Carbon functionalization method of non-activated olefin

Abstract

The invention discloses a brand new non-activated olefin carbon functionalization method, gas olefin and a non-activated olefin carbon functionalization product can be obtained through the method, and the method comprises the following steps: under the protection of gas and under the action of a nickel catalyst and an N-heterocyclic carbene ligand, reacting the non-activated olefin with the carbon functionalization product to obtain the non-activated olefin carbon functionalization product. The compound A is obtained by reacting the compound shown in the formula I, the compound shown in the formula II and the compound shown in the formula III in an organic solvent. The method provided by the invention has the advantages of high yield, simple operation, mild reaction conditions, strong chiral control ability and wide substrate applicability, and has high academic and application values. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of organic chemistry, and in particular relates to a method for carbon functionalization of non-activated olefins and gaseous olefins. Background Art

[0002] Gaseous olefins and non-activated olefins are present in large quantities in the petrochemical industry. For example, the annual global production of 1-butene alone is 4.2×10 7 Tons, the efficient and precise carbon functionalization of these bulk chemical products to construct high-value-added fine chemicals has important research significance and application value, and will play an important role in the synthesis of natural products, drug molecules, pesticides and material molecules.

[0003] The carbon functionalization of olefins is an important reaction in organic chemistry. Using inexpensive and readily available olefins as raw materials, high-value-added molecules can be synthesized directly and efficiently. Over the past decade, research on the carbon functionalization of olefins has primarily focused on activated olefins. In contrast, the development of non-activated olefins, especially gaseous olefins, remains limited. This is primarily due to the low reactivity of non-activated olefins. Furthermore, alkyl groups have little effect on the electrical properties and steric hindrance of olefins, making the regioselectivity of olefins difficult to control and the formation of difficult-to-separate mixtures. Most importantly, the enantioselective transformation of non-activated olefins has always been a challenge in organic chemistry.

[0004] Currently, the carbon functionalization reaction of non-activated alkenes often adopts the strategy of directing groups to control reactivity and selectivity. The installation and removal of directing groups increase the reaction steps. From the perspective of atom economy and step efficiency, this has to some extent limited the further application of non-activated alkenes.

[0005] Therefore, there is an urgent need in the art for a method for carbon functionalization of non-activated olefins, especially gaseous olefins, without the participation of a directing group. Summary of the Invention

[0006] The present invention aims to overcome the shortcomings of existing technologies, such as the need for pre-introduction of directing functional groups into reaction substrates, the limited substrate universality, and the limited range of functional group selection. The method provides a highly selective carbon-functionalization method for non-activated olefins and gaseous olefins. This method offers the advantages of high yield, simple operation, mild reaction conditions, strong chirality control, and wide substrate applicability, possessing high academic and practical value.

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

[0008] The present invention provides a method for carbon functionalization of non-activated olefins, comprising the following steps: in a solvent, in system 1 or system 2, reacting compound I, compound II, and compound III as shown below to obtain compound A; the system 1 comprises compound IV and bis(1,5-cyclooctadiene)nickel; the system 2 comprises compound V and bis(1,5-cyclooctadiene)nickel;

[0009]

[0010] or

[0011] in,

[0012] R 1 、R 1’ are each independently hydrogen, C 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 1-1 Substituted C 1-20 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkyl, occupies 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkenyl, -LR 1-1 ;

[0013] -L- is none, C 1-20 Alkylene, -OC 1-20 Alkylene-, -C 1-20 Alkylene-O-, -CO-C 1-20 Alkylene-, -C 1-20 Alkylene-CO-, -NH-C 1-20 Alkylene-, -C 1-20 Alkylene-NH-;

[0014] Each R 1-1 、R 1-2 are independently -OH, halogen, C 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -OC 1-20 Alkyl, C 6-10 Aromatic ring, 5-16 membered heteroaromatic ring, -SiR a R b R c , -GeR a R b R c , -NR d R e,-O-SiR f R g R i , Bpin, by 1, 2 or 3 R 2-1-1 Substituted C 6-10 Aromatic ring, surrounded by 1, 2 or 3 R 2-1-1 substituted 5-16 membered heterocycloalkyl;

[0015] R 2 Independently C 6-14 Aryl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 2-1 Substituted C 6-14 Aryl, substituted by 1, 2 or 3 R 2-2 Substituted C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 2-3 substituted 5-16 membered heteroaryl;

[0016] Each R 2-1 、R 2-2 、R 2-3 are independently -OH, halogen, C 1-20 Alkyl, -OC 1-20 Alkyl, -OC 1-20 Halogenated alkyl, -SC 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -C 1-6 Alkylene-5-16 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aromatic ring, C 6-10 Aromatic ring, 5- to 16-membered heteroaromatic ring, -SiR a R b R c , -NR d R e ,-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i ,Bpin,-CO-OC 1-20 Alkyl, or 1, 2 or 3 R 2-1-1 Substituted C 6-10 aromatic rings;

[0017] R a 、R b and R c Each independently is H, C 1-20 Alkyl or C 6-10 aromatic rings;

[0018] R d and R e Each independently is H, C 1-20 Alkyl, C 6-10 Aromatic ring or -C 1-6 Alkylene-C 6-10 aromatic rings;

[0019] R f 、R g and R i Each independently is H, C 1-20 Alkyl or C 6-10 aromatic rings;

[0020] Each R 2-1-1 are independently halogen, C 1-20 Alkyl or -OC 1-20 alkyl;

[0021] X is Cl, Br, I, OTs or OTf;

[0022] R 3 Independently C 6-14 Aryl, substituted by 1, 2 or 3 R 3-1 Substituted C 6-14 aryl, or

[0023] R 3’ Independently C 1-10 alkyl;

[0024] M is an alkali metal;

[0025] Each R 3-1 are independently hydrogen, amino, halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 1-4 Halogenated alkoxy, C 6-10 Aryl, or two adjacent R 3-1 Forming a 5-8 membered heteroalkane ring;

[0026] The 5-16 membered heteroaromatic ring is independently a 5-16 membered heteroaromatic ring in which the heteroatom species are selected from 1, 2 or 3 of N, O and S; the number of heteroatoms is 1, 2, 3 or 4;

[0027] The 5-16 membered heterocycloalkyl group is independently a 5-16 membered heterocycloalkyl group having 1, 2, or 3 heteroatoms selected from N, O, and S; and the number of heteroatoms is 1, 2, 3, or 4.

[0028] The structure of compound IV is:

[0029]

[0030] in,

[0031] R 0 Independently C 1-6 Alkyl or -OC 1-6 alkyl;

[0032] R 4a 、R 4b 、R 4c and R 4d Each independently is C 1-6 Alkyl, C 6-10 Aromatic ring, or 1, 2 or 3 R Ar Substituted C 6-10 aromatic rings;

[0033] Each R Ar Independently C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, occupies 1, 2 or 3 R Ar-1 Substituted C 1-6 Alkyl, 1, 2 or 3 R Ar-2 Replaced -OC 1-6 Alkyl, or 1, 2 or 3 R Ar-3 Substituted C 3-6 Cycloalkyl;

[0034] Each R Ar-1 、R Ar-2 and R Ar-3 are each independently halogen or C 1-6 alkyl;

[0035] Y - It is a monovalent anion;

[0036] The structure of the compound V is:

[0037]

[0038] in,

[0039] R 9a 、R 9b 、R 9c and R 9d Each independently is C1-6 Alkyl, unsubstituted or replaced by R 3a-1 Substituted C6-C 14 aryl;

[0040] Each R 3a-1 are independently C1-C4 alkyl;

[0041] R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Each is independently hydrogen or C1-C4 alkyl;

[0042] R5 and R6 are each independently hydrogen, C1-C4 alkyl, halogen, or C6-C 10 Aryl; wherein R 5-1 and R 5-2 Each is independently hydrogen or C1-C4 alkyl;

[0043] is a single bond or a double bond;

[0044] Alternatively, R5, R6 and the carbon atom to which they are attached together form

[0045] Z - It is a monovalent anion.

[0046] In a certain embodiment, in the compound IV, the definitions of certain groups may be as described below, and the definitions of other groups may be as described in any embodiment of the present invention (hereinafter referred to as "in a certain embodiment"):

[0047] In one scenario, R 1 、R 1’ are each independently hydrogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, substituted by 1, 2 or 3 R 1-1 Substituted C 1-10 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, occupies 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkenyl, -LR 1-1 .

[0048] In one scenario, R 1 、R 1’ are each independently hydrogen, C 1-10 Alkyl, C 3-8 Cycloalkyl, C3-8 Cycloalkenyl, substituted by 1, 2 or 3 R 1-1 Substituted C 1-10 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-8 Cycloalkyl, occupies 1, 2 or 3 R 1-2 Substituted C 3-8 Cycloalkenyl, -LR 1-1 .

[0049] In one scenario, R 1 、R 1’ are each independently hydrogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, substituted by 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, -LR 1-1 .

[0050] In one scenario, R 1 、R 1’ are each independently hydrogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, -LR 1-1 .

[0051] In one scenario, R 1 are independently hydrogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, substituted by 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, -LR 1-1 ; R 1’ Independently C 1-10 alkyl.

[0052] In one scenario, R 1 and R 1’ In the C 1-20 Alkyl and 1, 2 or 3 R 1-1 Substituted C 1-20 C in the alkyl group 1-20 The alkyl groups are independently C 1-10 Alkyl; for example, C 1-6 Alkyl; another example is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl.

[0053] In one scheme, -L- is none, C 1-10 Alkylene, -OC 1-10 Alkylene-, -C 1-10Alkylene-O-, -CO-C 1-10 Alkylene-, -C 1-10 Alkylene-CO-, -NH-C 1-10 Alkylene-, -C 1-10 Alkylene-NH-.

[0054] In one scheme, -L- is none, C 1-10 Alkylene, -C 1-10 Alkylene-O-, -C 1-10 Alkylene-CO-, -C 1-10 Alkylene-NH-.

[0055] In one scheme, each R 1-1 、R 1-2 are independently -OH, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 5-16 membered heterocycloalkyl, -OC 1-10 Alkyl, C 6-10 Aromatic ring, 5-16 membered heteroaromatic ring, -SiR a R b R c , -GeR a R b R c , -NR d R e ,-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i , Bpin, by 1, 2 or 3 R 2-1-1 Substituted C 6-10 Aromatic ring, surrounded by 1, 2 or 3 R 2-1-1 Substituted 5-16 membered heterocycloalkyl.

[0056] In one scheme, each R 1-1 、R 1-2 are each independently halogen, C 1-6 Alkyl, 5-16 membered heterocycloalkyl, C 6-10 Aromatic ring, surrounded by 1, 2 or 3 R 2-1-1 Substituted C 6-10 Aromatic ring, surrounded by 1, 2 or 3 R 2-1-1 Substituted 5-16 membered heterocycloalkyl.

[0057] In one scenario, R 1-1 In the C 1-6The alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl.

[0058] In one scenario, R 1-2 wherein the halogen is independently F, Cl, Br or I, for example, F.

[0059] In one scenario, R 2 Independently C 6-10 Aryl, C 3-16 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 2-1 Substituted C 6-10 Aryl.

[0060] In one scenario, R 2 Independently C 6-10 Aryl, C 3-12 Cycloalkenyl, 5-12 membered heterocycloalkyl, 5-12 membered heteroaryl, 1, 2 or 3 R 2-1 Substituted C 6-10 Aryl.

[0061] In one scenario, R 2 Independently C 6-10 Aryl, substituted by 1, 2 or 3 R 2-1 Substituted C 6-10 Aryl.

[0062] In one scenario, R 2 In the C 6-10 Aryl and said 1, 2 or 3 R 2-1 Substituted C 6-10 C in aromatic rings 6-10 Aryl is independently substituted phenyl or naphthyl.

[0063] In one scheme, each R 2-1 、R 2-2 、R 2-3 are independently -OH, halogen, C 1-10 Alkyl, -OC 1-10 Alkyl, -OC 1-10 Halogenated alkyl, -SC 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 5-8 membered heterocycloalkyl, -C 1-6 Alkylene-5-8 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aromatic ring, C 6-10 Aromatic ring, 5- to 8-membered heteroaromatic ring, -SiR a R b Rc , -NR d R e ,-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i ,-CO-OC 1-10 alkyl.

[0064] In one scheme, each R 2-1 、R 2-2 、R 2-3 are independently -OH, halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Halogenated alkyl, -SC 1-6 Alkyl, 5-8 membered heterocycloalkyl, -C 1-3 Alkylene-5-8 membered heterocycloalkyl, -OC 1-3 Alkylene-C 6-10 Aromatic ring, C 6-10 Aromatic ring, -SiR a R b R c , -NR d R e ,-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i ,-CO-OC 1-10 alkyl.

[0065] In one plan,

[0066] R a 、R b and R c Independently H, C 1-10 Alkyl or C 6-10 aromatic rings;

[0067] R d and R e Independently H, C 1-10 Alkyl, C 6-10 Aromatic ring or -C 1-3 Alkylene-C 6-10 aromatic rings;

[0068] R f 、R g and R iIndependently H, C 1-10 Alkyl or C 6-10 aromatic rings;

[0069] R 2-1-1 are independently halogen, C 1-10 Alkyl or -OC 1-10 alkyl.

[0070] In one plan,

[0071] R a 、R b and R c Independently H, C 1-6 Alkyl or C 6-10 aromatic rings;

[0072] R d and R e Independently H, C 1-6 Alkyl, C 6-10 Aromatic ring or -C 1-3 Alkylene-C 6-10 aromatic rings;

[0073] R f 、R g and R i Independently H, C 1-6 Alkyl or C 6-10 aromatic rings;

[0074] R 2-1-1 are independently halogen, C 1-6 Alkyl or -OC 1-6 alkyl.

[0075] In one scenario, R 3’ OM is a metal salt of an alcohol, and the alkali metal salt of the alcohol is independently an alkali metal salt of a primary alcohol and a secondary alcohol; for example, sodium ethoxide or sodium isopropoxide.

[0076] In one scenario, R 3’ OM is not sodium tert-butoxide.

[0077] In one scenario, R 3’ is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

[0078] In one scenario, R 3 In the C 6-14 Aryl is independently C 6-12 Aryl is, for example, phenyl or naphthyl.

[0079] In one embodiment, M is Li, Na or K.

[0080] In one scenario, R 3’OM is EtOLi, EtONa, EtOK, iPrOLi, iPrONa, iPrOK, preferably iPrONa.

[0081] In one scenario, R 3 MgBr is C 6-14 Aryl Grignard reagents, or 1, 2 or 3 R 3-1 Substituted C 6-14 Aryl Grignard reagents.

[0082] In one scenario, R 0 Independently C 1-4 Alkyl or -OC 1-4 alkyl.

[0083] In one scenario, R 0 and tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert-butoxy.

[0084] In one scenario, R 0 are independently methyl and methoxy.

[0085] In one scenario, R 4a 、R 4b 、R 4c and R 4d Same or different.

[0086] In one scenario, R 4a 、R 4b 、R 4c and R 4d In the C 6-10 The aromatic ring and the one, two or three R Ar Substituted C 6-10 C in aromatic rings 6-10 The aromatic rings are each independently a benzene ring or a naphthalene ring.

[0087] In one scenario, R 4a 、R 4b 、R 4c and R 4d Each independently is C 1-4 alkyl.

[0088] In one scenario, R 4a 、R 4b 、R 4c and R 4d Each is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0089] In one scenario, R 4a 、R4b 、R 4c and R 4d Each independently is C 6-10 Aromatic ring, or 1 or 2 R Ar Substituted C 6-10 Aromatic ring.

[0090] In one scenario, R 4a 、R 4b 、R 4c and R 4d Each independently is C 6-10 Aromatic rings,

[0091] In one scheme, each R Ar Independently C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-4 Cycloalkyl, occupies 1, 2 or 3 R Ar-1 Substituted C 1-6 Alkyl, 1, 2 or 3 R Ar-2 Replaced -OC 1-6 Alkyl, or 1, 2 or 3 R Ar-3 Substituted C 3-4 Cycloalkyl.

[0092] In one scheme, each R Ar Independently C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-4 Cycloalkyl, 1 R Ar-1 Substituted C 1-6 Alkyl, separated by 1 R Ar-2 Replaced -OC 1-6 Alkyl, or 1 R Ar-3 Substituted C 3-4 Cycloalkyl.

[0093] In one scheme, each R Ar Independently C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-4 Cycloalkyl.

[0094] In one scheme, each R Ar Independently C 1-6 Alkyl or -OC 1-6 alkyl.

[0095] In one scheme, each R Ar Independently C 1-4 Alkyl, -OC 1-4 Alkyl, C3 cycloalkyl.

[0096] In one scheme, each R Ar Independently C 1-4 Alkyl, -OC 1-4 alkyl.

[0097] In one scheme, each R Ar-1 、R Ar-2 and R Ar-3 are each independently halogen or C 1-3 alkyl.

[0098] In one scheme, each R Ar-1 、R Ar-2 and R Ar-3 Each is independently halogen, methyl or ethyl.

[0099] In one scenario, R Ar In the C 1-6 The alkyl groups are independently C 1-4 Alkyl, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl or tert-butyl.

[0100] In one scenario, R Ar In, the -OC 1-6 The alkyl groups are independently -OC 1-4 Alkyl, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy; another example is methoxy.

[0101] In one scheme, each R Ar is independently methyl, tert-butyl or methoxy.

[0102] In one scenario, R 4a 、R 4b 、R 4c and R 4d Each independently For example, R 4a 、R 4b 、R 4c and R 4d Same, for

[0103] In one scenario, Y - F - 、Cl - Br - , I - or BF4 - ; For example, Cl - .

[0104] In a certain embodiment, the structure of the compound V is selected from the following structures:

[0105]

[0106]

[0107] In one scenario, R 9a 、R 9b 、R 9c and R 9d Same or different.

[0108] In one scenario, R 9a 、R 9b 、R 9c and R 9d Each independently is C 1-6 Alkyl, C 6-10 Aromatic ring, or 1 or 2 R 3a-1 Substituted C 6-10 Aromatic ring.

[0109] In one scenario, R 9a 、R 9b 、R 9c and R 9d Each independently is C 1-6 Alkyl, C 6-10 Aromatic rings,

[0110] In one scenario, R 9a 、R 9b 、R 9c and R 9d In the C 6-14 The aromatic ring and the R 3a-1 Alkyl substituted C 6-14 C in aromatic rings 6-14 The aromatic rings are independently C 6-10 An aromatic ring, such as a benzene ring or a naphthalene ring.

[0111] In a certain embodiment, each of the R 3a-1 is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl or tert-butyl.

[0112] In one scenario, R 9a 、R 9b 、R 9c and R 9d Each is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0113] In one scenario, R 9a 、R9b 、R 9c and R 9d Each independently For example, R 9a 、R 9b 、R 9c and R 9d Same, for

[0114] In one scenario, R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Same or different.

[0115] In one scenario, R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Each is independently hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0116] In one scenario, R 7a 、R 7c 、R 8a and R 8c All are hydrogen, R 7b 、R 8b Each of R5 and R6 is independently C6-C 10 Aryl, or R5, R6 and the carbon atom to which they are attached together form

[0117] In a certain scheme, when R 9a 、R 9b 、R 9c and R 9d is unsubstituted or replaced by R 3a-1 Substituted C6-C 14 In the case of an aromatic group, R5, R6 and the carbon atom to which they are attached together form

[0118] In a certain scheme, when R 9a 、R 9b 、R 9c and R 9d C 1-6 When alkyl, R5 and R6 are each independently C6-C 10 Aryl.

[0119] In one scenario, Z - F - 、Cl - Br - , I - or BF4 - ; For example, Cl - or BF4 - .

[0120] In a certain embodiment, the compound I is selected from any one of the following compounds:

[0121]

[0122] In a certain embodiment, the compound II is selected from any one of the following compounds:

[0123]

[0124] In a certain embodiment, the compound III is selected from any one of the following compounds:

[0125]

[0126]

[0127] In a certain embodiment, the compound IV is selected from any one of the following compounds:

[0128]

[0129] In a certain embodiment, the compound V is selected from any one of the following compounds:

[0130] Ar is 3,5-dimethylphenyl. In one embodiment, the reaction is as follows:

[0131]

[0132] Among them, R 1 、R 1’ 、R 2 、R 3 , Compound IV is as described above;

[0133] The bonds are in bold, indicating a racemic form.

[0134] In one embodiment, the reaction is as follows:

[0135]

[0136] Among them, R 1 、R 1’、R 2 、R 3’ , Compound IV is as described above;

[0137] The bonds are in bold, indicating a racemic form.

[0138] In one embodiment, the reaction is as follows:

[0139]

[0140] Among them, R 1 、R 1’ 、R 2 、R 3’ As mentioned above;

[0141] Compound V is V-4.

[0142] In one embodiment, the reaction is as follows:

[0143]

[0144] Among them, R 1 、R 1’ 、R 2 、R 3’ As mentioned above;

[0145] The bold bonds indicate a racemic form;

[0146] Compound V is Compound V-1 or Compound V-4.

[0147] In one embodiment, the reaction is as follows:

[0148]

[0149] Among them, R 1 、R 1’ 、R 2 、R 3’ As mentioned above;

[0150] Compound V is Compound V-3.

[0151] In one embodiment, the reaction is as follows:

[0152]

[0153] Among them, R 1 、R 1’ 、R 2 、R 3’ As mentioned above;

[0154] The bold bonds indicate a racemic form;

[0155] Compound V is Compound V-2 or Compound V-3.

[0156] In a certain embodiment, when the configuration of the compound V changes, the configuration of the product compound A also changes accordingly.

[0157] In a certain embodiment, the ee value of compound A is more than 80%, preferably more than 85%, preferably more than 90%, such as 91%, 92%, 93%, 94%, or 95%.

[0158] In a certain embodiment, the compound A is selected from any one of the following compounds:

[0159]

[0160]

[0161] Among them, Ar is 2-naphthyl, Ar 1 =3-(Me2N)-C6H4,Ar 2 =2-MeO-C6H4,Ar 3 =2-Me-C6H4,Ar 4 =4-Me-C6H4.

[0162] In one embodiment, the molar ratio of the compound I to the compound II is 10:1 to 1:10, preferably 8:1 to 1:5, for example, 6:1, 4:1, 2:1, 1:1, 1:2, or 1:5.

[0163] In one embodiment, the molar ratio of the compound I to the compound III is 10:1 to 1:10, preferably 5:1 to 1:5, for example, 4:1, 2:1, 1:1, 1:2, 1:3, or 1:5.

[0164] In one embodiment, the molar ratio of the compound I to the bis(1,5-cyclooctadiene)nickel is 1:0.01-0.5, preferably 1:0.01-0.1, for example, 60:1, 50:1, 30:1, 20:1, or 10:1.

[0165] In one embodiment, the molar ratio of the compound IV to the bis(1,5-cyclooctadiene)nickel is 0.5-2:0.5-2, preferably 0.8-1.2:0.8-1.2, for example 1:1.

[0166] In one embodiment, the molar ratio of the compound V to the bis(1,5-cyclooctadiene)nickel is 0.5-2:0.5-2, preferably 0.8-1.2:0.8-1.2, for example 1:1.

[0167] In one embodiment, the solvent is an alkane solvent, an ether solvent, or a combination thereof.

[0168] In a certain embodiment, the solvent is selected from the group consisting of n-hexane, n-heptane, cyclohexane, cycloheptane, tetrahydrofuran, 1,4-dioxane, or a combination thereof.

[0169] In one embodiment, the reaction temperature is 10-50°C, preferably 15-40°C, for example 25°C.

[0170] In one embodiment, the reaction time is 8-14 hours; for example, 12 hours.

[0171] In one embodiment, the adding process of the method is carried out in a protective gas atmosphere. The protective gas is selected from the group consisting of nitrogen, helium, argon, or a combination thereof.

[0172] In one embodiment, the method comprises: mixing compound IV or compound V, compound III, bis(1,5-cyclooctadiene)nickel and a solvent under a protective gas atmosphere, then sequentially adding compound I and compound II thereto, then optionally removing the protective gas environment and reacting at room temperature.

[0173] In one embodiment, in the method, sodium tert-butoxide is absent in the reaction system.

[0174] In one embodiment, the reaction is carried out with stirring.

[0175] In one embodiment, the stirring speed is 100-1500 rpm.

[0176] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. DETAILED DESCRIPTION

[0177] After extensive and intensive research, the present inventors have discovered, for the first time, a highly selective method for the carbon functionalization of non-activated olefins. This method utilizes difficult-to-control non-activated olefins as starting materials, unexpectedly yielding highly selective products in a reaction system containing only specific ligands and a nickel catalyst. This is the basis for the present invention.

[0178] the term

[0179] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0180] Unless otherwise specified, the terms used in this invention have the following meanings:

[0181] In the present invention, the term "non-activated olefin" includes but is not limited to the structure shown in Compound I of the present invention.

[0182] In the present invention, the term "activated olefins" includes but is not limited to olefins of the structure CH2=CHRR', wherein R is selected from aryl, alkenyl, alkoxy, amino, silicon, and R' is selected from H or alkyl.

[0183] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0184] The term "alkyl" refers to a group having a specified number of carbon atoms (e.g., C 1-20 ). The alkyl group preferably includes 1 to 20, or 1 to 10, or 1 to 8, or 1 to 6, or 1 to 4 carbon atoms, and the alkyl group includes but is not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl and n-hexyl.

[0185] The term "cycloalkyl" refers to a cycloalkyl group having the specified number of carbon atoms (e.g., C 3-20 ) and is composed only of carbon atoms. The cycloalkyl group preferably includes 3 to 20, or 3 to 12, or 3 to 10, or 3 to 8, or 3 to 6 carbon atoms. The cycloalkyl group may include a fused cycloalkyl group, a bridged cycloalkyl group, or a spirocycloalkyl group. Preferably, the cycloalkyl group includes but is not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0186] The term "aromatic ring" refers to a ring having a specified number of carbon atoms (e.g., C 6-14 ) is a cyclic hydrocarbon group consisting only of carbon atoms, which is monocyclic or polycyclic, and at least one of the groups is aromatic (in accordance with Huckel's rule). Aryl groups include but are not limited to phenyl, naphthyl and anthracenyl.

[0187] The term "heteroaromatic ring" refers to a cyclic hydrocarbon group having a specified number of carbon atoms (e.g., 5-16 members), a specified number of heteroatoms (e.g., 1, 2, or 3 members), and a specified heteroatom species (one or more of N, O, and S), which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with Huckel's rule). The heteroaromatic ring preferably includes a 3-20 membered, or 3-12 membered, or 3-10 membered, or 3-8 membered, or 3-6 membered heteroaromatic ring, and the heteroaromatic ring may include a fused ring, a bridged ring, or a spiro ring. Preferably, the heteroaromatic ring includes, but is not limited to, a furan ring, a pyrrole ring, a thiophene ring, a pyrazole ring, an imidazole ring, an oxazole ring, a thiazole ring, a pyridine ring, a pyrimidine ring, and an indole ring.

[0188] The term "heterocycloalkyl" refers to a group having the specified number of carbon atoms (e.g., C 3-20), a saturated cyclic hydrocarbon group consisting of a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatoms (one or more of N, O, and S). Heterocycloalkyl preferably includes 3 to 20-membered, or 3 to 12-membered, or 3 to 10-membered, or 3 to 8-membered, or 3 to 6-membered heterocycloalkyls, and the heterocycloalkyl may include fused heterocycloalkyls, bridged heterocycloalkyls, or spiro heterocycloalkyls. Preferably, the heterocycloalkyl includes but is not limited to wait.

[0189] The term "cycloalkenyl" means a cyclic hydrocarbon group having at least one double bond (such as a carbon-carbon double bond), and which may be connected to the rest of the molecule via a single bond via any suitable carbon atom; for example, the cycloalkenyl group preferably comprises 3 to 20, or 3 to 12, or 3 to 10, or 3 to 8, or 3 to 6 carbon atoms, and the cycloalkenyl group may include a fused cycloalkenyl group, a bridged cycloalkenyl group or a spirocycloalkenyl group, preferably, the C 3-20 Cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl.

[0190] Those skilled in the art will understand that according to the conventions used in the art, the structural formulas used in this application to describe groups It means that the corresponding group R is connected to other fragments and groups in the compound through this site.

[0191] A "-" at the end of a group means that the group is attached to another fragment in the molecule through that site. For example, -OCH3 refers to a methoxy group, in which the oxygen atom is attached to the rest of the molecule.

[0192] When any variable (such as R Ar ) appears multiple times in the definition of a compound, the definition of each position of the variable is independent of the definition of the other positions, and their meanings are independent of each other and do not affect each other. Therefore, if a group is replaced by 1, 2 or 3 R Ar group substituted, that is, the group may be replaced by up to 3 R Ar Replace, the position R Ar Definition and other positions R Ar In addition, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0193] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0194] Method of the present invention

[0195] The present invention provides a method for carbon functionalization of non-activated olefins. In the method, only a compound of formula IV and Ni(cod)2, or a compound of formula V and Ni(cod)2, is used without using other bases or nucleophilic reagents, such as sodium tert-butoxide in the prior art, to complete the carbon functionalization reaction of the non-activated olefins with very high selectivity.

[0196] For example, in the present invention, the ee value of Example 2-35 reached 95%, while in the prior art, sodium tert-butoxide was also added to the system, and the ee value was only 88% (er value was 94:6), wherein the ratio of the dominant enantiomer to the other enantiomer was increased from 15.67:1 to 39:1; the ee value of Example 2-31 reached 95%, while in the prior art, sodium tert-butoxide was also added to the system, and the ee value was only 92% (er value was 96:4), wherein the ratio of the dominant enantiomer to the other enantiomer was increased from 24:1 to 39:1.

[0197] Furthermore, the present invention can change the configuration of the product by adjusting the configuration of the ligand to directly obtain a product with a high ee value.

[0198] The positive progress effect of the present invention is:

[0199] (1) The present invention is applicable to the carbon functionalization of non-activated olefins and gaseous olefins with high efficiency, regio- and stereoselectivity. This is of great significance for the efficient and accurate carbon functionalization of bulk chemical products.

[0200] (2) The yield of the alkyl aromatic compounds prepared by the method of the present invention is high and the reaction regioselectivity is high, with most of the yields being above 98 / 2.

[0201] (3) The method of the present invention has a wide range of substrate applicability and is very suitable for various types of olefins. The synthesized alkyl aromatic compounds have a variety of structures.

[0202] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0203] The reagents and raw materials used in the present invention are commercially available.

[0204] Example 1:

[0205]

[0206] General Method A: In a nitrogen-filled glove box, add compound IV (16.2 mg, 0.02 mmol, 10 mol%), compound III sodium isopropoxide (49.2 mg, 0.6 mmol, 3.0 equiv), Ni(cod)2 (5.5 mg, 0.02 mmol, 10 mol%), and 2 mL of cyclohexane to an 8 mL vial and stir at room temperature for 30 minutes. Then, compound I (1.2 mmol) and compound II (0.2 mmol) were added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography.

[0207] Wherein, the structural formula of compound IV is:

[0208]

[0209] General Method B: In a nitrogen-filled glove box, add compound IV (10.9 mg, 0.02 mmol, 10 mol%), compound III (aryl Grignard reagent) (0.6 mmol, 3.0 equiv), Ni(cod)2 (5.5 mg, 0.02 mmol, 10 mol%), and 2 mL of 1,4-dioxane to an 8 mL vial and stir at room temperature for 30 minutes. Compound I (1.2 mmol) and compound II (0.2 mmol) were then added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography.

[0210] Wherein, the structural formula of compound IV is:

[0211]

[0212] The structural formula of the compound prepared in this example is:

[0213]

[0214] Compound 1-1: prepared according to general method A as a colorless liquid with a yield of 85%. 1 H NMR (400MHz, CDCl3δ7.2-7.2(m,1H),6.8-6.8(m,1H),6.8-6.7(m,2H),3.8(s,3 H),2.7-2.5(m,1H),1.6-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).

[0215] Compound 1-2: prepared according to general method A as a colorless liquid with a yield of 80%. 1H NMR (400MHz, CDCl3) δ8.2-8.1(m,1H),7.9-7.8(m,1H),7.7-7.6(m,1H),7.5-7.4(m,3H),7.4-7.3(m ,1H),3.6-3.4(m,1H),1.9-1.8(m,1H),1.8-1.6(m,1H),1.4(d,J=6.8Hz,3H),0.9(t,J=7.4Hz,3H).

[0216] Compound 1-3: prepared according to general method A as a colorless liquid with a yield of 46%. 1 H NMR (400MHz, CDCl3) δ7.4-7.4(m,2H),7.4-7.3(m,3H),7.3-7.2(m,2H),7.2-7.1(m ,2H),2.8-2.7(m,1H),1.6-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.7(t,J=7.4Hz,3H).

[0217] Compound 1-4: prepared according to general method A as a colorless liquid with a yield of 92%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.6-6.5(m,3H),2.9(s,6H),2.6-2.4(m,1H),1.6-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).

[0218] Compound 1-5: prepared according to general method A as a colorless liquid with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.2-7.2(m,1H),7.1-7.0(m,2H),7.0-6.9(m,1H),2.6-2.5(m ,1H),2.5(s,3H),1.6(p,J=7.6Hz,2H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).

[0219] Compound 1-6: prepared according to general method A as a colorless liquid with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.4-7.2(m,3H),7.2-7.1(m,1H),2.7-2.5(m,1H),1.7-1.5(m,2H),1.3-1.2(m,3H),0.8(t,J=7.3Hz,3H),0.3(s,9H).

[0220] Compound 1-7: prepared according to general method A as a colorless liquid with a yield of 55%. 1 H NMR (400MHz, CDCl3) δ8.0(d,J=8.3Hz,2H),7.2(d,J=8.3Hz,2H),5.3-5.2(m,1H),2.7(q,J=7.0 Hz,1H),1.6(t,J=7.3Hz,2H),1.4(d,J=6.2Hz,6H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).

[0221] Compound 1-8: prepared according to general method A as a colorless liquid with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.2-7.0(m,4H),3.8(t,J=7.2Hz,2H),2.8(t,J=7.2Hz,2H),2.6-2.5 (m,1H),1.7-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.9(s,9H),0.8(t,J=7.4Hz,3H),0(s,6H).

[0222] Compound 1-9: prepared according to general method A as a colorless liquid with a yield of 83%. 1 H NMR(400MHz, CDCl3) δ6.8(d,J=8.2Hz,1H),6.7(d,J=2.1Hz,1H),6.7-6.6(m,1H),4.3-4 .2(m,4H),2.6-2.4(m,1H),1.6-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).

[0223] Compound 1-10: prepared according to general method A as a colorless liquid with a yield of 58%. 1 H NMR (400MHz, CDCl3) δ7.2(d,J=8.0Hz,2H),7.1(d,J=8.0Hz,2H),3.7(t,J=4.7Hz,4H),3.5(s,2H ),2.6-2.5(m,1H),2.4(t,J=4.7Hz,4H),1.6-1.5(m,2H),1.3-1.2(m,3H),0.8(t,J=7.4Hz,3H).

[0224] Compound 1-11: prepared according to general method A as a colorless liquid with a yield of 64%. 1H NMR (400MHz, CDCl3) δ7.9(d,J=7.5Hz,1H),7.7(d,J=1.9Hz,1H),7.6-7.5(m,1H),7.5(d,J=8.5Hz,1H),7.5 -7.4(m,1H),7.4-7.2(m,2H),2.9-2.7(m,1H),1.7-1.6(m,2H),1.3(d,J=6.9Hz,3H),0.9(t,J=7.4Hz,3H).

[0225] Compound 1-12: prepared according to general method A as a colorless liquid with a yield of 68%. 1 H NMR (400MHz, CDCl3) δ7.6-7.6(m,1H),7.5-7.4(m,1H),7.4(s,1H),7.3-7.3(m,1H),7.2-7.2(m,1 H),3.0-2.8(m,1H),1.9-1.7(m,1H),1.7-1.6(m,1H),1.3(d,J=6.9Hz,3H),0.9(t,J=7.4Hz,3H).

[0226] Compound 1-13: prepared according to general method A as a colorless liquid with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.3 (d, J = 7.7Hz, 1H), 7.2-7.2 (m, 1H), 7.2-7.1 (m, 2H), 5.9-5.8 (m, 1H), 2.8-2.6 (m,3H),2.3-2.1(m,2H),1.7-1.6(m,1H),1.5-1.4(m,1H),1.1(d,J=6.8Hz,3H),0.9(t,J=7.4Hz,3H).

[0227] Compound 1-14: prepared according to general method A as a colorless liquid with a yield of 58%. 1 H NMR (400MHz, CDCl3) δ7.5-6.9(m,4H),5.9(t,J=7.3Hz,1H),2.7-2.4(m,3H),2.2-1.9(m,2H), 1.9-1.7(m,2H),1.6-1.5(m,1H),1.4-1.2(m,1H),1.1(d,J=6.9Hz,3H),0.9(t,J=7.9Hz,3H).

[0228] Compound 1-15: prepared according to general method A as a colorless liquid with a yield of 76%. 1H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.7-6.4(m,3H),3.0(s,6H),2.7-2.6(m,1H),1.7-1.4(m,2H),1.4-1.1(m,5H),0.9(t,J=7.3Hz,3H).

[0229] Compound 1-16: prepared according to general method A as a colorless liquid with a yield of 65%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,2H),6.9(t,J=7.4,1.2Hz,1H),6.8(d,J=8.1,1.2Hz,1H),3.8(s, 3H),3.3-3.1(m,1H),1.7-1.4(m,2H),1.4-1.2(m,2H),1.2(d,J=7.0Hz,3H),0.9(t,J=7.3Hz,3H).

[0230] Compound 1-17: prepared according to general method A as a colorless liquid with a yield of 68%. 1 H NMR (400MHz, CDCl3) δ7.3(d,J=7.7Hz,1H),7.2-7.2(m,1H),7.2-7.1(m,2H),5.9(t,J=4.7,1.0Hz,1H),2.9-2.7(m,1H ),2.7(t,J=7.9Hz,2H),2.3-2.2(m,2H),1.7-1.5(m,1H),1.4-1.3(m,3H),1.1(d,J=6.8Hz,3H),0.9(d,J=6.9Hz,3H).

[0231] Compound 1-18: prepared according to general method A as a colorless liquid with a yield of 81%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.7-6.5(m,3H),2.9(s,6H),2.9-2.8(m,1H),1.3(d,J=6.9Hz,6H).

[0232] Compound 1-19: prepared according to general method A as a colorless liquid with a yield of 79%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.9-6.8(m,2H),6.7-6.5(m,1H),3.0(s,6H),1.3(s,9H).

[0233] Compound 1-20: prepared according to general method A as a colorless liquid with a yield of 86%. 1H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.7-6.6(m,2H),6.6-6.5(m,1H),2.9 (s,6H),1.8-1.6(m,2H),1.6-1.5(m,2H),1.2(s,3H),0.7(t,J=7.4Hz,6H).

[0234] Compound 1-21: prepared according to general method A as a colorless liquid with a yield of 64%. 1 H NMR (400MHz, CDCl3) δ7.2(t,J=8.2Hz,1H),6.8-6.7(m,2H),6.6-6.6(m,1H),3.0(s,6H),1.6(q,J=7.4Hz,2H),1.3(s,6H),0.7(t,J=7.4Hz,3H).

[0235] Compound 1-22: prepared according to general method B as a colorless liquid with a yield of 61%. 1 H NMR (400MHz, CDCl3) δ7.24-7.11(m,4H),7.08-6.97(m,2H),6.78-6.68(m,2H),6.65(t,J=2.0Hz,1H ),3.76(s,3H),2.86(d,J=7.3Hz,2H),2.75-2.63(m,1H),1.77-1.54(m,2H),0.76(t,J=7.4Hz,3H).

[0236] Compound 1-23: prepared according to general method B as a colorless liquid with a yield of 58%. 1 H NMR (400MHz, CDCl3) δ7.25-7.16(m,4H),7.16-7.12(m,1H),7.09-6.99(m,4H),3.13-3.00( m,1H),2.83(dd,J=7.3,2.8Hz,2H),2.11(s,3H),1.81-1.56(m,2H),0.75(t,J=7.3Hz,3H).

[0237] Compound 1-24: prepared according to general method B as a colorless liquid with a yield of 65%. 1H NMR (400MHz, CDCl3) δ7.33-7.08(m,4H),7.04-7.01(m,1H),6.72-6.60(m,2H),6.52(dd,J=7.9,1.7Hz,1H),5.94 -5.86(m,2H),2.89-2.73(m,2H),2.71-2.57(m,1H),1.77-1.64(m,1H),1.55-1.47(m,1H),0.76(t,J=7.3Hz,3H).

[0238] Compound 1-25: prepared according to general method B as a colorless liquid with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.25-7.18(m,2H),7.17-7.11(m,2H),7.11-7.04(m,2H),6.62-6.52(m,2H),6.47(t,J=2.0Hz, 1H),2.90(s,6H),2.88-2.78(m,2H),2.71-2.61(m,1H),1.76-1.64(m,1H),1.61-1.52(m,1H),0.77(t,J=7.4Hz,3H).

[0239] Compound 1-26: prepared according to general method B as a colorless liquid with a yield of 65%. 1 H NMR (400MHz, CDCl3) δ7.24-7.08(m,4H),7.06-6.96(m,2H),6.91-6.76(m,3H),2.93-2.8 0(m,2H),2.76-2.67(m,1H),1.79-1.66(m,1H),1.66-1.56(m,1H),0.77(t,J=7.4Hz,3H).

[0240] Compound 1-27: prepared according to general method B as a colorless liquid with a yield of 34%. 1 H NMR (400MHz, CDCl3) δ7.28-7.24(m,1H),7.23-7.10(m,5H),7.05-6.99(m,3H),2.90-2.79(m,2H ),2.74-2.63(m,1H),2.46(s,3H),1.78-1.65(m,1H),1.63-1.56(m,1H),0.75(t,J=7.3Hz,3H).

[0241] Compound 1-28: prepared according to general method B as a colorless liquid with a yield of 58%. 1H NMR (400MHz, CDCl3) δ7.26-7.23(m,2H),7.22-7.09(m,3H),7.04-6.96(m,3H),6.93(s,1H),2.9 7-2.87(m,1H),2.86-2.68(m,2H),1.81-1.69(m,1H),1.65-1.57(m,1H),0.78(t,J=7.4Hz,3H).

[0242] Compound 1-29: prepared according to general method B as a colorless liquid with a yield of 60%. 1 H NMR (400MHz, CDCl3) δ7.92 (d, J = 7.8Hz, 2H), 7.21-7.11 (m, 5H), 7.03-6.96 (m, 2H), 5.27-5.20 (m, 1H), 3.03-2.77(m,3H),1.83-1.70(m,1H),1.67-1.61(m,1H),1.36(d,J=6.2Hz,6H),0.76(t,J=7.2Hz,3H).

[0243] Compound 1-30: prepared according to general method B as a colorless liquid with a yield of 59%. 1 H NMR (400MHz, CDCl3) δ7.25-7.16(m,4H),7.15-7.10(m,1H),7.09-6.95(m,4H),3.71(t,J=4.7Hz,4H),3.46(s ,2H),2.90-2.82(m,2H),2.75-2.66(m,1H),2.42(t,J=4.7Hz,4H),1.78-1.52(m,2H),0.75(t,J=7.3Hz,3H).

[0244] Compound 1-31: prepared according to general method B as a colorless liquid with a yield of 52%. 1 H NMR (400MHz, CDCl3) δ7.23-7.11(m,4H),7.07-7.01(m,2H),6.75-6.68(m,2H),6.68-6.63(m,1H ),3.76(s,3H),2.92-2.71(m,3H),1.68-1.55(m,2H),1.23-1.05(m,2H),0.81(t,J=7.3Hz,3H).

[0245] Compound 1-32: prepared according to general method B as a colorless liquid with a yield of 76%. 1H NMR (400MHz, CDCl3) δ7.24-7.17(m,2H),7.17-7.10(m,2H),7.08-7.00(m,2H),6.61-6.52(m,2H),6.49 -6.43(m,1H),2.89(s,6H),2.86-2.77(m,3H),1.67-1.58(m,1H),1.46-1.34(m,2H),0.91-0.72(m,6H).

[0246] Compound 1-33: prepared according to general method B as a colorless liquid with a yield of 83%. 1 H NMR (400MHz, CDCl3) δ7.21-7.11(m,4H),6.91-6.85(m,2H),6.72(dd,J=7.7,1.7Hz,1H),6 .67(t,J=2.2Hz,1H),6.62(dd,J=8.2,2.6Hz,1H),2.90(s,6H),2.87(s,2H),1.30(s,6H).

[0247] Compound 1-34: prepared according to general method B as a colorless liquid with a yield of 36%. 1 H NMR (400MHz, CDCl3) δ7.17-7.00(m,4H),6.75-6.56(m,5H),3.04(d,J=13.1Hz,1H),2 .90(d,1H),2.87(s,6H),2.23-2.12(m,1H),1.12-1.00(m,6H),0.67(d,J=6.8Hz,3H).

[0248] Compound 1-35: prepared according to general method B as a colorless liquid with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ7.20-7.09(m,4H),6.84(dd,J=6.7,3.0Hz,2H),6.68-6.58(m,3H),2.93(d,J=13.0Hz,1H) ,2.90(s,6H),2.80(d,J=13.1Hz,1H),2.00-1.85(m,1H),1.58-1.49(m,1H),1.20(s,3H),0.71(t,J=7.4Hz,3H).

[0249] Compound 1-36: prepared according to general method B as a colorless liquid with a yield of 45%. 1H NMR (400MHz, CDCl3) δ7.18(t,J=7.9Hz,1H),7.10(t,J=7.5Hz,1H),6.96(d,J=7.8Hz,1H),6.91-6.81(m,2H),6.77-6.70(m,2H),6.67 (s,1H),3.77(s,3H),2.90-2.75(m,2H),2.73-2.63(m,1H),2.28(s,3H),1.75-1.64(m,1H),1.61-1.55(m,1H),0.75(t,J=7.4Hz,3H).

[0250] Compound 1-37: prepared according to general method B as a colorless liquid with a yield of 57%. 1 H NMR (400MHz, CDCl3) δ7.18 (t, J = 7.9Hz, 1H), 7.14-7.06 (m, 1H), 7.03-6.93 (m, 3H), 6.77-6.64 (m, 3H), 3. 77(s,3H),2.88-2.77(m,2H),2.72-2.62(m,1H),2.28(s,3H),1.77-1.57(m,2H),0.75(t,J=7.3Hz,3H).

[0251] Compound 1-38: prepared according to general method B as a colorless liquid with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.18(t,J=7.9Hz,1H),7.12(t,J=7.8Hz,1H),6.76-6.69(m,3H),6.69-6.64(m,2H),6.60-6.55(m,1H),3. 77(s,3H),3.72(s,3H),2.84(d,J=8.0Hz,2H),2.73-2.64(m,1H),1.77-1.64(m,1H),1.63-1.57(m,1H),0.76(t,J=7.3Hz,3H).

[0252] Compound 1-39: prepared according to general method B as a colorless liquid with a yield of 54%. 1 H NMR (400MHz, CDCl3) δ7.21-7.08(m,2H),6.87-6.78(m,2H),6.77-6.68(m,3H),6.66-6.62(m,1H ),3.77(s,3H),2.93-2.80(m,2H),2.75-2.63(m,1H),1.78-1.58(m,2H),0.77(t,J=7.4Hz,3H).

[0253] Compound 1-40: prepared according to general method B as a colorless liquid with a yield of 45%. 1 H NMR (400MHz, CDCl3) δ7.84-7.66(m,3H),7.50(s,1H),7.46-7.36(m,2H),7.23-7.14(m,2H),6.79-6.66( m,3H),3.75(s,3H),3.03(d,J=7.3Hz,2H),2.87-2.75(m,1H),1.81-1.59(m,2H),0.77(t,J=7.3Hz,3H).

[0254] Compound 1-41: prepared according to general method B as a colorless liquid with a yield of 62%. 1 H NMR (400MHz, CDCl3) δ7.70-7.63(m,1H),7.60-7.53(m,2H),7.45-7.39(m,3H),7.34-7.28(m,1H),7.22-7.16(m,1H),7.12(d,J= 7.9Hz,2H),6.78-6.66(m,3H),3.77(s,3H),2.91(d,J=7.3Hz,2H),2.78-2.69(m,1H),1.83-1.61(m,2H),0.79(t,J=7.3Hz,3H).

[0255] Example 2:

[0256]

[0257] General Method C: In a nitrogen-filled glove box, add Compound V (9.4 mg, 0.01 mmol, 5.0 mol%), Compound III sodium isopropoxide (49.2 mg, 0.6 mmol, 3.0 equiv), Ni(cod)2 (2.8 mg, 0.01 mmol, 5.0 mol%), and 2 mL of n-heptane to an 8 mL vial and stir at room temperature for 30 minutes. Compound I (0.2 mmol) and Compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography, and the product ee was determined by chiral HPLC.

[0258] Wherein, the structural formula of compound V is:

[0259] Ar is 3,5-dimethylphenyl.

[0260]

[0261] General Method D: In a nitrogen-filled glove box, add Compound V (12.6 mg, 0.02 mmol, 10.0 mol%), Compound III (aryl Grignard reagent) (0.6 mmol, 3.0 equiv), Ni(cod)2 (5.6 mg, 0.02 mmol, 10.0 mol%), and 2 mL of 1,4-dioxane to an 8 mL vial and stir at room temperature for 30 minutes. Compound I (0.2 mmol) and Compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography, and the ee value of the product was determined by chiral HPLC.

[0262] Wherein, the structural formula of compound V is:

[0263] Ar is 3,5-dimethylphenyl.

[0264] The structural formula of the compound prepared in this example is:

[0265]

[0266] Among them, Ar is 2-naphthyl, Ar 1 =3-(Me2N)-C6H4,Ar 2 =2-MeO-C6H4,Ar 3 =2-Me-C6H4,Ar 4 =4-Me-C6H4.

[0267] Compound 2-1: prepared according to general method C as a colorless liquid with a yield of 94%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.2 (m, 2H), 7.2-7.2 (m, 2H), 7.2-7.1 (m, 4H), 7.1-7.0 (m, 2H), 2.7-2.6 (m, 1H), 2.5-2.4 (m, 2H), 1.9-1.7 (m, 2H), 1.2 (d, J = 7.0 Hz, 3H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R (minor)=7.0min,t R (major)=7.9min.

[0268] Compound 2-2: prepared according to general method C as a colorless liquid with a yield of 98%. 1H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 1H), 6.7-6.6 (m, 3H), 3.0 (s, 6H), 2.7-2.6 (m, 1H), 1.7-1.5 (m, 2H), 1.3-1.2 (m, 11H), 0.9 (t, J = 6.8 Hz, 3H). HPLC analysis (OJ-H, 5% IPA in hexanes, 1 mL / min, 254 nm) found 99% ee:t R (minor)=4.6min,t R (major)=3.5min.

[0269] Compound 2-3: prepared according to general method C as a colorless liquid with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 6.9 (t, 1H), 6.8 (d, 1H), 3.8 (s, 3H), 3.0-2.9 (m, 1H), 1.9-1.8 (m, 1H), 1.8-1.7 (m, 1H), 1.6-1.6 (m, 2H), 1.5-1.4 (m, 2H), 1.2-1.0 (m, 6H), 1.0-0.8 (m, 2H). HPLC analysis (OJ-H, 0% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:t R (minor)=3.9min,t R (major)=4.0min.

[0270] Compound 2-4: prepared according to general method C as a colorless liquid with a yield of 68%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,2H),7.0-6.9(m,1H),6.9-6.8(m,1H),3.8(s,3H),3.6-3.6(m,1 H),3.5-3.4(m,3H),3.4-3.3(m,1H),1.3(d,J=6.8Hz,3H),1.2(t,J=7.0Hz,3H). HPLC analysis (OD-H, 2% IPA in hexanes, 1mL / min, 220nm) indicated 94%ee: tR (minor) = 4.2min, tR (major) = 4.4min.

[0271] Compound 2-5: prepared according to general method C as a colorless liquid with a yield of 70%. 1H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 6.9 (t, J = 7.4, 1.2 Hz, 1H), 6.9 (d, J = 8.0 Hz, 1H), 4.5 (t, J = 6.2 Hz, 1H), 4.4 (t, J = 6.2 Hz, 1H), 3.8 (s, 3H), 3.3-3.1 (m, 1H), 1.8-1.6 (m, 3H), 1.6-1.5 (m, 1H), 1.5-1.3 (m, 2H), 1.3-1.2 (m, 9H), 1.2 (d, J = 6.9 Hz, 4H). HPLC analysis (OJ-H, 0% IPA in hexanes, 1 mL / min, 254 nm) found 93% ee:t R (minor)=5.4min,t R (major)=5.7min.

[0272] Compound 2-6: prepared according to general method C as a colorless liquid with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 1H), 6.6-6.5 (m, 3H), 3.5-3.4 (m, 2H), 2.9 (s, 6H), 2.7-2.6 (m, 1H), 1.8-1.7 (m, 2H), 1.7-1.5 (m, 2H), 1.5-1.3 (m, 2H), 1.2 (d, J = 6.9 Hz, 3H). HPLC analysis (IB-H, 0.5% IPA in hexanes, 1 mL / min, 254 nm) determined 90% ee:t R (minor)=5.8min,t R (major)=5.3min.

[0273] Compound 2-7: prepared according to general method C as a colorless liquid with a yield of 67%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 7.0-6.9 (m, 1H), 6.8 (d, J = 8.1 Hz, 1H), 4.8 (t, J = 4.8 Hz, 1H), 4.0-3.9 (m, 2H), 3.9-3.8 (m, 2H), 3.8 (s, 3H), 3.2-3.1 (m, 1H), 1.7-1.5 (m, 3H), 1.5-1.4 (m, 1H), 1.4-1.3 (m, 2H), 1.3 (d, J = 7.0 Hz, 10H), 1.2 (d, J = 6.9 Hz, 3H). HPLC analysis (AD-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R(minor)=4.9min,t R (major)=4.6min.

[0274] Compound 2-8: prepared according to general method C as a colorless liquid with a yield of 68%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 7.0-6.9 (m, 1H), 6.8 (d, J = 8.2 Hz, 1H), 4.0-3.8 (m, 4H), 3.8 (s, 3H), 3.2-3.1 (m, 1H), 1.8-1.6 (m, 3H), 1.6-1.5 (m, 1H), 1.3 (s, 3H), 1.2 (d, J = 6.9 Hz, 3H). HPLC analysis (OD-H, 5% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (minor)=5.0min,t R (major)=4.7min.

[0275] Compound 2-9: prepared according to general method C as a colorless liquid with a yield of 57%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 6.9 (t, J = 7.5, 1.2 Hz, 1H), 6.8 (d, J = 8.1, 1.2 Hz, 1H), 3.8 (s, 3H), 3.3-3.1 (m, 1H), 1.7-1.6 (m, 1H), 1.6-1.5 (m, 1H), 1.4-1.3 (m, 2H), 1.2 (s, 12H), 1.2 (d, J = 6.9 Hz, 3H), 0.8 (t, J = 7.7 Hz, 2H). HPLC analysis (OJ-H, 0.5% IPA in hexanes, 1 mL / min, 214 nm) found 85% ee:t R (minor)=6.1min,t R (major)=5.8min.

[0276] Compound 2-10: prepared according to general method C as a colorless liquid with a yield of 88%. 1 H NMR (400 MHz, CDCl3) δ 7.5-7.4 (m, 2H), 7.4-7.3 (m, 3H), 7.3-7.2 (m, 2H), 7.2 (d, J = 7.4 Hz, 3H), 3.0-2.7 (m, 1H), 1.3-1.1 (m, 5H), 0.1 (s, 3H), 0.1 (s, 3H). HPLC analysis (OD-H, 0% IPA in hexanes, 1 mL / min, 220 nm) determined 94% ee:tR (minor)=6.9min,t R (major)=7.6min.

[0277] Compound 2-11: prepared according to general method C as a colorless liquid with a yield of 76%. 1 H NMR (400 MHz, CDCl3) δ 7.4-7.4 (m, 6H), 7.4-7.3 (m, 9H), 7.2-7.2 (m, 2H), 7.1-7.1 (m, 3H), 3.2-3.0 (m, 1H), 2.1-1.8 (m, 2H), 1.2 (d, J = 6.9 Hz, 3H). HPLC analysis (OD-H, 0% IPA in hexanes, 1 mL / min, 220 nm) determined 98% ee:t R (minor)=16.1min,t R (major)=18.3min.

[0278] Compound 2-12: prepared according to general method C as a colorless liquid with a yield of 50%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 6.9 (d, J = 7.4 Hz, 1H), 6.8 (d, J = 8.0 Hz, 1H), 5.1-4.9 (m, 1H), 3.8 (s, 3H), 3.3-3.1 (m, 1H), 2.2 (t, J = 7.5 Hz, 2H), 1.7-1.5 (m, 4H), 1.5-1.4 (m, 1H), 1.4-1.2 (m, 14H), 1.2 (d, J = 6.9 Hz, 4H). HPLC analysis (OJ-H, 0% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R (minor)=10.3min,t R (major)=11.1min.

[0279] Compound 2-13: prepared according to general method C as a colorless liquid with a yield of 48%. 1H NMR (400 MHz, CDCl3) δ 7.4-7.3 (m, 2H), 7.3-7.1 (m, 5H), 6.7-6.7 (m, 1H), 6.6-6.5 (m, 2H), 3.5 (s, 1H), 3.1-3.0 (m, 2H), 2.8-2.7 (m, 1H), 1.8-1.7 (m, 2H), 1.7-1.6 (m, 1H), 1.6-1.4 (m, 1H), 1.3 (d, J = 6.9 Hz, 3H). HPLC analysis (OD-H, 1% IPA in hexanes, 1 mL / min, 254 nm) determined 94% ee:t R (minor)=12.6min,t R (major)=13.4min.

[0280] Compound 2-14: prepared according to general method C as a colorless liquid with a yield of 82%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.1 (m, 2H), 6.9-6.9 (m, 1H), 6.9-6.8 (m, 1H), 3.8 (s, 3H), 3.7 (t, J = 4.6 Hz, 4H), 3.3-3.1 (m, 1H), 2.4 (t, J = 4.8 Hz, 4H), 2.3-2.2 (m, 2H), 1.7-1.5 (m, 1H), 1.5-1.4 (m, 3H), 1.3-1.2 (m, 8H), 1.2 (d, J = 6.9 Hz, 3H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 93% ee:t R (minor)=5.2min,t R (major) = 4.9 min.

[0281] Compound 2-15: prepared according to general method C as a colorless liquid with a yield of 90%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.0 (m, 1H), 6.8-6.5 (m, 5H), 6.1 (d, J = 2.1 Hz, 2H), 3.8 (t, J = 7.2 Hz, 2H), 2.9 (s, 6H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 2H), 1.6-1.4 (m, 2H), 1.3-1.1 (m, 7H). HPLC analysis (OJ-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 90% ee:t R (minor)=15.4min,t R (major)=16.8min.

[0282] Compound 2-16: prepared according to general method C as a colorless liquid with a yield of 84%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.2 (m, 1H), 7.1 (t, J = 5.2, 1.2 Hz, 1H), 7.0-6.9 (m, 1H), 6.9-6.8 (m, 1H), 6.7-6.6 (m, 3H), 3.0 (s, 6H), 2.9-2.7 (m, 3H), 2.1-1.9 (m, 2H), 1.4-1.3 (m, 3H). HPLC analysis (OJ-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 89% ee:t R (minor)=5.5min,t R (major)=6.1min.

[0283] Compound 2-17: prepared according to general method C as a colorless liquid with a yield of 95%. 1 H NMR (400 MHz, CDCl3) δ 7.3 (d, J = 1.9 Hz, 1H), 7.2 (t, J = 7.8 Hz, 1H), 6.7-6.5 (m, 3H), 6.4-6.2 (m, 1H), 6.0 (d, J = 3.2 Hz, 1H), 3.0 (s, 6H), 2.7-2.5 (m, 3H), 1.8-1.5 (m, 4H), 1.5-1.2 (m, 5H). HPLC analysis (OJ-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 91% ee:t R (minor)=6.1min,t R (major)=7.2min.

[0284] Compound 2-18: prepared according to general method C as a colorless liquid with a yield of 86%. 1 H NMR (400 MHz, CDCl3) δ 7.8-7.7 (m, 3H), 7.5 (s, 1H), 7.5-7.4 (m, 2H), 7.4-7.3 (m, 3H), 7.2-7.2 (m, 3H), 2.8-2.7 (m, 1H), 2.7-2.6 (m, 2H), 2.1-1.9 (m, 2H), 1.3 (d, J = 7.0 Hz, 3H). HPLC analysis (OJ-H, 5% IPA in hexanes, 1 mL / min, 220 nm) found 94% ee:t R (minor)=23.9min,t R (major)=11.9min.

[0285] Compound 2-19: prepared according to general method C as a colorless liquid with a yield of 80%. 1 H NMR (400 MHz, CDCl3) δ 7.9-7.7 (m, 3H), 7.5 (s, 1H), 7.5-7.4 (m, 2H), 7.3-7.2 (m, 2H), 7.1-7.1 (m, 2H), 7.0-6.9 (m, 1H), 2.8-2.6 (m, 3H), 2.5 (s, 3H), 2.1-1.9 (m, 2H), 1.3 (d, J = 6.9 Hz, 3H). HPLC analysis (AD-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 90% ee:t R (minor)=6.5min,t R (major) = 7.1 min.

[0286] Compound 2-20: prepared according to general method C as a colorless liquid with a yield of 70%. 1 H NMR (400 MHz, CDCl3) δ 7.8 (dd, J = 17.8, 7.9 Hz, 3H), 7.5 (s, 1H), 7.5-7.4 (m, 2H), 7.3 (dd, J = 8.4, 1.7 Hz, 1H), 7.2-7.1 (m, 2H), 7.0 (t, J = 8.7 Hz, 2H), 2.8-2.7 (m, 1H), 2.7-2.6 (m, 2H), 2.0-1.9 (m, 2H), 1.3 (d, J = 6.9 Hz, 3H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:t R (minor)=28.0min,t R (major)=25.9min.

[0287] Compound 2-21: prepared according to general method C as a colorless liquid with a yield of 54%. 1 H NMR (400 MHz, CDCl3) δ 7.8-7.7 (m, 3H), 7.6-7.5 (m, 1H), 7.5-7.3 (m, 3H), 7.3-7.2 (m, 3H), 7.2-7.1 (m, 1H), 3.4-3.3 (m, 1H), 2.8-2.7 (m, 1H), 2.7-2.6 (m, 1H), 2.2-2.0 (m, 1H), 2.0-1.9 (m, 1H), 1.3 (d, J = 6.8 Hz, 3H). HPLC analysis (OJ-H, 5% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (minor)=19.4min,tR (major)=10.1min.

[0288] Compound 2-22: prepared according to General Procedure D as a colorless liquid with a yield of 52%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.2 (m, 2H), 7.2-7.1 (m, 1H), 7.1-7.0 (m, 5H), 6.9 (d, J = 6.9 Hz, 1H), 3.0-2.7 (m, 3H), 2.2 (s, 3H), 1.7-1.6 (m, 2H), 1.3-1.0 (m, 8H), 0.8 (t, J = 6.8 Hz, 3H). HPLC analysis (OJ-H, 0% IPA in hexanes, 1 mL / min, 220 nm) found 96% ee:t R (minor)=5.3min,t R (major)=6.2min.

[0289] Compound 2-23: prepared according to general method D as a colorless liquid with a yield of 82%. 1 H NMR (500MHz, CDCl3) δ7.16-7.11(m,2H),7.10-7.05(m,1H),7.03-6.89(m,6H),3 .14(dd,J=13.6,5.3Hz,1H),2.79(dd,J=13.6,9.6Hz,1H),2.61(m,1H),2.28(s, 3H), 1.92 (m, 1H), 1.77-1.63 (m, 2H), 1.60-1.49 (m, 4H), 1.28-1.24 (m, 4H). HPLC analysis (ID, hexanes / i-PrOH=99.5:0.5, flowrate=0.5mL / min, wavelength=220nm,t R =8.5min for the major isomer,t R =7.9minfor the minor isomer) was measured to be 92% ee.

[0290] Compound 2-24: prepared according to General Method D as a colorless liquid with a yield of 80%. 1H NMR (400 MHz, CDCl3) δ 7.3 (t, J = 7.6 Hz, 2H), 7.2-7.2 (m, 1H), 7.2-7.1 (m, 4H), 7.0 (m, 3H), 6.9 (d, J = 7.3 Hz, 1H), 6.6 (t, J = 7.2 Hz, 1H), 6.5 (d, J = 8.1 Hz, 2H), 3.1 (t, J = 7.8 Hz, 2H), 2.9-2.8 (m, 2H), 2.8-2.7 (m, 4H), 2.2 (s, 3H), 2.1-2.0 (m, 1H), 2.0-1.8 (m, 1H). HPLC analysis (IB-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) found 97% ee:t R (minor)=8.4min,t R (major)=8.1min.

[0291] Compound 2-25: prepared according to General Procedure D as a colorless liquid with a yield of 72%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.2 (m, 2H), 7.2-7.0 (m, 6H), 7.0-6.9 (m, 1H), 3.0-2.9 (m, 1H), 2.9 (d, J = 7.1 Hz, 2H), 2.2 (s, 3H), 1.1-0.9 (m, 2H), -0.2 (s, 9H). HPLC analysis (OD-H, 0% IPA in hexanes, 1 mL / min, 220 nm) determined 94% ee:t R (minor)=12.7min,t R (major)=13.2min.

[0292] Compound 2-26: prepared according to General Procedure D as a colorless liquid with a yield of 70%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.2 (m, 15H), 7.1-7.0 (m, 3H), 7.0-7.0 (m, 2H), 7.0-6.9 (m, 1H), 6.9-6.8 (m, 2H), 6.8-6.7 (m, 1H), 3.2-3.0 (m, 1H), 3.0-2.8 (m, 2H), 2.1-1.9 (m, 5H). HPLC analysis (OD-H, 0% IPA in hexanes, 1 mL / min, 220 nm) found 96% ee:t R (minor)=28.9min,t R (major)=21.2min.

[0293] Compound 2-27: prepared according to General Procedure D as a colorless liquid with a yield of 72%. 1 H NMR (400 MHz, CDCl3) δ 7.4-7.3 (m, 2H), 7.3-7.2 (m, 1H), 7.2-7.2 (m, 2H), 7.2-7.1 (m, 3H), 7.1-7.1 (m, 1H), 7.0-6.9 (m, 2H), 6.8-6.7 (m, 1H), 3.1-2.9 (m, 3H), 2.8-2.6 (m, 2H), 2.3 (s, 3H), 2.2-2.1 (m, 2H). HPLC analysis (OJ-3 (SFC: 3.0 mm ID*150 mm), 90% CO2; 10% MeOH, 1 mL / min, 214 nm) found 96% ee:t R (minor)=5.1min,t R (major)=7.8min.

[0294] Compound 2-28: prepared according to General Procedure D as a colorless liquid with a yield of 52%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.3 (m, 2H), 7.3-7.2 (m, 1H), 7.2-7.0 (m, 5H), 7.0-7.0 (m, 1H), 6.9-6.8 (m, 2H), 6.6-6.5 (m, 2H), 4.2-4.1 (m, 2H), 3.3-3.2 (m, 2H), 3.2-3.1 (m, 2H), 2.9-2.9 (m, 2H), 2.9-2.7 (m, 1H), 2.3 (s, 3H), 1.8-1.7 (m, 2H), 1.6-1.4 (m, 2H), 1.3-1.1 (m, 2H). HPLC analysis (AD-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R (minor)=13.0min,t R (major)=11.1min.

[0295] Compound 2-29: Prepared according to General Procedure D as a colorless liquid with a yield of 72%. 1H NMR (400 MHz, CDCl3) δ 7.5 (d, J = 7.9 Hz, 1H), 7.2 (d, J = 8.2 Hz, 1H), 7.2-7.1 (m, 4H), 7.0-6.9 (m, 7H), 6.8 (d, J = 6.7 Hz, 1H), 6.4 (d, J = 3.1 Hz, 1H), 4.0 (t, J = 7.1 Hz, 2H), 2.9-2.6 (m, 3H), 2.1 (s, 3H), 1.8-1.6 (m, 2H), 1.6-1.5 (m, 2H), 1.2-1.1 (m, 6H), 1.1-0.9 (m, 2H). HPLC analysis (OJ-H, 2% IPA in hexanes, 1 mL / min, 220 nm) found 95% ee:t R (minor)=19.2min,t R (major)=22.8min.

[0296] Compound 2-30: prepared according to General Method D as a colorless liquid with a yield of 60%. 1 H NMR (400 MHz, CDCl3) δ 8.0 (d, J = 8.1 Hz, 2H), 7.5-7.3 (m, 2H), 7.3 (d, J = 8.1 Hz, 2H), 7.2-7.1 (m, 5H), 7.0-6.9 (m, 5H), 6.8 (d, J = 6.9 Hz, 1H), 4.2 (t, J = 7.2 Hz, 2H), 2.9-2.6 (m, 3H), 2.1 (s, 3H), 1.8-1.7 (m, 2H), 1.6-1.5 (m, 2H), 1.3-0.9 (m, 8H). HPLC analysis (IA-H, 2% IPA in hexanes, 1 mL / min, 220 nm) found 94% ee:t R (minor)=4.3min,t R (major) = 4.9 min.

[0297] Compound 2-31: prepared according to general method D as a colorless liquid with a yield of 61%. 1 H NMR(500MHz, CDCl3)δ7.23(t,J=7.4Hz,2H),7.22-7.10(m,6H),7.10-7.00(m,5H),6.99(m,1H),3.31-3.22(m ,1H),2.94(d,J=7.5Hz,2H),2.53-2.41(m,2H),2.09-1.94(m,2H). HPLC analysis (OD-H, hexanes / i-PrOH=99:1, flow rate=1.0mL / min,wavelength=220nm,tR =19.8min for the major isomer,t R =18.6min for the minor isomer) was measured to be 95% ee.

[0298] Compound 2-32: prepared according to General Procedure D as a colorless liquid with a yield of 70%. 1 H NMR (400 MHz, CDCl3) δ 7.2-7.0 (m, 7H), 7.0 (t, J = 6.8 Hz, 4H), 6.5 (t, J = 7.2 Hz, 2H), 6.4 (s, 1H), 2.9-2.8 (m, 8H), 2.8-2.7 (m, 1H), 2.5-2.4 (m, 1H), 2.4-2.3 (m, 1H), 2.0-1.7 (m, 2H). HPLC analysis (OD-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 92% ee:t R (minor)=6.2min,t R (major)=6.4min.

[0299] Compound 2-33: prepared according to General Procedure D as a colorless liquid with a yield of 70%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.1 (m, 10H), 7.1-7.0 (m, 2H), 7.0-6.9 (m, 2H), 3.0-2.8 (m, 3H), 2.6-2.5 (m, 1H), 2.4-2.3 (m, 1H), 2.1-1.9 (m, 2H), 0.2 (s, 9H). HPLC analysis (OD-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R (minor)=4.6min,t R (major)=4.8min.

[0300] Compound 2-34: prepared according to General Procedure D as a colorless liquid with a yield of 70%. 1H NMR (500MHz, CDCl3) δ7.25-7.07(m,10H),5.37-5.27(m,1H),2.70-2.60(m,2H),2.60-2.54(m,1H),2.43(m,1H),2.26-2.18(m ,1H),1.99-1.91(m,2H),1.70-1.64(m,2H),1.64-1.57(m,4H),1.57-1.52(m,2H). HPLC analysis (OJ-H, hexanes / i-PrOH=99:1, flow rate=1mL / min,wavelength=220nm,t R =19.8min for the major isomer,t R =18.6min for the minor isomer) was measured to be 81% ee.

[0301] Compound 2-35: prepared according to General Procedure D as a colorless liquid with a yield of 70%. 1 H NMR (500MHz, CDCl3) δ7.23(dd,J=8.0,6.8Hz,2H),7.17-7.13(m,1H),7.10(d,J=7.7Hz,2H),7.09-6.99(m,4H),6.95-6.89(m,2H),6.77-6.72(m,2H) ),3.77(s,3H),2.86-2.80(m,2H),2.82-2.73(m,1H),2.53-2.34(m,2H),2.34(s,3H),2.04-1.84(m,2H). HPLC analysis (OJ-H, hexanes / i-PrOH=99:1, flow rate=1mL / min,wavelength=220nm,t R =39min for the major isomer,t R =16.8min for the minor isomer) was measured to be 93% ee.

[0302] Compound 2-36: prepared according to General Procedure D as a colorless liquid with a yield of 63%. 1H NMR (500MHz, CDCl3) δ7.26-7.12(m,3H),7.12-7.03(m,4H),7.04-6.94(m,6H),2.91-2.82(m,2H),2.80-2 .74(m,1H),2.52-2.36(m,2H),2.33(s,3H),2.03-1.87(m,2H).HPLC analysis (OJ-H, hexanes / i-PrOH=99:1, flow rate=1mL / min,wavelength=220nm,t R =13.4min for the major isomer,t R =8.4min for the minor isomer) was measured to be 90% ee.

[0303] Compound 2-37: prepared according to General Procedure D as a colorless liquid with a yield of 72%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.7-6.5(m,3H),2.9(s,6H),2.6-2.5(m,1 H), 1.6-1.6 (m, 2H), 1.2 (d, J = 6.9Hz, 3H), 0.8 (t, J = 7.4Hz, 3H). HPLC analysis (OJ-H, 1% IPA in hexanes,1mL / min,254nm)indicated 88%ee:t R (minor)=4.4min,t R (major)=4.6min.

[0304] Compound 2-38: prepared according to General Procedure D as a colorless liquid with a yield of 65%. 1 H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.6-6.5(m,3H),2.9(s,6H),2.7-2.6(m ,1H),1.7-1.4(m,2H),1.3-1.2(m,5H),0.9(t,J=7.3Hz,3H).HPLC analysis (OJ-H,1% IPA in hexanes,1mL / min,254nm)indicated 84%ee:t R (minor)=3.9min,t R (major)=4.2min.

[0305] Compound 2-39: prepared according to general procedure D as a colorless liquid with a yield of 58%. 1H NMR (400MHz, CDCl3) δ7.2-7.1(m,1H),6.8-6.7(m,1H),6.7-6.6(m,2H),3.7(s,3H),2.6-2 .4(m,1H),1.5-1.5(m,2H),1.2(d,J=6.9Hz,3H),0.8(t,J=7.4Hz,3H).HPLC analysis (OD-H,0%IPA in hexanes,1mL / min,220nm)indicated 80%ee:t R (minor)=9.1min,t R (major) = 9.4 min.

[0306] Compound 2-40: prepared according to General Procedure D as a colorless liquid with a yield of 49%. 1 H NMR (400MHz, CDCl3) δ7.5-7.4(m,2H),7.4-7.4(m,2H),7.4-7.3(m,1H),7.1-7.1(m,2H),7.0-

[0307] 6.9 (m, 2H), 5.0 (s, 2H), 2.7-2.5 (m, 1H), 1.6-1.5 (m, 3H), 1.2 (d, J = 6.9Hz, 3H), 0.8 (t, J = 7.4Hz, 3H). HPLC analysis (AD-H, 0% IPA in hexanes,1mL / min,220nm)indicated82%ee:t R (minor)=10.6min,t R (major) = 9.3 min.

[0308] Example 3:

[0309]

[0310] General Method E: In a nitrogen-filled glove box, add Compound V (9.4 mg, 0.01 mmol, 5.0 mol%), Compound III sodium isopropoxide (49.2 mg, 0.6 mmol, 3.0 equiv), Ni(cod)2 (2.8 mg, 0.01 mmol, 5.0 mol%), and 2 mL of n-heptane to an 8 mL vial and stir at room temperature for 30 minutes. Compound I (0.2 mmol) and Compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography, and the ee value of the product was determined by chiral HPLC.

[0311] Wherein, the structural formula of compound V is: Ar is 3,5-dimethylphenyl.

[0312]

[0313] General Procedure F: In a nitrogen-filled glove box, add compound V (12.6 mg, 0.02 mmol, 10.0 mol%), compound III (aryl Grignard reagent) (0.6 mmol, 3.0 equiv), Ni(cod)2 (5.6 mg, 0.02 mmol, 10.0 mol%), and 2 mL of 1,4-dioxane to an 8 mL vial and stir at room temperature for 30 minutes. Compound I (0.2 mmol) and compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography, and the ee value of the product was determined by chiral HPLC.

[0314] Wherein, the structural formula of compound V is: The structural formula of the compound prepared in this example is:

[0315]

[0316] Compound 2-41: prepared according to General Procedure E as a colorless liquid with a yield of 90%. 1 H NMR (400 MHz, CDCl3) δ 7.3-7.1 (m, 2H), 7.2-7.2 (m, 2H), 7.2-7.1 (m, 4H), 7.1-7.0 (m, 2H), 2.7-2.6 (m, 1H), 2.5-2.4 (m, 2H), 1.9-1.7 (m, 2H), 1.2 (d, J = 7.0 Hz, 3H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 93% ee:t R (minor)=7.2min,t R (major)=8.1min.

[0317] Compound 2-42: prepared according to General Procedure F as a colorless liquid with a yield of 70%. 1H NMR (400 MHz, CDCl3) δ 7.2-7.0 (m, 7H), 7.0 (t, J = 6.8 Hz, 4H), 6.5 (t, J = 7.2 Hz, 2H), 6.4 (s, 1H), 2.9-2.8 (m, 8H), 2.8-2.7 (m, 1H), 2.5-2.4 (m, 1H), 2.4-2.3 (m, 1H), 2.0-1.7 (m, 2H). HPLC analysis (OD-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 92% ee:t R (minor)=6.1min,t R (major)=6.3min.

[0318] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A method for carbon functionalization of non-activated olefins, comprising the following steps: In a solvent, in system 1 or system 2, compound I, compound II and compound III are reacted as shown below; The system 1 is compound IV and bis(1,5-cyclooctadiene)nickel; the system 2 is compound V and bis(1,5-cyclooctadiene)nickel; or in, R 1 , R 1’ are independently hydrogen, C 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 1-1 Substituted C 1-20 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkenyl, -LR 1-1 ; -L- is none, C 1-20 Alkylene, -OC 1-20 Alkylene-, -C 1-20 Alkylene-O-, -CO-C 1-20 Alkylene-, -C 1-20 Alkylene-CO-, -NH-C 1-20 Alkylene-, -C 1-20 Alkylene-NH-; Each R 1-1 , R 1-2 are independently -OH, halogen, C 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -OC 1-20 Alkyl, C 6-10 Aromatic ring, 5-16 membered heteroaromatic ring, -SiR a R b R c , -GeR a R b R c , -NR d R e , -O-SiR f R g R i , Bpin, by 1, 2 or 3 R 2-1-1 Substituted C 6-10 Aromatic ring, 1, 2 or 3 R 2-1-1 Substituted 5-16 membered heterocycloalkyl; R 2 Independently for C 6-14 Aryl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 2 -1 Substituted C 6-14 Aryl, substituted with 1, 2 or 3 R 2-2 Substituted C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 2-3 substituted 5-16 membered heteroaryl; Each R 2-1 , R 2-2 , R 2-3 are independently -OH, halogen, C 1-20 Alkyl, -OC 1-20 Alkyl, -OC 1-20 Haloalkyl, -SC 1-20 Alkyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -C 1-6 Alkylene-5-16 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aromatic ring, C 6-10 Aromatic ring, 5- to 16-membered heteroaromatic ring, -SiR a R b R c , -NR d R e , -O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i , -C 1-6 Alkylene-O-SiR f R g R i , Bpin, -CO-OC 1-20 Alkyl, or 1, 2 or 3 R 2-1-1 Substituted C 6-10 Aromatic rings; R a , R b and R c Each independently is H, C 1-20 Alkyl or C 6-10 Aromatic rings; R d and R e Each independently is H, C 1-20 Alkyl, C 6-10 Aromatic ring or -C 1-6 Alkylene-C 6-10 Aromatic rings; R f , R g and R i Each independently is H, C 1-20 Alkyl or C 6-10 Aromatic rings; Each R 2-1-1 are independently halogen, C 1-20 Alkyl or -OC 1-20 alkyl; X is Cl, Br, I, OTs or OTf; R 3 Independently for C 6-14 Aryl, substituted with 1, 2 or 3 R 3-1 Substituted C 6-14 Aryl, or R 3’ Independently for C 1-10 alkyl; M is an alkali metal; Each R 3-1 are independently hydrogen, amino, halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 1-4 Halogenated alkoxy, C 6-10 Aryl, or two adjacent R 3-1 Form a 5-8 membered heteroalkane ring; The 5-16 membered heteroaromatic ring is independently a 5-16 membered heteroaromatic ring having 1, 2 or 3 heteroatoms selected from N, O and S; and the number of heteroatoms is 1, 2, 3 or 4; The 5-16 membered heterocycloalkyl group is independently a 5-16 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S; and the number of heteroatoms is 1, 2, 3 or 4; The structure of the compound IV is: in, R 0 Independently for C 1-6 Alkyl or -OC 1-6 alkyl; R 4a , R 4b , R 4c and R 4d Each independently is C 1-6 Alkyl, C 6-10 Aromatic ring, or 1, 2 or 3 R Ar Substituted C 6-10 Aromatic rings; Each R Ar Independently for C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 1, 2 or 3 R Ar-1 Substituted C 1-6 Alkyl, 1, 2 or 3 R Ar-2 Replaced-OC 1-6 Alkyl, or 1, 2 or 3 R Ar-3 Substituted C 3-6 Cycloalkyl; Each R Ar-1 , R Ar-2 and R Ar-3 are each independently halogen or C 1-6 alkyl; Y - It is a monovalent anion; The structure of the compound V is: in, R 9a , R 9b , R 9c and R 9d Each independently is C 1-6 Alkyl, unsubstituted or replaced by R 3a-1 Substituted C6-C 14 Aryl; Each R 3a-1 are independently C1-C4 alkyl; R 7a , R 7b , R 7c , R 8a , R 8b and R 8c Each is independently hydrogen or C1-C4 alkyl; R5 and R6 are each independently hydrogen, C1-C4 alkyl, halogen, or C6-C 10 Aryl; wherein R 5-1 and R 5-2 Each is independently hydrogen or C1-C4 alkyl; is a single bond or a double bond; Alternatively, R5, R6 and the carbon atom to which they are attached together form Z - It is a monovalent anion.

2. The method according to claim 1, characterized in that R 0 are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy; R 4a , R 4b , R 4c and R 4d are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, Y - F - , Cl - Br - ,I - or BF4 - ; R 9a , R 9b , R 9c and R 9d are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, R 7a , R 7b , R 7c , R 8a , R 8b and R 8c are each independently hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; R5 and R6 are each independently C6-C 10 Aryl, or R5, R6 and the carbon atom to which they are attached together form Z - F - , Cl - Br - ,I - or BF4 - ; For example, Cl - or BF4 - .

3. The method according to claim 1, characterized in that The compound IV is selected from any of the following compounds: The compound V is selected from any of the following compounds: Ar is 3,5-dimethylphenyl.

4. The method according to claim 1, characterized in that R 1 , R 1’ are independently hydrogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, substituted by 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, -LR 1-1 ; -L- is none, C 1-10 Alkylene, -OC 1-10 Alkylene-, -C 1-10 Alkylene-O-, -CO-C 1-10 Alkylene-, -C 1-10 Alkylene-CO-, -NH-C 1-10 Alkylene-, -C 1-10 Alkylene-NH-; R 2 Independently for C 6-10 Aryl, C 3-12 Cycloalkenyl, 5-12 membered heterocycloalkyl, 5-12 membered heteroaryl, 1, 2 or 3 R 2 -1 Substituted C 6-10 Aryl; R 3’ OM is a metal salt of an alcohol, wherein the alkali metal salt of the alcohol is independently an alkali metal salt of a primary alcohol and a secondary alcohol, R 3 MgBr is C 6-14 Aryl Grignard reagents, or 1, 2 or 3 R 3-1 Substituted C 6-14 Aryl Grignard reagents.

5. The method according to claim 1, characterized in that In the method, there is no sodium tert-butoxide in the reaction system.

6. The method according to claim 1, characterized in that The molar ratio of the compound I to the compound II is 10:1 to 1:10, preferably 8:1 to 1:5, and the molar ratio of the compound I to the compound III is 10:1 to 1:10, preferably 5:1 to 1:

5.

7. The method according to claim 1, characterized in that The molar ratio of the compound I to the bis(1,5-cyclooctadiene)nickel is 1:0.01-0.5, preferably 1:0.01-0.

1. The molar ratio of the compound IV to the bis(1,5-cyclooctadiene)nickel is 0.5-2:0.5-2, preferably 0.8-1.2:0.8-1.2, The molar ratio of the compound V to the bis(1,5-cyclooctadiene)nickel is 0.5-2:0.5-2, preferably 0.8-1.2:0.8-1.

2.

8. The method according to claim 1, characterized in that The solvent is selected from the group consisting of n-hexane, n-heptane, cyclohexane, cycloheptane, tetrahydrofuran, 1,4-dioxane, or a combination thereof.

9. The method according to claim 1, characterized in that The reaction temperature of the reaction is 10-50°C, preferably 15-40°C, and the reaction time of the reaction is 8-14h.

10. The method according to claim 1, characterized in that The method comprises: mixing compound IV or compound V, compound III, bis(1,5-cyclooctadiene)nickel and a solvent under a protective gas atmosphere, then sequentially adding compound I and compound II thereto, and then optionally removing the protective gas environment and reacting at room temperature.

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