw materials to conveniently and rapidly synthesize various medium- and large-cyclic lactones, and is simple, economical, and environmentally friendly.

Description

Technical Field

[0001] This invention relates to a lactone compound and a method for synthesizing a cerium-catalyzed lactone compound. Background Technology

[0002] Lactone compounds are of great value in drug research, and the challenges of their synthesis have attracted widespread research interest from organic chemists.

[0003] Lactones have become a research hotspot in the field of organic synthesis due to their unique synthetic complexity and their prominent role in antibiotic drug discovery and research. The increasing antibiotic resistance of bacteria necessitates the development of newer, more widely applicable macrocyclic lactones, which in turn creates a pressing need for efficient synthetic methods for macrocyclic lactones.

[0004] However, in current synthetic methods, the classic "end-to-end" cyclization strategy, whether through lactone bond formation or olefin metathesis cyclization, requires significant time and reagent consumption to synthesize complex bifunctional cyclization precursors. This makes the rapid synthesis of a large variety of compounds difficult and fails to meet the synthetic requirements of drug development experiments. Furthermore, the construction of 8- to 11-membered rings is considered one of the most challenging types of cyclization reactions. The unique ring strain presents the synthesis of these intermediate-ring lactones with dual challenges in terms of ring strain and kinetics, making it difficult to efficiently synthesize these target molecules using traditional synthetic methods.

[0005] There is an urgent need in this field to develop efficient methods for synthesizing lactone compounds to meet the demand for lactone compounds. Summary of the Invention

[0006] The technical problem this invention aims to solve is to overcome the shortcomings of existing methods for synthesizing lactones, such as difficulty in synthesizing medium- and macrocyclic lactones, low yields, long steps, long reaction times, and the need for expensive metal catalysts or high-temperature conditions. Therefore, this invention provides a method for synthesizing lactones and cerium-catalyzed lactones. The synthesis method of this invention can efficiently synthesize medium- and macrocyclic lactones, with mild reaction conditions, economic applicability, and environmental friendliness.

[0007] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0008] This invention provides a method for synthesizing lactone compounds, comprising the following steps: under visible light irradiation, in an oxygen atmosphere, and in the presence of a photocatalyst and a cerium catalyst, a cyclic ketone compound containing a structural fragment as shown in Formula II is subjected to a cyclization reaction in a solvent as follows, to obtain a lactone compound containing a structural fragment as shown in Formula I.

[0009]

[0010] Where n is 0, 1, 2 or 3;

[0011] M is C1-C 20 alkylene, by R 1-1 Replacement C1-C 20 Alkylene, C1-C 20 heteroalkyl, by R 1-2 Replacement C1-C 20 heteroalkyl or C2-C 15 The subalkenyl group, the C1-C 20 heteroalkyl and R 1-2 Replacement C1-C 20 The heteroatoms in the heteroalkylene group are independently one or more of O, S and N, and the number is 1, 2 or 3;

[0012] R 1-1 Independently halogenated, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or R-containing 1-1-1 Substituted C2-C4 alkynyl groups, C6-C 14 aryl, 3-6 cycloalkyl, and R 1-1-2 Substituted 3-6 cycloalkyl groups, -OR 1-1-3 or -(C=O)OR 1 -1-4 ;

[0013] R 1-1-1 Independently

[0014] R 1-1-1-1a R 1-1-1-1b and R 1-1-1-1c Alkyl groups that are independently C1-C4;

[0015] R 1-1-2 Alkyl groups that are independently C1-C4;

[0016] R 1-1-3 It is a C1-C4 alkyl group, a C1-C4 alkyl group substituted with a phenyl group, or a C6-C group. 14 aryl, benzoyl or (-TBS);

[0017] R 1-1-4 It is a C1-C4 alkyl group;

[0018] Or, any two adjacent R 1-1 Together with the carbon atoms it is attached to, they form C6-C. 14 aryl, R 1-1a Replacement C6-C14 aryl, 3-6 cycloalkyl, and R 1-1b Substituted 3-6 cycloalkyl groups

[0019] R 1-1a and R 1-1b Independently halogenated, C1-C4 alkoxy or C6-C 14 aryl;

[0020] Or, any two non-adjacent R 1-1 Together with the carbon atom attached thereto, they form a 3-6 membered heterocyclic alkyl group or a 3-6 membered heterocyclic alkyl group substituted with an amino protecting group, wherein the heteroatom in the 3-6 membered heterocyclic alkyl group or the 3-6 membered heterocyclic alkyl group substituted with an amino protecting group is N, and the number is 1 or 2.

[0021] R 1-2 -(C=O)R 1-2-1 ;

[0022] R 1-2-1 For C6-C 14 aryl or

[0023] The R mentioned 1-1 The R mentioned above 1-2 The R mentioned above 1-1-1 The R mentioned above 1-1-2 The R mentioned above 1-1a and the R mentioned above 1-1b The number of each can be 1, 2, or 3 independently.

[0024] In the cyclization reaction described herein, those skilled in the art will understand that the visible light is not used for illumination purposes; rather, the visible light provides the energy required to activate the reaction in this invention. The visible light is preferably blue light. The wavelength of the blue light is preferably 380-650 nm.

[0025] In the cyclization reaction, the intensity of the visible light illumination can be a conventional light intensity in the art, preferably 0.1-0.2 W / cm². 2 For example, 0.12 W / cm 2 .

[0026] In the cyclization reaction described above, the oxygen atmosphere refers to a gaseous atmosphere containing oxygen, which can be a conventional oxygen atmosphere in the art. The volume content of oxygen in the oxygen atmosphere is preferably 5-100%, such as oxygen or air.

[0027] In the cyclization reaction, the photocatalyst can be a conventional photocatalyst in the art, preferably an organic photocatalyst. The organic photocatalyst is preferably...

[0028] One or more of them, more preferably One or more of them, the most preferred is

[0029] In the cyclization reaction, the molar ratio of the photocatalyst to the cyclic ketone compound containing the structural fragment shown in Formula II can be a conventional molar ratio in the art, preferably 0.01:1-0.1:1, for example 0.02:1.

[0030] In the cyclization reaction, the cerium catalyst can be a conventional cerium catalyst in the art, preferably one or more of CeCl3, [(n-Bu)4N]2[CeCl6], CeBr3, CeF3, Ce(OTf)3, Ce(OTf)4, Ce(NO3)3·3H2O and Ce(OAc)3·1.5H2O, more preferably one or more of CeCl3, [(n-Bu)4N]2[CeCl6], Ce(OTf)3, Ce(OTf)4 and Ce(NO3)3·3H2O, most preferably Ce(OTf)3 or Ce(OTf)4, and most preferably Ce(OTf)3.

[0031] In the cyclization reaction, the molar ratio of the cerium catalyst to the cyclic ketone compound containing the structural fragment shown in Formula II can be a conventional amount in the art, preferably 0.01:1-0.1:1, for example 0.02:1.

[0032] In the cyclization reaction, the solvent can be a conventional solvent in the art, preferably one or more of the following: nitrile solvents (e.g., acetonitrile), ester solvents (e.g., ethyl acetate), ketone solvents (e.g., acetone), chlorinated hydrocarbon solvents (e.g., dichloromethane or trichloromethane), sulfoxide solvents (dimethyl sulfoxide), amide solvents (N,N-dimethylformamide), ether solvents (e.g., tetrahydrofuran), and aromatic hydrocarbon solvents (e.g., trifluorotoluene, benzonitrile, chlorobenzene, fluorobenzene), preferably ester solvents and / or ketone solvents, more preferably ester solvents.

[0033] In the cyclization reaction, the amount of solvent used is not specifically limited, as long as it does not affect the reaction. The molar concentration of the cyclic ketone compound containing the structural fragment shown in Formula II is preferably 0.02-0.1 M, for example, 0.05 M.

[0034] The cyclization reaction can be carried out at a temperature that is conventional for such reactions in the art, preferably 25°C.

[0035] In this invention, the progress of the cyclization reaction can be detected using conventional monitoring methods in the art (TLC, NMR, HPLC), and the reaction endpoint is generally defined as the disappearance or cessation of reaction of the cyclic ketone compound containing the structural fragment shown in Formula II. The preferred reaction time is 12 hours.

[0036] In a preferred embodiment of the invention, the cyclization reaction is carried out in the presence of trifluoroacetic acid. The molar ratio of the trifluoroacetic acid to the compound containing the structural fragment shown in Formula II is preferably 0.1:1 to 1.0:1, for example, 0.6.

[0037] In a preferred embodiment of the present invention, the cyclization reaction is carried out in the presence of an additive.

[0038] The additives are preferably quaternary ammonium salts and / or quaternary phosphine salts.

[0039] The quaternary ammonium salt is preferably one or more of (n-Bu)4NCl, Et4NCl, (n-Bu)4NBr, (n-Bu)4NOTf, and (n-Bu)4NHSO4, more preferably one or more of (n-Bu)4NCl, Et4NCl, (n-Bu)4NOTf, and (n-Bu)4NH2PO4, and most preferably (n-Bu)4NCl.

[0040] The quaternary phosphine salt is preferably one or more of (n-Bu)4PCl, (n-Bu)4PBr and (n-Bu)4NH2PO4, and more preferably (n-Bu)4PCl.

[0041] The molar ratio of the additive to the compound containing the structural fragment shown in Formula II can be a conventional molar ratio in the art, preferably 0.02:1-0.08:1, more preferably 0.02:1-0.04:1.

[0042] In a preferred embodiment of the present invention, the oxygen atmosphere is oxygen;

[0043] The photocatalyst is

[0044] The cerium catalyst is Ce(OTf)3;

[0045] The solvent is an ester solvent;

[0046] The cyclization reaction is carried out in the presence of an additive;

[0047] The additive mentioned is (n-Bu)4PCl.

[0048] In a preferred embodiment of the present invention, the oxygen atmosphere is oxygen;

[0049] The photocatalyst is

[0050] The cerium catalyst is Ce(OTf)3;

[0051] The solvent is an ester solvent;

[0052] The cyclization reaction was carried out in the presence of an additive and trifluoroacetic acid;

[0053] The additive mentioned is (n-Bu)4PCl.

[0054] In a preferred embodiment of the present invention, n is 0.

[0055] In a preferred embodiment of the present invention, when M is C1-C 20 When alkylene, the C1-C 20 The alkylene group is C1-C 13 Alkylene, further can be

[0056] In a preferred embodiment of the present invention, when M is the subject of R 1-1 Replacement C1-C 20 When alkylene, the C1-C 20 The alkylene group is a C4-C7 alkylene group, and can further be...

[0057] In a preferred embodiment of the present invention, when the R 1-1 The R mentioned above 1-2 The R mentioned above 1-1-1 The R mentioned above 1-1-2 The R mentioned above 1-1a and the R mentioned above 1-1b When the number of elements is independently 2 or 3, the R... 1-1 The R mentioned above 1-2 The R mentioned above 1 -1-1 The R mentioned above 1-1-2 The R mentioned above 1-1a Or the R mentioned above 1-1b Independently the same or different.

[0058] In a preferred embodiment of the present invention, when R 1-1 When it is a halogen on its own, the halogen is F, Cl, Br or I, and may also be F or Br.

[0059] In a preferred embodiment of the present invention, when R1-1 When independently a C1-C4 alkyl group, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl, isopropyl, or tert-butyl.

[0060] In a preferred embodiment of the present invention, when R 1-1 Independently for R 1-1-1 When the C2-C4 alkynyl group is substituted, the C2-C4 alkynyl group is an acetylene group.

[0061] In a preferred embodiment of the present invention, when R 1-1-1-1a R 1-1-1-1b and R 1-1-1-1c When independently a C1-C4 alkyl group, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl.

[0062] In a preferred embodiment of the present invention, when R 1-1 Independently for R 1-1-1 When the C2-C4 alkynyl group is substituted, the R- 1-1-1 The substituted C2-C4 acetylene group is

[0063] In a preferred embodiment of the present invention, when R 1-1 Independently for C6-C 14 When the aryl group is present, the C6-C 14 The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0064] In a preferred embodiment of the present invention, when R 1-1 Independently 3-6 cycloalkyl or R 1-1-2 When the 3-6 cyclic alkyl group is substituted, the 3-6 cyclic alkyl group is cyclopropane, cyclobutane, cyclopentane, or cyclohexane, and may also be cyclohexane.

[0065] In a preferred embodiment of the present invention, when R 1-1-2 When the alkyl group is independently C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be n-propyl.

[0066] In a preferred embodiment of the present invention, when R 1-1 Independently for R 1-1-2 When the 3-6 membered cycloalkyl group is substituted, the R- 1-1-2 The substituted 3-6 cycloalkyl group is

[0067] In a preferred embodiment of the present invention, when R1-1-3 When the alkyl group is C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl.

[0068] In a preferred embodiment of the present invention, when R 1-1-3 When the alkyl group is a C1-C4 alkyl group substituted with a phenyl group, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl.

[0069] In a preferred embodiment of the present invention, when R 1-1-3 For C6-C 14 When the aryl group is present, the C6-C 14 The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0070] In a preferred embodiment of the present invention, when R 1-1-3 When the alkyl group is C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be tert-butyl.

[0071] In a preferred embodiment of the present invention, when any two adjacent R 1-1 Together with the carbon atoms it is attached to, they form C6-C. 14 aryl or R 1-1a Replacement C6-C 14 When the aryl group is present, the C6-C 14 The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0072] In a preferred embodiment of the present invention, when R 1-1a and R 1-1b When it is a halogen on its own, the halogen is F, Cl, Br or I, and may also be Br.

[0073] In a preferred embodiment of the present invention, when R 1-1a and R 1-1b When the alkoxy group is independently C1-C4, the C1-C4 alkoxy group can be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, or tert-butoxy, and may also be methoxy.

[0074] In a preferred embodiment of the present invention, when R 1-1a and R 1-1b Independently for C6-C 14 When the aryl group is present, the C6-C 14 The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0075] In a preferred embodiment of the present invention, when any two adjacent R 1-1 Together with the carbon atoms it is attached to, they form R 1 -1a Replacement C6-C 14 When the aryl group is present, the R group is... 1-1a Replacement C6-C 14 The aryl group is

[0076] In a preferred embodiment of the present invention, when any two adjacent R 1-1 Together with the carbon atom it is attached to, it forms a 3-6 membered cycloalkyl group or is R 1-1b When the 3-6 cyclic alkyl group is substituted, the 3-6 cyclic alkyl group is cyclopropane, cyclobutane, cyclopentane, or cyclohexane, and may also be cyclopropane.

[0077] In a preferred embodiment of the present invention, when any two adjacent R 1-1 Together with the carbon atoms it is attached to, they form R 1 -1b When the 3-6 membered cycloalkyl group is substituted, the R- 1-1b The substituted 3-6 cycloalkyl group is

[0078] In a preferred embodiment of the present invention, when any two non-adjacent R... 1-1 When the ring atoms attached to it form a 3-6 membered heterocyclic alkyl group substituted with an amino protecting group, the 3-6 membered heterocyclic alkyl group substituted with an amino protecting group is...

[0079] In a preferred embodiment of the present invention, when M is the subject of R 1-1 Replacement C1-C 20 When alkylene, the R 1-1 Replacement C1-C 20 The alkylene group is

[0080] In a preferred embodiment of the present invention, when M is C1-C 20 heteroalkyl or R 1-2 Replacement C1-C 20 When the heteroalkylene group is used, the C1-C 20 The heteroalkylene compounds are C1-C5 heteroalkylene compounds.

[0081] In a preferred embodiment of the present invention, when R 1-2-1 For C6-C 14 When the aryl group is present, the C6-C 14The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0082] In a preferred embodiment of the present invention, when M is the subject of R 1-2 Replacement C1-C 20 When the heteroalkylene group is used, the C1-C 20 Hesines are

[0083] In a preferred embodiment of the present invention, when M is C2-C 20 When the sub-alkenyl group is present, the C2-C 20 The alkenyl group is a C2-C6 alkenyl group, further being...

[0084] In a preferred embodiment of the present invention, the cyclic ketone compound containing the structural fragment shown in Formula II is the compound shown in Formula II-a, and correspondingly, the lactone compound containing the structural fragment shown in Formula I is the compound shown in Formula Ia.

[0085]

[0086] Wherein, the definitions of M and n are as described in any of the above schemes;

[0087] R 2a R 2b R 3a R 3b R 4a and R 4b Independently hydrogen, C1-C4 alkyl, and R 2a-1 Substituted C1-C4 alkyl groups, -OR 2a-2 C2-C4 alkenyl, C2-C4 alkynyl, and R 2a-3 Substituted C2-C4 alkynyl groups, C6-C 14 aryl, -(C=O)OR 2a-4 3-6 cyclic alkyl groups, 3-6 heterocyclic alkyl groups, and R 2a-5 Substituted 3-6 membered heterocyclic alkyl groups; the 3-6 membered heterocyclic alkyl groups and the R 2a-5 The heteroatoms in the substituted 3-6-membered heterocyclic alkyl groups are selected from one or more of N, S and O, and the number is 1, 2 or 3.

[0088] R 2a-1 Independently halogenated, -S(=O)2Ph, adamantyl, C6-C 14 aryl, R 2a-1-1 Replacement C6-C 14 aryl or OR 2a-1-2 ;

[0089] R2a-1-1 It is independently a halogen or a C1-C4 alkyl group;

[0090] R 2a-1-2 For C2-C6 alkynyl groups, (-TBS), C6-C 14 aryl, R 2a-1-2-1 Replacement C6-C 14 aryl or benzyl (-Bn); R 2a-1-2-1 It is independently a halogen or a C1-C4 alkyl group;

[0091] R 2a-2 and R 2a-3 Independently R 2a-3-1a R 2a-3-1b and R 2a-3-1c Alkyl groups that are independently C1-C4;

[0092] R 2a-4 It is a C1-C4 alkyl group;

[0093] R 2a-5 Independently -(C=O)R 2a-5-1 ;

[0094] R 2a-5-1 For C6-C 14 aryl or

[0095] The R mentioned 2a-1 The R mentioned above 2a-3 The R mentioned above 2a-5 The R mentioned above 2a-1-1 and R 2a-1-2-1 The number of each can be 1, 2, or 3 independently.

[0096] In a preferred embodiment of the present invention, R 2a R 2b R 3a R 3b R 4a and R 4b It is independently hydrogen, a C1-C4 alkyl group, or a 3-6 cycloalkyl group.

[0097] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b When independently a C1-C4 alkyl group, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl, n-butyl, or tert-butyl.

[0098] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b Independently for R 2a-1 When the substituted C1-C4 alkyl group is substituted, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl or ethyl.

[0099] In a preferred embodiment of the present invention, when R 2a-1 When the halogen is halogen, the halogen is F, Cl, Br or I, and it can also be F.

[0100] In a preferred embodiment of the present invention, when R 2a-1 For C6-C 14 aryl or R 2a-1-1 Replacement C6-C 14 When the aryl group is present, the C6-C 14 The aryl group can be phenyl, naphthyl, anthraceneyl, or phenanthrene, and can also be phenyl.

[0101] In a preferred embodiment of the present invention, when R 2a-1-1 When the halogen is halogen, the halogen is F, Cl, Br or I, and it can also be Br.

[0102] In a preferred embodiment of the present invention, when R 2a-1-1 When the alkyl group is C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be tert-butyl.

[0103] In a preferred embodiment of the present invention, when R 2a-1 For R 2a-1-1 Replacement C6-C 14 When the aryl group is present, the R... 2a-1-1 Replacement C6-C 14 The aryl group is

[0104] In a preferred embodiment of the present invention, when R 2a-1-2 When the alkynyl group is C2-C6, the C2-C6 alkynyl group is an acetylene group.

[0105] In a preferred embodiment of the present invention, when R 2a-1-2 For C6-C 14 When the aryl group is present, the C6-C 14 The aryl group is phenyl, naphthyl, or anthracene, preferably phenyl.

[0106] In a preferred embodiment of the present invention, when R 2a-1-2 For R 2a-1-2-1 Replacement C6-C 14 When the aryl group is present, the C6-C 14 The aryl group is phenyl, naphthyl, or anthracene, preferably phenyl.

[0107] In a preferred embodiment of the present invention, when R 2a-1-2-1 When the halogen is halogen, the halogen is F, Cl, or Br, and it can also be Br.

[0108] In a preferred embodiment of the present invention, when R 2a-1-2-1 When the alkyl group is C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be tert-butyl.

[0109] In a preferred embodiment of the present invention, when R 2a-1-2 For R 2a-1-2-1 Replacement C6-C 14 When the aryl group is present, the R... 2a-1-2-1 Replacement C6-C 14 The aryl group is

[0110] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b Independently for R 2a-1 When the C1-C4 alkyl group is substituted, the R 2a-1 The substituted C1-C4 alkyl groups are

[0111] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b When the alkenyl group is independently C2-C4, the C2-C4 alkenyl group can be butenyl, or more specifically, […].

[0112] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b Independently a C2-C4 alkynyl group or a group consisting of R 2a-3When the C2-C4 alkynyl group is substituted, the C2-C4 alkynyl group can be a propynyl group.

[0113] In a preferred embodiment of the present invention, when R 2a-3-1a R 2a-3-1b and R 2a-3-1c When independently a C1-C4 alkyl group, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be methyl or tert-butyl. In a preferred embodiment of the invention, when R... 2a R 2b R 3a R 3b R 4a and R 4b Independently for R 2a-3 When the C2-C4 alkynyl group is substituted, the R- 2a-3 The substituted C2-C4 alkynyl group is

[0114] In a preferred embodiment of the present invention, when R 2a-4 When the alkyl group is C1-C4, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl, and may also be ethyl.

[0115] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b When independently a 3-6 membered cycloalkyl group, the 3-6 membered cycloalkyl group is cyclohexane.

[0116] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b Independently a 3-6 membered heterocyclic alkyl group or a derivative thereof. 2a-5 When the substituted 3-6 membered heterocyclic alkyl group is replaced, the 3-6 membered heterocyclic alkyl group is piperidinyl.

[0117] In a preferred embodiment of the present invention, when R 2a R 2b R 3a R 3b R 4a and R 4b Independently for R 2a-5 When the 3-6 membered heterocyclic alkyl group is substituted, the R 2a-5The substituted 3-6 membered heterocyclic alkyl group is

[0118] In a preferred embodiment of the present invention, when the R 2a-1 The R mentioned above 2a-3 The R mentioned above 2a-5 The R mentioned above 2a-1-1 and R 2a-1-2-1 When the number of elements is independently 2 or 3, the R... 2a-1 The R mentioned above 2a-3 The R mentioned above 2a-5 The R mentioned above 2a-1-1 Or R 2a -1-2-1 Independently the same or different.

[0119] The method for synthesizing the lactone compound may further include the following steps: under the action of a Lewis acid, in a solvent, the compound shown in Formula III and the compound containing the structural fragment shown in Formula IV are subjected to an alkylation reaction as follows to obtain the cyclic ketone compound containing the structural fragment shown in Formula II.

[0120]

[0121] Among them, Q + Potassium ions or lithium ions;

[0122] The definitions of M and n are as described in the previous section.

[0123] The conditions and procedures for the alkylation reaction described herein can be conventional conditions and procedures for such reactions in the art, but the following conditions and procedures are particularly preferred in this invention:

[0124] In the alkylation reaction, the Lewis acid is preferably boron trifluoride, such as boron trifluoride diethyl ether solution.

[0125] In the alkylation reaction, the solvent is preferably an ether solvent, and more preferably tetrahydrofuran and / or diethyl ether.

[0126] In the alkylation reaction, the molar ratio of the compound containing the structural fragment shown in Formula IV to the compound shown in Formula III is preferably 4.0:1 to 1.0:1, for example 2.0:1.

[0127] The preferred temperature for the alkylation reaction is (-78°C) to (-70°C), for example, -78°C.

[0128] The alkylation reaction can be monitored using conventional methods in the art (e.g., TLC, HPLC, NMR), and the reaction endpoint is generally defined as the point at which the compound represented by Formula III ceases to react or disappears. The reaction time is preferably 4-5 hours, for example, 3 hours.

[0129] In a preferred embodiment of the present invention, the compound containing the structural fragment shown in Formula IV is the compound shown in Formula IV-a; correspondingly, the cyclic ketone containing the structural fragment shown in Formula II is the compound shown in Formula II-a.

[0130]

[0131] Among them, Q, M, n, R 2a R 2b R 3a R 3b R 4a and R 4b The definitions are the same as those described in any of the above schemes.

[0132] In a preferred embodiment of the present invention, the compound represented by Formula III is any of the following compounds:

[0133]

[0134] In a preferred embodiment of the present invention, the compound represented by formula IV-a is any of the following compounds:

[0135] The method for synthesizing the lactone compound may further include the following steps: in the presence of a basic reagent, in a solvent, a cyclic ketone compound containing formula V is subjected to a dehydrogenation reaction as shown in the following formula to obtain the compound containing formula III.

[0136]

[0137] The definitions of Q and M are the same as those in the previous scheme.

[0138] In the aforementioned dehydrogenation reaction, the solvent can be a conventional solvent used in such reactions in the art, preferably an ether solvent, and more preferably tetrahydrofuran and / or diethyl ether.

[0139] In the aforementioned dehydrogenation reaction, the alkaline reagent can be a conventional alkaline reagent used in such reactions in the art, preferably an amino alkali metal salt, and more preferably bis(trimethylsilyl)aminopotassium (KHMDS) and / or bis(trimethylsilyl)aminolithium (LiHMDS).

[0140] In the aforementioned dehydrogenation reaction, the molar ratio of the basic reagent to the compound containing the structural fragment shown in Formula V can be a conventional molar ratio for such reactions in the art, preferably 1.0:1-1.5:1, for example 1.2:1.

[0141] The preferred temperature for the hydrogen removal reaction is (-78℃) to (-70℃), for example, -78℃.

[0142] In a preferred embodiment of the present invention, the compound represented by formula V is any of the following compounds:

[0143]

[0144]

[0145] This invention also provides a method for synthesizing lactone compounds, comprising the following steps:

[0146] Step 1: In the presence of an alkaline reagent, the compound shown in Formula V is subjected to a dehydrogenation reaction in a solvent to obtain a mixture;

[0147] Step 2: Under the action of Lewis acid, in a solvent, the mixture obtained according to the preparation method in Step 1 is subjected to an alkylation reaction with a compound containing the structural fragment shown in Formula IV to obtain an alkylated product;

[0148] Step 3: Under visible light irradiation, in an oxygen atmosphere, and in the presence of a photocatalyst and a cerium catalyst, the alkylated product obtained according to the preparation method in Step 2 is subjected to a cyclization reaction in a solvent to obtain a lactone compound containing the structural fragment shown in Formula I.

[0149]

[0150] The definitions of M and n are the same as those described in any of the above schemes;

[0151] The conditions and operations in steps 1, 2 and 3 are the same as those described in any of the above schemes.

[0152] In a preferred embodiment of the present invention, the compound containing the structural fragment shown in Formula IV is the compound shown in Formula IV-a; correspondingly, the lactone compound containing the structural fragment shown in Formula I is the compound shown in Formula Ia;

[0153]

[0154] Among them, M, n, R 2a R 2b R 3a R 3b R4a and R 4b The definitions are the same as those in the previous scheme.

[0155] The present invention also provides a compound as shown in Formula Ia:

[0156]

[0157] Among them, n, M, R 2a R 2b R 3a R 3b R 4a and R 4b The definitions are the same as those described above, and the compound shown in formula Ia is not one of the following compounds.

[0158] The compound represented by formula Ia is any one of the following compounds:

[0159]

[0160]

[0161]

[0162] The present invention also provides the use of a compound of formula Ia in the preparation of a compound of formula VII;

[0163] The preparation method of the compound shown in Formula VII includes the following steps: in the presence of a reducing agent, the compound shown in Formula Ia is subjected to a reduction reaction in a solvent as follows to obtain the compound shown in Formula VII;

[0164]

[0165] Among them, n, M, R 2a R 2b R 3a R 3b R 4a and R 4b The definitions are the same as those described above.

[0166] The conditions and procedures for the reduction reaction can be those conventional in the art.

[0167] In this invention, "alkyl" refers to a straight-chain or branched alkyl group having a specified number of carbon atoms.

[0168] In this invention, "alkylene" refers to a subunit of a saturated straight-chain or branched hydrocarbon formed by the formal elimination of two monovalent or one divalent atom or group. The two valences can be on the same carbon atom or on different carbon atoms (e.g., the two valences are on the carbon atoms at opposite ends). For example, methylene can be (-CH2-), and ethylene can be -CH2CH2- or -CH(CH3)-.

[0169] In this invention, "heteroalkylene" refers to a subunit of a saturated straight-chain or branched heteroalkane formed by formally eliminating two monovalent or one divalent atom or group. The two valences can be on the same carbon atom or on different carbon atoms (e.g., the two valences are on the carbon atoms at opposite ends). For example, an ethylene containing an oxygen atom can be -CH2OCH2- or -CHO(CH3)-, etc., and a butylene containing an nitrogen atom can be... wait.

[0170] In this invention, "alkenyl" refers to a subunit of a straight-chain or branched olefin having one or more carbon-carbon double bonds and no carbon-carbon triple bonds, formed by formally eliminating two monovalent or one divalent atom or group. The one or more carbon-carbon double bonds can be internal or terminal, for example, a butenyl subunit with the double bond internal. or double bond at the terminal butenyl group The two valences can reside on the same carbon atom or on different carbon atoms (e.g., the two valences are on the carbon atoms at opposite ends). For example, the n-pentene group can be... wait.

[0171] In this invention, "alkynyl" refers to a straight-chain or branched monovalent hydrocarbon group (e.g., C2-C6 alkynyl, or C2-C4 alkynyl) having one or more triple bonds with a specific number of carbon atoms. The one or more carbon-carbon triple bonds can be internal or terminal, for example, butynyl with the triple bond internal. or a butynediyl group at the end of the triple bond wait.

[0172] In this invention, "cycloalkyl" refers to a monocyclic ring system having a stable cyclic structure. Examples of such cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

[0173] In this invention, "heterocyclic alkyl" refers to a "heterocyclic alkyl" system that is not aromatic. "Heterocyclic alkyl" is a monocyclic heterocyclic group.

[0174] In this invention, "aryl" refers to a group having 6-14 atoms and zero heteroatoms, a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 shared p electrons in a cyclic array) ("C6-C14 aryl").

[0175] In this invention, "heteroaryl" refers to a group ("5-10-membered heteroaryl") having a carbon atom and 1-3 heteroatoms (each heteroatom being independently selected from nitrogen, oxygen, and sulfur) in the aromatic ring system of a 4n+2 aromatic ring system of a 5-10 member, either monocyclic or bicyclic (e.g., having 6 or 10 shared p electrons in a cyclic array).

[0176] In this invention, unless otherwise defined as "substituted by" certain substituents, the substituent is considered unsubstituted, for example, "C1-C". 20 "Hypoalkylene" indicates that it has not been substituted by any substituents, "substituted by R" indicates that it has not been substituted by any substituents. 1-1 Replacement C1-C 20 "alkylene" indicates that it is only used by R 1-1 Substituent substitution.

[0177] Generally, the term "substituted" indicates that one or more hydrogen atoms in a given structure are substituted by a specific substituent. Further, when the group is substituted by more than one of the substituents, the substituents are independent of each other; that is, the more than one substituent can be different or the same. Unless otherwise indicated, a substituent can be substituted at each substituted position of the substituted group. When more than one position in a given structural formula can be substituted by one or more substituents selected from a specific group, the substituents can be substituted at the same or different positions.

[0178] In this invention, The left-hand site is connected to the carbonyl group, and the right-hand site is connected to the alkylene group.

[0179] Following the reading convention of left to right and top to bottom, for example, in this invention, the site on the left or top side of the M group is connected to a carbonyl group, and the site on the right or bottom side is connected to an alkylene group. For example, when M is... In this case, site 1 (i.e., the left side) is connected to the carbonyl group, and site 2 (i.e., the right side) is connected to the alkylene group; for example, when M is... At this time, site 1 (i.e., the upper side) is connected to the carbonyl group, and site 2 (i.e., the lower side) is connected to the alkylene group.

[0180] Those skilled in the art will understand that, according to conventions used in the art, the structural formulas of the groups described in this invention are... This refers to the fact that the corresponding group is connected to other fragments or groups in the compound through this site.

[0181] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0182] The reagents and raw materials used in this invention are all commercially available.

[0183] The positive and progressive effects of this invention are as follows: the synthesis method of this invention starts from simple and readily available raw materials (cyclic ketones, epoxides and oxetanes), which can conveniently and quickly synthesize various medium-cyclic and macrocyclic lactones, and is simple to operate, economical and applicable and environmentally friendly. Detailed Implementation

[0184] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0185] In the following embodiments, the wavelength of the blue LED is 380-650nm and the luminous intensity is 0.12W / cm². 2 .

[0186] Example 1

[0187] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0188] Cycloheptanone (1.0 equiv.) was added dropwise to a tetrahydrofuran solution of LHMDS (1.0 M in THF, 1.2 equiv.). After stirring for 30 minutes, a tetrahydrofuran solution of ethylene oxide (2.0 equiv.) was added to the reaction solution. After stirring for 5 minutes, boron trifluoride diethyl ether was slowly added dropwise (0.1 mL / min) to the reaction system. After the addition was complete, stirring was continued at -78 °C for 3 hours. The reaction was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the alkylated cyclic ketone compound (GC-MS (m / z) 156.1). The obtained alkylated cyclic ketone compound (0.1 mmol, 1.0 equiv.), 2 mol% cerium trifluoromethanesulfonate (1.2 mg, 0.002 mmol.), 4 mol% tetrabutylphosphine chloride (1.2 mg, 0.004 mmol), 2 mol% 9,10-diphenylanthracene (0.7 mg, 0.002 mmol), and ethyl acetate (2.0 mL) were added to the reaction flask. The flask was then saturated with oxygen for three minutes and sealed. Afterwards, the mixture was incubated at room temperature (25 °C) under a blue LED lamp (380-650 nm, 0.12 W / cm²). 2 Under irradiation conditions, the reaction proceeded for 12 hours to obtain the lactone product. The reaction equation is as follows:

[0189]

[0190] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (13.6 mg, 80% yield).

[0191] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.44 (t, J = 6.0Hz, 2H), 2.72 (t, J = 6.0Hz, 2H), 2.44 (t, J = 6.4Hz, 2H), 2.31 (t, J = 6.4Hz, 2H), 1.69–1.64 (m, 4H), 1.40–1.37 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.9,173.3,61.5,43.1,39.5,34.8,25.1,23.0,22.2;

[0192] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C9H) 15 O3 + (M+H) + 171.1016, detected value 171.1012.

[0193] Example 2

[0194] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0195] Cyclohexanone (1.0 equiv.) was added dropwise to a tetrahydrofuran solution of KHMDS (1.0 M in THF, 1.2 equiv.) at -78 °C. After stirring for 30 minutes, a tetrahydrofuran solution of ethylene oxide (2.0 equiv.) was added to the reaction solution. After stirring for 5 minutes, boron trifluoride diethyl ether was slowly added dropwise (0.1 mL / min) to the reaction system. After the addition was complete, stirring was continued at -78 °C for 3 hours. The reaction was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the alkylated cyclic ketone compound. The obtained alkylated cyclic ketone compound (0.1 mmol, 1.0 equiv.), 2 mol% cerium trifluoromethanesulfonate (1.2 mg, 0.002 mmol.), 4 mol% tetrabutylphosphine chloride (1.2 mg, 0.004 mmol), 2 mol% 9,10-diphenylanthracene (0.7 mg, 0.002 mmol), 0.6 eq trifluoroacetic acid (5 μL), and ethyl acetate (2.0 mL) were added to the reaction flask. The flask was then saturated with oxygen for three minutes and sealed. Afterwards, the mixture was incubated at room temperature (25 °C) under a blue LED lamp (380-650 nm, 0.12 W / cm²). 2 Under irradiation conditions, the reaction proceeded for 12 hours to obtain the lactone product. The reaction equation is as follows:

[0196]

[0197] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (11.1 mg, 65% yield).

[0198] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.26 (t, J = 5.2Hz, 2H), 2.43 (t, J = 4.8Hz, 2H), 2.42–2.34 (m, 4H), 2.16–2.10 (m, 2H), 1.78–1.73 (m, 4H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.7,173.2,64.2,41.7,38.9,34.4,26.6,22.7,20.6;

[0199] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C9H) 15 O3 + (M+H)+ 171.1016, detected value 171.1009.

[0200] Example 3

[0201] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0202] Cyclohexanone (1.0 equiv.) was added dropwise to a tetrahydrofuran solution of LHMDS (1.0 M in THF, 1.2 equiv.) at -78 °C. After stirring for 30 minutes, a tetrahydrofuran solution of ethylene oxide (2.0 equiv.) was added to the reaction solution. After stirring for 5 minutes, boron trifluoride diethyl ether was slowly added dropwise (0.1 mL / min) to the reaction system. After the addition was complete, stirring was continued at -78 °C for 3 hours. The reaction was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the alkylated cyclic ketone compound. The obtained alkylated cyclic ketone compound (0.1 mmol, 1.0 equiv.), 2 mol% cerium trifluoromethanesulfonate (1.2 mg, 0.002 mmol.), 4 mol% tetrabutylphosphine chloride (1.2 mg, 0.004 mmol), 2 mol% 9,10-diphenylanthracene (0.7 mg, 0.002 mmol), 0.6 eq trifluoroacetic acid (5 μL), and ethyl acetate (2.0 mL) were added to the reaction flask. The flask was then saturated with oxygen for three minutes and sealed. Afterwards, the mixture was incubated at room temperature (25 °C) under a blue LED lamp (380-650 nm, 0.12 W / cm²). 2 Under irradiation conditions, the reaction proceeded for 12 hours to obtain the lactone product. The reaction equation is as follows:

[0203]

[0204] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (16.7 mg, 70% yield).

[0205] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.12 (q, J = 8.0Hz, 1H), 2.71 (d, J = 8.0Hz, 2H), 2.51–2.45 (m, 2H), 2.24–2.28 (m, 2H), 2.10–2.07 (m, 1H), 1.92–1.88 (m, 1H), 1.80–1.58 (m, 8H), 1.28–1.14 (m, 3H), 1.07–0.99 (m, 2H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ210.2,174.8,75.8,46.7,42.5,40.1,34.9,28.4,28.4,26.2,25.7,25.6,24.0,23.8;

[0206] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 23 O3 + (M+H) + 239.1642, detected value 239.1635.

[0207] Example 4

[0208] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0209] The operation steps are the same as in Example 3.

[0210] The reaction equation is as follows:

[0211]

[0212] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (21.7 mg, 67% yield).

[0213] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ 7.93–7.91 (d, J = 8.0 Hz, 2H), 7.70–7.66 (t, J = 7.2 Hz, 1H), 7.61–7.57 (t, J = 7.2 Hz, 2H), 5.38–5.31 (m, 1H), 3.20–3.16 (t, J = 8.0 Hz, 2H), 2.85 (dd, J = 13.6 Hz, 6.0 Hz, 1H), 2.57 (dd, J = 13.6 Hz, 8.0 Hz, 1H), 2.45–2.40 (m, 2H), 2.30–2.20 (m, 2H), 2.19–2.02 (m, 3H), 1.89–1.83 (m, 1H), 1.71–1.67 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.6,174.7,138.87,133.9,129.4,128.0,70.3,52.6,47.9,40.3,34.7,28.0,23.9,23.7;

[0214] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21O5S + (M+H) + 325.1104, detected value 325.1102.

[0215] Example 5:

[0216] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0217] The operation steps are the same as in Example 3.

[0218] The reaction equation is as follows:

[0219]

[0220] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.2 mg, 63% yield).

[0221] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 5.88–5.76 (m, 1H), 5.41–5.31 (m, 1H), 5.11–4.95 (m, 2H), 2.85 (dd, J = 13.6, 6.2 Hz, 1H), 2.64–2.42 (m, 3H), 2.33–2.22 (m, 2H), 2.19–0.04 (m, 3H), 1.99–1.82 (m, 2H), 1.79–1.62 (m, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.7,174.8,137.2,115.4,71.5,48.2,40.5,34.8,34.3,29.4,24.0,23.9;

[0222] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 19 O3 + (M+H) + 211.1329, detected value 211.1327.

[0223] Example 6:

[0224] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0225] The operation steps are the same as in Example 3.

[0226] The reaction equation is as follows:

[0227]

[0228] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (21.0 mg, 62% yield, 1.3:1 d.r.).

[0229] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.23 (q, J = 8.0 Hz, 1H), 3.9–3.58 (br, 2H), 2.92 (t, J = 11.0 Hz, 1H), 2.80–2.75 (m, 3H), 2.49–2.45 (m, 2H), 2.30–2.24 (m, 2H), 2.13–2.00 (m, 1H), 1.92–1.82 (m, 2H), 1.75–1.62 (m, 4H), 1.45 (s, 9H), 1.36–1.33 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.4,174.7,154.8,79.7,72.7,46.7,40.5,40.2,38.4,34.8,29.7,28.4,28.3,26.0,23.9,23.7;

[0230] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 29 NNaO5 + (M+Na) + 362.1938, detected value 362.1929.

[0231] Example 7:

[0232] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0233] The operation steps are the same as in Example 3.

[0234] The reaction equation is as follows:

[0235]

[0236] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (20.1 mg, 66% yield).

[0237] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.59–5.53 (m, 1H), 2.82 (dd, J = 12.4 Hz, 6.0 Hz, 1H), 2.58–2.46 (m, 2H), 2.42–2.21 (m, 3H), 2.09–2.04 (m, 1H), 1.93–1.89 (m, 4H), 1.73–1.56 (m, 15H), 1.29 (dd, J = 14.8, 3.6 Hz, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.3,174.3,68.5,49.9,49.8,42.4,41.9,36.9,35.132.6,28.5,24.3,23.8;

[0238] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 19 H 29 O3 + (M+H) + 305.2111, detected value 305.2107.

[0239] Example 8:

[0240] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0241] The operation steps are the same as in Example 3.

[0242] The reaction equation is as follows:

[0243]

[0244] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (11.4 mg, 51% yield).

[0245] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3): 1 ¹H NMR (400MHz, CDCl₃) δ 5.50 (m, 1H), 4.21 (d, J = 2.0Hz, 2H), 3.76–3.66 (m, 2H), 2.85 (dd, J = 13.2, 6.0Hz, 1H), 2.72–2.66 (dd, J = 13.6, 8.0Hz, 1H), 2.55–2.45 (m, 3H), 2.34–2.24 (m, 2H), 2.12–2.02 (m, 1H), 1.98–1.88 (m, 1H), 1.76–1.65 (m, 2H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ209.4,174.5,79.0,75.1,70.3,69.6,58.5,44.3,40.8,34.8,24.0,23.9;

[0246] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 17 O4 + (M+H) + 225.1121, detected value 225.1116.

[0247] Example 9:

[0248] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0249] The operation steps are the same as in Example 3.

[0250] The reaction equation is as follows:

[0251]

[0252] After the reaction was completed, the product was concentrated and separated by column chromatography to obtain the target product (18.4 mg, 68% yield, 1.8:1 d.r.).

[0253] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.18 (dd, J = 10.0, 6.8 Hz, 1H), 3.71 (s, 3H), 3.01 (dd, J = 16.0, 8.0 Hz, 1H), 2.86 (dd, J = 11.6, 10.0 Hz, 1H), 2.79–2.73 (m, 2H), 2.66 (dt, J = 16.0, 4.4 Hz, 1H), 2.55–2.50 (dd, J = 12.0, 6.8 Hz, 1H), 2.36–2.28 (m, 1H), 2.12–2.07 (m, 2H), 0.95 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ207.7,174.8,173.4,79.0,52.2,43.8,43.8,41.2,34.6,33.8,26.1,25.2;

[0254] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 23 O5 + (M+H) + 271.1540, detected value 271.1532

[0255] Example 10:

[0256] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0257] The operation steps are the same as in Example 3.

[0258] The reaction equation is as follows:

[0259]

[0260] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.1 mg, 71% yield).

[0261] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 4.51 (dd, J=7.9, 4.5Hz, 2H), 3.06–2.95 (m, 1H), 2.54–2.39 (m, 3H), 2.25–2.11 (m, 2H), 1.90–1.79 (m, 1H), 1.69–1.62 (m, 1H), 1.52–1.40 (m, 1H), 0.90 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.5,174.5,61.4,49.2,44.5,39.6,36.1,34.3,27.9,27.1;

[0262] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 21 O3+(M+H) + 213.1485, detected value 213.1475

[0263] Example 11:

[0264] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0265] The operation steps are the same as in Example 3.

[0266] The reaction equation is as follows:

[0267]

[0268] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.8 mg, 65% yield).

[0269] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (500MHz, CDCl3) δ7.31-7.22(m,5H),5.52-5.47(m,1H),3.11(dd,J=14.0,7.0Hz, 1H),2.91(dd,J=14.0,7.5Hz,1H),2.82(dd,J=14.0,7.0Hz,1H),2.57(d,J=15.7Hz,1 2.49–2.41 (m, 2H), 2.37–2.30 (m, 1H), 2.04 (td, J = 14.3 Hz, 4.0 Hz, 1H), 1.95 (d, J = 15.7 Hz, 1H), 1.33 (dt, J = 14.5 Hz, 4.0 Hz, 1H), 1.23 (s, 3H), 0.96 (s, 3H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (125MHz, CDCl3) δ208.4,174.6,136.3,129.4,128.5,126.8,72.1,49.9,48.0,41.1,35.4,35.2,31.8,31.3,28.8;

[0270] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 23 O3 + (M+H) + 275.1642, detected value 275.1633.

[0271] Example 12:

[0272] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0273] The operation steps are the same as in Example 3.

[0274] The reaction equation is as follows:

[0275]

[0276] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (15.4 mg, 61% yield).

[0277] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.07–5.00 (m, 1H), 4.22–4.16 (m, 1H), 3.27–3.21 (m, 1H), 2.92–2.86 (m, 1H), 2.78–2.54 (m, 3H), 2.48–2.40 (m, 2H), 2.19–2.10 (m, 1H), 1.79–1.73 (m, 1H), 0.15 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.1,174.1,107.5,86.6,60.1,45.0,41.6,31.5,28.4,28.3,-0.1;

[0278] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 21 O3Si + (M+H) + 253.1254, detected value 253.1248.

[0279] Example 13:

[0280] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0281] The operation steps are the same as in Example 3.

[0282] The reaction equation is as follows:

[0283]

[0284] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (18.3 mg, 72% yield, 3.1:1 d.r.).

[0285] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.98 (dd, J = 12.0, 4.0 Hz, 1H), 3.02 (m, 1H), 2.87 (t, J = 11.2 Hz, 1H), 2.40 (d, J = 14.4 Hz, 1H), 2.34 (dd, J = 11.2, 4.4 Hz, 1H), 2.20 (d, J = 14.4 Hz, 1H), 1.85 (dd, J = 15.2, 6.0 Hz, 1H), 1.18–1.13 (m, 4H), 1.03 (d, J = 7.6 Hz, 6H), 0.95 (s, 9H); The data from the carbon NMR characterization are as follows: 13C NMR (125MHz, CDCl3) δ215.8,171.8,79.1,46.5,45.6,43.5,43.2,34.5,33.9,33.4,28.1,25.5,19.9;

[0286] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 27 O3 + (M+H) + 255.1955, detected value 255.1951.

[0287] Example 14:

[0288] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0289] The operation steps are the same as in Example 3.

[0290] The reaction equation is as follows:

[0291]

[0292] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (8.3 mg, 43% yield).

[0293] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 4.64 (t, J = 7.0Hz, 2H), 3.01 (t, J = 14.5Hz, 2H), 2.87 (t, J = 7.0Hz, 2H), 2.58–2.55 (m, 2H), 2.36–2.30 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ 202.1, 172.2, 121.6 (t, J = 245.0 Hz, 1C), 60.3, 47.8 (t, J = 23.8 Hz, 1C), 42.0, 32.3 (t, J = 27.5 Hz, 1C), 29.9 (t, J = 6.3 Hz, 1C); The data for fluorine NMR characterization are as follows: 19 F NMR (471MHz, CDCl3) δ-84.07;

[0294] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C8H) 11 F2O3 + (M+H) + 193.0671, detected value 193.0667.

[0295] Example 15:

[0296] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0297] The operation steps are the same as in Example 3.

[0298] The reaction equation is as follows:

[0299]

[0300] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (22.5 mg, 67% yield).

[0301] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.10 (q, J = 5.2Hz, 1H), 2.78 (dd, J = 14.0, 10.4Hz, 1H), 2.53 (dd, J = 14.0Hz, 5.2Hz, 1H), 2.31–2.25 (m, 4H), 2.06–2.03 (m, 1H), 1.89–1.85 (m, 1H), 1.77–1.59 (m, 6H), 1.30–1.26 (m, 3H), 1.15–1.12 (m, 3H), 0.95–0.84 (m, 15H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ212.3,172.8,79.5,49.9,46.0,44.5,42.0,40.6,37.5,35.4,34.2,33.2,33.1,30.4,29.2,29.1,25.3,20.0,14.4;

[0302] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 37 O3 + (M+H) + 337.2737, detected value 337.2729.

[0303] Example 16:

[0304] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0305] The operation steps are the same as in Example 3.

[0306] The reaction equation is as follows:

[0307]

[0308] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (17.6 mg, 71% yield).

[0309] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.85 (d, J = 8.4 Hz, 1H), 6.82 (dd, J = 8.5, 2.3 Hz, 1H), 6.70 (d, J = 2.0 Hz, 1H), 5.52–5.39 (m, 1H), 3.89–3.76 (m, 4H), 2.93–2.73 (m, 4H), 2.50–2.39 (m, 1H), 1.48 (d, J = 6.4 Hz, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.2,168.6,162.6,145.1,133.7,122.5,117.1,111.8,69.9,55.4,47.4,46.5,32.4,20.5;

[0310] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 17 O4+(M+H) + 249.1121, detected value 249.1114.

[0311] Example 17:

[0312] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0313] The operation steps are the same as in Example 2.

[0314] The reaction equation is as follows:

[0315]

[0316] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (18.2 mg, 70% yield).

[0317] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.32–7.17 (m, 5H), 4.15 (dd, J = 10.8, 4.0 Hz, 1H), 4.06 (t, J = 10.8 Hz, 1H), 2.86–2.82 (m, 1H), 2.67 (dd, J = 13.6, 6.8 Hz, 1H), 2.56 (dd, J = 14.0, 8.0 Hz, 1H), 2.42–2.30 (m, 5H), 2.22 (t, J = 11.2 Hz, 1H), 1.85–1.67 (m, 4H); The data from the carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.7,173.0,138.4,129.00,128.6,126.6,67.9,47.6,39.9,39.5,38.0,34.3,22.7,20.5;

[0318] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21 O3 + (M+H) + 261.1485, detected value 261.1485.

[0319] Example 18:

[0320] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0321] The operation steps are the same as in Example 2.

[0322] The reaction equation is as follows:

[0323]

[0324] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (14.2 mg, 63% yield).

[0325] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.36–4.24 (m, 1H), 4.10 (td, J = 10.9, 10.0, 3.9 Hz, 1H), 2.54–2.21 (m, 6H), 2.04–1.92 (m, 1H), 1.82–1.68 (m, 2H), 1.66–1.54 (m, 2H), 0.90 (s, 9H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ211.5,173.5,63.9,45.8,44.6,39.4,35.4,33.9,27.5,25.2,25.0;

[0326] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 23 O3 + (M+H) + 227.1642, detected value 227.1635.

[0327] Example 19:

[0328] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0329] The operation steps are the same as in Example 2.

[0330] The reaction equation is as follows:

[0331]

[0332] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (9.5 mg, 48% yield).

[0333] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 3.94 (s, 2H), 2.37–2.35 (m, 4H), 2.20 (s, 2H), 1.77–1.75 (m, 4H), 1.10 (s, 6H); The data for carbon NMR characterization are as follows: 13 CNMR (100MHz, CDCl3) δ208.7,173.4,73.1,53.8,41.1,37.7,34.4,25.5,22.9,20.1;

[0334] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 11 H 19 O3 + (M+H) + 199.1329, detected value 199.1325.

[0335] Example 20:

[0336] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0337] The operation steps are the same as in Example 2.

[0338] The reaction equation is as follows:

[0339]

[0340] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.9 mg, 65% yield).

[0341] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 8.05 (d, J = 8.9 Hz, 1H), 6.83 (dd, J = 8.8, 2.2 Hz, 1H), 6.73 (d, J = 2.1 Hz, 1H), 4.10 (s, 2H), 3.84 (s, 3H), 3.17 (t, J = 6.7 Hz, 2H), 2.64 (t, J = 6.7 Hz, 2H), 2.45 (s, 2H), 1.15 (s, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.8,167.2,162.9,145.0,134.5,121.2,117.1,111.9,74.2,55.4,54.1,45.4,37.0,33.7,26.6;

[0342] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21 O4 + (M+H) + 277.1434, detected value 277.1427.

[0343] Example 21:

[0344] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0345] The operation steps are the same as in Example 1.

[0346] The reaction equation is as follows:

[0347]

[0348] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (18.1 mg, 80% yield).

[0349] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.12 (dd, J = 11.2, 4.0 Hz, 1H), 2.90–2.81 (m, 2H), 2.47 (dt, J = 12.8, 4.8 Hz, 1H), 2.37 (dd, J = 12.0, 4.0 Hz, 1H), 2.30–2.20 (m, 2H), 1.77–1.71 (m, 2H), 1.69–1.60 (m, 3H), 1.16–1.07 (m, 1H), 0.93 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.5,172.7,78.7,43.0,41.5,35.3,35.0,25.7,24.2,21.7,21.0;

[0350] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 23 O3 + (M+H) + 227.1642, detected value 227.1636.

[0351] Example 22:

[0352] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0353] The operation steps are the same as in Example 3.

[0354] The reaction equation is as follows:

[0355]

[0356] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (19.0 mg, 73% yield).

[0357] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (400MHz, CDCl3) δ7.35-7.23(m,5H),5.36-5.29(m,1H),3.13(dd,J=13.6,5.6Hz ,1H),2.93(dd,J=13.2,7.6Hz,1H),2.83-2.75(m,1H),2.69(dd,J=12.4,8.8Hz,1H), 2.59 (dd, J = 12.0, 4.0 Hz, 1H), 2.49 (dt, J = 14.2, 5.6 Hz, 1H), 2.31–2.26 (m, 2H), 1.87–1.78 (m, 1H), 1.73–1.69 (m, 1H), 1.66–1.60 (m, 3H), 1.19–1.17 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ211.4,172.6,136.2,129.5,128.5,126.9,73.6,45.4,41.7,41.0,35.2,25.0,22.6,21.2;

[0358] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21 O3 + (M+H) + 261.1485, detected value 261.1478.

[0359] Example 23:

[0360] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0361] The operation steps are the same as in Example 1.

[0362] The reaction equation is as follows:

[0363]

[0364] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (23.3 mg, 71% yield).

[0365] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 5.26–5.22 (m, 1H), 3.66 (t, J = 6.0 Hz, 2H), 2.80–2.64 (m, 3H), 2.45–2.40 (m, 1H), 2.31–2.23 (m, 2H), 2.00–1.96 (m, 1H), 1.84–1.78 (m, 2H), 1.69–1.52 (m, 4H), 1.21–1.16 (m, 1H), 0.87 (s, 9H), 0.03 (s, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.36,172.81,70.78,59.08,46.02,41.87,37.52,35.19,25.84,25.08,22.44,21.24,18.18,-5.48;

[0366] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 33 O4Si + (M+H) + 329.2143, detected value 329.2134.

[0367] Example 24:

[0368] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0369] The operation steps are the same as in Example 1.

[0370] The reaction equation is as follows:

[0371]

[0372] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (11.9 mg, 60% yield).

[0373] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 2.81 (s, 2H), 2.56 (t, J = 6.8Hz, 2H), 2.30 (t, J = 6.0Hz, 2H), 1.70–1.64 (m, 4H), 1.58 (s, 6H), 1.45–1.42 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.2,173.1,81.8,52.4,40.8,36.2,27.0,25.5,22.9,21.3;

[0374] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 11 H 19 O3 + (M+H) + 199.1329, detected value 199.1320

[0375] Example 25:

[0376] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0377] The operation steps are the same as in Example 1, except that 1-pyrrolidine-1-cycloheptene is used as the raw material for the alkylation part.

[0378] The reaction equation is as follows:

[0379]

[0380] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (117.2 mg, 70% yield).

[0381] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.40–7.29 (m, 5H), 6.06 (dd, J = 11.2, 4.0 Hz, 1H), 3.20 (t, J = 11.2 Hz, 1H), 3.11–3.04 (m, 1H), 2.64 (dd, J = 12.4, 3.6 Hz, 1H), 2.55 (dd, J = 15.2, 4.8 Hz, 1H), 2.36–2.24 (m, 2H), 1.90–1.81 (m, 2H), 1.71–1.58 (m, 3H), 1.08–1.01 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.7,171.9,139.2,128.7,128.4,126.1,74.6,49.7,41.1,35.2,24.8,22.6,20.8;

[0382] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 19 O3 + (M+H) + 247.1329, detected value 247.1325.

[0383] Example 26:

[0384] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0385] The operation steps are the same as in Example 1.

[0386] The reaction equation is as follows:

[0387]

[0388] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.5 mg, 71% yield).

[0389] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CD₃OD) δ 7.31 (d, J = 7.5Hz, 1H), 7.24 (td, J = 7.0Hz, 1.0Hz, 1H), 7.19 (td, J = 7.5Hz, 1.0Hz, 1H), 7.15 (d, J = 8.0, 1H), 4.32 (s, 2H), 3.87 (s, 2H), 3.05 (t, J = 5.5Hz, 2H), 2.68 (t, J = 6.5Hz, 2H), 2.52 (t, J = 6.0Hz, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ209.4,171.3,137.9,133.1,130.6,130.6,127.8,127.2,60.5,47.8,40.1,37.1,28.1;

[0390] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 15 O3 + (M+H) + 219.1016, detected value 219.1007.

[0391] Example 27:

[0392] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0393] The operation steps are the same as in Example 1.

[0394] The reaction equation is as follows:

[0395]

[0396] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (20.6 mg, 61% yield).

[0397] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 4.85 (td, J = 10.5, 4.0 Hz, 1H), 4.04 (m, 1H), 2.96 (td, J = 11.0, 5.5 Hz, 1H), 2.69–2.63 (m, 2H), 2.59 (dt, J = 11.5, 4.0 Hz, 1H), 2.51 (dd, J = 16.0, 10.5 Hz, 1H), δ 2.42 (td, J = 13.5, 3.5 Hz, 1H), 2.20–2.14 (m, 2H), 1.72–1.60 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.8,171.1,61.1,42.9,41.7,33.6,32.9,32.5,30.1,23.0;

[0398] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 13 Br2O3 + (M+H) + 340.9205, detected value 340.9196.

[0399] Example 28:

[0400] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0401] The operation steps are the same as in Example 1.

[0402] The reaction equation is as follows:

[0403]

[0404] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (10.8 mg, 64% yield).

[0405] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CD3CN) δ 5.67–5.39 (m, 2H), 4.30–4.28 (m, 2H), 3.22 (d, J = 4.0 Hz, 2H), 2.59 (t, J = 16.0 Hz, 2H), 2.45–2.43 (m, 4H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CD3CN) δ210.4,172.5,131.4,126.0,61.5,43.7,42.7,35.1,23.9;

[0406] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C9H) 13 O3 + (M+H) + 169.0859, detected value 169.0856.

[0407] Example 29:

[0408] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0409] The operation steps are the same as in Example 3.

[0410] The reaction equation is as follows:

[0411]

[0412] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.9 mg, 65% yield).

[0413] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 7.55–7.53 (m, 2H), 7.47–7.45 (m, 3H), 4.42 (t, J = 11.5 Hz, 2H), 3.87 (s, 2H), 3.40 (t, J = 5.5 Hz, 2H), 2.74 (t, J = 5.5 Hz, 2H), 2.54 (t, J = 5.5 Hz, 2H), 2.03–2.02 (m, 2H); The data from the carbon NMR characterization are as follows: 13 CNMR(125MHz, CDCl3)δ207.2,175.5,172.2,135.3,130.0,128.7,126.9,61.8,57.6,51.0,38.2,33.6,23.1;

[0414] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 18 NO4 + (M+H) + 276.1230, detected value 276.1223.

[0415] Example 30:

[0416] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0417] The operation steps are the same as in Example 1.

[0418] The reaction equation is as follows:

[0419]

[0420] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (19.9 mg, 72% yield).

[0421] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.37–7.29 (m, 5H), 4.63–4.57 (m, 1H), 4.50 (s, 2H), 4.28–4.22 (m, 1H), 3.96–3.93 (m, 1H), 2.91 (dd, J = 14.8 Hz, 10.0 Hz, 1H), 2.72–2.67 (m, 3H), 2.45–2.40 (m, 1H), 2.29–2.22 (m, 1H), 1.91–1.81 (m, 2H), 1.70–1.69 (m, 1H), 1.45–1.41 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.7,172.7,138.1,128.5,127.8,127.8,74.7,70.8,61.7,48.7,41.0,34.7,30.6,19.1;

[0422] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21 O4 + (M+H) + 277.1434, detected value 277.1427.

[0423] Example 31:

[0424] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0425] The operation steps are the same as in Example 1.

[0426] The reaction equation is as follows:

[0427]

[0428] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.7 mg, 74% yield).

[0429] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 4.56–4.52 (m, 1H), 4.40 (td, J = 11.5, 4.5 Hz, 1H), 3.22 (ddd, J = 13.1, 11.6, 5.6 Hz, 1H), 2.59 (ddd, J = 14.1, 8.5, 2.6 Hz, 1H), 2.33 (dd, J = 12.5, 4.5 Hz, 1H), 2.28–2.19 (m, 2H), 2.04 (t, J = 12.0 Hz, 1H), 1.91–1.86 (m, 1H), 1.65–1.42 (m, 4H), 1.13–1.10 (m, 1H), 0.85 (dd, J = 9.0 Hz, 7.0 Hz, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.8,173.7,61.7,44.1,41.3,38.9,37.8,33.00,28.7,23.5,19.4,19.0;

[0430] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 21 O3 + (M+H) + 213.1485, detected value 213.1480.

[0431] Example 32:

[0432] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0433] The operation steps are the same as in Example 1.

[0434] The reaction equation is as follows:

[0435]

[0436] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (16.2 mg, 66% yield).

[0437] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (500MHz, CDCl3) δ7.32-7.17(m,5H),4.57(td,J=10.5,4.0Hz,1H),4.52-4.48(m, 1H),3.21(ddd,J=13.1,11.1,5.6Hz,1H),3.08-3.05(m,1H),2.79-2.74(m,1H),2.61 (dd, J = 13.5, 4.5 Hz, 1H), 2.50 (t, J = 12.0 Hz, 1H), 2.41 (dt, J = 13.5, 3.5 Hz, 1H), 2.33–2.28 (m, 1H), 1.97–1.93 (m, 1H), 1.78–1.75 (m, 1H), 1.66–1.57 (m, 2H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (125MHz, CDCl3) δ211.7,171.8,145.6,128.7,126.9,126.6,62.7,43.5,42.8,40.9,39.4,33.5,22.5;

[0438] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 19 O3 + (M+H) + 247.1329, detected value 247.1322.

[0439] Example 33:

[0440] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0441] The operation steps are the same as in Example 3.

[0442] The reaction equation is as follows:

[0443]

[0444] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (16.6 mg, 76% yield).

[0445] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 7.82 (d, J = 7.5Hz, 1H), 7.40 (t, J = 7.5Hz, 1H), 7.30 (t, J = 7.5Hz, 1H), 7.20 (d, J = 7.5Hz, 1H), 4.74 (t, J = 5.5Hz, 2H), 2.77 (t, J = 7.0Hz, 4H), 2.50 (t, J = 6.0Hz, 2H), 2.01–1.98 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.9,168.3,142.6,132.1,131.0,130.9,130.8,126.6,63.1,45.3,39.1,33.5,26.7;

[0446] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 15 O3 + (M+H) + 219.1016, detected value 219.1008.

[0447] Example 34:

[0448] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0449] The operation steps are the same as in Example 1.

[0450] The reaction equation is as follows:

[0451]

[0452] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (20.3 mg, 73% yield).

[0453] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 6.35 (d, J = 1.7Hz, 1H), 6.31 (d, J = 1.7Hz, 1H), 4.65 (t, J = 6.0Hz, 2H), 3.82 (s, 3H), 3.81 (s, 3H), 2.77 (t, J = 7.5Hz, 2H), 2.52–2.50 (m, 4H), 2.01–1.98 (m, 2H); The data for carbon NMR characterization are as follows: 13C NMR (125MHz, CDCl3) δ212.0,166.5,161.9,159.0,143.3,115.1,106.8,96.6,62.8,55.9,55.4,44.7,39.8,32.8,25.2;

[0454] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 19 O5 + (M+H) + 279.1227, detected value 279.1215.

[0455] Example 35:

[0456] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0457] The operation steps are the same as in Example 1.

[0458] The reaction equation is as follows:

[0459]

[0460] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (12 mg, 66% yield).

[0461] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 5.51–5.50 (m, 2H), 4.34 (t, J = 5.5 Hz, 2H), 3.16 (d, J = 6.5 Hz, 2H), 2.76 (t, J = 6.0 Hz, 2H), 2.33 (t, J = 6.5 Hz, 2H), 2.21–2.17 (m, 2H), 1.87–1.85 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.9,173.7,132.3,122.8,60.7,42.1,41.8,33.5,25.6,24.1;

[0462] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 15 O3 + (M+H) + 183.1016, detected value 183.1012.

[0463] Example 36:

[0464] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0465] The operation steps are the same as in Example 1.

[0466] The reaction equation is as follows:

[0467]

[0468] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (16.7 mg, 72% yield).

[0469] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.25–7.20 (m, 4H), 3.75–3.73 (m, 4H), 2.92–2.88 (m, 2H), 2.80–2.77 (m, 2H), 2.37–2.34 (m, 2H), 2.06–2.04 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.8,171.4,139.7,133.3,132.3,128.6,128.0,126.9,64.3,51.6,35.7,35.1,25.5,22.8;

[0470] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 17 O3 + (M+H) + 233.1172, detected value 233.1170.

[0471] Example 37:

[0472] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0473] The operation steps are the same as in Example 1.

[0474] The reaction equation is as follows:

[0475]

[0476] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (19.5 mg, 62% yield).

[0477] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 4.66–4.60 (m, 1H), 4.36–4.32 (m, 1H), 4.24–4.19 (m, 1H), 2.87–2.80 (m, 1H), 2.77–2.71 (m, 1H), 2.65–2.59 (m, 1H), 2.54 (dd, J = 13.2, 4.0 Hz, 1H), 2.47–2.40 (m, 1H), 2.24–2.18 (m, 1H), 1.80–1.65 (m, 3H), 1.48–1.39 (m, 2H), 1.28–1.26 (m, 1H), 0.87 (s, 9H), 0.08 (d, J = 1.6 Hz, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.6,173.6,66.9,60.9,51.9,41.5,33.7,33.1,25.7,22.4,22.2,18.0,-4.6,-4.7;

[0478] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 31 O4Si + (M+H) + 315.1986, detected value 315.1973.

[0479] Example 38:

[0480] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0481] The operation steps are the same as in Example 2.

[0482] The reaction equation is as follows:

[0483]

[0484] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (30.4 mg, 72% yield).

[0485] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 6.32 (s, 1H), 6.29 (s, 1H), 4.61–4.35 (m, 2H), 3.97 (dd, J = 10.8, 4.4 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 2.98 (dd, J = 14.4, 9.2 Hz, 1H), 2.73–2.67 (m, 1H), 2.56–2.46 (m, 2H), 2.30–2.22 (m, 3H), 1.78–1.70 (m, 1H), 0.89 (s, 9H), 0.11 (d, J = 1.2 Hz, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.7,167.3,161.7,158.0,142.0,116.8,105.6,96.4,68.4,67.9,55.8,55.4,47.6,41.8,31.1,25.8,25.6,18.1,-4.9;

[0486] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 22 H 34 NaO6Si + (M+Na) + 445.2017, detected value 445.2005.

[0487] Example 39:

[0488] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0489] The operation steps are the same as in Example 1.

[0490] The reaction equation is as follows:

[0491]

[0492] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.8 mg, 61% yield).

[0493] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.14 (t, J = 5.2Hz, 2H), 2.64 (t, J = 6.0Hz, 2H), 2.41–2.34 (m, 4H), 1.96–1.91 (m, 2H), 1.72–1.58 (m, 4H), 1.36–1.19 (m, 8H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ211.2,173.6,62.8,42.3,36.7,34.6,26.1,26.0,25.9,25.5,24.5,24.2,22.0;

[0494] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 23 O3 + (M+H) + 227.1642, detected value 227.1640.

[0495] Example 40:

[0496] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0497] The operation steps are the same as in Example 1.

[0498] The reaction equation is as follows:

[0499]

[0500] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.6 mg, 65% yield).

[0501] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 4.37 (t, J = 5.0Hz, 2H), 2.70 (t, J = 5.0Hz, 2H), 2.47 (t, J = 6.5Hz, 2H), 2.31 (t, J = 7.0Hz, 2H), 1.68–1.62 (m, 4H), 1.37–1.21 (m, 12H); The data from the carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.7173.9,59.8,42.2,41.4,33.7,27.2,27.1,26.6,26.1,25.9,25.8 24.6,22.1;

[0502] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 25 O3 + (M+H) + 241.1798, detected value 241.1787.

[0503] Example 41:

[0504] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0505] The operation steps are the same as in Example 1.

[0506] The reaction equation is as follows:

[0507]

[0508] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (19.7 mg, 70% yield).

[0509] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 4.36–4.33 (m, 2H), 2.71–2.69 (m, 2H), 2.44–2.42 (m, 2H), 2.28–2.25 (m, 2H), 1.59–1.58 (m, 4H), 1.29–1.27 (m, 18H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.2,173.6,59.3,42.9,41.1,34.4,27.9,27.6,27.6,27.6,26.9,26.9,26.8,26.7,26.3,24.4,22.9;

[0510] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 31 O3 + (M+H) + 283.2268, detected value 283.2256.

[0511] Example 42:

[0512] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0513] The operation steps are the same as in Example 3.

[0514] The reaction equation is as follows:

[0515]

[0516] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.8 mg, 60% yield).

[0517] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 4.12 (t, J = 5.6Hz, 2H), 2.51 (t, J = 7.2Hz, 2H), 2.38 (t, J = 7.4Hz, 2H), 2.30 (t, J = 7.2Hz, 2H), 1.94–1.91 (m, 2H), 1.63–1.60 (m, 4H), 1.29 (m, 18H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.8,173.8,63.4,42.7,39.2,34.4,28.3,28.2,27.99,27.7,27.6,27.5,27.3,27.1,27.0,24.7,23.7,22.9;

[0518] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 33 O3 + (M+H) + 297.2424, detected value 297.2419.

[0519] Example 43:

[0520] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0521] The operation steps are the same as in Example 3.

[0522] The reaction equation is as follows:

[0523]

[0524] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (16.3 mg, 55% yield).

[0525] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CD₃CN) δ 4.41–4.34 (m, 2H), 3.98–3.96 (m, 1H), 3.87–3.85 (m, 1H), 3.06–2.84 (m, 2H), 2.44–2.39 (m, 2H), 2.28–2.22 (m, 1H), 2.04–1.99 (m, 2H), 1.95–1.94 (m, 1H), 1.72–1.58 (m, 2H), 1.48 (s, 9H); The data for carbon NMR characterization are as follows: 13C NMR (125MHz, DMSO-d6) δ210.9,170.2,154.6,79.7,66.2,62.9,54.1,38.4,33.1,30.9,27.8,24.6,24.1;

[0526] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 23 NNaO5+(M+Na) + 320.1468, detected value 320.1463.

[0527] Example 44:

[0528] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0529] The operation steps are the same as in Example 1.

[0530] The reaction equation is as follows:

[0531]

[0532] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (32.5 mg, 72% yield).

[0533] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 8.04 (d, J = 7.5Hz, 2H), 7.54 (t, J = 7.3Hz, 1H), 7.43 (d, J = 7.3Hz, 2H), 5.06–5.05 (m, 1H), 4.83 (t, J = 8.3Hz, 1H), 4.13–4.11 (m, 1H), 3.02–2.99 (m, 1H), 2.54 (d, J = 17.2Hz, 1H), 2.36–2.25 (m, 6H), 1.95–1.64 (m, 4H), 1.38–1.19 (m, 9H), 1.02–1.01 (m, 1H), 0.91 (s, 3H), 0.85 (s, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.8,174.8,166.5,132.7,130.8,129.5,128.3,83.3,60.3,50.6,48. 3,47.5,42.8,42.34,42.3,42.1,39.4,36.8,34.8,31.2,29.5,27.9,23.7,21.1,15.5,12.2;

[0534] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 28 H 37 O5 + (M+H) + 453.2636, detected value 453.2627.

[0535] Example 45:

[0536] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0537] The operation steps are the same as in Example 1.

[0538] The reaction equation is as follows:

[0539]

[0540] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (28.9 mg, 65% yield).

[0541] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.08–5.02 (m, 1H), 4.15–4.08 (m, 1H), 3.01–2.96 (m, 1H), 2.55 (d, J = 17.2 Hz, 1H), 2.42–2.16 (m, 5H), 1.97–1.95 (m, 1H), 1.83–1.81 (m, 2H), 1.64–1.48 (m, 2H), 1.39–1.22 (m, 11H), 1.15–0.97 (m, 8H), 0.90–0.85 (m, 9H), 0.82 (s, 3H), 0.63 (s, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.8,174.9,60.2,56.3,56.0,48.2,47.4,42.4,42.3,42.2,39.7,39.5, 39.4,36.1,35.8,34.9,31.6,29.7,28.3,28.0,24.2,23.8,22.8,22.5,21.6,18.6,15.4,11.9;

[0542] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 29 H 49 O3 + (M+H) + 445.3676, detected value 445.3671.

[0543] Example 46:

[0544] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0545] The operation steps are the same as in Example 3.

[0546] The reaction equation is as follows:

[0547]

[0548] After the reaction was completed, the product was concentrated and separated by column chromatography to obtain the target product (8.9 mg, 57% yield).

[0549] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.57 (t, J = 6.6Hz, 2H), 2.78 (t, J = 6.6Hz, 2H), 2.42–2.35 (m, 4H), 1.90–1.86 (m, 2H), 1.82–1.78 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.0,174.7,60.5,42.1,41.4,34.9,24.4,23.6;

[0550] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C8H) 13 O3 + (M+H) + 157.0859, detected value 157.0854.

[0551] Example 47:

[0552] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0553] The operation steps are the same as in Example 3.

[0554] The reaction equation is as follows:

[0555]

[0556] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.6 mg, 51% yield).

[0557] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.44–5.37 (m, 1H), 2.96 (dd, J = 13.7, 6.1 Hz, 1H), 2.76 (dd, J = 13.7, 8.1 Hz, 1H), 2.69–2.58 (m, 2H), 2.53–2.44 (m, 2H), 2.35–2.23 (m, 2H), 2.09–2.03 (m, 1H), 1.94–1.91 (m, 1H), 1.77–1.61 (m, 2H), 0.15 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.7,174.1,100.8,87.9,69.6,46.7,40.9,34.9,26.1,24.1,24.0,-0.1;

[0558] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 23 O3Si + (M+H) + 267.1411, detected value 267.1407.

[0559] Example 48:

[0560] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0561] The operation steps are the same as in Example 3.

[0562] The reaction equation is as follows:

[0563]

[0564] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.0 mg, 61% yield).

[0565] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.32–7.28 (m, 2H), 7.25–7.23 (m, 3H), 5.55–5.49 (m, 1H), 3.11 (dd, J = 13.7, 6.9 Hz, 1H), 2.93 (dd, J = 13.7, 7.3 Hz, 1H), 2.80 (dd, J = 13.7, 6.2 Hz, 1H), 2.59 (dd, J = 13.5, 7.6 Hz, 1H), 2.54–2.42 (m, 2H), 2.31–2.21 (m, 2H), 2.11–2.05 (m, 1H), 1.95–1.92 (m, 1H), 1.75–1.62 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ210.0,174.4,136.3,129.4,128.6,126.9,72.2,46.9,41.0,40.9,34.8,24.1,24.0;

[0566] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 19 O3 + (M+H) + 247.1329, detected value 247.1324.

[0567] Example 49:

[0568] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0569] The operation steps are the same as in Example 3.

[0570] The reaction equation is as follows:

[0571]

[0572] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (17.2 mg, 54% yield).

[0573] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR(400MHz, CDCl3)δ7.30(d,J=8.7Hz,2H),6.85(d,J=8.8Hz,2H),5.67-5.61(m,1H), 4.17(dd,J=10.1,6.0Hz,1H),4.08(dd,J=10.1,5.2Hz,1H),2.97(dd,J=13.6,6.5Hz,1H ), 2.79 (dd, J=13.6, 7.6Hz, 1H), 2.59-2.47 (m, 2H), 2.38-2.27 (m, 2H), 2.13-2.05 (m, 1H), 2.00-1.91 (m, 1H), 1.79-1.72 (m, 1H), 1.71-1.62 (m, 1H), 1.30 (s, 9H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ209.5,174.3,156.0,144.1,126.3,114.1,69.4,68.6,44.3,40.9,34.8,34.1,31.5,24.1,24.0;

[0574] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 19 H 27 O4 + (M+H) + 319.1904, detected value 319.1898.

[0575] Example 50:

[0576] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0577] The operation steps are the same as in Example 3.

[0578] The reaction equation is as follows:

[0579]

[0580] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (20.6 mg, 49% yield).

[0581] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (400MHz, CDCl3) δ7.68 (d, J=2.3Hz, 1H), 7.37 (dd, J=8.6, 2.2Hz, 1H), 6.79 (d, J=8.8Hz ,1H),5.71-5.65(m,1H),4.21(dd,J=10.0,5.9Hz,1H),4.14(dd,J=9.9,5.2Hz,1H),3.01(d d, J = 13.5, 6.5 Hz, 1H), 2.87 (dd, J = 13.5, 7.5 Hz, 1H), 2.58-2.47 (m, 2H), 2.43-2.28 (m, 2H), 2.12-2.05 (m, 1H), 1.97-1.92 (m, 1H), 1.81-1.74 (m, 1H), 1.73-1.66 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ209.4,174.0,154.1,135.7,131.28,114.9,114.0,113.5,69.9,68.9,44.0,41.4,34.8,24.2,24.0;

[0582] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 17 Br2O4 + (M+H) + 418.9488, detected value 418.9485.

[0583] Example 51:

[0584] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0585] The operation steps are the same as in Example 3.

[0586] The reaction equation is as follows:

[0587]

[0588] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (8.6 mg, 37% yield).

[0589] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.38–7.29 (m, 5H), 4.74 (dd, J = 10.8, 7.4 Hz, 1H), 4.66 (t, J = 10.5 Hz, 1H), 4.41 (dd, J = 10.2, 7.4 Hz, 1H), 2.50–2.40 (m, 4H), 1.98–1.93 (m, 2H), 1.88–1.83 (m, 2H); The data for carbon NMR characterization are as follows: 13 CNMR (100MHz, CDCl3) δ210.3,174.5,134.5,128.8,128.5,127.9,66.3,56.5,41.7,35.0,24.0,23.8;

[0590] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 17 O3 + (M+H) + 233.1172, detected value 233.1167.

[0591] Example 52:

[0592] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0593] The operation steps are the same as in Example 3.

[0594] The reaction equation is as follows:

[0595]

[0596] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (10.9 mg, 59% yield).

[0597] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.47 (t, J = 6.5Hz, 2H), 2.76 (t, J = 6.5Hz, 2H), 2.32–2.29 (m, 2H), 2.15 (s, 2H), 1.79–1.76 (m, 2H), 1.06 (s, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.8,172.5,59.6,47.0,41.3,37.8,36.1,34.9,29.1;

[0598] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 17 O3+ (M+H) + 185.1172, detected value 185.1166.

[0599] Example 53:

[0600] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0601] The operation steps are the same as in Example 3.

[0602] The reaction equation is as follows:

[0603]

[0604] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (12.1 mg, 44% yield).

[0605] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 8.04–8.02 (m, 2H), 7.59–7.56 (m, 1H), 7.47–7.44 (m, 2H), 5.63–5.59 (m, 1H), 5.03–4.98 (m, 1H), 4.33–4.28 (m, 1H), 2.95–2.90 (m, 2H), 2.85–2.78 (m, 2H), 2.62–2.58 (m, 2H), 2.28–2.26 (m, 1H), 2.12–2.09 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ206.1,173.8,165.4,133.2,129.9,129.6,128.4,70.8,60.4,46.2,41.8,30.9,29.2;

[0606] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 17 O5 + (M+H) + 277.1071, detected value 277.1064.

[0607] Example 54:

[0608] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0609] The operation steps are the same as in Example 3.

[0610] The reaction equation is as follows:

[0611]

[0612] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (14.6 mg, 63% yield).

[0613] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.28–7.10 (m, 5H), 4.95–4.89 (m, 1H), 4.32–4.26 (m, 1H), 3.63–3.30 (m, 1H), 2.93 (dd, J = 14.8 Hz, 10.8 Hz, 1H), 2.82–2.78 (m, 2H), 2.49–2.40 (m, 3H), 2.39–2.30 (m, 1H), 2.14–2.12 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.2,174.8,145.3,128.8,127.2,126.7,60.5,48.1,41.5,41.2,32.8,32.1;

[0614] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 17 O3 + (M+H) + 233.1172, detected value 233.1163.

[0615] Example 55:

[0616] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0617] The operation steps are the same as in Example 3.

[0618] The reaction equation is as follows:

[0619]

[0620] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (19.7 mg, 63% yield, 1.2:1 d.r.).

[0621] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.20–5.16 (m, 1H), 3.17–3.11 (m, 1H), 2.79–2.65 (m, 3H), 2.56–2.51 (m, 1H), 2.44–2.39 (m, 2H), 2.20–2.12 (m, 1H), 1.94–1.87 (m, 1H), 1.45 (s, 9H), 0.94 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.2,174.2,172.9,81.2,78.0,43.9,41.4,41.1,34.8,32.4,28.0,25.5,25.3;

[0622] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 29 O5 + (M+H) + 313.2010, detected value 313.2010.

[0623] Example 56:

[0624] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0625] The operation steps are the same as in Example 3.

[0626] The reaction equation is as follows:

[0627]

[0628] After the reaction was completed, the product was concentrated and separated by column chromatography to obtain the target product (14.8 mg, 61% yield, 1:1 d.r.).

[0629] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.10 (dd, J = 11.0, 5.5Hz, 1H), 3.55–3.47 (m, 1H), 3.32 (s, 3H), 3.05–2.90 (m, 2H), 2.71 (dd, J = 15.1, 3.3Hz, 1H), 2.66–2.58 (m, 1H), 2.41–2.27 (m, 2H), 2.22–2.07 (m, 1H), 2.02–1.93 (m, 1H), 0.96 (s, 9H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ208.9,173.1,79.7,78.5,56.3,49.3,44.4,34.3,31.8,31.2,25.3;

[0630] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 23 O4 + (M+H) + 243.1591, detected value 243.1590.

[0631] Example 57:

[0632] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0633] The operation steps are the same as in Example 3.

[0634] The reaction equation is as follows:

[0635]

[0636] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.8 mg, 54% yield, 2:3 d.r.).

[0637] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ8.06(d,J=7.6Hz,2H),7.57(t,J=7.4Hz,1H),7.45(t,J=7 .8Hz,2H),5.82(td,J=10.1,6.4Hz,1H),5.32(dt,J=7.8,3.4Hz,2H),5.12-4.9 5(m,2H),3.08(dd,J=15.6,7.7Hz,1H),2.90(dd,J=15.4,3.8Hz,1H),2.81-2.6 1(m,3H),2.55-2.42(m,1H),2.42-2.29(m,1H),2.22-2.03(m,3H),1.99-1.91(m 1H), 1.82-1.72 (m, 1H); data from carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ206.1,173.4,165.5,136.9,133.1,130.1,129.7,128.4,115.6,72.9,71.6,48.3,47.0,34.3,31.7,30.2,29.3;

[0638] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 19 H 23 O5 + (M+H) + 331.1540, detected value 331.1536.

[0639] Example 58:

[0640] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0641] The operation steps are the same as in Example 3.

[0642] The reaction equation is as follows:

[0643]

[0644] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (14.0 mg, 46% yield).

[0645] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.32–7.29 (m, 5H), 5.57–5.43 (m, 1H), 4.65–4.50 (m, 2H), 3.67 (dd, J = 10.5, 6.6 Hz, 1H), 3.56 (dd, J = 10.7, 5.0 Hz, 1H), 2.85 (dd, J = 13.9, 7.0 Hz, 1H), 2.65–2.44 (m, 3H), 2.38 (td, J = 15.2, 14.0, 3.4 Hz, 1H), 2.10–1.94 (m, 2H), 1.33 (dt, J = 14.7, 4.3 Hz, 1H), 1.22 (s, 3H), 0.97 (s, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.0,174.7,137.6,128.5,127.8,127.7,73.3,70.8,69.6,49.9,45.7,35.3,35.2,31.8,31.4,28.7;

[0646] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 25 O4 + (M+H) + 305.1747, detected value 305.1740.

[0647] Example 59:

[0648] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0649] The operation steps are the same as in Example 3.

[0650] The reaction equation is as follows:

[0651]

[0652] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (12.1 mg, 51% yield).

[0653] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.89–5.74 (m, 1H), 5.38–5.26 (m, 1H), 5.10–4.95 (m, 2H), 2.86 (dd, J = 13.7, 6.6 Hz, 1H), 2.58 (d, J = 15.7 Hz, 1H), 2.51–2.30 (m, 3H), 2.18–2.10 (m, 2H), 2.08–1.92 (m, 2H), 1.89–1.81 (m, 1H), 1.75–1.63 (m, 1H), 1.33 (dt, J = 14.5, 4.3 Hz, 1H), 1.22 (s, 3H), 0.98 (s, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.1,174.9,137.2,115.4,71.2,49.6,49.4,35.2,35.0,34.4,31.8,31.5,29.3,28.6;

[0654] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 23 O3 + (M+H) + 239.1642, detected value 239.1641.

[0655] Example 60:

[0656] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0657] The operation steps are the same as in Example 3.

[0658] The reaction equation is as follows:

[0659]

[0660] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (8.7 mg, 41% yield, 8.8:1 d.r.).

[0661] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.37–5.29 (m, 1H), 2.94 (dd, J = 14.2, 6.0 Hz, 1H), 2.56–2.51 (m, 1H), 2.44 (dd, J = 14.6, 7.5 Hz, 1H), 2.15 (d, J = 11.2 Hz, 1H), 2.06–2.01 (m, 2H), 1.35 (d, J = 6.8 Hz, 3H), 1.25–1.24 (m, 1H), 1.10 (s, 3H), 1.03–1.01 (m, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ213.8,172.4,67.0,47.7,47.5,46.0,40.9,34.8,33.8,24.3,20.8,20.2;

[0662] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 21 O3 + (M+H) + 213.1485, detected value 213.1481.

[0663] Example 61:

[0664] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0665] The operation steps are the same as in Example 3.

[0666] The reaction equation is as follows:

[0667]

[0668] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (16.5 mg, 59% yield).

[0669] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 8.10 (d, J = 1.6 Hz, 1H), 7.68–7.62 (m, 3H), 7.48 (t, J = 7.5 Hz, 2H), 7.41–7.38 (m, 1H), 7.32–7.28 (m, 1H), 4.77 (t, J = 6.2 Hz, 2H), 3.40–3.37 (m, 2H), 2.94 (t, J = 6.3 Hz, 2H), 2.73–2.70 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.7,169.1,141.6,140.1,139.4,131.8,131.0,130.7,129.6,128.9,127.8,126.9,61.9,45.8,41.2,31.9;

[0670] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 17 O3 + (M+H) + 281.1172, detected value 281.1160.

[0671] Example 62:

[0672] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0673] The operation steps are the same as in Example 3.

[0674] The reaction equation is as follows:

[0675]

[0676] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (14.7 mg, 52% yield).

[0677] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.96 (d, J = 1.6Hz, 1H), 7.54 (dd, J = 8.2, 1.8Hz, 1H), 7.10 (d, J = 8.1Hz, 1H), 4.73 (t, J = 6.2Hz, 2H), 3.29–3.26 (m, 2H), 2.90 (t, J = 6.2Hz, 2H), 2.66–2.63 (m, 2H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ211.3,167.7,141.5,135.2,133.8,132.8,132.4,120.7,62.2,45.5,41.0,31.7;

[0678] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 12 BrO3 + (M+H) + 282.9964, detected value 282.9957.

[0679] Example 63:

[0680] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0681] The operation steps are the same as in Example 3.

[0682] The reaction equation is as follows:

[0683]

[0684] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (14.0 mg, 60% yield).

[0685] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.84 (d, J = 8.7Hz, 1H), 6.82 (dd, J = 8.5, 2.3Hz, 1H), 6.71 (d, J = 1.9Hz, 1H), 4.68 (t, J = 6.3Hz, 2H), 3.84 (s, 3H), 3.33–3.26 (m, 2H), 2.86 (t, J = 6.2Hz, 2H), 2.67–2.60 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.8,168.8,162.6,145.3,133.7,122.6,117.0,111.8,61.7,55.4,45.9,41.3,32.6;

[0686] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 15 O4 + (M+H) + 235.0965, detected value 235.0958.

[0687] Example 64:

[0688] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0689] The operation steps are the same as in Example 3.

[0690] The reaction equation is as follows:

[0691]

[0692] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (18.0 mg, 51% yield).

[0693] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (500MHz, CDCl3) δ7.86 (d, J = 8.5Hz, 1H), 7.38-7.33 (m, 4H), 7.32-7.28 (m, 1H), 6 .82(dd,J=8.7,2.6Hz,1H),6.70(d,J=2.6Hz,1H),5.52-5.44(m,1H),4.70-4.56(m, 2H), 3.92-3.86 (m, 1H), 3.84 (s, 3H), 3.78-3.71 (m, 2H), 3.17 (dd, J = 12.7, 8.7 Hz, 1H), 2.87-2.78 (m, 2H), 2.69 (dd, J = 12.7, 4.8 Hz, 1H), 2.48-2.40 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (125MHz, CDCl3) δ210.1,168.5,162.8,145.1,137.7,134.0,128.4,12 7.8,127.7,122.3,117.2,111.9,73.4,71.9,70.7,55.4,46.9,42.5,32.4;

[0694] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 23 O5 + (M+H) + 355.1540, detected value 355.1526.

[0695] Example 65:

[0696] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0697] The operation steps are the same as in Example 3.

[0698] The reaction equation is as follows:

[0699]

[0700] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (14.7 mg, 51% yield).

[0701] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ7.86 (d, J=8.7Hz, 1H), 6.82 (dd, J=8.6, 2.2Hz, 1H), 6.70 (d, J=2.1Hz ,1H),5.93-5.77(m,1H),5.41-5.27(m,1H),5.14-4.96(m,2H),3.97-3.84(m,1H),3.83(s ,3H), 2.94(dd,J=12.1,8.3Hz,1H), 2.87-2.76(m,2H), 2.73(dd,J=12.1,4.9Hz,1H), 2.43(t,J=10.0Hz,1H), 2.29-2.16(m,2H), 2.00-1.87(m,1H), 1.86-1.74(m,1H); the data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.2,168.6,162.7,144.9,137.2,133.9,122.4,117.2,115.4,111.9,73.3,55.4,47.0,45.8,33.7,32.4,29.5;

[0702] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 21 O4 + (M+H) + 289.1434, detected value 289.1425.

[0703] Example 66:

[0704] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0705] The operation steps are the same as in Example 1.

[0706] The reaction equation is as follows:

[0707]

[0708] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.8 mg, 75% yield).

[0709] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 5.22–5.12 (m, 1H), 2.85 (ddd, J = 14.2, 9.2, 4.3 Hz, 1H), 2.72 (dd, J = 12.2, 9.7 Hz, 1H), 2.57 (dd, J = 12.2, 4.0 Hz, 1H), 2.47 (dt, J = 15.2, 4.9 Hz, 1H), 2.30–2.19 (m, 2H), 1.82–1.68 (m, 2H), 1.62–1.51 (m, 3H), 1.36 (d, J = 6.3 Hz, 3H), 1.11–1.01 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.3,172.6,70.1,48.7,41.2,35.2,25.0,22.6,20.9,20.9;

[0710] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 17 O3 + (M+H) + 185.1172, detected value 185.1169.

[0711] Example 67:

[0712] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0713] The operating steps are the same as in Example 3, except that 1-pyrrolidine-1-cycloheptene is used as the raw material for the alkylation portion.

[0714] The reaction equation is as follows:

[0715]

[0716] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (8.1 mg, 34% yield).

[0717] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.64–5.49 (m, 1H), 3.08 (t, J = 11.7 Hz, 1H), 2.93 (ddd, J = 15.5, 9.0, 4.2 Hz, 1H), 2.68–2.54 (m, 2H), 2.33 (ddd, J = 15.9, 10.4, 6.3 Hz, 2H), 1.86–1.62 (m, 5H), 1.04–0.90 (m, 1H); The data from the carbon NMR characterization are as follows:13 C NMR (100MHz, CDCl3) δ 207.8, 170.8, 124.4 (t, J = 279 Hz, 1C), 67.9 (t, J = 33.0 Hz, 1C), 41.8, 40.6, 34.5, 24.2, 21.9, 20.7; The data for fluorine NMR characterization are as follows: 19 F NMR (376MHz, CDCl3) δ-77.52;

[0718] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 14 F3O3 + (M+H) + 239.0890, detected value 239.0833.

[0719] Example 68:

[0720] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0721] The operating steps are the same as in Example 3, except that 1-pyrrolidine-1-cycloheptene is used as the raw material for the alkylation portion.

[0722] The reaction equation is as follows:

[0723]

[0724] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (10.9 mg, 45% yield).

[0725] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.38 (dd, J = 10.5, 4.3Hz, 1H), 4.25 (q, J = 7.0Hz, 2H), 3.07 (dd, J = 12.2, 10.8Hz, 1H), 2.87 (ddd, J = 16.6, 13.9, 4.3Hz, 2H), 2.66–2.56 (m, 1H), 2.32 (m, 2H), 1.86–1.73 (m, 2H), 1.69–1.60 (m, 3H), 1.30 (t, J = 7.1Hz, 3H), 1.10–0.96 (m, 1H); The data from the carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ209.5,171.8,168.6,70.0,62.0,43.3,41.7,34.7,24.8,22.9,21.1,14.1;

[0726] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 19 O5 + (M+H) + 243.1227, detected value 243.1221.

[0727] Example 69:

[0728] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0729] The operation steps are the same as in Example 1.

[0730] The reaction equation is as follows:

[0731]

[0732] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (16.6 mg, 60% yield).

[0733] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ7.21(t,J=7.8Hz,2H),6.90(t,J=7.3Hz,1H),6.83(d,J=8.1Hz,2H) ,5.33(dd,J=8.7,4.4Hz,1H),4.08(d,J=4.4Hz,2H),2.92(dd,J=12.5,8.9Hz,1H),2.81(d dd, J = 14.3, 8.6, 4.7 Hz, 1H), 2.70 (dd, J = 12.6, 4.3 Hz, 1H), 2.43 (dt, J = 14.5, 5.1 Hz, 1H), 2.32–2.14 (m, 2H), 1.83–1.72 (m, 1H), 1.65–1.42 (m, 4H), 1.15–0.99 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ211.0,172.7,158.2,129.5,121.3,114.5,70.9,68.5,43.1,41.9,35.0,25.0,22.6,21.1;

[0734] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 21 O4 + (M+H) + 277.1434, detected value 277.1427.

[0735] Example 70:

[0736] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0737] The operation steps are the same as in Example 3.

[0738] The reaction equation is as follows:

[0739]

[0740] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (23.7 mg, 70% yield).

[0741] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 7.90 (d, J = 7.3Hz, 2H), 7.67 (t, J = 7.4Hz, 1H), 7.58 (t, J = 7.7Hz, 2H), 5.22–5.09 (m, 1H), 3.21–3.08 (m, 2H), 2.80–2.64 (m, 2H), 2.58 (dd, J = 12.4, 4.0Hz, 1H), 2.47–2.37 (m, 1H), 2.33–2.13 (m, 3H), 2.07 (m, 1H), 1.80–1.49 (m, 5H), 1.14–0.98 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ210.0,172.8,138.8,133.9,129.4,128.0,71.1,52.6,46.4,41.8,35.0,28.1,24.7,22.3,21.1;

[0742] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 23 O5S + (M+H) + 339.1261, detected value 339.1252.

[0743] Example 71:

[0744] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0745] The operation steps are the same as in Example 1.

[0746] The reaction equation is as follows:

[0747]

[0748] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.0 mg, 61% yield).

[0749] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (500MHz, CDCl₃) δ 5.19–5.14 (m, 1H), 2.91 (dd, J = 12.2, 9.6 Hz, 1H), 2.88–2.80 (m, 1H), 2.71 (dd, J = 12.3, 4.1 Hz, 1H), 2.66–2.64 (m, 2H), 2.48 (dt, J = 15.0, 4.8 Hz, 1H), 2.31–2.22 (m, 2H), 1.81–1.71 (m, 2H), 1.63–1.58 (m, 3H), 1.10–1.05 (m, 1H), 0.16 (s, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.0,172.4,100.8,88.2,70.8,45.6,41.6,35.1,26.1,24.9,22.7,21.0,-0.1;

[0750] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 25 O3Si + (M+H) + 281.1567, detected value 281.1567.

[0751] Example 72:

[0752] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0753] The operation steps are the same as in Example 1.

[0754] The reaction equation is as follows:

[0755]

[0756] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (18.9 mg, 57% yield).

[0757] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (400MHz, CDCl3) δ7.31-7.29(m,2H),6.86-6.83(m,2H),5.41-5.37(m,1H),4.14(d ,J=4.7Hz,2H),2.99(dd,J=12.6,8.8Hz,1H),2.88(ddd,J=15.1,8.8,4.8Hz,1H),2.76( dd, J = 12.6, 4.5 Hz, 1H), 2.53–2.46 (m, 1H), 2.37–2.42 (m, 2H), 1.87–1.81 (m, 1H), 1.73–1.63 (m, 2H), 1.62–1.57 (m, 2H), 1.29 (s, 9H), 1.18–1.13 (m, 3.2 Hz, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ211.1,172.7,156.0,144.1,126.3,114.0,71.0,68.7,43.2,41.9,35.1,34.1,31.5,25.1,22.6,21.2;

[0758] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 20 H 29 O4 + (M+H) + 333.2060, detected value 333.2054.

[0759] Example 73:

[0760] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0761] The operation steps are the same as in Example 3.

[0762] The reaction equation is as follows:

[0763]

[0764] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (11.8 mg, 65% yield).

[0765] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.63–5.23 (m, 2H), 5.13–5.00 (m, 1H), 3.69 (dd, J = 13.8, 11.0 Hz, 1H), 2.90–2.73 (m, 3H), 2.64 (dt, J = 14.8, 4.1 Hz, 1H), 2.47 (dd, J = 12.4, 6.8 Hz, 1H), 2.40–2.29 (m, 1H), 2.15–2.02 (m, 1H), 1.29 (d, J = 6.4 Hz, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.8,171.2,130.1,125.2,67.9,48.4,43.4,34.6,22.9,19.6;

[0766] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 15 O3 + (M+H) + 183.1016, detected value 183.1011.

[0767] Example 74:

[0768] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0769] The operation steps are the same as in Example 3.

[0770] The reaction equation is as follows:

[0771]

[0772] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (12.5 mg, 68% yield).

[0773] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.48–4.41 (m, 2H), 2.47–2.41 (m, 2H), 2.78–2.69 (m, 2H), 2.35–2.28 (m, 2H), 1.82–1.68 (m, 4H), 1.48–1.39 (m, 2H), 1.32–1.25 (m, 2H); The data from the carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.3,173.9,61.1,43.4,39.8,33.9,27.0,24.7,22.0,21.7;

[0774] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 17 O3 + (M+H) + 185.1172, detected value 185.1168.

[0775] Example 75:

[0776] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0777] The operation steps are the same as in Example 3.

[0778] The reaction equation is as follows:

[0779]

[0780] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.6 mg, 57% yield).

[0781] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ5.84-5.74(m,1H),5.44-5.38(m,1H),5.05-4.95(m,2H),2.92(dd,J=13.7,10 .8Hz,1H),2.56(ddd,J=13.5,7.6,2.7Hz,1H),2.43(ddd,J=15.2,8.5,3.0Hz,1H),2.37(dd,J=13.7 ,2.7Hz, 1H), 2.32-2.25(m, 1H), 2.22-2.15(m, 1H), 2.10-2.04(m, 2H), 1.93-1.83(m, 2H), 1.82-1.76(m, 1H), 1.70-1.65(m, 1H), 1.62-1.53(m, 2H), 1.45-1.32(m, 3H), 1.02-0.95(m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.5,172.8,137.3,115.2,71.9,45.4,44.2,34.7,34.1,29.4,27.1,25.0,21.5,21.2;

[0782] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 23 O3 + (M+H) + 239.1642, detected value 239.1641.

[0783] Example 76:

[0784] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0785] The operation steps are the same as in Example 3.

[0786] The reaction equation is as follows:

[0787]

[0788] After the reaction was completed, the product was concentrated and separated by column chromatography to obtain the target product (10.2 mg, 52% yield).

[0789] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ 5.43–5.35 (m, 1H), 2.91 (dd, J = 13.6, 11.0 Hz, 1H), 2.54 (ddd, J = 13.9, 7.5, 2.9 Hz, 1H), 2.43 (ddd, J = 15.3, 8.9, 3.3 Hz, 1H), 2.36–2.29 (m, 2H), 2.19 (ddd, J = 15.2, 9.1, 3.2 Hz, 1H), 1.98–1.92 (m, 1H), 1.87–1.79 (m, 1H), 1.63–1.53 (m, 2H), 1.47–1.42 (m, 1H), 1.38–1.30 (m, 5H), 1.05–0.97 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.6,172.7,69.4,47.7,43.5,34.6,26.9,25.1,21.6,21.3,20.8;

[0790] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 11 H 19 O3 + (M+H) + 199.1329, detected value 199.1331.

[0791] Example 77:

[0792] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0793] The operation steps are the same as in Example 3.

[0794] The reaction equation is as follows:

[0795]

[0796] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (23.0 mg, 66% yield).

[0797] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ7.31-7.26(m,2H),6.85-6.83(m,2H),5.65-5.61(m,1H),4.12-4.04(m,2H) ,3.20(dd,J=13.9,10.7Hz,1H),2.63(ddd,J=13.5,7.7,2.8Hz,1H),2.54(dd,J=13.9,2.7Hz,1H), 2.46 (ddd, J = 15.3, 8.5, 3.0 Hz, 1H), 2.38–2.31 (m, 1H), 2.21 (ddd, J = 15.4, 9.8, 2.9 Hz, 1H), 2.00–1.92 (m, 2H), 1.68–1.58 (m, 2H), 1.52–1.32 (m, 3H), 1.29 (s, 9H), 1.06–0.99 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.5,172.8,156.1,144.0,126.3,114.0,70.4,68.8,44.3,42.4,34.5,34.1,31.5,27.1,25.1,21.4,21.3;

[0798] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 31 O4 + (M+H) + 347.2217, detected value 347.2213.

[0799] Example 78:

[0800] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0801] The operation steps are the same as in Example 3.

[0802] The reaction equation is as follows:

[0803]

[0804] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (17.0 mg, 62% yield).

[0805] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ7.32-7.19(m,5H),5.58-5.51(m,1H),3.04(dd,J=13.5,5.7 Hz,1H),2.88-2.80(m,2H),2.51(ddd,J=13.5,7.5,2.8Hz,1H),2.42(ddd,J=15.3, 8.6, 3.1 Hz, 1H), 2.35–2.24 (m, 2H), 2.21–2.14 (m, 1H), 1.94–1.81 (m, 2H), 1.65–1.56 (m, 2H), 1.49–1.41 (m, 1H), 1.40–1.30 (m, 2H), 1.03–0.97 (m, 1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.6,172.6,136.4,129.5,128.5,126.8,72.8,44.7,44.0,41.0,34.6,27.1,25.0,21.5,21.2;

[0806] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 23 O3 + (M+H) + 275.1642, detected value 275.1637.

[0807] Example 79:

[0808] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0809] The operation steps are the same as in Example 3.

[0810] The reaction equation is as follows:

[0811]

[0812] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (14.9 mg, 62% yield).

[0813] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1H NMR (400MHz, CDCl3) δ5.41-5.34(m,1H),2.91(dd,J=13.7,10.9Hz,1H),2.57(ddd,J=13.6, 7.5,2.7Hz,1H),2.44(ddd,J=15.2,8.4,3.0Hz,1H),2.35(dd,J=13.7,2.6Hz,1H),2.31-2. 24 (m, J = 13.9, 11.4, 3.0 Hz, 1H), 2.17 (ddd, J = 15.3, 9.9, 2.9 Hz, 1H). 1.95–1.84 (m, 2H), 1.69–1.52 (m, 4H), 1.46–1.25 (m, 7H), 1.03–0.96 (m, 1H), 0.88 (t, J = 7.0 Hz, 3H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.8,172.8,72.4,45.5,44.2,34.8,34.7,27.2,27.2,25.1,22.5,21.5,21.2,13.9;

[0814] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 25 O3 + (M+H) + 241.1798, detected value 241.1795.

[0815] Example 80:

[0816] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0817] The operation steps are the same as in Example 3.

[0818] The reaction equation is as follows:

[0819]

[0820] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (13.6 mg, 64% yield).

[0821] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 2.80 (s, 2H), 2.48–2.44 (m, 2H), 2.27–2.24 (m, 2H), 1.74–1.69 (m, 4H), 1.61 (s, 6H), 1.49–1.42 (m, 2H), 1.35–1.32 (m, 2H); The data for carbon NMR characterization are as follows:13 C NMR (100MHz, CDCl3) δ210.9,173.7,81.8,51.2,44.7,35.2 27.1,26.3,25.6,22.4,21.7;

[0822] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 21 O3 + (M+H) + 213.1485, detected value 213.1485.

[0823] Example 81:

[0824] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0825] The operation steps are the same as in Example 3.

[0826] The reaction equation is as follows:

[0827]

[0828] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (17.1 mg, 59% yield).

[0829] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (400MHz, CDCl3) δ7.30-7.26(m,2H),6.98-6.89(m,3H),5.67-5.62(m,1H),4.41-4.06(m,2H),3.20 (dd,J=13.9,10.6Hz,1H),2.63(ddd,J=13.5,7.7,2.8Hz,1H),2.56(dd,J=13.9,2.7Hz,1H),2.46(ddd,J =15.3,8.5,3.0Hz,1H), 2.35(ddd,J=13.7,11.2,3.0Hz,1H), 2.22(ddd,J=15.3,9.8,2.9Hz,1H), 2.01-1.87(m,2H), 1.66-1.57(m,2H), 1.50-1.46(m,1H), 1.42-1.34(m,2H), 1.06-0.99(m,1H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (100MHz, CDCl3) δ210.4,172.8,158.3,129.5,121.3,114.6,70.3,68.7,44.4,42.3,34.5,27.1,25.1,21.5,21.3;

[0830] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 23 O4 + (M+H) + 291.1591, detected value 291.1591.

[0831] Example 82:

[0832] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0833] The operation steps are the same as in Example 3.

[0834] The reaction equation is as follows:

[0835]

[0836] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (16.6 mg, 69% yield).

[0837] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.33 (dd, J = 11.4, 2.1Hz, 1H), 3.00 (dd, J = 13.8, 11.4Hz, 1H), 2.63 (ddd, J = 12.9, 7.4, 2.4Hz, 1H), 2.46 (ddd, J = 15.3, 7.6, 2.5Hz, 1H), 2.25–2.10 (m, 3H), 1.98–1.85 (m, 2H), 1.61–1.52 (m, 2H), 1.46–1.41 (m, 2H), 1.40–1.32 (m, 1H), 0.97–0.93 (m, 1H), 0.91 (m, 9H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.8,172.7,77.9,45.3,40.5,35.1,34.8,27.6,25.8,24.9,21.1,20.9;

[0838] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 25 O3 + (M+H) + 241.1798, detected value 241.1794.

[0839] Example 83:

[0840] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0841] The operation steps are the same as in Example 3.

[0842] The reaction equation is as follows:

[0843]

[0844] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (13.2 mg, 72% yield).

[0845] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.17–4.07 (m, 2H), 2.56–2.49 (m, 2H), 2.49–2.44 (m, 2H), 2.34–2.25 (m, 2H), 2.14–2.04 (m, 2H), 1.72–1.62 (m, 2H), 1.61–1.54 (m, 2H), 1.43–1.34 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.7,173.5,64.0,41.2,40.1,34.8,26.1,24.2,22.1,22.0;

[0846] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 10 H 17 O3 + (M+H) + 185.1172, detected value 185.1167.

[0847] Example 84:

[0848] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0849] The operation steps are the same as in Example 3.

[0850] The reaction equation is as follows:

[0851]

[0852] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (15.5 mg, 51% yield).

[0853] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 7.38–7.26 (m, 5H), 5.14–5.00 (m, 1H), 4.58–4.47 (m, 2H), 3.59–3.47 (m, 2H), 2.51–2.40 (m, 4H), 2.40–2.20 (m, 3H), 2.04–1.91 (m, 1H), 1.79–1.67 (m, 2H), 1.64–1.51 (m, 3H), 1.41–1.31 (m, 1H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ211.4,173.7,137.9,128.4,127.7,127.6,73.1,72.5,70.9,42.3,38.1,35.3,26.7,25.6,22.6,22.3;

[0854] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 25 O4 + (M+H) + 305.1747, detected value 305.1739.

[0855] Example 85:

[0856] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0857] The operation steps are the same as in Example 3.

[0858] The reaction equation is as follows:

[0859]

[0860] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (11.9 mg, 56% yield).

[0861] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 3.85 (s, 2H), 2.51–2.40 (m, 2H), 2.40–2.30 (m, 4H), 1.80–1.62 (m, 4H), 1.36–1.28 (m, 2H), 1.10 (s, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.7,173.5,71.5,50.4,43.5,34.7,33.9,26.5,25.5,22.6,21.8;

[0862] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 12 H 21 O3 + (M+H) + 213.1485, detected value 213.1478.

[0863] Example 86:

[0864] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0865] The operation steps are the same as in Example 3.

[0866] The reaction equation is as follows:

[0867]

[0868] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (19.8 mg, 63% yield).

[0869] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 H NMR (500MHz, CDCl3) δ4.44-4.33 (m, 1H), 4.17 (dd, J = 11.0, 3.5Hz, 1H), 3.90 (dd, J = 10. 9,7.4Hz,1H),2.89(dd,J=14.5,9.6Hz,1H),2.84-2.73(m,1H),2.49(dd,J=14.6,3.3H z, 1H), 2.45–2.35 (m, 1H), 2.33–2.23 (m, 2H), 1.84–1.73 (m, 1H), 1.71–1.63 (m, 1H), 1.61–1.48 (m, 3H), 1.28–1.16 (m, 1H), 0.88 (s, 9H), 0.10 (d, J = 4.9 Hz, 6H); The data characterized by carbon NMR spectroscopy are as follows: 13 C NMR (125MHz, CDCl3) δ209.1,173.0,67.6,67.4,49.6,42.2,34.5,25.8,25.7,21.9,21.8,18.0,-4.9,-5.0;

[0870] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 31 O4Si + (M+H) + 315.1986, detected value 315.1974.

[0871] Example 87:

[0872] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0873] The operation steps are the same as in Example 3.

[0874] The reaction equation is as follows:

[0875]

[0876] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.5 mg, 68% yield).

[0877] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.13–4.06 (m, 2H), 2.57–2.49 (m, 2H), 2.48–2.42 (m, 2H), 2.36–2.29 (m, 2H), 2.12–2.02 (m, 2H), 1.82–1.71 (m, 2H), 1.66–1.56 (m, 2H), 1.44–1.32 (m, 2H), 1.30–1.19 (m, 2H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ210.4,174.0,64.7,40.7,40.6,33.5,24.9,24.7,23.2,22.7,21.1;

[0878] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 11 H 19 O3 + (M+H) + 199.1329, detected value 199.1320.

[0879] Example 81:

[0880] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0881] The operation steps are the same as in Example 3.

[0882] The reaction equation is as follows:

[0883]

[0884] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (21.7 mg, 66% yield).

[0885] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (500MHz, CDCl₃) δ 4.50–4.41 (m, 1H), 4.10 (dd, J = 11.0, 3.2 Hz, 1H), 3.95 (dd, J = 10.8, 8.4 Hz, 1H), 2.90 (dd, J = 15.7, 9.6 Hz, 1H), 2.66–2.51 (m, 2H), 2.43–2.27 (m, 3H), 2.02–1.91 (m, 1H), 1.67–1.49 (m, 3H), 1.46–1.38 (m, 1H), 1.35–1.19 (m, 3H), 0.88 (s, 9H), 0.10 (d, J = 2.2 Hz, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (125MHz, CDCl3) δ208.3,173.4,68.08,66.4,50.3,41.3,33.4,25.7,24.9,24.7,23.2,21.0,18.0,-4.9,-5.0;

[0886] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 17 H 33 O4Si + (M+H) + 329.2143, detected value 329.2131.

[0887] Example 89:

[0888] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0889] The operation steps are the same as in Example 3.

[0890] The reaction equation is as follows:

[0891]

[0892] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (13.3 mg, 59% yield).

[0893] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.18–4.11 (m, 2H), 2.62 (t, J = 6.8 Hz, 2H), 2.42–2.30 (m, 4H), 1.98–1.89 (m, 2H), 1.72–1.60 (m, 4H), 1.43–1.21 (m, 8H); The data for carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ208.3,173.7,59.0,41.5,41.2,33.7,26.2,25.9,25.7,25.4,25.3,24.4,22.9;

[0894] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 13 H 23 O3 + (M+H) + 227.1642, detected value 227.1641.

[0895] Example 90:

[0896] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0897] The operation steps are the same as in Example 3.

[0898] The reaction equation is as follows:

[0899]

[0900] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (12.5 mg, 52% yield).

[0901] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 4.18–4.11 (m, 2H), 2.62 (t, J = 6.8 Hz, 2H), 2.42–2.30 (m, 4H), 1.98–1.89 (m, 2H), 1.72–1.60 (m, 4H), 1.43–1.21 (m, 10H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ211.4,174.1,63.1,41.8,39.2,34.0,27.4,27.1,26.7,26.4,26.3,24.9,24.8,22.1;

[0902] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 14 H 25 O3 + (M+H) + 241.1798, detected value 241.1794.

[0903] Example 91:

[0904] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0905] The operation steps are the same as in Example 3.

[0906] The reaction equation is as follows:

[0907]

[0908] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (13.2 mg, 52% yield).

[0909] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.39–5.35 (m, 1H), 2.78 (dd, J = 15.8, 10.0 Hz, 1H), 2.47–2.421 (m, 3H), 2.30–2.26 (m, 2H), 1.76–1.70 (m, 2H), 1.56–1.51 (m, 2H), 1.36–1.19 (m, 15H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.0,173.0,67.5,48.6,42.0,33.7,27.0,26.9,26.5,25.7,25.7,25.3,24.2,21.3,20.2;

[0910] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 15 H 27 O3 + (M+H) + 255.1955, detected value 255.1951.

[0911] Example 92:

[0912] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0913] The operation steps are the same as in Example 3.

[0914] The reaction equation is as follows:

[0915]

[0916] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (17.5 mg, 53% yield).

[0917] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.31–7.19 (m, 5H), 5.55–5.49 (m, 1H), 3.02 (dd, J = 13.4, 5.3 Hz, 1H), 2.77 (dd, J = 13.4, 8.1 Hz, 1H), 2.70 (dd, J = 16.1, 10.0 Hz, 1H), 2.48–2.26 (m, 5H), 1.74–1.67 (m, 2H), 1.56–1.48 (m, 2H), 1.38–1.17 (m, 12H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.0,172.9,136.7,129.5,128.5,126.8,71.1,45.6,42.1,40.4,33.6,27.0,26.9,26.5,25.7,25.6,25.3,24.1,21.3;

[0918] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 31 O3 + (M+H) + 331.2268, detected value 331.2262.

[0919] Example 93:

[0920] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0921] The operation steps are the same as in Example 3.

[0922] The reaction equation is as follows:

[0923]

[0924] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (16.3 mg, 47% yield).

[0925] NMR analysis: The data for the proton NMR spectrum (400 MHz, deuterated chloroform as solvent) are as follows: 1¹H NMR (400MHz, CDCl₃) δ 7.30–7.26 (m, 2H), 6.98–6.89 (m, 3H), 5.68–5.62 (m, 1H), 4.07 (d, J = 4.7 Hz, 2H), 3.07 (dd, J = 16.7, 9.9 Hz, 1H), 2.71 (dd, J = 16.7, 2.3 Hz, 1H), 2.52–2.45 (m, 2H), 2.36–2.26 (m, 2H), 1.83–1.78 (m, 1H), 1.74–1.69 (m, 1H), 1.63–1.50 (m, 2H), 1.43–1.30 (m, 6H), 1.29–1.18 (m, 6H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.5,173.0,158.4,129.5,121.2,114.4,68.3,68.3,43.8,42.2,33.6,27.2,27.0,26.6,25.9,25.8,25.5,24.3,21.5;

[0926] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 31 O4 + (M+H) + 347.2217, detected value 347.2213.

[0927] Example 94:

[0928] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0929] The operation steps are the same as in Example 3.

[0930] The reaction equation is as follows:

[0931]

[0932] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (14.8 mg, 50% yield).

[0933] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.35–5.29 (m, 1H), 2.74 (dd, J = 15.8, 9.8 Hz, 1H), 2.51–2.41 (m, 3H), 2.31–2.27 (m, 2H), 1.75–1.69 (m, 2H), 1.66–1.60 (m, 2H), 1.57–1.49 (m, 3H), 1.39–1.18 (m, 15H), 0.88 (t, J = 7.0 Hz, 3H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ208.3,173.0,70.6,46.7,42.2,34.1,33.6,27.3,27.0,26.9,26.5,25.7,25.6,25.3,24.1,22.5,21.3,13.9;

[0934] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 33 O3 + (M+H) + 297.2424, detected value 297.241.

[0935] Example 95:

[0936] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0937] The operation steps are the same as in Example 3.

[0938] The reaction equation is as follows:

[0939]

[0940] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (12.1 mg, 45% yield).

[0941] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 2.88 (s, 2H), 2.47 (t, J = 6.9Hz, 2H), 2.28–2.24 (m, 2H), 1.65–1.57 (m, 5H), 1.52 (s, 6H), 1.38–1.31 (m, 5H), 1.29–1.22 (m, 6H); The data from the carbon NMR characterization are as follows: 13C NMR (100MHz, CDCl3) δ208.4,173.6,80.3,52.3,42.9,34.5,27.0,27.0,26.9,26.4,25.6,25.5,25.0,24.0,20.8;

[0942] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 16 H 29 O3 + 269.2111, detected value 269.2108.

[0943] Example 96:

[0944] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0945] The operation steps are the same as in Example 3.

[0946] The reaction equation is as follows:

[0947]

[0948] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (14.7 mg, 50% yield).

[0949] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.83–5.73 (m, 1H), 5.38–5.32 (m, 1H), 5.05–4.95 (m, 2H), 2.75 (dd, J = 15.9, 9.6 Hz, 1H), 2.52 (dd, J = 15.9, 2.4 Hz, 1H), 2.45–2.41 (m, 2H), 2.32–2.27 (m, 2H), 2.09–2.03 (m, 2H), 1.78–1.67 (m, 3H), 1.66–1.60 (m, 1H), 1.58–1.49 (m, 2H), 1.39–1.18 (m, 12H); The data for carbon NMR characterization are as follows: 13 CNMR(100MHz, CDCl3)δ208.0,173.0,137.4,115.2,70.1,46.7,42.2,33.6,33.5,29.4,27.0,26.8,26.5,25.7,25.6,25.3,24.1,21.3;

[0950] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 31 O3 + (M+H)+ 295.2268, detected value 295.2263.

[0951] Example 97:

[0952] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0953] The operation steps are the same as in Example 3.

[0954] The reaction equation is as follows:

[0955]

[0956] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (16.9 mg, 57% yield).

[0957] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 5.35–5.28 (m, 1H), 2.75 (dd, J = 16.1, 8.7 Hz, 1H), 2.51 (dd, J = 16.1, 4.1 Hz, 1H), 2.41 (t, J = 7.0 Hz, 2H), 2.24 (td, J = 7.4, 2.5 Hz, 2H), 1.65–1.51 (m, 4H), 1.34–1.25 (m, 21H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.9,173.0,67.1,48.4,43.1,34.6,28.0,27.6,27.6,26.9,26.8,26.7,26.2,24.4,22.9,20.1;

[0958] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 18 H 33 O3 + (M+H) + 297.2424, detected value 297.2421.

[0959] Example 98:

[0960] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0961] The operation steps are the same as in Example 3.

[0962] The reaction equation is as follows:

[0963]

[0964] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (18.5 mg, 48% yield).

[0965] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1 ¹H NMR (400MHz, CDCl₃) δ 7.30–7.27 (m, 2H), 6.98–6.89 (m, 3H), 5.59–5.55 (m, 1H), 4.11 (d, J = 4.5 Hz, 2H), 2.99 (dd, J = 17.0, 8.5 Hz, 1H), 2.81 (dd, J = 17.0, 4.2 Hz, 1H), 2.48–2.43 (m, 2H), 2.31–2.26 (m, 2H), 1.65–1.55 (m, 5H), 1.34–1.25 (m, 17H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.4,173.1,158.4,129.5,121.2,114.6,68.2,68. 1,43.2,43.2,34.5,28.0,27.7,27.6,27.0,26.9,26.8,26.3,24.5,23.0;

[0966] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 24 H 37 O4 + (M+H) + 389.2686, detected value 389.2682.

[0967] Example 99:

[0968] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0969] The operation steps are the same as in Example 3.

[0970] The reaction equation is as follows:

[0971]

[0972] After the reaction was completed, the product was concentrated directly and separated by column chromatography to obtain the target product (20.1 mg, 54% yield).

[0973] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.31–7.26 (m, 2H), 7.24–7.19 (m, 3H), 5.49–5.43 (m, 1H), 3.02 (dd, J = 13.5, 5.6 Hz, 1H), 2.82 (dd, J = 13.5, 7.5 Hz, 1H), 2.67 (dd, J = 16.3, 8.8 Hz, 1H), 2.50 (dd, J = 16.3, 3.8 Hz, 1H), 2.36 (t, J = 7.0 Hz, 2H), 2.29–2.20 (m, 2H), 1.63–1.47 (m, 5H), 1.33–1.24 (m, 17H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.8,173.0,136.8,129.6,128.5,126.7,70.8,45. 4,43.2,40.1,34.5,28.0,27.6,26.9,26.8,26.8,26.6,26.2,24.4,22.8;

[0974] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 24 H 37 O3 + (M+H) + 373.2737, detected value 373.2734.

[0975] Example 100:

[0976] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0977] The operation steps are the same as in Example 3.

[0978] The reaction equation is as follows:

[0979]

[0980] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (18.5 mg, 55% yield).

[0981] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 5.82–5.74 (m, 1H), 5.32–5.26 (m, 1H), 5.04–4.95 (m, 2H), 2.72 (dd, J = 16.0, 8.4 Hz, 1H), 2.57 (dd, J = 16.0, 4.2 Hz, 1H), 2.41 (td, J = 7.1, 2.3 Hz, 2H), 2.25 (t, J = 7.3 Hz, 2H), 2.07 (q, J = 7.5 Hz, 2H), 1.77–1.51 (m, 6H), 1.37–1.25 (m, 18H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.9,173.1,137.4,115.1,69.8,46.6,43.2,34.4,33.3,29.4,27.9,27.6,27.5,26.9,26.7,26.6,26.3,24.4,22.9;

[0982] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 21 H 37 O3 + (M+H) + 337.2737, detected value 337.2732.

[0983] Example 101:

[0984] A cerium-catalyzed method for modular synthesis of macrocyclic lactones via cyclic ketone ring expansion, comprising the following steps:

[0985] The operation steps are the same as in Example 3.

[0986] The reaction equation is as follows:

[0987]

[0988] After the reaction was completed, the product was directly concentrated and separated by column chromatography to obtain the target product (22.6 mg, 51% yield).

[0989] Nuclear magnetic resonance analysis: The data characterized by proton nuclear magnetic resonance spectroscopy are as follows 1¹H NMR (400MHz, CDCl₃) δ 7.31–7.27 (m, 2H), 6.87–6.82 (m, 2H), 5.59–5.54 (m, 1H), 4.09 (d, J = 4.5 Hz, 2H), 2.99 (dd, J = 17.0, 8.6 Hz, 1H), 2.80 (dd, J = 17.0, 4.1 Hz, 1H), 2.50–2.40 (m, 2H), 2.32–2.23 (m, 2H), 1.70–1.51 (m, 4H), 1.38–1.26 (m, 27H); The data for carbon NMR characterization are as follows: 13 C NMR (100MHz, CDCl3) δ207.5,173.1,156.1,143.9,126.3,114.0,68.2,68.2,43.2,43. 2,34.5,34.1,31.5,31.5,28.0,27.7,27.5,27.0,26.9,26.8,26.8,26.3,24.5,22.9;

[0990] High-resolution mass spectrometry analysis (HRMS(ESI+): Theoretical value C) 28 H 45 O4 + (M+H) + 445.3312, detected value 445.3315.

[0991] Example 102 Conditional Screening

[0992] 1. Screening of cerium catalysts

[0993]

[0994] Table 1

[0995] serial number catalyst Yield / % 1 <![CDATA[CeCl3]]> 62 2 <![CDATA[[(n-Bu)4N]2[CeCl6]]]> 61 3 <![CDATA[CeBr3]]> 12 4 <![CDATA[Ce(OTf)3]]> 81 5 <![CDATA[Ce(OTf)4]]> 75 6 <![CDATA[Ce(NO3)3·6H2O]]> 64

[0996] Table 1 shows the screening of cerium catalysts. Reaction conditions: alkyl ketone (0.1 mmol), cerium catalyst (0.02 equivalence), 9,10-diphenylanthracene (0.02 equivalence), tetrabutylphosphine chloride (0.04 equivalence), ethyl acetate (0.05 mol / L), blue LED lamp (380-650 nm, 0.12 W / cm²). 2 ).

[0997] 2. Additive screening

[0998]

[0999] Table 2

[1000] serial number additive Yield / % 1 <![CDATA[(n-Bu)4NCl]]> 70 2 <![CDATA[Et4NCl]]> 67 3 <![CDATA[(n-Bu)4PCl]]> 81 4 <![CDATA[(n-Bu)4NBr]]> 17 5 <![CDATA[(n-Bu)4PBr]]> 20 6 <![CDATA[(n-Bu)4NOTf]]> 58 7 <![CDATA[(n-Bu)4NHSO4]]> 47 8 <![CDATA[(n-Bu)4NH2PO4]]> 55 9 <![CDATA[0%(n-Bu)4PCl]]> 16 10 <![CDATA[2%(n-Bu)4PCl]]> 77 11 <![CDATA[6%(n-Bu)4PCl]]> 66 12 <![CDATA[8%(n-Bu)4PCl]]> 59

[1001] Table 2 shows the additive screening. Reaction conditions: alkylated ketone (0.1 mmol), cerium(III) trifluoromethanesulfonate (0.02 equivalent), 9,10-diphenylanthracene (0.02 equivalent), additive (0.02 equivalent), ethyl acetate (0.05 mol / L), blue LED lamp (380-650 nm, 0.12 W / cm²). 2 ).

[1002] 3. Screening of organic photocatalysts

[1003]

[1004] Application Example: Synthesis of Sonnerlactone

[1005] In Sonnerlactone-type compounds, this benzo[a] ten-membered lactone ring represents a novel natural skeletal structure, but such structures present numerous challenges in traditional cyclization synthetic strategies. Early syntheses using the Mitsunobu or RCM reactions required meticulous retrosynthetic design and lengthy preparation of cyclization precursors, totaling up to 17 and 12 synthetic steps, respectively.

[1006] The inventors of this application creatively applied a cerium-catalyzed ring-expansion strategy to the synthesis of this compound, designing a significantly simpler synthetic route. Dimethoxybenzocycloheptanone 67 and (R)-propylene oxide were modularly assembled via a cyclization / expansion method, yielding a convenient benzodelactone skeleton from which the corresponding stereochemical conformation could be obtained at the C3 position using inexpensive chiral epoxides.

[1007] Notably, the photocatalytic ring expansion was carried out using a continuous flow apparatus in a microreactor made of glass, achieving a reaction efficiency comparable to that in a small glass vial. Using this simple flow apparatus, the target ketolactone 68 was synthesized in 80% yield at a reactant flow rate of 0.15 mL / min and an oxygen pressure of 1500 kPa. Subsequently, the target natural product was obtained via deprotection and the Noyori reaction, following an existing synthetic protocol. In summary, (3R, 5S)-Sonnerlactone was synthesized from commercially available cyclic ketones in four steps (overall yield 36%).

[1008]

[1009] At 0 °C, an anhydrous dichloromethane solution (2.0 mL) of compound 68 (80 mg, 0.27 mmol, 1.0 equiv.) was added dropwise to an anhydrous dichloromethane solution (8.0 mL) of aluminum trichloride (215 mg, 1.7 mmol, 6.0 equiv.). After the addition was complete, the reaction mixture was heated to 40 °C and stirred for 24 hours. After the reaction was complete, the mixture was quenched with water, extracted three times with dichloromethane, and the organic phases were combined and washed with a saturated sodium chloride aqueous solution. The organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (10% acetone / n-hexane) to give an intermediate (72.3 mg, 68%). This intermediate (33 mg, 0.13 mmol, 1.0 equiv.) was dissolved in anhydrous dichloromethane (3 mL). Under argon protection, a dichloromethane solution (1 mL) of formic acid (40 mg, 0.87 mmol, 7.0 equiv.) and triethylamine (87 mg, 0.87 mmol, 7.0 equiv.) was added to the above solution. After stirring the reaction solution for five minutes, a ruthenium catalyst (1.6 mg, 0.0026 mmol, 0.02 equiv., CAS: 192139-92-7) was added, and the mixture was then heated to room temperature and stirred for 24 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution, separated, and extracted three times with dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (15% acetone / n-hexane) to obtain the target product (3R,5S)-Sonnerlactone (27.2 mg, 82%, 25:1 d.r.).[α] D 25 = +55.6 (c 0.5, EtOH); 1 H NMR (400MHz, acetone-d6) δ11.54(s,1H),9.17(s,1H),6.25(d,J=1.9Hz,1H),6.20(d,J=2.0Hz,1H),5.38-5.35(m,1H),4.22-4. 17(m,1H),3.76(d,J=3.9Hz,1H),3.37-3.31(m,1H),2.38-2.34(m,1H),2.14-2.08(m,1H),1.86-1.73(m,3H),1.48-1.40(m,5H); 13 C NMR (100MHz, acetone-d6) δ 171.6, 166.6, 163.6, 149.9, 112.1, 105.2, 101.8, 70.4, 66.8, 42.9, 37.3, 36.2, 28.5, 20.2; HRMS (ESI+): Theoretical value C 14 H 19 O5 + (M+H)+ 267.1227, detected value 267.1220.

Claims

1. A method for synthesizing a lactone compound, characterized by, It comprises the following steps: The cyclization reaction of the cyclic ketone compound containing the structural fragment as shown in formula II in a solvent under visible light irradiation in an oxygen atmosphere in the presence of a photocatalyst and a cerium catalyst to obtain the lactone compound containing the structural fragment as shown in formula I, namely; ； Wherein, n is 0, 1, 2 or 3; M is C1-C 20 alkylene, C1-C 1-1 alkylene substituted by R 20 alkylene, C1-C 20 heteroalkylene, C1-C 1-2 heteroalkylene substituted by R 20 heteroalkylene or C2-C 15 alkenylene, the heteroatom(s) in said C1-C 20 heteroalkylene and C1-C 1-2 heteroalkylene substituted by R 20 heteroalkylene being one or more, independently, O, S and N, in a number of 1, 2 or 3; R 1-1 Independently halogenated, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or R-containing 1-1-1 Substituted C2-C4 alkynyl groups, C6-C 14 aryl, 3-6 cycloalkyl, and R 1-1-2 Substituted 3-6 cycloalkyl groups, -OR 1-1-3 or -(C=O)OR 1-1-4 ; R 1-1-1 independently ; R 1-1-1-1a , R 1-1-1-1b , and R 1-1-1-1c are independently C1-C4alkyl; R 1-1-2 independently C1-C4alkyl; R 1-1-3 is C1-C4alkyl, C1-C4alkyl substituted by phenyl, C6-C10aryl, benzoyl or 14 is C1-C4alkyl, C1-C4alkyl substituted by phenyl, C6-C10aryl, benzoyl or ; R 1-1-4 Ci-C4-alkyl; or, any two adjacent R 1-1 together with the carbon atom to which they are attached form a C6-C 14 aryl, C6-C 1-1a aryl substituted by R 14 aryl, 3- to 6-membered cycloalkyl, 3- to 6-membered cycloalkyl 1-1b substituted by R or ; R 1-1a and R 1-1b independently are halogen, C1-C4alkoxy or C6-C 14 aryl; or, any two non-adjacent R 1-1 together with the carbon atom to which they are attached form a 3-6 membered heterocycloalkyl or a 3-6 membered heterocycloalkyl substituted with an amino protecting group, the heteroatom in said 3-6 membered heterocycloalkyl or 3-6 membered heterocycloalkyl substituted with an amino protecting group being N in a number of 1 or 2; R 1-2 -(C=O)R 1-2-1 ; R 1-2-1 is C6-Ci4-aryl or 14 is C6-Ci4-aryl or ; R 1-1 R 1-2 R 1-1-1 R 1-1-2 R 1-1a R 1-1b are independently 1, 2, or 3. Said visible light is blue light; Said cerium catalyst is one or more of CeCl3, [(n-Bu)4N]2[CeCl6], CeBr3, CeF3, Ce(OTf)3, Ce(OTf)4, Ce(NO3)3·3H2O and Ce(OAc)3·1.5H2O; Said cyclization reaction is carried out in the presence of an additive, and said additive is a quaternary ammonium salt and / or a quaternary phosphonium salt; Said quaternary ammonium salt is one or more of (n-Bu)4NCl, Et4NCl, (n-Bu)4NBr, (n-Bu)4NOTf and (n-Bu)4NHSO4; Said quaternary phosphonium salt is one or more of (n-Bu)4PCl, (n-Bu)4PBr and (n-Bu)4NH2PO4; The photocatalyst is an organic photocatalyst, and the organic photocatalyst is one or more of , , , , , , , , , , , , , , , and .

2. The synthesis method of the lactone compound according to claim 1, wherein, The illumination intensity of the visible light is 0.1-0.2 W / cm 2 ; And / or, the oxygen atmosphere is that the volume content of oxygen in the oxygen atmosphere is 5-100%; And / or, the molar ratio of the photocatalyst to the cyclic ketone compound containing the structural fragment as shown in formula II is 0.01:1-0.1:1; And / or, the cerium catalyst is one or more of CeCl3, [(n-Bu)4N]2[CeCl6], Ce(OTf)3, Ce(OTf)4 and Ce(NO3)3·3H2O; And / or, the molar ratio of the cerium catalyst to the cyclic ketone compound containing the structural fragment as shown in formula II is 0.01:1-0.1:1; And / or, the solvent is one or more of a nitrile solvent, an ester solvent, a ketone solvent, a chlorinated hydrocarbon solvent, a sulfoxide solvent, an amide solvent, an ether solvent and an aromatic hydrocarbon solvent; And / or, the molar concentration of the cyclic ketone compound containing the structural fragment as shown in formula II is 0.02-0.1M; And / or, the cyclization reaction is carried out in the presence of trifluoroacetic acid; And / or, n is 0; and / or, when M is C1-C 20 alkylene, said C1-C 20 alkylene is C1-C 13 alkylene; And / or, when M is R 1-1 Replacement C1-C 20 When alkylene, the C1-C 20 The alkylene group is a C4-C7 alkylene group; and / or, when R 1-1 when independently halogen, said halogen is F or Br; and / or, when R 1-1 independently C1-C4alkyl, said C1-C4alkyl is methyl, isopropyl or tert-butyl; and / or, when R 1-1 independently is C2-C4alkynyl substituted with R 1-1-1 when said C2-C4alkynyl is independently substituted with R and / or, when R 1-1-1-1a , R 1-1-1-1b , and R 1-1-1-1c are independently C1-C4 alkyl, said C1-C4 alkyl is methyl; and / or, when R 1-1 independently C6-C 14 aryl, said C6-C 14 aryl is phenyl; and / or, when R 1-1 is independently 3-6 membered cycloalkyl or 3-6 membered cycloalkyl substituted with R 1-1-2 substituted with R is cyclohexyl; and / or, when R 1-1-2 independently C1-C4alkyl, said C1-C4alkyl is n-propyl; and / or, when R 1-1-3 is C1-C4alkyl, said C1-C4alkyl is methyl; and / or, when R 1-1-3 is C6-C 14 aryl, said C6-C 14 aryl is phenyl; and / or, when R 1-1-3 is C1-C4alkyl, said C1-C4alkyl is tert-butyl; and / or, when any two adjacent R 1-1 together with the carbon atom to which they are attached form a C6-C 14 aryl or C6-C 1-1a substituted C6-C 14 aryl, said C6-C 14 aryl is phenyl; and / or, when R 1-1a and R 1-1b when independently halogen, said halogen is Br; and / or, when R 1-1a and R 1-1b independently is C1-C4alkoxy, said C1-C4alkoxy is methoxy; and / or, when any two adjacent R 1-1 with the carbon atom to which it is attached forms a 3-6 membered cycloalkyl or a 3-6 membered cycloalkyl substituted by R 1-1b substituted 3-6 membered cycloalkyl, said 3-6 membered cycloalkyl is cyclopropyl; and / or, when any two non-adjacent R 1-1 when taken together with the ring atom to which it is attached forms a 3-6 membered heterocycloalkyl substituted with an amino protecting group, said 3-6 membered heterocycloalkyl substituted with an amino protecting group is ; And / or, when M is C1-C 20 heteroalkyl or R 1-2 Replacement C1-C 20 When the heteroalkylene group is used, the C1-C 20 The heteroalkylene groups are C1-C5 heteroalkylene groups; and / or, when R 1-2-1 is C6-C 14 aryl, said C6-C 14 aryl is phenyl; And / or, when M is C2-C 20 When the sub-alkenyl group is present, the C2-C 20 The alkenyl group is a C2-C6 alkenyl group.

3. The synthesis method of the lactone compound according to claim 2, wherein, The visible light illumination intensity is 0.12 W / cm 2 ; And / or, the oxygen atmosphere is that the volume content of oxygen in the oxygen atmosphere is oxygen or air; And / or, the molar ratio of the photocatalyst to the cyclic ketone compound containing the structural fragment as shown in formula II is 0.02:1; And / or, the cerium catalyst is Ce(OTf)3 or Ce(OTf)4; And / or, the molar ratio of the cerium catalyst to the cyclic ketone compound containing the structural fragment as shown in formula II is 0.02:1; And / or, the solvent is an ester solvent and / or a ketone solvent; And / or, the molar concentration of the cyclic ketone compound containing the structural fragment as shown in formula II is 0.05M; and / or, when M is C1-C 20 alkylene, said C1-C 20 alkylene is , , , , or ; and / or, when M is substituted C1-C 1-1 alkylene, said C1-C 20 alkylene is 20 or ;​ and / or, when M is C2-C 20 alkenylene of 2-4 carbon atoms, said C2-C 20 alkenylene of 2-4 carbon atoms is .

4. The method according to claim 3, wherein the cerium catalyst is Ce(OTf)3; and / or the solvent is an ester solvent. When the visible light is blue light, the wavelength of the blue light is 380-650 nm. When the solvent is an ester solvent, the ester solvent is ethyl acetate.

5. The method for synthesizing lactone compounds as described in claim 2, characterized in that, When the cyclization reaction is carried out in the presence of an additive, the additive is a quaternary ammonium salt and / or a quaternary phosphonium salt; the quaternary ammonium salt is one or more of (n-Bu)4NCl, Et4NCl, (n-Bu)4NOTf, and (n-Bu)4NH2PO4; the quaternary phosphonium salt is (n-Bu)4PCl. and / or, when the photocatalyst is an organic photocatalyst, the organic photocatalyst is one or more of 、 、 、 、 、 、 、 、 、 、 、 、and . When the cyclization reaction is carried out in the presence of trifluoroacetic acid, the molar ratio of the trifluoroacetic acid to the compound containing the structural fragment of formula II is 0.1:1-1.0:

1. When the cyclization reaction is carried out in the presence of an additive, the molar ratio of the additive to the compound containing the structural fragment of formula II is 0.02:1-0.08:

1.

6. The method according to claim 5, wherein the cerium catalyst is Ce(OTf)3; and / or the solvent is an ester solvent. When the cyclization reaction is carried out in the presence of an additive, the additive is a quaternary ammonium salt and / or a quaternary phosphonium salt; the quaternary ammonium salt is (n-Bu)4NCl. and / or, when M is substituted C1-C6alkylene 1-1 substituted C1-C6alkylene 20 substituted C1-C6alkylene 1-1 substituted C1-C6alkylene 20 substituted C1-C6alkylene , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or ; and / or, when M is substituted C1-C6heteroalkylene, said R 1-2 substituted C1-C6alkyl is 20 substituted C1-C6heteroalkylene is 1-2 substituted C1-C6alkyl is 20 substituted C1-C6heteroalkylene is . When the cyclization reaction is carried out in the presence of trifluoroacetic acid, the molar ratio of the trifluoroacetic acid to the compound containing the structural fragment of formula II is 0.

6. When the photocatalyst is an organic photocatalyst, the organic photocatalyst is ; When the cyclization reaction is carried out in the presence of an additive, the molar ratio of the additive to the compound containing the structural fragment of formula II is 0.02:1-0.04:

1. The compound containing the structural fragment of formula II is a compound of formula II-a, and accordingly, the lactone compound containing the structural fragment of formula I is a compound of formula I-a; wherein M and n are as defined in any one of claims 1-6.

7. The method for synthesizing lactone compounds as described in claim 1, characterized in that, The oxygen atmosphere is oxygen; the photocatalyst is ; the cerium catalyst is Ce(OTf)3; the solvent is an ester solvent; the cycloaddition reaction is carried out in the presence of an additive; and the additive is (n-Bu)4PCl; Alternatively, the oxygen atmosphere is oxygen; the photocatalyst is ; the cerium catalyst is Ce(OTf)3; the solvent is an ester solvent; the cycloaddition reaction is carried out in the presence of an additive and trifluoroacetic acid; and the additive is (n-Bu)4PCl.

8. The method for synthesizing lactone compounds as described in claim 1, characterized in that, 10. The method according to claim 9, wherein the compound containing the structural fragment of formula IV is prepared by the following steps: ； wherein M and n are as defined in any one of claims 1-6. R 2a , R 2b , R 3a , R 3b , R 4a , and R 4b are independently hydrogen, C1-C4alkyl, C1-C4alkyl substituted by R 2a-1 , -OR 2a-2 , C2-C4alkenyl, C2-C4alkynyl, C2-C4alkynyl substituted by R 2a-3 , C6-C 14 aryl, -(C=O)OR 2a-4 , 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 3-6 membered heterocycloalkyl substituted by R 2a-5 ; the heteroatoms in said 3-6 membered heterocycloalkyl and said 3-6 membered heterocycloalkyl substituted by R 2a-5 are selected from one or more of N, S and O, in a number of 1, 2 or 3; R 2a-1 independently halogen, -S(=0)2Ph, adamantyl, C6-C 14 aryl, C6-C 2a-1-1 aryl substituted by R 14 ; or OR 2a-1-2 ; R 2a-1-1 independently halogen or C1-C4alkyl; R 2a-1-2 is C2-C6alkynyl, , C6-C 14 aryl, C6-C 2a-1-2-1 aryl or benzyl substituted by R 14 ; R 2a -1-2-1 independently halogen or C1-C4alkyl; R 2a-2 and R 2a-3 are independently , R 2a-3-1a , R 2a-3-1b and R 2a-3-1c are independently C1-C4 alkyl; R 2a-4 Ci-C4-alkyl; R 2a-5 independently -(C=0)R 2a-5-1 ; R 2a-5-1 is C6-Ci4-aryl or 14 is C6-Ci4-aryl or ; R 2a-1 R 2a-3 R 2a-5 R 2a-1-1 and R 2a-1-2-1 are independently 1, 2 or 3.

9. The method for synthesizing lactone compounds as described in claim 8, characterized in that, R 2a , R 2b , R 3a , R 3b , R 4a , and R 4b are independently hydrogen, C1-C4alkyl, or 3-6 membered cycloalkyl; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently C1-C4alkyl, said C1-C4alkyl is methyl, n-butyl or t-butyl; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a , and R 4b are independently C1-C4alkyl substituted with R 2a-1 , said C1-C4alkyl is methyl or ethyl; and / or, when R 2a-1 is halogen, said halogen is F, Cl, Br or I; and / or, when R 2a-1 is C6-C 14 aryl or C6-C 2a-1-1 aryl substituted by R 14 , said C6-C 14 aryl is phenyl; and / or, when R 2a-1-1 is halogen, said halogen is F, Cl, Br or I; and / or, when R 2a-1-1 is C1-C4alkyl, said C1-C4alkyl is tert-butyl; And / or, when R 2a-1-2 When the alkynyl group is C2-C6, the C2-C6 alkynyl group is an acetylenyl group; and / or, when R 2a-1-2 is C6-C 14 aryl, said C6-C 14 aryl is phenyl; and / or, when R 2a-1-2 is R 2a-1-2-1 substituted C6-C 14 aryl, said C6-C 14 aryl is phenyl; and / or, when R 2a-1-2-1 is halogen, said halogen is Br; and / or, when R 2a-1-2-1 is C1-C4alkyl, said C1-C4alkyl is tert-butyl; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently C2-C4alkenyl, said C2-C4alkenyl is butenyl; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently C2-C4alkynyl or C2-C4alkynyl substituted by R 2a-3 , said C2-C4alkynyl is propynyl; and / or, when R 2a-3-1a , R 2a-3-1b and R 2a-3-1c are independently C1-C4alkyl, said C1-C4alkyl is methyl or tert-butyl; and / or, when R 2a-4 is C1-C4alkyl, said C1-C4alkyl is ethyl; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently a 3-6 membered cycloalkyl, said 3-6 membered cycloalkyl is cyclohexane; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a , and R 4b are independently 3-6 membered heterocycloalkyl or 3-6 membered heterocycloalkyl substituted with R 2a-5 , said 3-6 membered heterocycloalkyl is piperidinyl. In the alkylation reaction, the Lewis acid is boron trifluoride. when R 2a-1 is halogen, said halogen is F; and / or, when R 2a-1-1 is halogen, said halogen is Br; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently C2-C4 alkenyl, said C2-C4 alkenyl is .

11. The method for synthesizing lactone compounds as described in claim 9, characterized in that, When R 2a R 2b R 3a R 3b R 4a and R 4b Independently for R 2a-1 When the C1-C4 alkyl group is substituted, the R 2a-1 The substituted C1-C4 alkyl groups are , , , , , , , , , or ; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently C2-C4alkynyl substituted with R 2a-3 , said C2-C4alkynyl substituted with R 2a-3 is ; and / or, when R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are independently 3-6 membered heterocycloalkyl substituted by R 2a-5 , said 3-6 membered heterocycloalkyl substituted by R 2a-5 is .

12. The method for synthesizing lactone compounds as described in claim 1, characterized in that, In the alkylation reaction, the solvent is an ether solvent. ； wherein Q + is potassium ion or lithium ion; In the alkylation reaction, the molar ratio of the compound containing the structural fragment of formula IV to the compound of formula III is 4.0:1-1.0:

1.

13. The method for synthesizing lactone compounds as described in claim 12, characterized in that, 14. The method according to claim 13, wherein the compound containing the structural fragment of formula IV is prepared by the following steps: ​ ​ ​ The solvent in the alkylation reaction is tetrahydrofuran and / or diethyl ether.

15. The method for synthesizing lactone compounds as described in claim 12, characterized in that, The compound containing the structural fragment as shown in formula IV is a compound as shown in formula IV-a; and correspondingly, the cyclic ketone containing the structural fragment as shown in formula II is a compound as shown in formula II-a; ； wherein M and n are as defined in any one of claims 1-6; R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are each as defined in any one of claims 8-11.

16. The method for synthesizing lactone compounds as described in claim 15, characterized in that, The compound as shown in formula III is any one of the following compounds: ； The compound as shown in formula IV-a is any one of the following compounds: ； 。 17. The method for synthesizing lactone compounds as described in claim 12, characterized in that, The compound as shown in formula IV-a is any one of the following compounds: ； The compound as shown in formula IV-a is any one of the following compounds:

18. A method for synthesizing a lactone compound, characterized in that, wherein Q is as defined in claim 12; and M is as defined in any one of claims 1-6. The synthesis method comprises the following steps: Step 1: performing dehydrogenation reaction on the compound as shown in formula V in the presence of a basic reagent in a solvent to obtain a mixture; Step 2: performing alkylation reaction on the mixture obtained according to the preparation method of step 1 with a compound containing a structural fragment as shown in formula IV in the presence of a Lewis acid in a solvent to obtain an alkylation product; ； Step 3: performing cyclization reaction on the alkylation product obtained according to the preparation method of step 2 in the presence of a photocatalyst and a cerium catalyst in a solvent under irradiation of visible light in an oxygen atmosphere to obtain a lactone compound containing a structural fragment as shown in formula I, and the reaction is completed; 19. The method for synthesizing lactone compounds as described in claim 18, characterized in that, wherein M and n are as defined in any one of claims 1-6; the conditions and operations of step 1 are as defined in claim 17; the conditions and operations of step 2 are as defined in any one of claims 12-14; and the conditions and operations of step 3 are as defined in any one of claims 1-7. ； The compound containing the structural fragment as shown in formula IV is a compound as shown in formula IV-a; and correspondingly, the lactone compound containing the structural fragment as shown in formula I is a compound as shown in formula I-a; R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are each as defined in any one of claims 8-11. wherein M and n are as defined in any one of claims 1-6; ； wherein, n and M are each as defined in any one of claims 1 to 6, R 2a , R 2b , R 3a , R 3b , R 4a and R 4b are each as defined in any one of claims 8 to 11 ; and the compound as shown in Formula I-a is not the compound , , or .

21. The compound of claim 20, having Formula I-a, ###00010### I-a 20. A compound as shown in formula I-a: The compound as shown in formula I-a is any one of the following compounds: The compound as shown in formula I-a is any one of the following compounds: 。

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