A method for preparing a spirooxindole compound

Abstract

The present specification discloses a preparation method of spirooxindole compounds, which is based on modified 1,7-alkenyl alkyne compounds and alpha-bromocarbonyl compounds as raw materials, adding a photocatalyst fac-Ir(ppy)3 and Cs2CO3, and reacting in a solvent at a certain temperature under the irradiation of light with a wavelength of 457 nm to obtain different substituted spirooxindole compounds through a radical cascade cyclization process. The preparation method disclosed by the present application has the advantages of simple reaction process, green and mild reaction conditions, no need for high temperature, strong operability, high atom economy and high potential for large-scale application.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and particularly relates to a method for preparing spiro-oxidized indole compounds. Background Technology

[0002] The spirocyclic indole skeleton is the core structure of many natural alkaloids. These heterocyclic compounds generally possess excellent pharmacological activities; typical examples include Horsfiline, Elacomine, and Spirobacillene, all of which use this spirocyclic structure as their core pharmacodynamic skeleton (Expert Opin. Drug Discov. 2020, 15, 603-625). Benefiting from their high rigidity and unique three-dimensional configuration, the introduction of the spirocyclic skeleton can effectively regulate the biological activity and physicochemical properties of candidate drug molecules, possessing significant application value in new drug development and the preparation of bioactive molecules. Therefore, developing novel and efficient synthetic processes to construct spirocyclic indole skeletons has become a research hotspot in the field of organic synthetic chemistry.

[0003] In existing technologies, cycloaddition reactions and dearomatization cyclization reactions of indole derivatives are the two most mainstream synthetic methods for constructing spirooxidindole compounds (Eur. J. Org. Chem. 2021, 2021, 1653-1675; Adv. Synth. Catal. 2020, 362, 4446-4461). Specifically, for 2-oxidindole containing a C=X double bond at the 3-position, cycloaddition reactions can prepare various substituted spirooxidindole compounds. Furthermore, researchers have also developed transition metal-catalyzed, visible light-induced dearomatization spirocyclization processes for indole derivatives to achieve the synthesis of spirooxidindole compounds.

[0004] However, current synthetic methods all rely on the pre-construction of a complete indole core substrate, followed by intramolecular cyclization to form a spirocyclic structure. This synthetic approach severely limits the structural diversity of the substrates, resulting in a narrow range of applicable substrates and significantly hindering the derivatization and large-scale application of these active spirocyclic compounds. Therefore, there is an urgent need in the industry to develop green and simple synthetic methods that can rapidly construct spirooxidized indole skeletons from structurally diverse raw materials. Summary of the Invention

[0005] To address the aforementioned deficiencies in existing technologies, this invention provides a novel visible-light-promoted radical spirocyclization method that constructs a spiro-oxidized indole skeleton using 1,7-enyne and α-bromocarbonyl compounds as core raw materials. Under visible-light irradiation, this process utilizes the α-bromocarbonyl compound to generate a carbon-centered radical. This radical is then captured by the 1,7-enyne substrate, leading to a specific spirocyclization reaction. This allows for the single-step construction of multiple chemical bonds, efficiently and conveniently preparing spiro-oxidized indole derivatives, overcoming the technical challenges of substrate limitations and cumbersome synthesis in traditional processes.

[0006] The technical solution of the present invention is as follows:

[0007] A method for preparing the spirooxidized indole compound shown in formula (I),

[0008]

[0009] in,

[0010] R 1 Selected from alkyl, alkoxy, and halogen;

[0011] R 2 and R 3 Selected from aryl;

[0012] R 4 Selected from sulfonyl and alkyl groups;

[0013] R 5 Selected from alkyl, alkoxy, and aryl groups;

[0014] in,

[0015] The compound shown in formula (II) (a 1,7-enyne compound with different substitutions) and the compound shown in formula (III) (an α-bromocarbonyl compound) were reacted in a solvent with the photocatalysts fac-Ir(ppy)3 and Cs2CO3 under 457 nm light at a certain temperature to obtain the compound shown in formula (I):

[0016]

[0017] in,

[0018] R 1 R 2 R 3 R 4 and R 5 The definition is the same as that of formula (I).

[0019] According to the present invention, the aryl group may be substituted or unsubstituted; the aryl group may have one or more substituents, and there is no particular limitation on the position of the substituents, which may be ortho, meta, or para; the substituents are not limited in any way, and common substituents include alkyl, alkoxy, disubstituted amino, nitro, cyano, ester, aldehyde, ketone carbonyl, and halogen atoms, etc.; when there are multiple substituents, these multiple substituents may be the same or different, and two adjacent substituents may be independent of each other or form a ring.

[0020] According to the present invention, the alkyl group may be a substituted or unsubstituted primary, secondary or tertiary alkyl group; the substituent is not limited in any way, and common substituents include alkyl, alkoxy, disubstituted amino, nitro, cyano, ester, aldehyde, ketone carbonyl and halogen atom, etc.; when there are multiple substituents, these multiple substituents may be the same or different, and two adjacent or close substituents may be independent of each other or cyclic.

[0021] According to the present invention, the sulfonyl group and sulfur atom may be substituted with alkyl or aryl groups. The substituents are not limited in any way, and common substituents include alkyl, alkoxy, disubstituted amino, nitro, cyano, ester, aldehyde, ketone carbonyl, and halogen atoms, etc.; when multiple substituents are present, these multiple substituents may be the same or different, and two adjacent or close substituents may be independent of each other or form a ring.

[0022] According to the present invention, the alkyl group preferably refers to an alkyl group having 1 to 10 carbon atoms, and the substituents on the alkyl group are preferably alkoxy, nitro, cyano, ester, aldehyde, ketone carbonyl, and halogen atoms, more preferably halogen atoms, such as fluorine, chlorine, and bromine, and the alkyl group is, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, neopentyl, or halogenated C. 1-10 alkyl.

[0023] According to the present invention, the aryl group is preferably a monocyclic or bicyclic aryl group, more preferably an aryl group with 6-14 carbon atoms, such as phenyl or naphthyl. The substituents on the aryl group are preferably alkyl, alkoxy, nitro, cyano, ester, aldehyde, ketone carbonyl, and halogen atoms.

[0024] According to the present invention, the sulfonyl group preferably refers to arylsulfonyl and alkylsulfonyl groups, such as p-toluenesulfonyl, benzenesulfonyl, p-chlorobenzenesulfonyl, p-fluorobenzenesulfonyl, o-chlorobenzenesulfonyl, m-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, p-nitrobenzenesulfonyl, methanesulfonyl, ethanesulfonyl, and isopropylsulfonyl.

[0025] According to the present invention, the halogen atom refers to a fluorine, chlorine, bromine, or iodine atom, etc.

[0026] According to the present invention, the solvent is tert-butanol.

[0027] According to the present invention, the preferred molar ratio of the reactants is:

[0028] Compounds of formula (II): Compounds of formula (III) = 1:1.5~3.

[0029] According to the present invention, the reaction temperature and reaction time vary slightly depending on the raw materials. The reaction temperature is usually between 10°C and 60°C, preferably between 30°C and 40°C, and the reaction time is generally between 10 and 24 hours. If heating is required, an oil bath (e.g., silicone oil, paraffin oil, etc.) or other heating methods can be used.

[0030] According to the present invention, the method further includes a concentration step. Preferably, the concentration process can be carried out by methods such as atmospheric distillation or vacuum distillation.

[0031] According to the present invention, the method further includes a purification step. Preferably, the purification process obtains a pure product through column chromatography, vacuum distillation, and / or recrystallization. More preferably, the purification process involves column chromatography followed by vacuum distillation to obtain the purified product.

[0032] Compared with existing publicly available technologies, the method for preparing spiro-oxidized indole compounds provided by this invention has the following significant technical advantages and innovations:

[0033] 1. Existing spirooxidized indole synthesis is highly dependent on pre-prepared indole core substrates, resulting in fixed substrate structures and limited applicability. This invention uses readily available 1,7-enyne and α-bromocarbonyl compounds as starting materials, eliminating the need for prior construction of an indole cyclic core. The starting material structure is highly tunable, allowing for the convenient introduction of various substituted functional groups, greatly expanding the substrate applicability and product structural diversity.

[0034] 2. This invention employs a visible light-induced free radical tandem spirocyclic reaction mode, abandoning the traditional fused ring cyclization reaction pathway. It allows for the simultaneous construction of multiple chemical bonds in a single reaction, completing the construction of complex spirocyclic skeletons in one step. The reaction process is simple, with high atom utilization, significantly improving the synthesis efficiency of spirooxidized indole compounds.

[0035] 3. This invention requires no high-temperature heating throughout the entire process, and the reaction can be efficiently triggered by visible light catalysis. The reaction conditions are green, safe, and easy to operate. Furthermore, this invention exhibits good universality for 1,7-enyne substrates with different substitution types and α-bromocarbonyl reagents, enabling the efficient preparation of a series of multi-substituted spirooxyindole derivatives, and possesses promising prospects for large-scale application. Detailed Implementation

[0036] As described above, this invention discloses a method for preparing spiro-oxidized indole compounds of formula (I).

[0037]

[0038] in,

[0039] R 1 Selected from alkyl, alkoxy, and halogen;

[0040] R 2 and R 3 Selected from aryl;

[0041] R 4 Selected from sulfonyl and alkyl groups;

[0042] R 5 Selected from alkyl, alkoxy, and aryl groups;

[0043] in,

[0044] The compound shown in formula (II) (a 1,7-enyne compound with different substitutions) and the compound shown in formula (III) (an α-bromocarbonyl compound) were reacted in a solvent with the photocatalysts fac-Ir(ppy)3 and Cs2CO3 under 457 nm light at a certain temperature to obtain the compound shown in formula (I):

[0045]

[0046] in,

[0047] R 1 R 2 R 3 R 4 and R 5 The definition is the same as that of formula (I).

[0048]

[0049] As previously stated, the reaction of the present invention has good tolerance to functional groups.

[0050] The present invention will be described in detail through the following embodiments. However, those skilled in the art will understand that the present invention is not limited thereto, and any improvements and variations made based on the present invention are within the scope of protection of the present invention. Therefore, the following description should be understood as being of general knowledge to those skilled in the art, and is not intended to limit the present invention.

[0051] Example 1

[0052] Preparation of ethyl 1'-methyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate

[0053] Molecular formula: C28 H 25 NO3

[0054]

[0055] Operating steps:

[0056] To a 10 mL reaction flask, 1a (101.1 mg, 0.3 mmol), ethyl bromoacetate (100.2 mg, 0.6 mmol), fac-Ir(ppy)3 (3.9 mg, 0.006 mmol), Cs₂CO₃ (195.5 mg, 0.6 mmol), and dichloromethane (3 mL) were added sequentially, and the reaction was carried out at room temperature under light for 24 h. After the reaction was complete, the solvent was concentrated under reduced pressure, and the residue was purified by rapid column chromatography (petroleum ether: dichloromethane = 1:5) to give 89.1 mg of a white solid, with a yield of 65%.

[0057] The characterization data of the obtained compounds are as follows:

[0058] 1 H NMR (500 MHz, Chloroform-d) δ 7.16 – 7.07 (m, 5H), 7.05 – 6.95 (m,7H), 6.92 (t, J = 7.3 Hz, 1H), 6.63 – 6.52 (m, 2H), 4.57 (d, J = 10.7 Hz,1H), 4.44 (dd, J = 10.8, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.10 (s, 3H),1.19 (t, J = 7.1 Hz, 3H).

[0059] 13 C NMR (126 MHz, Chloroform-d) δ 177.6, 171.8, 145.3, 142.8, 135.5,134.2, 129.2, 128.8, 128.7, 128.6, 128.2, 127.6, 127.1, 126.0, 124.4, 122.3,108.2, 67.2, 61.2, 59.5, 52.3, 26.4, 14.2.

[0060] HRMS (ESI) m / z: [M + Na] + calcd for C 28 H 25 NO3Na +, 446.1727; found, 446.1730

[0061] Examples 2-34

[0062] Examples 2-34 were prepared using the same method as Example 1, and the specific raw material ratios are shown in Table 1.

[0063] Table 1 Reactants and their specific raw material ratios in Examples 2-34

[0064] Table 1 (continued)

[0066] The product names, yields, and characterization results of Examples 2-34 are as follows:

[0067] Example 2:

[0068] Chemical name:

[0069] ethyl 5'-chloro-1'-methyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0070] Molecular formula: C 28 H 24 ClNO3; Appearance: White solid; Yield: 65%

[0071] Characterization data:

[0072] 1 H NMR (400 MHz, CDCl3) δ 7.16 (d, J = 7.9 Hz, 3H), 7.10 – 7.02 (m,5H), 6.98 (td, J = 7.8, 2.9 Hz, 4H), 6.62 (d, J = 2.1 Hz, 1H), 6.48 (d, J =8.9 Hz, 1H), 4.57 (d, J = 10.8 Hz, 1H), 4.42 (d, J = 12.8 Hz, 1H), 4.15 (q, J= 7.1 Hz, 2H), 3.09 (s, 3H), 1.20 (t, J = 7.2 Hz, 3H).

[0073] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 177.2, 171.6, 144.8, 141.4, 135.1,133.9, 130.7, 129.6, 128.7, 128.6, 128.4, 128.1, 127.85, 127.78, 127.4,126.0, 124.7, 109.1, 67.4, 61.3, 59.6, 52.1, 26.6, 14.2.

[0074] HRMS (ESI) m / z: [M + Na] + calcd for C 28 H 24 ClNO3Na + , 480.1337; found, 480.1341

[0075] Example 3:

[0076] Chemical name:

[0077] ethyl 5'-bromo-1'-methyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0078] Molecular formula: C 28 H 24 BrNO3; Appearance: white solid; Yield: 59%

[0079] Characterization data:

[0080] 1 H NMR (500 MHz, CDCl3) δ 7.23 (d, J = 7.0 Hz, 2H), 7.16 (d, J = 7.5Hz, 3H), 7.06 (dd, J = 5.2, 2.0 Hz, 3H), 7.02 – 6.92 (m, 4H), 6.62 (d, J =2.1 Hz, 1H), 6.43 (d, J = 8.9 Hz, 1H), 4.56 (d, J = 10.7 Hz, 1H), 4.42 (dd, J= 10.7, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 1H), 3.08 (s, 3H), 1.20 (t, J = 7.1Hz, 3H).

[0081] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.1, 171.6, 144.7, 141.8, 135.0,133.8, 131.5, 131.1, 129.6, 128.7, 128.4, 128.1, 127.8, 127.42, 127.40,126.0, 115.0, 109.6, 67.3, 61.3, 59.7, 52.1, 26.5, 14.2.

[0082] HRMS (ESI) m / z: [M + Na] + calcd for C 28 H 24 BrNO3Na + , 524.0832; found, 524.0840

[0083] Example 4:

[0084] Chemical name:

[0085] ethyl 5'-methoxy-1'-methyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0086] Molecular formula: C 29 H 27 NO4; Appearance: White solid; Yield: 53%

[0087] Characterization data:

[0088] 1H NMR (500 MHz, CDCl3) δ 7.18 – 7.11 (m, 3H), 7.07 – 6.95 (m, 7H), 6.72 (d, J = 2.6 Hz, 1H), 6.64 (dd, J = 8.4, 2.6 Hz, 1H), 6.60 (d, J = 2.1Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 4.57 (d, J = 10.8 Hz, 1H), 4.42 (dd, J =10.7, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.72 (s, 3H), 3.09 (s, 3H), 1.19(t, J = 7.1 Hz, 3H).

[0089] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.8, 155.8, 145.4, 136.6,135.6, 134.2, 130.2, 129.2, 128.6, 128.2, 127.7, 127.2, 126.1, 112.9, 112.0,108.5, 67.6, 61.2, 59.4, 56.0, 52.3, 26.6, 14.3.

[0090] HRMS (ESI) m / z: [M + Na] + calcd for C 29 H 27 NO4Na + , 476.1832; found, 476.1839

[0091] Example 5:

[0092] Chemical name:

[0093] ethyl 1',6'-dimethyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0094] Molecular formula: C 29 H 27 NO3; Appearance: White solid; Yield: 67%

[0095] Characterization data:

[0096] 1 H NMR (400 MHz, CDCl3) δ 7.16 – 7.10 (m, 3H), 7.04 – 6.93 (m, 8H), 6.73 (d, J = 7.5 Hz, 1H), 6.55 (s, 1H), 6.39 (s, 1H), 4.54 (d, J = 10.8 Hz,1H), 4.41 (d, J = 10.8 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 3.08 (s, 3H), 2.25(s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0097] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 177.9, 172.0, 145.6, 142.9, 138.8,135.8, 134.4, 129.0, 128.6, 128.3, 128.1, 127.6, 127.1, 126.1, 125.8, 124.2,122.9, 109.2, 67.1, 61.2, 59.4, 52.5, 26.4, 21.9, 14.3.

[0098] HRMS (ESI) m / z: [M + Na] + calcd for C 29 H 27 NO3Na + , 460.1883; found, 460.1885

[0099] Example 6:

[0100] Chemical name:

[0101] ethyl (5R)-1'-methyl-2'-oxo-5-phenyl-2-(p-tolyl)spiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0102] Molecular formula: C 29 H 27 NO3; Appearance: White solid; Yield: 50%

[0103] Characterization data:

[0104] 1 H NMR (500 MHz, CDCl3) δ 7.14 – 7.09 (m, 2H), 7.03 – 6.96 (m, 5H), 6.93 (q, J = 7.9 Hz, 3H), 6.89 – 6.82 (m, 2H), 6.61 – 6.51 (m, 2H), 4.56 (d,J = 10.7 Hz, 1H), 4.42 (dd, J = 10.8, 2.0 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.10 (s, 3H), 2.22 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0105] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.7, 171.9, 145.2, 142.8, 138.1,135.6, 131.4, 129.3, 129.0, 128.6, 128.2, 127.6, 127.1, 125.9, 124.4, 122.3,108.2, 67.2, 61.2, 59.5, 52.3, 26.5, 21.2, 14.3.

[0106] HRMS (ESI) m / z: [M +H] + calcd for C 29 H 28 NO3 + , 438.2064; found, 438.2069

[0107] Example 7:

[0108] Chemical name:

[0109] ethyl (5R)-2-(4-fluorophenyl)-1'-methyl-2'-oxo-5-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0110] Molecular formula: C 28 H 24 FNO3; Appearance: White solid; Yield: 53%

[0111] Characterization data:

[0112] 1 H NMR (500 MHz, CDCl3) δ 7.12 (t, J = 7.0 Hz, 2H), 7.05 – 6.89 (m,8H), 6.83 (t, J = 8.7 Hz, 2H), 6.57 (d, J = 8.1 Hz, 1H), 6.52 (s, 1H), 4.56(d, J = 10.7 Hz, 1H), 4.43 (d, J = 10.7 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.10 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0113] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.5, 171.8, 162.6 (d, J = 247.8 Hz), 144.3, 142.8, 135.4, 130.5 (d, J = 3.3 Hz), 129.2, 128.8, 128.6, 128.2, 127.9 (d, J = 8.1 Hz), 127.7, 127.2, 124.4, 122.4, 115.6 (d, J = 21.5 Hz), 108.3, 67.4, 61.3, 59.5, 52.3, 26.5, 14.3.

[0114] 19 F NMR (471 MHz, CDCl3) δ -113.54.

[0115] HRMS (ESI) m / z: [M + Na] + calcd for C 28 H 24 FNO3Na + , 464.1632; found, 464.1634

[0116] Example 8:

[0117] Chemical name:

[0118] ethyl (5R)-2-(4-chlorophenyl)-1'-methyl-2'-oxo-5-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0119] Molecular formula: C 28 H 24 ClNO3; Appearance: White solid; Yield: 49%

[0120] Characterization data:

[0121] 1 H NMR (500 MHz, CDCl3) δ 7.11 (dd, J = 8.1, 3.1 Hz, 4H), 7.04 – 7.00(m, 3H), 6.99 – 6.88 (m, 5H), 6.62 – 6.52 (m, 2H), 4.56 (d, J = 10.8 Hz, 1H), 4.42 (dd, J = 10.8, 2.2 Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 3.10 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0122] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.4, 171.7, 144.3, 142.8, 135.4,134.0, 132.8, 129.9, 128.9, 128.8, 128.5, 128.2, 127.7, 127.4, 127.2, 124.4,122.4, 108.3, 67.3, 61.3, 59.5, 52.4, 26.5, 14.2.

[0123] HRMS (ESI) m / z: [M +H] + calcd for C 28 H 25 ClNO3 + , 458.1517; found, 458.1523

[0124] Example 9:

[0125] Chemical name:

[0126] ethyl (5R)-2-(4-bromophenyl)-1'-methyl-2'-oxo-5-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0127] Molecular formula: C 28 H 24 BrNO3; Appearance: white solid; Yield: 57%

[0128] Characterization data:

[0129] 1 H NMR (500 MHz, CDCl3) δ 7.27 (s, 1H), 7.25 (s, 1H), 7.15 – 7.09 (m,2H), 7.05 – 7.00 (m, 3H), 6.99 – 6.91 (m, 3H), 6.83 (d, J = 8.5 Hz, 2H), 6.63– 6.52 (m, 2H), 4.56 (d, J = 10.8 Hz, 1H), 4.41 (dd, J = 10.7, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.10 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0130] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.4, 171.6, 144.3, 142.8, 135.4,133.3, 131.8, 130.0, 128.9, 128.5, 128.2, 127.73, 127.68, 127.3, 124.4,122.5, 122.3, 108.3, 67.2, 61.3, 59.5, 52.4, 26.5, 14.2.

[0131] HRMS (ESI) m / z: [M + Na] + calcd for C 28 H 24 BrNO3Na + , 524.0832; found,524.0836

[0132] Example 10:

[0133] Chemical name:

[0134] ethyl (5R)-5'-chloro-1'-methyl-2'-oxo-2-phenyl-5-(p-tolyl)spiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0135] Molecular formula: C 29 H 26 ClNO3; Appearance: White solid; Yield: 62%

[0136] Characterization data:

[0137] 1 H NMR (500 MHz, CDCl3) δ 7.16 (d, J = 7.5 Hz, 3H), 7.09 (d, J = 7.2Hz, 2H), 6.96 (d, J = 7.9 Hz, 2H), 6.86 (d, J = 3.5 Hz, 4H), 6.60 (d, J = 2.0Hz, 1H), 6.50 (d, J = 9.0 Hz, 1H), 4.54 (d, J = 10.8 Hz, 1H), 4.42 – 4.36 (m,1H), 4.14 (q, J = 7.1 Hz, 2H), 3.10 (s, 3H), 2.17 (s, 3H), 1.20 (t, J = 7.1Hz, 3H).

[0138] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.6, 144.9, 141.5, 136.9,133.9, 132.0, 130.9, 129.7, 128.7, 128.6, 128.4, 128.0, 127.7, 126.0, 124.7,109.2, 67.3, 61.3, 59.4, 52.3, 26.6, 21.1, 14.3.

[0139] HRMS (ESI) m / z: [M + Na] + calcd for C 29 H 26 ClNO3Na + , 494.1493; found, 494.1499

[0140] Example 11:

[0141] Chemical name:

[0142] ethyl(5R)-5'-chloro-5-(4-methoxyphenyl)-1'-methyl-2'-oxo-2-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0143] Molecular formula: C 29 H 26 ClNO4; Appearance: White solid; Yield: 45%

[0144] Characterization data:

[0145] 1 H NMR (500 MHz, CDCl3) δ 7.16 (d, J = 7.2 Hz, 3H), 7.10 (d, J = 7.3Hz, 2H), 6.96 (d, J = 7.8 Hz, 2H), 6.91 (d, J = 7.3 Hz, 2H), 6.60 (d, J = 2.4Hz, 3H), 6.51 (d, J = 7.5 Hz, 1H), 4.51 (d, J = 10.8 Hz, 1H), 4.34 (d, J =9.0 Hz, 1H), 4.14 (q, J = 7.0 Hz, 2H), 3.68 (s, 3H), 3.09 (s, 3H), 1.20 (t, J= 7.1 Hz, 3H).

[0146] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.7, 158.8, 144.8, 141.4,133.9, 130.8, 129.6, 129.2, 128.7, 128.6, 128.4, 127.7, 127.1, 126.0, 124.6,113.2, 109.2, 67.3, 61.3, 59.2, 55.2, 52.5, 26.6, 14.3.

[0147] HRMS (ESI) m / z: [M + Na] + calcd for C 29 H26 ClNO4Na + , 510.1443; found,510.1444

[0148] Example 12:

[0149] Chemical name:

[0150] ethyl(5R)-5'-chloro-1'-methyl-2'-oxo-2-phenyl-5-(4-(trifluoromethyl)phenyl)spiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0151] Molecular formula: C 29 H 23 ClF3NO3; Appearance: White solid; Yield: 41%

[0152] Characterization data:

[0153] 1 H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 7.18 (t, J = 7.6Hz, 3H), 7.12 (d, J = 9.8 Hz, 4H), 6.96 (d, J = 6.3 Hz, 2H), 6.62 (d, J = 2.1Hz, 1H), 6.52 (d, J = 8.9 Hz, 1H), 4.61 (d, J = 10.8 Hz, 1H), 4.43 (dd, J =10.7, 2.1 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H), 3.11 (s, 3H), 1.20 (t, J = 7.2Hz, 3H).

[0154] 13 C{ 1H} NMR (126 MHz, CDCl3) δ 176.8, 171.2, 144.8, 141.3, 139.5,133.6, 130.1, 129.7 (d, J = 32.2 Hz), 129.2, 129.1, 128.8, 128.60, 128.57,128.0, 126.0, 125.1, 124.9, 124.8 (q, J = 3.6 Hz), 124.6, 124.1 (q, J = 272.0Hz), 109.5, 67.2, 61.5, 59.0, 52.1, 26.7, 14.2.

[0155] 19 F NMR (471 MHz, CDCl3) δ -62.60.

[0156] HRMS (ESI) m / z: [M +H] + calcd for C 29 H 24 ClF3NO3 + , 526.1391; found, 526.1401

[0157] Example 13:

[0158] Chemical name:

[0159] ethyl(5R)-5-([1,1'-biphenyl]-4-yl)-5'-chloro-1'-methyl-2'-oxo-2-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0160] Molecular formula: C 34 H 28 ClNO3; Appearance: White solid; Yield: 38%

[0161] Characterization data:

[0162] 1H NMR (500 MHz, CDCl3) δ 7.48 (d, J = 7.9 Hz, 2H), 7.38 (t, J = 7.7Hz, 2H), 7.31 (d, J = 8.2 Hz, 3H), 7.17 (d, J = 7.5 Hz, 3H), 7.13 (d, J = 2.1Hz, 1H), 7.10 – 7.05 (m, 3H), 6.98 (d, J = 5.8 Hz, 2H), 6.64 (d, J = 2.1 Hz, 1H), 6.49 (d, J = 8.2 Hz, 1H), 4.61 (d, J = 10.8 Hz, 1H), 4.45 (d, J = 10.7Hz, 1H), 4.17 (q, J = 7.1 Hz, 2H), 3.11 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H).

[0163] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.2, 171.6, 144.8, 141.5, 140.5,140.0, 134.3, 133.9, 130.7, 129.6, 128.8, 128.73, 128.71, 128.6, 128.4,127.8, 127.4, 127.0, 126.4, 126.0, 124.7, 109.3, 67.4, 61.4, 59.4, 52.3,26.6, 14.3.

[0164] 19 F NMR (471 MHz, CDCl3) δ -104.31.

[0165] HRMS (ESI) m / z: [M +H] + calcd for C 34 H 29 ClNO3 + , 534.1830; found, 534.1835

[0166] Example 14:

[0167] Chemical name:

[0168] ethyl (5R)-5'-chloro-1'-methyl-2'-oxo-2-phenyl-5-(o-tolyl)spiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0169] Molecular formula: C 29 H 26 ClNO3; Appearance: white solid; Yield: 56%

[0170] Characterization data:

[0171] 1 H NMR (500 MHz, CDCl3) δ 7.17 – 7.09 (m, 4H), 7.01 – 6.92 (m, 6H), 6.90 – 6.86 (m, 1H), 6.67 (d, J = 2.3 Hz, 1H), 6.53 (d, J = 8.2 Hz, 1H), 4.96(d, J = 9.3 Hz, 1H), 4.30 (d, J = 9.3 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 3.09(s, 3H), 2.25 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H).

[0172] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.8, 171.6, 144.1, 141.8, 137.8,134.4, 133.9, 131.0, 130.3, 128.7, 128.6, 128.32, 128.30, 127.6, 127.0,126.1, 125.8, 125.0, 109.0, 66.6, 61.3, 55.4, 53.4, 26.6, 19.8, 14.3. HRMS(ESI) m / z: [M +Na] + calcd for C 29 H 26 ClNO3Na + , 494.1493; found, 494.1499

[0173] Example 15:

[0174] Chemical name:

[0175] ethyl (5R)-5'-chloro-1'-methyl-2'-oxo-2-phenyl-5-(m-tolyl)spiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0176] Molecular formula: C 29 H 26 ClNO3; Appearance: white solid; Yield: 51%

[0177] Characterization data:

[0178] 1 H NMR (500 MHz, CDCl3) δ 7.16 (d, J = 7.2 Hz, 3H), 7.08 (dd, J = 6.2,2.5 Hz, 2H), 6.98 (d, J = 5.6 Hz, 2H), 6.92 (d, J = 7.6 Hz, 1H), 6.85 (d, J =7.6 Hz, 1H), 6.81 – 6.76 (m, 2H), 6.62 (d, J = 2.1 Hz, 1H), 6.48 (d, J = 8.9Hz, 1H), 4.54 (d, J = 10.7 Hz, 1H), 4.41 (dd, J = 10.7, 2.1 Hz, 1H), 4.16 (t,J = 7.2 Hz, 2H), 3.10 (s, 3H), 2.16 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H).

[0179] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.6, 144.6, 141.4, 137.3,135.0, 133.9, 130.9, 129.7, 129.0, 128.7, 128.5, 128.4, 128.1, 127.7, 127.6,126.0, 125.2, 124.8, 109.1, 67.4, 61.3, 59.6, 52.2, 26.6, 21.3, 14.3. HRMS(ESI) m / z: [M +H] + calcd for C 29 H 27 ClNO3 +, 472.1674; found, 472.1681

[0180] Example 16:

[0181] Chemical name:

[0182] ethyl(5R)-5'-chloro-1'-methyl-5-(naphthalen-1-yl)-2'-oxo-2-phenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0183] Molecular formula: C 32 H 26 ClNO3; Appearance: White solid; Yield: 40%

[0184] Characterization data:

[0185] 1 H NMR (500 MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 1H), 7.69 (d, J = 9.6Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.50 – 7.46 (m, 1H), 7.38 (t, J = 7.5 Hz,1H), 7.24 (s, 1H), 7.21 – 7.13 (m, 4H), 7.05 (d, J = 2.1 Hz, 1H), 7.01 – 6.93(m, 3H), 6.73 (s, 1H), 6.23 (d, J = 8.2 Hz, 1H), 5.56 (d, J = 9.9 Hz, 1H), 4.60 (d, J = 12.2 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 2.71 (s, 3H), 1.13 (t, J= 7.1 Hz, 3H).

[0186] 13 C{ 1H} NMR (126 MHz, CDCl3) δ 177.5, 171.6, 143.7, 141.4, 134.0,133.5, 132.5, 131.9, 131.2, 130.2, 128.7, 128.5, 128.34, 128.33, 127.9,127.5, 126.19, 126.16, 126.1, 125.5, 125.3, 124.3, 123.6, 108.9, 67.0, 61.4,54.6, 52.8, 26.3, 14.2.

[0187] HRMS (ESI) m / z: [M +H] + calcd for C 32 H 27 ClNO3 + , 508.1674; found, 508.1681

[0188] Example 17:

[0189] Chemical name:

[0190] ethyl 1'-ethyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0191] Molecular formula: C 29 H 27 NO3; Appearance: White solid; Yield: 58%

[0192] Characterization data:

[0193] 1H NMR (500 MHz, CDCl3) δ 7.16 – 7.09 (m, 5H), 7.01 (s, 5H), 6.98 (dd,J = 7.8, 1.8 Hz, 2H), 6.92 (t, J = 7.5 Hz, 1H), 6.61 – 6.56 (m, 2H), 4.58 (d,J = 10.8 Hz, 1H), 4.43 (dd, J = 10.8, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.73 (dt, J = 14.5, 7.2 Hz, 1H), 3.62 (dq, J = 14.2, 7.2 Hz, 1H), 1.19 (t, J= 7.1 Hz, 3H), 1.07 (t, J = 7.2 Hz, 3H).

[0194] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.1, 171.9, 145.6, 142.0, 135.5,134.3, 129.2, 129.0, 128.6, 128.53, 128.46, 128.2, 127.6, 127.2, 126.1,124.7, 122.1, 108.4, 67.0, 61.2, 59.4, 52.5, 34.8, 14.3, 12.4.

[0195] HRMS (ESI) m / z: [M +H] + calcd for C 29 H 28 NO3 + , 438.2064; found, 438.2068

[0196] Example 18:

[0197] Chemical name:

[0198] ethyl 1'-butyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0199] Molecular formula: C 31 H 31 NO3; Appearance: White solid; Yield: 55%

[0200] Characterization data:

[0201] 1 H NMR (500 MHz, CDCl3) δ 7.13 (td, J = 12.4, 8.0 Hz, 5H), 7.01 (s,5H), 6.97 (d, J = 7.8 Hz, 2H), 6.92 (t, J = 7.4 Hz, 1H), 6.63 – 6.54 (m, 2H), 4.57 (d, J = 10.8 Hz, 1H), 4.42 (dd, J = 10.8, 2.1 Hz, 1H), 4.14 (q, J = 7.1Hz, 2H), 3.67 – 3.53 (m, 2H), 1.51 – 1.38 (m, 2H), 1.19 (t, J = 7.2 Hz, 5H),0.88 (t, J = 7.3 Hz, 3H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.9, 145.7,142.6, 135.6, 134.3, 129.1, 129.0, 128.6, 128.5, 128.2, 127.6, 127.2, 126.2,124.7, 122.0, 108.5, 67.1, 61.2, 59.4, 52.7, 40.1, 29.5, 20.4, 14.3, 13.9.

[0202] HRMS (ESI) m / z: [M +H] + calcd for C 31 H 32 NO3 + , 466.2377; found, 466.2380

[0203] Example 19:

[0204] Chemical name:

[0205] ethyl 1'-benzyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0206] Molecular formula: C 34 H 29NO3; Appearance: White solid; Yield: 42%

[0207] Characterization data:

[0208] 1 H NMR (500 MHz, CDCl3) δ 7.24 – 7.15 (m, 5H), 7.11 (t, J = 7.5 Hz,2H), 7.09 – 7.00 (m, 6H), 6.97 (d, J = 7.0 Hz, 4H), 6.92 (t, J = 7.0 Hz, 1H), 6.58 (s, 1H), 6.46 (d, J = 7.6 Hz, 1H), 4.87 (d, J = 15.7 Hz, 1H), 4.77 (d, J= 15.7 Hz, 1H), 4.63 (d, J = 10.7 Hz, 1H), 4.44 (d, J = 13.0 Hz, 1H), 4.15(q, J = 7.1 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H).

[0209] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.6, 171.9, 145.9, 142.2, 135.6,135.6, 134.3, 129.2, 128.9, 128.7, 128.7, 128.6, 128.2, 127.9, 127.55,127.49, 127.3, 126.4, 124.7, 122.4, 109.5, 67.3, 61.2, 59.6, 53.0, 44.1,14.3.

[0210] HRMS (ESI) m / z: [M + Na] + calcd for C 34 H 29 NO3Na + , 522.2040; found,522.2041

[0211] Example 20:

[0212] Chemical name:

[0213] ethyl 1'-allyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0214] Molecular formula: C 30 H 27 NO3; Appearance: White solid; Yield: 45%

[0215] Characterization data:

[0216] 1 H NMR (500 MHz, CDCl3) δ 7.19 – 7.09 (m, 5H), 7.02 (s, 5H), 7.00 –6.92 (m, 3H), 6.61 – 6.56 (m, 2H), 5.63 – 5.56 (m, 1H), 5.05 (d, J = 13.3 Hz, 1H), 4.85 (d, J = 17.1 Hz, 1H), 4.59 (d, J = 10.8 Hz, 1H), 4.44 (d, J = 2.1Hz, 1H), 4.36 – 4.31 (m, 1H), 4.21 – 4.12 (m, 3H), 1.19 (t, J = 7.1 Hz, 3H).

[0217] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.3, 171.9, 145.7, 142.2, 135.5,134.3, 131.2, 129.2, 128.9, 128.63, 128.61, 128.57, 128.2, 127.7, 127.3,126.3, 124.6, 122.3, 117.7, 109.3, 67.2, 61.2, 59.6, 52.8, 42.6, 14.3. HRMS(ESI) m / z: [M +H] + calcd for C 30 H 28 NO3 + , 450.2064; found, 450.2066

[0218] Example 21:

[0219] Chemical name:

[0220] ethyl 1'-cyclopropyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0221] Molecular formula: C 31 H 29 NO3; Appearance: White solid; Yield: 44%

[0222] Characterization data:

[0223] 1 H NMR (500 MHz, CDCl3) δ 7.12 (dt, J = 13.1, 6.6 Hz, 5H), 7.02 (d, J= 6.7 Hz, 7H), 6.91 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 7.6 Hz, 1H), 6.59 (d, J= 2.1 Hz, 1H), 4.58 (d, J = 10.7 Hz, 1H), 4.44 (dd, J = 10.8, 2.1 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.57 – 3.46 (m, 2H), 1.19 (t, J = 7.1 Hz, 3H), 1.02(dt, J = 12.2, 5.0 Hz, 1H), 0.48 – 0.26 (m, 4H).

[0224] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.6, 172.0, 145.6, 142.6, 135.6,134.2, 129.0, 128.9, 128.6, 128.5, 128.4, 128.1, 127.6, 127.1, 126.2, 124.7,122.1, 108.6, 67.0, 61.2, 59.3, 52.6, 44.5, 14.3, 9.6, 4.2, 3.8. HRMS (ESI)m / z: [M +H] + calcd for C 31 H 30 NO3 + , 464.2220; found, 464.2225

[0225] Example 22:

[0226] Chemical name:

[0227] ethyl-2'-oxo-2,5-diphenyl-1'-tosylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0228] Molecular formula: C 34 H 29 NO5S; Appearance: White solid; Yield: 61%

[0229] Characterization data:

[0230] 1 H NMR (500 MHz, CDCl3) δ 7.90 (d, J = 8.3 Hz, 2H), 7.71 (d, J = 8.2Hz, 1H), 7.28 (d, J = 8.1 Hz, 2H), 7.19 – 7.14 (m, 1H), 7.07 (dt, J = 7.3,4.3 Hz, 2H), 7.01 (td, J = 7.5, 2.0 Hz, 2H), 6.95 – 6.89 (m, 4H), 6.81 (d, J= 7.5 Hz, 2H), 6.73 (d, J = 7.7 Hz, 2H), 6.55 (d, J = 2.1 Hz, 1H), 4.51 (d, J= 10.5 Hz, 1H), 4.37 (dd, J = 10.5, 2.1 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 2.45 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H).

[0231] 13 C NMR (126 MHz, CDCl3) δ 176.4, 171.4, 145.6, 144.8, 138.4, 135.2,134.7, 133.3, 129.8, 129.5, 129.4, 128.5, 128.2, 128.11, 128.07, 128.0,127.9, 127.4, 125.9, 124.8, 124.5, 113.6, 67.2, 61.4, 60.1, 52.5, 21.8, 14.2.

[0232] HRMS (ESI) m / z: [M +H]+ calcd for C 34 H 30 NO5S + , 564.1839; found, 564.1846

[0233] Example 23:

[0234] Chemical name:

[0235] 4-benzoyl-5'-chloro-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0236] Molecular formula: C 32 H 24 ClNO2; Appearance: White solid; Yield: 66%

[0237] Characterization data:

[0238] 1 H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.8 Hz, 2H), 7.61 (t, J = 6.7Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.24 (s, 1H), 7.18 – 7.09 (m, 4H), 7.01(s, 5H), 6.93 (d, J = 7.9 Hz, 2H), 6.61 (s, 1H), 6.51 (d, J = 8.4 Hz, 1H), 5.28 (d, J = 10.1 Hz, 1H), 4.96 (d, J = 10.3 Hz, 1H), 3.11 (s, 3H).

[0239] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 196.5, 177.4, 145.2, 141.7, 136.4,135.4, 133.9, 133.6, 131.2, 130.0, 129.0, 128.8, 128.72, 128.66, 128.5,128.3, 127.9, 127.7, 127.4, 126.1, 124.8, 109.2, 67.2, 58.4, 55.6, 26.6. HRMS(ESI) m / z: [M +H]+ calcd for C 32 H 25 ClNO2 + , 490.1568; found, 490.1573

[0240] Example 24:

[0241] Chemical name:

[0242] 5'-chloro-1'-methyl-4-(4-methylbenzoyl)-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0243] Molecular formula: C 33 H 26 ClNO2; Appearance: White solid; Yield: 69%

[0244] Characterization data:

[0245] 1 H NMR (500 MHz, CDCl3) δ 8.00 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.1Hz, 2H), 7.25 (s, 1H), 7.18 – 7.10 (m, 4H), 7.01 (s, 5H), 6.92 (d, J = 6.6Hz, 2H), 6.61 (s, 1H), 6.51 (d, J = 8.4 Hz, 1H), 5.26 (d, J = 12.4 Hz, 1H), 4.97 (d, J = 10.2 Hz, 1H), 3.11 (s, 3H), 2.43 (s, 3H).

[0246] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 196.0, 177.4, 145.0, 144.5, 141.7,135.5, 133.94, 133.92, 131.2, 130.3, 129.6, 129.0, 128.7, 128.6, 128.4,128.3, 127.9, 127.6, 127.3, 126.0, 124.8, 109.2, 67.1, 58.4, 55.4, 26.6,21.8.

[0247] HRMS (ESI) m / z: [M + Na] + calcd for C 33 H 26 ClNO2Na + , 526.1544; found, 526.1550

[0248] Example 25:

[0249] Chemical name:

[0250] 5'-chloro-4-(4-fluorobenzoyl)-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0251] Molecular formula: C 32 H 23 ClFNO2; Appearance: White solid; Yield: 54%

[0252] Characterization data:

[0253] 1 H NMR (500 MHz, CDCl3) δ 8.15 – 8.08 (m, 2H), 7.24 (s, 1H), 7.15 (dt,J = 17.9, 9.2 Hz, 6H), 7.02 (s, 5H), 6.94 (d, J = 7.6 Hz, 2H), 6.61 – 6.48(m, 2H), 5.23 (dd, J = 10.2, 2.0 Hz, 1H), 4.92 (d, J = 10.1 Hz, 1H), 3.10 (s,3H).

[0254] 13 C{ 1H} NMR (126 MHz, CDCl3) δ 195.2, 177.3, 166.0 (d, J = 255.6 Hz), 145.4, 141.7, 135.3, 133.8, 132.8 (d, J = 2.9 Hz), 131.5 (d, J = 9.4 Hz),131.0, 129.7, 128.73, 128.70, 128.5, 128.3, 127.9, 127.7, 127.5, 126.09,126.05, 124.8, 116.1 (d, J = 21.8 Hz), 109.2, 67.2, 58.6, 55.6, 26.6.

[0255] 19 F NMR (471 MHz, CDCl3) δ -104.31.

[0256] HRMS (ESI) m / z: [M +H] + calcd for C 32 H 24 ClFNO2 + , 508.1474; found, 508.1480

[0257] Example 26:

[0258] Chemical name:

[0259] 5'-chloro-4-(4-chlorobenzoyl)-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0260] Molecular formula: C 32 H 23 Cl₂NO₂; Appearance: White solid; Yield: 59%

[0261] Characterization data:

[0262] 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.5Hz, 2H), 7.22 (d, J = 2.3 Hz, 1H), 7.18 – 7.11 (m, 4H), 7.02 (d, J = 9.3 Hz,5H), 6.93 (d, J = 7.8 Hz, 2H), 6.58 (d, J = 2.1 Hz, 1H), 6.52 (d, J = 8.2 Hz,1H), 5.21 (dd, J = 10.1, 2.1 Hz, 1H), 4.90 (d, J = 10.1 Hz, 1H), 3.11 (s,3H).

[0263] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 195.6, 177.3, 145.4, 141.7, 140.1,135.2, 134.7, 133.8, 131.0, 130.3, 129.5, 129.3, 128.8, 128.7, 128.6, 128.3,128.0, 127.7, 127.5, 126.1, 124.8, 109.3, 67.2, 58.6, 55.7, 26.6. HRMS (ESI)m / z: [M +H] + calcd for C 32 H 24 Cl2NO2 + , 524.1179; found, 524.1183

[0264] Example 27:

[0265] Chemical name:

[0266] 5'-chloro-4-(4-methoxybenzoyl)-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0267] Molecular formula: C 33 H 26 ClNO3; Appearance: White solid; Yield: 47%

[0268] Characterization data:

[0269] 1 H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 9.0 Hz, 2H), 7.26 – 7.24 (m,1H), 7.18 – 7.09 (m, 4H), 6.99 (d, J = 19.2 Hz, 7H), 6.93 (d, J = 6.6 Hz,2H), 6.61 (d, J = 2.0 Hz, 1H), 6.51 (d, J = 8.2 Hz, 1H), 5.24 (d, J = 12.4Hz, 1H), 4.96 (d, J = 10.2 Hz, 1H), 3.88 (s, 3H), 3.10 (s, 3H).

[0270] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 195.0, 177.4, 163.9, 144.9, 141.7,135.5, 134.0, 131.2, 131.2, 130.4, 129.4, 128.7, 128.6, 128.4, 128.3, 127.8,127.6, 127.3, 126.0, 124.7, 114.1, 109.2, 67.1, 58.6, 55.7, 55.2, 26.6.

[0271] HRMS (ESI) m / z: [M +H] + calcd for C 33 H 27 ClNO3 + , 520.1674; found, 520.1677

[0272] Example 28:

[0273] Chemical name:

[0274] 4-([1,1'-biphenyl]-4-carbonyl)-5'-chloro-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0275] Molecular formula: C 38 H 28 ClNO2; Appearance: White solid; Yield: 43%

[0276] Characterization data:

[0277] 1 H NMR (500 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4Hz, 2H), 7.64 (d, J = 7.9 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.42 (t, J = 7.3Hz, 1H), 7.27 (s, 1H), 7.15 (q, J = 8.6 Hz, 4H), 7.03 (s, 5H), 6.95 (d, J =7.9 Hz, 2H), 6.66 (d, J = 2.0 Hz, 1H), 6.53 (d, J = 8.2 Hz, 1H), 5.31 (d, J =12.5 Hz, 1H), 4.99 (d, J = 10.2 Hz, 1H), 3.12 (s, 3H).

[0278] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 196.1, 177.4, 146.3, 145.2, 141.7,139.9, 135.4, 135.1, 133.9, 131.2, 130.0, 129.5, 129.2, 128.74, 128.67,128.50, 128.47, 128.3, 127.9, 127.7, 127.6, 127.5, 127.4, 126.1, 124.8,109.2, 67.2, 58.5, 55.6, 26.6.

[0279] HRMS (ESI) m / z: [M + Na] + calcd for C 38 H 28 ClNO2Na + , 588.1701; found, 588.1707

[0280] Example 29:

[0281] Chemical name:

[0282] 4-(3-bromobenzoyl)-5'-chloro-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0283] Molecular formula: C 32 H 23 BrClNO2; Appearance: White solid; Yield: 44%

[0284] Characterization data:

[0285] 1 H NMR (500 MHz, CDCl3) δ 8.16 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.72(d, J = 7.9 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 2.1 Hz, 1H), 7.18– 7.11 (m, 4H), 7.06 – 6.98 (m, 5H), 6.93 (d, J = 6.7 Hz, 2H), 6.52 (d, J =8.4 Hz, 2H), 5.20 (d, J = 12.4 Hz, 1H), 4.90 (d, J = 10.2 Hz, 1H), 3.11 (s, 3H).

[0286] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 195.5, 177.3, 145.5, 141.7, 138.1,136.4, 135.2, 133.7, 131.8, 131.0, 130.5, 129.3, 128.8, 128.6, 128.3, 128.0,127.7, 127.5, 127.3, 126.1, 124.8, 123.3, 109.3, 67.2, 58.5, 55.8, 26.6.

[0287] HRMS (ESI) m / z: [M + Na] + calcd for C 32 H 23 BrClNO2Na + , 590.0493; found, 590.0499

[0288] Example 30:

[0289] Chemical name:

[0290] 5'-chloro-1'-methyl-2,5-diphenyl-4-pivaloylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0291] Molecular formula: C 30 H 28 ClNO2; Appearance: White solid; Yield: 38%

[0292] Characterization data:

[0293] 1 H NMR (500 MHz, CDCl3) δ 7.19 (s, 1H), 7.12 (dd, J = 15.3, 6.8 Hz, 4H), 7.02 (s, 3H), 6.93 (d, J = 6.0 Hz, 4H), 6.48 (d, J = 8.4 Hz, 1H), 6.39 (s, 1H), 4.89 – 4.74 (m, 2H), 3.05 (s, 3H), 1.15 (s, 9H).

[0294] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 212.6, 177.2, 145.4, 141.6, 134.9,133.9, 131.2, 130.4, 128.7, 128.6, 128.3, 127.7, 127.5, 127.4, 126.0, 124.7,109.1, 67.0, 60.0, 53.5, 44.8, 26.5, 26.2.

[0295] HRMS (ESI) m / z: [M +H] + calcd for C 30 H 29 ClNO2 + , 470.1881; found,470.1888

[0296] Example 31:

[0297] Chemical name:

[0298] 5'-chloro-4-(cyclopropanecarbonyl)-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0299] Molecular formula: C 29 H 24 ClNO2; Appearance: white solid; Yield: 51%

[0300] Characterization data:

[0301] 1 H NMR (500 MHz, CDCl3) δ 7.20 – 7.12 (m, 4H), 7.10 – 7.01 (m, 6H), 6.99 (d, J = 6.1 Hz, 2H), 6.71 (s, 1H), 6.48 (d, J = 8.2 Hz, 1H), 4.57 (d, J= 1.8 Hz, 2H), 3.10 (s, 3H), 2.12 – 2.01 (m, 1H), 1.07 – 0.99 (m, 2H), 0.91 –0.79 (m, 2H).

[0302] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 208.5, 177.4, 145.0, 141.4, 135.2,134.0, 130.9, 129.8, 128.7, 128.6, 128.4, 128.3, 128.0, 127.8, 127.5, 126.0,124.9, 109.1, 67.7, 60.4, 59.6, 26.6, 19.2, 11.8, 11.7.

[0303] HRMS (ESI) m / z: [M +H] + calcd for C 29 H 25 ClNO2 + , 454.1568; found, 454.1574

[0304] Example 32:

[0305] Chemical name:

[0306] 4-((3r,5r,7r)-adamantane-1-carbonyl)-5'-chloro-1'-methyl-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-en-2'-one;

[0307] Molecular formula: C 36 H 34 ClNO2; Appearance: white solid; Yield: 41%

[0308] Characterization data:

[0309] 1 H NMR (500 MHz, CDCl3) δ 7.20 (s, 1H), 7.17 – 7.08 (m, 4H), 7.04 –6.98 (m, 3H), 6.97 – 6.88 (m, 4H), 6.47 (d, J = 8.2 Hz, 1H), 6.38 (s, 1H), 4.89 (d, J = 10.2 Hz, 1H), 4.80 (d, J = 10.4 Hz, 1H), 3.06 (s, 3H), 2.06 (s,3H), 1.87 (d, J = 12.4 Hz, 3H), 1.79 – 1.66 (m, 9H).

[0310] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 211.8, 177.3, 145.2, 141.6, 135.1,133.9, 131.3, 130.3, 128.6, 128.54, 128.50, 128.3, 127.7, 127.5, 127.3,126.0, 124.6, 109.1, 66.9, 59.4, 52.6, 47.0, 37.9, 36.5, 27.9, 26.5. HRMS(ESI) m / z: [M +H] + calcd for C 36 H 35 ClNO2 + , 548.2351; found, 548.2356

[0311] Example 33:

[0312] Chemical name:

[0313] phenyl 5'-chloro-1'-methyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0314] Molecular formula: C 32 H 24 ClNO3; Appearance: White solid; Yield: 60%

[0315] Characterization data:

[0316] 1 H NMR (500 MHz, CDCl3) δ 7.35 – 7.31 (m, 2H), 7.19 (d, J = 7.3 Hz,4H), 7.12 – 7.04 (m, 7H), 7.01 (d, J = 8.5 Hz, 4H), 6.77 (s, 1H), 6.51 (d, J= 9.0 Hz, 1H), 4.68 (s, 2H), 3.12 (s, 3H).

[0317] 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 177.1, 170.2, 150.7, 145.4, 141.5,134.9, 133.8, 130.5, 129.5, 128.9, 128.8, 128.6, 128.2, 128.0, 127.9, 127.6,126.12, 126.06, 124.8, 121.5, 109.2, 67.4, 59.8, 52.3, 26.6.

[0318] HRMS (ESI) m / z: [M +H] + calcd for C 32 H 25 ClNO3 + , 506.1517; found, 506.1509

[0319] Example 34:

[0320] Chemical name:

[0321] ethyl-5'-chloro-1',4-dimethyl-2'-oxo-2,5-diphenylspiro[cyclopentane-1,3'-indolin]-2-ene-4-carboxylate;

[0322] Molecular formula: C 29 H 26 ClNO3; Appearance: White solid; Yield: 42%

[0323] Characterization data:

[0324] 1 H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 2.1 Hz, 1H), 7.22 (dd, J = 8.4, 2.1 Hz, 1H), 7.18 – 7.09 (m, 4H), 7.05 (dd, J = 8.3, 6.5 Hz, 2H), 6.98 – 6.90(m, 4H), 6.73 (s, 1H), 6.57 (d, J = 8.3 Hz, 1H), 4.64 (s, 1H), 4.17 (qd, J =7.1, 4.8 Hz, 2H), 2.99 (s, 3H), 1.61 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H).

[0325] 13 C NMR (101 MHz, CDCl3) δ 178.1, 174.9, 142.5, 141.8, 136.7, 134.8,133.8, 131.7, 131.0, 128.9, 128.7, 128.2, 127.7, 127.6, 127.5, 126.3, 125.9,109.4, 67.9, 62.1, 61.3, 58.2, 26.6, 23.4, 14.3.

[0326] HRMS (ESI) m / z: [M +H] + calcd for C 29 H 27 ClNO3 + , 472.1674; found, 472.1669

[0327] The spiro-oxidized indole compounds prepared in the above examples demonstrate that the preparation method of the present invention has good tolerance to functional groups, such as halogens, alkyl groups with different substitutions, aryl groups, etc., do not participate in the reaction and are retained in the prepared spiro-oxidized indole compounds. Moreover, the characterization data of the products prove that the method of the present invention successfully prepares spiro-oxidized indole compounds.

[0328] The preferred embodiments of the present invention have been described above, but are not intended to limit the invention. Those skilled in the art can make modifications and variations to the embodiments disclosed herein without departing from the scope and spirit of the invention.

Claims

1. A method for preparing spiro-oxidized indole compounds, characterized in that, The 1,7-enyne compounds used as raw materials are selected from: N-methyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyneamide, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methyl-3-phenylpropyneamide, N-(4-bromo-2-(1-phenylvinyl)phenyl)-N-methyl-3-phenylpropyneamide, N-(4-methoxy-2-(1-phenylvinyl)phenyl)-N-methyl-3-phenylpropyneamide, N-methyl-N-(5-methyl-2-(1-phenylvinyl)phenyl)-3-phenylpropyneamide, N-methyl-3-phenyl-N-(2-(1-(p-tolyl)vinyl)phenyl)propyneamide, N-(2-(1-(4-fluorophenyl)vinyl)phenyl)-N-methyl-3-phenylpropyneamide, N-(2-(1-(4-fluorophenyl)vinyl)phenyl)-N-methyl-3-phenylpropyneamide, N-(2-(1-(4-chlorophenyl)vinyl) (Phenyl)-N-methyl-3-phenylpropynamide, N-(2-(1-(4-bromophenyl)vinyl)phenyl)-N-methyl-3-phenylpropynamide, N-(4-chloro-2-(1-phenylvinyl) N-(4-chloro-2-(1-phenylvinyl)phenyl)-3-(4-methoxyphenyl)-N-methylpropynamide, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)propynamide, 3-([1,1'-biphenyl]-4-yl)-N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methylpropynamide, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methyl-3-(o-tolyl)propynamide, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methyl-3-(m-tolyl)propynamide Any one of the following: propyne amide, N-(4-chloro-2-(1-phenylvinyl)phenyl)-N-methyl-3-(naphth-1-yl)propyne amide, N-ethyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyne amide, N-butyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyne amide, N-benzyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyne amide, N-allyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyne amide, N-cyclopropyl-3-phenyl-N-(2-(1-phenylvinyl)phenyl)propyne amide, and 3-phenyl-N-(2-(1-phenylvinyl)phenyl)-N-p-toluenesulfonyl propyne amide; The α-bromocarbonyl compounds used as raw materials are selected from any one of the following: ethyl 2-bromoacetate, 2-bromo-1-phenylethane-1-one, 2-bromo-1-(p-tolyl)ethane-1-one, 2-bromo-1-(4-fluorophenyl)ethane-1-one, 2-bromo-1-(4-chlorophenyl)ethane-1-one, 2-bromo-1-(4-methoxyphenyl)ethane-1-one, 1-([1,1'-biphenyl]-4-yl)-2-bromoethane-1-one, 2-bromo-1-(3-bromophenyl)ethane-1-one, 1-bromo-3,3-dimethylbut-2-one, 2-bromo-1-cyclopropylethane-1-one, 1-((3r,5r,7r)-adamantane-1-yl)-2-bromoethane-1-one, phenyl 2-bromoacetate, and ethyl 2-bromopropionate. The 1,7-enyne compound and the α-bromocarbonyl compound were mixed in a molar ratio of 1:(1.5~3) in a solvent, namely dichloromethane. Simultaneously, photocatalysts fac-Ir(ppy)3 and Cs2CO3 were added. The mixture was reacted at 20℃-50℃ for 10-24 hours under 475nm wavelength light irradiation to obtain spiro-oxidized indole compounds. The reaction formula is as follows: ； In the reaction formula, R 1 R 2 R 3 R 4 and R 5 The definition is the same as that of the substituent at the corresponding site in the raw material.

2. The method according to claim 1, characterized in that, The method also includes a concentration step.

3. The method according to claim 2, characterized in that, The concentration step is performed by atmospheric distillation or vacuum distillation.

4. The method according to claim 1, characterized in that, The method also includes a purification step.

5. The method according to claim 4, characterized in that, The purification steps are column chromatography, vacuum distillation, and / or recrystallization to obtain a pure product.

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