A method for preparing 1,3-disubstituted allene compounds based on gold carbene catalytic system at room temperature

Abstract

The invention discloses a method for preparing 1,3-disubstituted allene compounds based on a gold carbene catalyst under room temperature conditions, that is, by reacting in an organic solvent under the action of a gold catalyst and a molecular sieve by terminal alkynes, aldehydes and amines, 1,3-disubstituted allene compounds are synthesized in the next step under room temperature conditions. The method of the invention is simple to operate, raw materials and reagents are easily available, reaction conditions are mild, substrate universality is wide, functional group compatibility is good, yield is high (36-93%), it can be enlarged (11g), and it is practical. The 1,3-disubstituted allene compounds obtained by the present invention can be used as important intermediates for constructing delta-caprolactone, trans-allyl alcohol, other allene-derived compounds, and natural product molecules, etc.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and specifically relates to a method for efficiently synthesizing 1,3-disubstituted allene compounds at room temperature. Background Art

[0002] Allenes are a class of organic compounds containing cumulative diene functional groups. (Ref: (a) DR Taylor, Chem. Rev. 1967, 67, 317-359; (b) N. Krause, ASK Hashmi, Modern Allene Chemistry, Wiley-VCH, Weinheim, 2004.) Due to the high reactivity and rich reaction sites of the cumulative diene functional groups, allenes have high chemical synthesis value. At the same time, allenes are widely distributed in a variety of natural products, active pharmaceutical molecules and material science, and are a very important class of compounds. Therefore, the efficient synthesis of allenes has always been a hot topic for synthetic chemists. The ATA (Allenation of Terminal Alkynes) reaction is a method for efficiently synthesizing allenes in one step from aldehydes or ketones, terminal alkynes, and amines. (Ref:(a)P.Crabbé,H.Fillion, D.André,J.-L.Luche,J.Chem.Soc.,Chem.Commun.1979,859-860; (b)J.Kuang,S.Ma,J.Org.Chem.2009,74,1763-1765;(c)J.Kuang,S.Ma,J.Am.Chem.Soc.2010, 132,1786-1787; (d) S. Kitagaki, M. Komizu, C. Mukai, Synlett 2011, 8, 1129-1132; (e)J.Kuang,H.Luo,S.Ma,Adv.Synth.Catal.2012,354,933-944; (f)X.Tang,C.Zhu,T.Cao,J.Kuang,W.Lin,S.Ni,J.Zhang,S.Ma,Nat.Commun.2013,4,2450; (g)X.Huang, T.Cao, Y.Han, account, see: (i) X. Huang, S. Ma, Acc. Chem. Res. 2019, 52, 1301-1312.) In 1979, Crabbe's group first reported this method, but because the reaction can only be applied to the synthesis of terminal allenes from polyformaldehyde and the yield is low, it has not received enough attention and development for a long time.In 2009, our research group optimized Crabbe's conditions, improved the yield of the reaction, and began to gradually expand the scope of application of the reaction to general aldehydes and ketones. However, there are still two difficulties in the ATA reaction that have not been solved: 1) The reaction consists of two steps, A. 3 The coupling reaction generates propargyl amine, which then undergoes 1,5-hydrogen migration and undergoes β-elimination to generate allene. The 1,5-hydrogen migration step requires overcoming a very high energy barrier and is usually carried out at a high temperature of more than 100 degrees. Such harsh conditions not only increase energy loss and safety hazards, but also often have low yields or no products for unstable allene synthesis. 2) The water and imine generated in situ in the reaction will reduce the catalytic performance of the metal species, resulting in the fact that in most cases, the metal catalysts used in the ATA reaction are not catalytic. Summary of the invention

[0003] In order to overcome the above problems existing in the prior art, the purpose of the present invention is to provide a method for synthesizing 1,3-disubstituted allene compounds in one step under room temperature conditions, that is, terminal alkynes (2), aldehydes (1) and amines (3) are reacted in an organic solvent under the action of a gold carbene catalyst and a molecular sieve to synthesize 1,3-disubstituted allene compounds in one step under room temperature conditions.

[0004] The present invention is achieved by adopting the following specific technical solutions:

[0005] The present invention provides a method for synthesizing 1,3-disubstituted allene compounds in one step under room temperature conditions, comprising: reacting terminal alkynes (2), aldehydes (1) and amines (3) containing different substituents in an organic solvent under the action of a gold carbene catalyst and a molecular sieve to generate 1,3-disubstituted allene compounds at room temperature, wherein the reaction process is shown in the following reaction formula (a):

[0006]

[0007] in,

[0008] R 1 It is a hydrocarbon group, a hydrocarbon group with a functional group, a phenyl group, an aryl group, and a heterocyclic group;

[0009] R 2 It is a hydrocarbon group, a hydrocarbon group with a functional group, a phenyl group, an aryl group, and a heterocyclic group;

[0010] R 1 , R 2 The functional group is selected from carbon-carbon double bonds, halogen atoms, hydroxyl groups, silyl ether groups, carbonyl groups, nitrile groups, ester groups and amide groups; the aromatic groups are phenyl and polyphenyl ring substituents having electron-donating or electron-withdrawing substituents at the ortho, meta or para positions; the heterocyclic groups are furyl, benzofuranyl, thienyl, pyridyl, indolyl and indazolyl.

[0011] Preferably,

[0012] R 1 C1-C10 hydrocarbon group, C1-C10 hydrocarbon group with functional group, phenyl group, aryl group and heterocyclic group;

[0013] R 2 C1-C10 hydrocarbon group, C1-C10 hydrocarbon group with functional group, phenyl group, aryl group and heterocyclic group;

[0014] R 1 , R 2 The functional group is selected from carbon-carbon double bonds, halogen atoms, hydroxyl groups, silyl ether groups, carbonyl groups, nitrile groups, ester groups and amide groups; the aromatic groups are phenyl and polyphenyl ring substituents having electron-donating or electron-withdrawing substituents at the ortho, meta and para positions, the electron-donating substituents include hydrocarbon groups, methoxy groups, benoxy groups and borate groups, the electron-withdrawing substituents include halogen groups, nitrile groups, ester groups, trifluoromethyl groups and nitro groups; the heterocyclic groups are furyl groups, benzofuranyl groups, thienyl groups, pyridyl groups, indolyl groups and indazolyl groups.

[0015] More preferably,

[0016] R 1 is a C1-C10 straight-chain alkyl group, a C3-C10 cycloalkyl group, a C1-C10 straight-chain alkyl group with a functional group, a C3-C10 cycloalkyl group with a functional group, a phenyl group, an aryl group, and a heterocyclic group;

[0017] R 2 is a C1-C10 straight-chain alkyl group, a C3-C10 cycloalkyl group, a C1-C10 straight-chain alkyl group with a functional group, a C3-C10 cycloalkyl group with a functional group, a phenyl group, an aryl group, and a heterocyclic group;

[0018] R 1 , R 2 The functional group is selected from carbon-carbon double bonds, halogen atoms, hydroxyl groups, silyl ether groups, carbonyl groups, nitrile groups, ester groups and amide groups; the aromatic groups are phenyl and polyphenyl ring substituents having electron-donating or electron-withdrawing substituents at the ortho, meta and para positions, the electron-donating substituents include hydrocarbon groups, methoxy groups, benoxy groups and borate groups, the electron-withdrawing substituents include halogen groups, nitrile groups, ester groups, trifluoromethyl groups and nitro groups; the heterocyclic groups are furyl groups, benzofuranyl groups, thienyl groups, pyridyl groups, indolyl groups and indazolyl groups.

[0019] More preferably,

[0020] R 1is selected from n-pentyl, isobutyl, cyclohexyl, n-octyl, phenyl, p-methoxyphenyl, p-benzyloxyphenyl, p-boronic acid pinacol ester phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-nitrile phenyl, p-ester phenyl, p-trifluoromethylphenyl, p-nitrophenyl, naphthyl, phenanthrenyl, pyrenyl, furanyl, benzofuranyl, thienyl, pyridyl, indolyl and indazolyl.

[0021] R 2 Selected from cyclopropyl, n-pentyl, n-hexyl, cyclohexyl, n-octyl, n-decyl, benzyl, buten-4-yl, 4-chlorobutyl, 2-bromoethyl, (dimethyl-tert-butylsilyloxy)pentyl, 5-hydroxypentyl, 4-cyanobutyl, 3-methoxypropyl, tert-butyloxycarbonyl-protected piperidinyl, (p-methoxybenzoyl)propyl and phenyl.

[0022] As a further improvement, the specific operating steps of the present invention are as follows:

[0023] Under argon atmosphere, molecular sieves, gold carbene catalyst and a certain volume of organic solvent are added to a dry reaction tube in sequence. Then, aldehyde (1), amine (3) and terminal alkyne (2) are added in sequence under stirring. The reaction is carried out at room temperature for 24-72 hours. After the reaction is completed, the reaction solution is filtered through a silica gel short column and washed with a certain volume of ether. After the mixed solution is concentrated, 1,3-disubstituted allene compounds are obtained by rapid column chromatography.

[0024] The certain volume of organic solvent refers to the amount of the terminal alkyne (2) shown in formula (a) as a reference, and the amount of the organic solvent is 0.5-5 mL / mmol; preferably, 1 mL / mmol.

[0025] The room temperature is 10-60°C; preferably, 10-40°C; more preferably, 25-35°C.

[0026] The certain volume of diethyl ether refers to the amount of the terminal alkyne (2) shown in formula (a) as a reference, and the amount of the diethyl ether is 10-100 mL / mol; preferably, 30 mL / mol.

[0027] As a further improvement, the amine (3) described in the present invention is morpholine (3a), piperidine (3b), pyrrolidine (3c), 1,2,3,4-tetrahydroquinoline (3d), 1,2,3,4-tetrahydroisoquinoline (3e), 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f), diethylamine (3g), diallylamine (3h), dicyclohexylamine (3i) and diisopropylamine (3j); preferably, it is 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f).

[0028] As a further improvement, the gold carbene catalyst of the present invention is selected from one or more of the following structures Au1-Au3. Wherein, R is a C1-C30 hydrocarbon group, a C1-C30 hydrocarbon group with a functional group, a phenyl group, an aryl group, and a heterocyclic group; the functional group is selected from a carbon-carbon double bond, a carbon-carbon triple bond, a halogen atom, a hydroxyl group, a carboxyl group, an amino group, a silyl ether group, a carbonyl group, a nitrile group, an ester group, and an amide group; the aryl group refers to a phenyl group and a polyphenyl ring substituent group with electron-donating or electron-withdrawing substituents at the ortho, meta, and para positions; the electron-donating substituents include hydrocarbon groups, alkoxy groups, and borate ester groups, and the electron-withdrawing substituents include halogens, nitrile groups, ester groups, trifluoromethyl groups, and nitro groups.

[0029] Wherein, X is a counter anion, including a halogen anion, a hydroxide anion, a bis(trifluoromethanesulfonyl)imide anion, a methanesulfonate anion, a trifluoromethanesulfonate anion, a p-toluenesulfonate anion, a perchlorate anion, a tetrafluoroborate anion, a hexafluorophosphate anion, and a hexafluoroantimonate anion.

[0030] Preferably, the gold carbene catalyst is Au3, and the counter anion is a bis(trifluoromethanesulfonyl)imide anion.

[0031]

[0032] As a further improvement, the gold carbene catalyst of the present invention is selected from one or more of Au3a, Au3b, Au3c, Au3d and Au3e; wherein the structures of Au3a, Au3b, Au3c, Au3d and Au3e are as follows:

[0033]

[0034] As a further improvement, the molecular screening method of the present invention is Molecular sieves, Molecular sieves and Molecular sieve; preferably, Molecular sieve.

[0035] As a further improvement, the organic solvent described in the present invention is selected from one or more of 2,2,2-trifluoroethanol, 2,2,3,3-tetrafluoropropanol, 2,2,3,3,3-pentafluoropropanol and 1,1,1,3,3,3-hexafluoroisopropanol; preferably, it is 2,2,2-trifluoroethanol.

[0036] As a further improvement, the molar ratio of the terminal alkyne (2), aldehyde (1), amine (3) and gold carbene catalyst is 1.0:(1.0-1.8):(1.0-1.4):(0.01-0.1); preferably, it is 1.0:1.8:1.4:0.05.

[0037] As a further improvement, the amount of the molecular sieve is 100-500 mg / mmol; preferably, 250 mg / mmol, based on the amount of the terminal alkyne (2).

[0038] As a further improvement, the amount of the organic solvent is 0.5-5 mL / mmol; preferably, 1 mL / mmol, based on the amount of the terminal alkyne (2).

[0039] Under the gold carbene catalytic conditions of the present invention, the following two technical difficulties in the synthesis of 1,3-disubstituted allene compounds are mainly overcome, and the reaction process is shown in the following formula (b):

[0040]

[0041]

[0042] 1) In the known method, A 3 The coupling reaction generates propargylamine compounds, and the 1.5-hydrogen migration step is the rate-determining step, which needs to overcome a high activation energy barrier, so the reaction temperature is usually between 70-200°C. This not only increases energy loss and safety hazards, but also often results in a very low yield or no product for the synthesis of unstable allenes.

[0043] 2) The water and imine generated in situ during the reaction will reduce the catalytic performance of the metal species, resulting in the fact that in most cases, the metal catalyst used in the ATA reaction is not a catalytic amount.

[0044] The present invention develops a gold carbene catalysis method, which can effectively overcome the above technical difficulties and successfully achieve the synthesis of 1,3-disubstituted allene compounds under room temperature conditions.

[0045] The present invention proposes the following possible mechanism for the reaction described in the present invention, as shown in formula (c):

[0046] (1) The terminal alkyne (2) reacts with a gold carbene catalyst (Au3d) in the presence of a base to generate an alkyne-containing gold intermediate I;

[0047] (2) Aldehyde (1) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f) are dehydrated in situ to generate imine intermediate II;

[0048] (3) The acetylenic gold intermediate I undergoes a 1,2-addition reaction with the imine intermediate II to generate gold carbene-coordinated propargylamine intermediates IIIA and IIIB;

[0049] (4) The gold carbene-coordinated propargylamine intermediate IIIA undergoes a 1,5-hydrogen migration of the hydrogen at the 3-position to obtain the ene gold intermediate IVA; the gold carbene-coordinated propargylamine intermediate IIIB undergoes a 1,5-hydrogen migration of the hydrogen at the 1-position to obtain the ene gold intermediate IVB;

[0050] (5) The ene-gold intermediates IVA and IVB undergo β-elimination reaction to finally generate allenes, and the active species gold carbene catalyst is regenerated at the same time.

[0051]

[0052]

[0053] The present invention also provides a class of 1,3-disubstituted allene compounds, the structure of which is shown in Formula 4

[0054]

[0055] R 1 , R 2 The definition of is the same as that of reaction formula (a).

[0056] The compound newly prepared in the synthesis process of the present invention is shown in Table 1 below:

[0057] Table 1

[0058]

[0059] The present invention also provides the use of 1,3-disubstituted allene compounds (4) in the preparation of δ-caprolactone, trans-allyl alcohol, other allene-derived compounds, and natural product molecules, as shown in Table 2:

[0060] Table 2

[0061]

[0062] Comparison table of the method of the present invention and the existing method:

[0063] Table 3

[0064]

[0065] The innovative features of the present invention include:

[0066] (1) The reaction of the present invention starts from the easily available terminal alkyne (2), aldehyde (1) and amine (3), based on the gold carbene catalytic system, and undergoes A 3 Coupling reaction, 1,5-hydrogen transfer reaction and β-elimination reaction were used to successfully synthesize 1,3-disubstituted allenes at room temperature.

[0067] (2) The present invention uses gold carbene (Au3d) as a metal catalyst, 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f) as an amine, and 2,2,2-trifluoroethanol as an organic solvent, successfully overcoming or breaking through the technical barriers and technical limitations existing in the original ATA reaction at high temperature, reducing the activation energy barrier of the 1,5-hydrogen migration rate-determining step in the ATA reaction, and allowing the reaction to proceed smoothly at room temperature.

[0068] (3) Due to the superior catalytic activity of gold carbene catalysts, this method can effectively overcome the reduction in the catalytic performance of metal catalysts caused by water and imine generated in situ during the reaction under gold carbene catalysis conditions, thus achieving the synthesis of 1,3-disubstituted allenes catalyzed by gold carbene at room temperature.

[0069] The beneficial effects of the present invention include: the present invention uses easily available terminal alkynes (2), aldehydes (1) and amines (3) as starting materials, and realizes the catalytic synthesis of 1,3-disubstituted allene compounds under room temperature conditions for the first time under the action of gold carbene catalysts, molecular sieves and organic solvents. The method of the present invention reduces the energy loss and safety hazards of allene synthesis, and is suitable for synthesizing unstable allenes. The method of the present invention is simple to operate, raw materials and reagents are readily available, reaction conditions are mild, substrates are widely universal, functional groups are compatible, and the method is highly practical. The 1,3-disubstituted allene compounds obtained by the present invention can be used as important intermediates for the construction of δ-caprolactone, trans-allyl alcohol, other allene-derived compounds, and natural product molecules. DETAILED DESCRIPTION

[0070] The present invention is further described in detail with reference to the following specific examples. The process, conditions, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are all common knowledge and common common sense in the art and are not particularly limited by the present invention.

[0071] Example 1

[0072]

[0073] Where mol means mole, equiv. means equivalent, MS molecular sieve, TFE represents 2,2,2-trifluoroethanol, Ar represents argon atmosphere, and yield represents yield.

[0074] Under the protection of argon atmosphere, add into a dry reaction tube Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol) and 2,2,2-trifluoroethanol (1 mL). Then, under stirring, aldehyde 1a (191.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were added in sequence. After reacting at room temperature for 24 hours, the reaction solution was filtered through a silica gel short column and the filter cake was washed with ether (30 mL). After concentration, it was purified by rapid column chromatography (eluent: petroleum ether) to obtain the allene product 4aa (168.7 mg, 84% yield): oily liquid; 1 H NMR (400MHz, CDCl3): δ=7.36-7.26(m,4H,Ar-H),7.22-7.14(m,1H,Ar-H),6.12(dt,J1=6.1Hz, J2=3.0Hz,1H,=CH),5.56(q,J=6.7Hz,1H,=CH),2.12(qd,J1=7.1Hz,J2=2.9 Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.18(m,6H,CH2x3),0.88(t,J=6.8 Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.1,135.1,128.5,126.55,126.52, 95.1,94.5,31.6,29.1,28.9,28.7,22.7,14.1;IR(neat):ν=2956,2924,2854,1949,1598,1495,1458cm -1 ; MS (FI) m / z (%): 200 (M + ); HRMS Calcd.for C 15 H 20 (M + ): 200.1560,found200.1564.

[0075] Example 2

[0076]

[0077] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1a (191.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2b (166.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ab (205.5 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.33-7.25 (m, 4H, Ar-H), 7.21-7.12 (m, 1H, Ar-H), 6.11 (dt, J1 = 6.1Hz, J2 = 3.1Hz, 1H, = CH), 5.56 (q, J = 6.5Hz, 1H, = CH), 2.12 (qd, J1=7.0Hz, J2=2.7Hz,2H,CH2),1.52-1.41(m,2H,CH2),1.40-1.12(m,14H,CH2x7),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.1,135.2, 128.5,126.56,126.55,95.1,94.5,31.9,29.64,29.60,29.4,29.3,29.20,29 .17,28.8,22.7,14.1;IR(neat):ν=2922,2852,1949,1598,1495,1460,1071cm -1 ;MS(70eV, EI)m / z(%):256(M + ,1.02),130(100).

[0078] Example 3

[0079]

[0080] The operation is the same as in Example 1. Molecular sieves (251.0 mg), Au3d (43.6 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2c (67.5 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ac (124.8 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.33-7.23 (m, 4H, Ar-H), 7.21-7.13 (m, 1H, Ar-H), 6.20(d,J=6.0Hz,1H,=CH),5.43(t,J=6.8Hz,1H,=CH),1.39-1.25(m,1H,CH),0.80-0.68(m,2H,CH2),0.51-0.37(m,2H,CH2); 13 C NMR (100MHz, CDCl3): δ=204.8,134.9,128.5,126.8,126.6,99.4,96.2,9.4,7.0,6.8; IR(neat):ν=3081,3004,1946,1597,1492,1458,1423,1251,1047,1020cm -1 ;MS(70eV,EI)m / z(%): 156(M + ,86.83),115(100).

[0081] Example 4

[0082]

[0083] The operation is the same as in Example 1. Molecular sieves (250.9 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2d (118.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ad (111.0 mg, 54% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.35-7.24 (m, 8H, Ar-H), 7.24-7.15 (m, 2H, Ar-H), 6.17 (dt, J1 = 5.5Hz, J2 = 2.8Hz, 1H, = CH), 5.72 (q, J = 7.1Hz, 1H, = CH), 3.47 (dd, J1=7.4Hz, J2=2.2Hz, 2H, CH2); 13C NMR (100MHz, CDCl3): δ=205.7,140.0, 134.6,128.5,128.4,126.8,126.7,126.3,94.9,94.4,35.5;IR(neat):ν=3028,1948,1599,1493,1454,1072,1028cm -1 ;MS(70eV,EI)m / z(%):206(M + ,100).

[0084] Example 5

[0085]

[0086] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2e (102.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ae (118.8 mg, 62% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ=7.43-7.26(m,8H,Ar-H), 7.26-7.16(m,2H,Ar-H), 6.59(s,2H,=CHx2); 13 C NMR (100MHz, CDCl3): δ = 207.7, 133.5, 128.7, 127.3, 127.0, 98.4; IR (neat): ν = 3027, 1935, 1596, 1491, 1449, 1254, 1071, 1027cm -1 ;MS (70eV, EI) m / z(%):192(M + ,100).

[0087] Example 6

[0088]

[0089] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.2 mg, 0.05 mmol), aldehyde 1b (223.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ba (185.6 mg, 85% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ=7.29-7.17(m,2H,Ar-H), 7.03-6.91(m,2H,Ar-H), 6.08(dt,J1=6.1Hz, J2=3.1Hz,1H,=CH), 5.56(q,J=6.7Hz,1H,=CH), 2.17(qd, J1=7.1Hz, J2=3.0Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.18(m,6H,CH2x3),0.88(t,J=6.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ = 204.9 (d, J= 2.5Hz), 161.7 (d, J = 244.5Hz), 131.1 (d, J = 3.2Hz), 127.9 (d, J = 8.1Hz), 115.4 (d, J = 21.4Hz), 95.3, 93.6, 31.6, 29.1, 28.9, 28.8, 22.7, 14.0; 19 F NMR (376MHz, CDCl3): δ = -116.5; IR (neat): ν = 2925, 2855, 1948, 1602, 1506, 1463, 1226, 1154 cm -1 ;MS(70eV,EI)m / z(%):218(M + ,2.01),148(100).

[0090] Example 7

[0091]

[0092] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1c (253.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2a (109.6 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ca (190.2 mg, 81% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.25 (d, J = 8.8Hz, 2H, Ar-H), 7.20 (d, J = 8.4Hz, 2H, Ar-H), 6.07 (dt, J1 = 6.4Hz, J2 = 3.1Hz, 1H, = CH), 5.57 (q, J = 6.7Hz, 1H, =CH),2.12(qd,J1=7.1Hz,J2=3.0Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.18(m,6H,CH2x3),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.2,133.7,132.1,128.6,127.7,95.4,93.7,31.6,29.0,28.8,28.6,22.6, 14.0; IR(neat):ν=2924,2854,1949,1490,1462,1090,1012cm -1 ;MS (70eV, EI) m / z (%): 234 (M + ( 35 Cl),1.40),236(M + ( 37 Cl),0.62),129(100).

[0093] Example 8

[0094]

[0095] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1d (333.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4da (215.8 mg, 77% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.40 (d, J = 8.4Hz, 2H, Ar-H), 7.14 (d, J = 8.0Hz, 2H, Ar-H), 6.11-6.01 (m, 1H, = CH), 5.56 (q, J = 6.7Hz, 1H, = CH), 2.12 (qd, J1 = 7.1Hz,J1=2.4Hz,2H,CH2),1.52-1.41(m,2H,CH2),1.41-1.18(m,6H,CH2x3), 0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.2,134.2,131.5,128.0,120.1,95.5,93.8,31.6,29.0,2 8.8,28.6,22.6,14.0;IR(neat):ν=2924,2853,1948,1486,1463,1382,1069,1009cm -1 ;MS(70eV,EI)m / z(%):278(M + ( 79 Br), 1.71),280(M + ( 81 Br),1.61),129(100).

[0096] Example 9

[0097]

[0098] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1e (417.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2a (110.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ea (228.3 mg, 70% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid;1 H NMR (400MHz, CDCl3): δ = 7.60 (d, J = 8.8Hz, 2H, Ar-H), 7.02 (d, J = 8.0Hz, 2H, Ar-H), 6.04 (dt, J1 = 6.1Hz, J2 = 3.0Hz, 1H, = CH), 5.56 (q, J = 6.8Hz, 1H, =CH),2.12(qd,J1=7.1Hz,J2=2.8Hz,2H,CH2),1.52-1.40(m,2H,CH2),1.40-1.18(m,6H,CH2x3),0.88(t,J=6.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.3,137.5,134.8,128.3,95.5,93.9,91.4,31.6,29.0,28.8,28.6,22.6, 14.1; IR(neat):ν=2923,2852,1948,1483,1462,1381,1058,1004cm -1 ;MS(70eV, EI)m / z(%):326(M + ,2.26),129(100);HRMS Calcd.for C 15 H 19 I(M + ):326.0526, found 326.0529.

[0099] Example 10

[0100]

[0101] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1f (245.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.4 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4fa (180.1 mg, 78% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.21 (d, J = 8.4Hz, 2H, Ar-H), 6.84 (d, J = 8.4Hz, 2 H, Ar-H), 6.08 (dt, J1 = 6.1Hz, J2 = 3.0Hz, 1H, = CH), 5.53 (q, J = 6.7Hz, 1H, =CH),3.80(s,3H,OCH3),2.11(qd,J1=7.1Hz,J2=3.1Hz,2H,CH2),1.52-1.41 (m,2H,CH2),1.41-1.18(m,6H,CH2x3),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=204.4,158.5,127.5,127.4,114.0,95.0,93.9,55.2,31.6,29.1, 28.9,28.8,22.6,14.0;IR(neat):ν=2925,2854,1947,1607,1510,1462,1300,1243,1170,1035cm -1 ;MS(70eV,EI)m / z(%):230(M + ,20.68),160(100).

[0102] Embodiment 11

[0103]

[0104] The operation is the same as in Example 1. Molecular sieves (250.3 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1g (237.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2a (112.6 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ga (175.2 mg, 78% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.59-7.53 (m, 2H, Ar-H), 7.38-7.33 (m, 2H, Ar-H), 6.13 (dt, J1 = 6.3Hz, J2 = 3.1Hz, 1H, = CH), 5.66 (q, J = 6.7Hz, 1H, = CH), 2.15 (qd, J1=7.1Hz, J2=3.0Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.20(m,6H,CH2x3),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=206.5,140.4, 132.2,126.9,119.1,109.6,96.0,93.9,31.5,28.9,28.8,28.3,22.5,14.0; IR(neat):ν=2925,2854,2225,1946,1604,1503,1462,1394,1173cm -1 ;MS(70eV,EI)m / z(%): 225(M + ,3.53),129(100);HRMS Calcd.for C 16 H 19 N(M + ):225.1512,found 225.1515.

[0105] Example 12

[0106]

[0107] The operation is the same as in Example 1. Molecular sieves (250.8 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1h (301.8 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (112.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ha (199.1 mg, 77% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 100 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.96 (d, J = 8.0Hz, 2H, Ar-H), 7.33 (d, J = 8.0Hz, 2H, Ar-H), 6.18-6.11 (m, 1H, = CH), 5.61 (q, J = 6.7Hz, 1H,=CH),3.90(s,3H,OCH3),2.14(qd,J1=7.1Hz,J2=2.7Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.20(m,6H,CH2x3),0.88(t,J=6.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=206.3,166.9,140.3,129.8,128.1,126.3,95.5,94.2, 51.9,31.6,29.0,28.8,28.5,22.6,14.0; IR(neat):ν=2925,2854,1947,1718,1606,1434,1272,1173,1105cm -1 ;MS(70eV,EI)m / z(%):258(M + ,1.27),129(100); HRMS Calcd.for C 17 H 22 O2(M + ):258.1614,found 258.1613.

[0108] Example 13

[0109]

[0110] The operation is the same as in Example 1. Molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1i (313.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.5 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ia (215.2 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.50 (d, J = 8.4Hz, 2H, Ar-H), 7.34 (d, J = 8.0Hz, 2 H, Ar-H), 6.12 (dt, J1 = 6.3Hz, J2 = 3.1Hz, 1H, = CH), 5.60 (q, J = 6.7Hz, 1H, =CH),2.13(qd,J1=7.1Hz,J2=3.0Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.40-1.21(m,6H,CH2x3),0.87(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=206.2, 139.2, 128.6 (q, J= 32.2Hz), 126.6, 125.4 (q, J= 3.8Hz), 124.4 (q, J=269.9Hz),95.7,93.8,31.7,29.1,28.9,28.5,22.7,14.0; 19 F NMR (376MHz, CDCl3) δ = -62.9; IR (neat): ν = 2927, 2856, 1950, 1615, 1439, 1322, 1163, 1121, 1064cm -1 ;MS(70eV,EI)m / z(%):268(M + ,1.13),129(100).

[0111] Embodiment 14

[0112]

[0113] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1j (272.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2f (209.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4jf (276.2 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 8.16 (d, J = 9.2Hz, 2H, Ar-H), 7.40 (d, J = 8.8Hz, 2H, Ar-H), 6.27 (dd, J1 = 6.6Hz, J2 = 3.0Hz, 1H, = CH), 5.71 (t, J = 6.0 Hz,1H,=CH),4.27-3.84(br,2H,CH2),2.82(t,J=12.2Hz,2H,CH2),2.42-2.28 (m,1H,CH),1.88-1.73(m,2H,CH2),1.45(s,9H,OC(CH3)3),1.43-1.29(m,2H,CH2); 13 C NMR (100MHz, CDCl3): δ=206.1,154.6,146.3,142.0,126.8,123.9, 100.2,95.1,79.4,43.4,35.4,31.7,28.3;IR(neat):ν=2976,2932,2852,1946,1680,1595,1515,1421,1338,1229,1164,1110cm -1 ;MS(ESI)m / z(%):367(M+Na + ); HRMS Calcd.for C 19 H 24 O4N2Na(M+Na + ):367.1628, found 367.1623.

[0114] Embodiment 15

[0115]

[0116] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1k (417.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (80.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to obtain 4 kg (249.2 mg, 84% yield) of allene product (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 200 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.73 (d, J = 8.0Hz, 2H, Ar-H), 7.28(d,J=8.0Hz,2H,Ar-H),6.23-6.06(m,1H,=CH),5.94-5.77(m,1H,=CH),5.67-5.50(m,1H,=CH),5.05(dd,J1=17.0Hz,J2=1.4Hz,1H,oneproton of =CH2),5.00(d,J=10.0Hz,1H,one proton of=CH2),2.32-2.15(m,4H,CH2x2), 1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ=205.7,137.9,137.8,135.0,125.9,115.2,95.1,94.4,83.6,3 3.1,28.0,24.81,24.79;IR(neat):ν=2977,2926,1947,1607,1356,1320,1142,1086cm -1 ;MS(FI)m / z(%):296(M + ( 11 B)); HRMS Calcd.forC 19 H 25 O2 10 B(M + ):295.1978,found 295.1977.

[0117] Example 16

[0118]

[0119] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (417.6 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2h (116.4 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4kh (243.2 mg, 73% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 80 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.74 (d, J = 7.6Hz, 2H, Ar-H), 7.27 (d, J = 8.0Hz, 2H, Ar-H), 6.15 (dt, J1 = 6.3Hz, J2 = 3.1Hz, 1H, = CH), 5.57 (q, J=6.7Hz,1H,=CH),3.53(t,J=6.6Hz,2H,CH2),2.17(qd,J1=6.9Hz,J2=2.8 Hz,2H,CH2),1.91-1.79(m,2H,CH2),1.70-1.56(m,2H,CH2),1.34(s,12H,CH3x4); 13 CNMR (100MHz, CDCl3): δ=205.7,137.7,135.0,125.8,95.1,94.3,83.6, 44.6,31.9,27.7,26.1,24.8,24.7;IR(neat):ν=2977,2935,1947,1607,1356,1319,1142,1086cm -1 ; MS (FI) m / z (%): 332 (M + ( 11 B, 35 Cl)); HRMS Calcd.for C 19 H 26 O2 10 B 35 Cl(M + ):331.1745,found331.1751.

[0120] Embodiment 17

[0121]

[0122] The operation is the same as in Example 1. Molecular sieves (250.5 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (418.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 2i (133.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ki (199.9 mg, 57% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 200 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.74 (d, J = 8.0Hz, 2H, Ar-H), 7.31 (d, J = 7.6Hz, 2H, Ar-H), 6.22 (dt, J1 = 6.1Hz, J2 = 3.0Hz, 1H, = CH), 5.62 (q, J=6.7Hz,1H,=CH),3.48(t,J=6.8Hz,2H,CH2),2.78-2.62(m,2H,CH2),1.34 (s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ=206.2,137.0,135.0,126.1,95.9, 92.5,83.6,32.0,31.6,24.81,24.78;IR(neat):ν=2977,1949,1607,1393,1356,1320,1269,1142,1085cm -1 ;MS(70eV,EI)m / z(%):347(M + ( 10 B, 79 Br),5.98),348 (M + ( 11 B, 79 Br),22.06),349(M + ( 10 B, 81 Br),9.26),350(M + ( 11 B, 81 Br),20.95),169 (100); HRMSCalcd.for C 17 H 22 O2 10 B 79 Br(M + ):347.0927,found 347.0931.

[0123] Embodiment 18

[0124]

[0125] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (417.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2j (226.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give allene product 4kj (355.3 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether (200 mL); petroleum ether / ethyl acetate = 80 / 1 (405 mL))): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.73 (d, J = 8.0Hz, 2H, Ar-H), 7.28 (d, J = 8.0Hz, 2H, Ar-H), 6.12 (dt, J1 = 6.3Hz, J2=3.1Hz,1H,=CH),5.58(q,J=6.7Hz,1H,=CH),3.58(t,J=6.6Hz,2H,OCH2),2.14(qd,J1=7.0Hz,J2=2.9Hz,2H,CH2),1.57-1.44(m,4H,CH2x2), 1.44-1.36(m,2H,CH2),1.34(s,12H,CH3x4),0.89(s,9H,C(CH3)3),0.04(s,6H, CH3x2); 13 C NMR (100MHz, CDCl3): δ=205.7,138.1,135.0,125.9,95.0,94.8, 83.6,63.2,32.6,28.9,28.6,26.0,25.4,24.9,24.8,18.4,-5.3; IR(neat):ν=2931,2857,1997,1608,1358,1144,1088cm -1 ;MS(FI)m / z(%):442(M + ( 11 B)); HRMS Calcd.for C 26 H 43 O3Si 10 B(M + ):441.3105,found441.3108.

[0126] Embodiment 19

[0127]

[0128] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1k (417.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2k (112.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give allene product 4kk (258.5 mg, 96% purity, 76% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1)): oily liquid; 1 H NMR (400MHz, CDCl3): δ=7.73 (d, J=7.6Hz, 2H, Ar-H), 7.28 (d, J=8.0Hz, 2H, Ar-H), 6.13 (dt, J1=6.4Hz, J2=3.1Hz, 1H, =CH),5.58(q,J=6.5Hz,1H,=CH),3.62(t,J=6.6Hz,2H,CH2),2.15(qd,J1= 6.9Hz,J2=3.0Hz,2H,CH2),1.80-1.62(brs,1H,OH),1.62-1.47(m,4H,CH2x2), 1.47-1.38(m,2H,CH2),1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ = 205.6, 138.0, 134.9, 125.8, 94.8, 94.7, 83.6, 62.6, 32.3, 28.7, 28.4, 25.2, 24.73, 24.70; IR(neat):ν=3354,2977,2931,2858,1947,1607,1356,1319,1142,1086cm -1 ;MS (FI) m / z (%): 328 (M + ( 11 B)); HRMS Calcd.for C 20 H 29 O3 10 B(M + ):327.2241, found 327.2245.

[0129] Embodiment 20

[0130]

[0131] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1k (417.9 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 2l (107.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4kl (262.8 mg, 81% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 40 / 1 (410 mL); petroleum ether / ethyl acetate = 20 / 1 (420 mL)): oily liquid; 1 H NMR (400MHz, CDCl3): δ=7.74 (d, J=8.0Hz, 2H, Ar-H), 7.27 (d, J=8.0Hz, 2H, Ar-H), 6.17 (dt, J1=6.1Hz,J2=3.0Hz,1H,=CH),5.57(q,J=6.5Hz,1H,=CH),2.33(t,J=7.0 Hz,2H,CH2),2.18(qd,J1=7.0Hz,J2=3.0Hz,2H,CH2),1.80-1.69(m,2H,CH2), 1.69-1.58(m,2H,CH2),1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ= 205.7,137.6,135.0,125.8,119.5,95.3,94.0,83.7,27.7,27.6,24.81,24.78,24.73, 16.9;IR(neat):ν=2975,2937,2896,1949,1605,1355,1323,1147,1089cm -1 ; MS (FI) m / z (%): 323 (M + ( 11 B)); HRMS Calcd.for C 20 H 26 O2N 10 B(M + ):322.2087,found 322.2081.

[0132] Embodiment 21

[0133]

[0134] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1k (418.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2m (126.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4km (240.6 mg, 70% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 80 / 1 (405 mL); petroleum ether / ethyl acetate = 40 / 1 (820 mL)): oily liquid; 1 H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.0 Hz, 2H, Ar-H), 7.27 (d, J = 9.2 Hz, 2H, Ar-H), 6.16(dt,J1=6.1Hz,J2=3.0Hz,1H,=CH),5.57(q,J=6.7Hz,1H,=CH),3.66(s, 3H,OCH3),2.39(t,J=7.6Hz,2H,CH2),2.25-2.12(m,2H,CH2),1.89-1.75(m,2 H,CH2),1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ=205.8,173.8, 137.7,135.0,125.9,95.2,94.1,83.6,51.4,33.3,27.9,24.80,24.77,24.1; IR(neat):ν=2977,1947,1737,1607,1356,1142,1086cm -1 ;MS(FI)m / z(%):342(M + ( 11 B)); HRMS Calcd.for C 20 H 27 O4 10 B(M + ):341.2033, found 341.2039.

[0135] Embodiment 22

[0136]

[0137] The operation is the same as in Example 1. Molecular sieves (12.5025 g), Au3d (1.0851 g, 1.25 mmol), aldehyde 1k (20.8894 g, 90 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (8.8317 g, 60 mmol) and terminal alkyne 2m (6.3093 g, 50 mmol) were reacted in 2,2,2-trifluoroethanol (50 mL) to give the allene product 4km (10.9863 g, 64% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 40 / 1)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.73 (d, J = 8.0Hz, 2H, Ar-H), 7.27 (d, J = 9.2Hz, 2H, Ar-H), 6.16 (dt, J1 = 6.1Hz, J2 = 3.0Hz, 1H, = CH), 5.57 (q, J=6.7Hz,1H,=CH),3.66(s,3H,OCH3),2.39(t,J=7.4Hz,2H,CH2),2.18(qd, J1=6.9Hz,J2=2.9Hz,2H,CH2),1.89-1.74(m,2H,CH2),1.34(s,12H,CH3x4).

[0138] Embodiment 23

[0139]

[0140] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1l (263.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (177.1 mg, 1.2 mmol) and terminal alkyne 2n (96.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ln (208.9 mg, 93% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.59 (d, J = 2.4Hz, 1H, Ar-H), 7.48 (s, 1H, Ar-H), 7.42(d,J=8.8Hz,1H,Ar-H),7.31-7.22(m,1H,Ar-H),6.75-6.68(m,1H,Ar-H) ,6.22(dt,J1=6.3Hz,J2=3.1Hz,1H,=CH),5.58(q,J=6.7Hz,1H,=CH),2.14(qd, J1=7.1Hz, J2=2.9Hz,2H,CH2),1.54-1.43(m,2H,CH2),1.42-1.23(m,4H,CH2x2),0.89(t,J=7.0Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=204.7,154.1, 145.2,129.9,127.8,123.1,118.9,111.3,106.4,95.1,94.6,31.4,28.8,22.4,14.0; IR (neat):ν=2925,2855,1948,1466,1452,1262,1192,1111,1031cm -1 ;MS (70eV, EI) m / z (%): 226 (M + ,12.48),170(100);HRMS Calcd.for C 16 H 18 O(M + ):226.1352, found 226.1356.

[0141] Embodiment 24

[0142]

[0143] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1m (193.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2n (96.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4mn (152.3 mg, 81% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ=8.51 (d, J=1.6Hz, 1H, Ar-H), 8.41 (dd, J1=4.8Hz, J2=1.2Hz, 1H, Ar-H), 7.58 (dt, J1=7.6Hz, J2=1.6Hz, 1H, Ar-H),7.21(dd,J1=7.6Hz,J2=4.8Hz,1H,Ar-H),6.10(dt,J1=6.4Hz,J2=3.2 Hz,1H,=CH),5.63(q,J=6.7Hz,1H,=CH),2.14(qd,J1=7.2Hz,J2=3.1Hz,2H, CH2),1.57-1.41(m,2H,CH2),1.40-1.22(m,4H,CH2x2),0.89(t,J=7.0Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.4,147.9,147.5,133.1,130.9,123.2, 95.6,91.2,31.2,28.6,28.3,22.3,13.9;IR(neat):ν=2925,2855,1949,1570,1480,1444,1390,1180,1120,1023cm -1 ;MS(70eV,EI)m / z(%):187(M + ,1.42),130 (100); HRMS Calcd.for C 13 H 17 N(M + ):187.1356,found 187.1359.

[0144] Embodiment 25

[0145]

[0146] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1n (173.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2n (96.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4nn (63.8 mg, 36% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.38-7.31 (m, 1H, Ar-H), 6.37 (dd, J1 = 3.2Hz, J2 = 2.0Hz, 1H, Ar-H), 6.18 (d, J = 3.2Hz, 1H, Ar-H), 6.10 (dt, J1 = 6.3Hz, J2 = 3.1 Hz,1H,=CH),5.60(q,J=6.8Hz,1H,=CH),2.12(qd,J1=7.1Hz,J2=3.0Hz,2H, CH2),1.53-1.42(m,2H,CH2),1.40-1.22(m,4H,CH2x2),0.89(t,J=7.0Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=204.4,149.0,141.7,111.3,106.5,95.6,85.3, 31.3,28.8,28.5,22.4,14.0;IR(neat):ν=2926,2856,1950,1462,1249,1174,1150,1076,1010cm -1 ;MS(70eV,EI)m / z(%):176(M + ,11.56),120(100); HRMS Calcd. for C 12 H 16 O(M + ):176.1196,found 176.1200.

[0147] Embodiment 26

[0148]

[0149] The operation is the same as in Example 1. Molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1o (201.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2n (96.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4on (154.0 mg, 80% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.24 (dd, J1 = 5.2Hz, J2 = 2.8Hz, 1H, Ar-H), 7.06 (d, J = 4.8Hz, 1H, Ar-H), 7.03 (d, J = 2.8Hz, 1H, Ar-H), 6.18 (dt, J1 = 6.1Hz, J2 = 3.1Hz, 1H, = CH), 5.49 (q, J = 6.5Hz, 1H, = CH), 2.10 (qd, J1 = 7.1Hz, J2 = 3.0Hz, 2H,CH2),1.52-1.42(m,2H,CH2),1.39-1.24(m,4H,CH2x2),0.89(t,J=7.0Hz, 3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.4,136.5,126.2,125.6,120.0,94.2, 89.1,31.3,28.78,28.77,22.4,14.0; IR(neat):ν=2924,2854,1950,1462,1378,1261,1232,1077cm -1 ;MS(70eV,EI)m / z(%):192(M + ,5.72),135(100); HRMS Calcd.for C 12 H 16 S(M + ):192.0967,found 192.0966.

[0150] Embodiment 27

[0151]

[0152] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1p (263.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2o (108.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4po (203.0 mg, 85% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 4 / 1)): white solid; mp 152.0-152.9 ° C (recrystallized from ethyl acetate); 1H NMR (400MHz, CDCl3): δ= 10.80-10.04(brs,1H,NH),8.03(s,1H,Ar-H),7.59(s,1H,Ar-H),7.43(s,2H, Ar-H),6.28(dd,J1=6.4Hz,J2=2.8Hz,1H,=CH),5.60(t,J=6.0Hz,1H,=CH), 2.23-2.04(m,1H,CH),1.94-1.82(m,2H),1.82-1.68(m,2H),1.68-1.57(m,1H),1.40-1.08(m,5H); 13 C NMR (100MHz, CDCl3): δ=203.7,139.4,134.7,128.4,126.0,123.7,118.1,109.9,101.2,95.5,37.7,33 .2,33.1,26.1,26.02,26.01;IR(neat):ν=3139,2918,2848,1946,1623,1506,1442,1341,1307,1081cm -1 ;MS(ESI)m / z(%):239(M+H + ); Anal.Calcd.for C 16 H 18 N2:C 80.63,H,7.61,N 11.75,found C 80.49,H7.69,N11.72.

[0153] Embodiment 28

[0154]

[0155] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1q (261.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2o (107.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4qo (133.6 mg, 57% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 40 / 1)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 8.22-7.85 (brs, 1H, NH), 7.52 (s,1H,Ar-H),7.29(d,J=8.4Hz,1H,Ar-H),7.22(t,J=7.6Hz,1H,Ar-H)7.13(s, 1H,Ar-H),6.49(s,1H,Ar-H),6.28(dd,J1=6.0Hz,J2=2.8Hz,1H,=CH),5.56(t, J=6.2Hz,1H,=CH),2.22-2.05(m,1H,CH),1.95-1.80(m,2H),1.80-1.68(m,2H),1.68-1.58(m,1H),1.38-1.08(m,5H); 13 C NMR (100MHz, CDCl3): δ = 203.3, 134.9,128.1,126.7,124.5,120.9,118.5,111.2,102.4,100.8,96.1,37.7,33.2,33 .1,26.1,26.03,26.02; IR(neat):ν=3410,2921,2848,1945,1447,1415,1319,1285, 1091cm -1 ;MS(ESI)m / z(%):238(M+H + ); HRMS Calcd.for C 17 H 20 N(M+H + ): 238.1590, found 238.1588.

[0156] Embodiment 29

[0157]

[0158] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1r (281.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2g (80.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4rg (145.7 mg, 66% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.82-7.70 (m, 3H, Ar-H), 7.64 (s, 1H, Ar-H), 7.53-7.47(m,1H,Ar-H),7.47-7.36(m,2H,Ar-H),6.37-6.26(m,1H,=CH),5.96-5.78(m,1H,=CH),5.65(q,J=6.1Hz,1H,=CH),5.08(d,J=17.6Hz,1H, one proton of=CH2),5.02(d,J=10.0Hz,1H, one proton of=CH2),2.36-2.17(m,4 H,CH2x2); 13 C NMR (100MHz, CDCl3): δ=205.7,137.8,133.7,132.5,132.4, 128.1,127.63,127.58,126.1,125.4,125.3,124.6,115.2,95.3,94.6,33.1,28.1;IR (neat):ν=3054,2976,2909,2843,1945,1639,1597,1507,1435,1264cm -1 ;MS(70 eV,EI)m / z(%):220(M + ,91.99),178(100); HRMS Calcd.for C 17 H 16 (M + ): 220.1247, found 220.1248.

[0159] Embodiment 30

[0160]

[0161] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1s (371.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (80.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4sg (139.9 mg, 52% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 8.74-8.66 (m, 1H, Ar-H), 8.62 (d, J = 8.0Hz, 1H, Ar-H),8.36-8.27(m,1H,Ar-H),7.87-7.81(m,1H,Ar-H),7.78(s,1H,Ar-H),7. 69-7.48(m,4H,Ar-H),6.87-6.78(m,1H,=CH),5.96-5.80(m,1H,=CH),5.64(q, J=6.5Hz,1H,=CH),5.08(d,J=17.2Hz,1H,one proton of=CH2),5.01(d,J=10.0Hz,1H,one proton of=CH2),2.39-2.22(m,4H,CH2x2); 13 C NMR (100MHz, CDCl3): δ=206.7,137.9,131.8,130.7,130.2,129.8,129.6,128.3,126.7,126.5, 126.34,126.28,125.9,124.4,123.1,122.5,115.3,93.2,91.7,33.2,28.2 ;IR(neat):ν=3073,2973,2909,2844,1946,1639,1494,1428,1243,1114cm -1 ;MS (70eV, EI) m / z (%): 270 (M + ,100);HRMSCalcd.for C 21 H 18 (M + ):270.1403,found 270.1408.

[0162] Embodiment 31

[0163]

[0164] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1t (414.6 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (79.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to obtain the allene product 4tg (151.6 mg, 52% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 8.40 (d, J = 9.2Hz, 1H, Ar-H), 8.18-8.04 (m, 5H, Ar-H), 8.04-7.94 (m, 3H, Ar-H), 7.23-7.10 (m, 1H, = CH), 5.98-5.83 (m, 1H, = CH), 5.75(q,J=6.1Hz,1H,=CH),5.10(d,J=16.8Hz,1H,one proton of=CH2),5.03 (d,J=10.8Hz,1H,one proton of=CH2),2.43-2.24(m,4H,CH2x2); 13 C NMR (100MHz, CDCl3): δ=207.2,137.9,131.4,130.8,130.1,128.5,127.5,127.4,127.3,126.9,125.8,125.2,125.1,125.04,1 24.96,124.9,124.7,122.7,115.3,94.0,92.0,33.3,28.2; IR(neat):ν=3040,2973,2906,2842,1941,1639,1599,1435,1269, 1182cm -1 ;MS (70eV, EI) m / z (%): 294 (M + ,94.55),253(100); HRMS Calcd.for C 23 H 18 (M + ):294.1403,found 294.1407.

[0165] Embodiment 32

[0166]

[0167] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1u (256.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to give the allene product 4ua (195.7 mg, 83% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 5.06 (quintet, J = 4.8Hz, 2H, = CHx2), 2.07-1.86 (m, 4H, CH2x2), 1.48-1.13 (m, 20H, CH2x10), 0.96-0.77 (m, 6H, CH3x2); 13 C NMR (150MHz, CDCl3): δ=204.0,90.87,90.86,32.0,31.8,29.6,29.4,29.32,29.28, 29.2,29.084,29.078,28.9,22.75,22.73,14.09,14.08;IR(neat):ν=2957,2922,2853,1963,1462,1378,1261cm -1 ; MS (FI) m / z (%): 236 (M + ); HRMS Calcd.forC 17 H 32 (M + ):236.2499,found 236.2500.

[0168] Embodiment 33

[0169]

[0170] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1v (180.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to give the allene product 4va (126.1 mg, 65% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 5.06 (quintet, J = 4.8Hz, 2H, = CHx2), 2.06-1.86 (m, 4H, CH2x2), 1.48-1.16 (m, 14H, CH2x7), 0.97-0.74 (m, 6H, CH3x2); 13C NMR (100MHz, CDCl3): δ=203.8,90.9,31.8,31.4,29.2,29.04,29.00,28.9,28.8, 22.7,22.5,14.08,14.07;IR(neat):ν=2957,2924,2855,1962,1462,1378,1261,1104,1018cm -1 ;MS(FI)m / z(%):194(M + ); HRMS Calcd.for C 14 H 26 (M + ):194.2029,found194.2032.

[0171] Embodiment 34

[0172]

[0173] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1w (155.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.2 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to give the allene product 4wa (148.0 mg, 82% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 5.11-4.94 (m, 2H, = CHx2), 2.02-1.92 (m, 2H, CH2), 1.92-1.78 (m, 2H, CH2), 1.72-1.58 (m, 1H, CH), 1.43-1.19 (m, 8H, CH2x4), 1.02-0.78(m,9H,CH3x3); 13 C NMR (100MHz, CDCl3): δ=204.5,90.2,89.4,38.6,31.7,29.2,29.0,28.8,28.5,22.7, 22.3,22.2,14.1;IR(neat):ν=2956,2925,2855,1963,1464,1381,1366,1261,1105cm -1 ;MS(FI)m / z(%):180(M + ); HRMS Calcd. for C 13 H 24 (M+ ):180.1873,found 180.1875.

[0174] Embodiment 35

[0175]

[0176] The operation is the same as in Example 1. Molecular sieves (250.1 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1x (202.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (2 mL) to give the allene product 4xa (161.2 mg, 78% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ=5.20-4.97(m,2H,=CHx2),2.06-1.86(m,3H, CH2and CH),1.82-1.67(m,4H),1.67-1.58(m,1H),1.46-1.00(m,13H),0.89(t,J =6.8Hz,3H,CH3); 13 C NMR (150MHz, CDCl3): δ=202.7,97.0,91.8,37.3,33.18, 33.15,31.7,29.2,29.1,28.9,26.2,26.10,26.09,22.7,14.1;IR(neat):ν=2922,2851,1960,1448,1260cm -1 ;MS(70eV,EI)m / z(%):206(M + ,2.43),136(100);HRMSCalcd.for C 15 H 26 (M + ):206.2029,found 206.2032.

[0177] Embodiment 36

[0178]

[0179] The operation is the same as in Example 1. Molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1u (256.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2e (102.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to obtain the allene product 4ue (161.1 mg, 70% yield, 99% purity) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.36-7.26 (m, 4H, Ar-H), 7.22-7.13 (m, 1H, Ar-H), 6.12 (dt, J1 = 6.0Hz, J2 = 2.9Hz, 1H, = CH), 5.56 (q, J = 6.7Hz, 1H, =CH),2.12(qd,J1=7.1Hz,J2=2.7Hz,2H,CH2),1.53-1.41(m,2H,CH2), 1.41-1.11(m,10H,CH2x5),0.88(t,J=6.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.1,135.1,128.5,126.54,126.52,95.1,94.5,31.8,29.4,29.3,29.2, 29.1,28.7,22.7,14.1;IR(neat):ν=2923,2853,1949,1598,1494,1459cm -1 ;MS (FI) m / z (%): 228 (M + ); HRMS Calcd.for C 17 H 24 (M + ):228.1873,found 228.1869.

[0180] Embodiment 37

[0181]

[0182] The operation is the same as in Example 1. Molecular sieves (250.0 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1x (202.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2e (102.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (2 mL) to give the allene product 4xe (145.4 mg, 73% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.36-7.26 (m, 4H, Ar-H), 7.22-7.11 (m, 1H, Ar-H), 6.15 (dd, J1 = 6.2Hz, J2 = 3.0Hz, 1H, = CH), 5.56 (t, J = 6.2Hz, 1H, = CH), 2.18-2.04(m,1H,CH),1.92-1.78(m,2H),1.78-1.68(m,2H),1.68-1.57(m,1H),1.37-1.08(m,5H); 13 C NMR (100MHz, CDCl3): δ=204.0,135.2,128.5,126.5, 126.4,101.0,95.4,37.6,33.15,33.09,26.09,26.08,26.02;IR(neat):ν=2921,2849,1946,1597,1493,1446cm -1 ;MS(70eV,EI)m / z(%):198(M + ,5.19),105(100).

[0183] Embodiment 38

[0184]

[0185] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1c (253.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 2q (138.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4cq (200.1 mg, 76% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ=7.28-7.22(m,2H,Ar-H),7.22-7.16(m,2H,Ar-H), 6.07(dt,J1=6.3Hz,J2=3.1Hz,1H,=CH),5.57(q,J=6.7Hz,1H,=CH),2.12(qd, J1=7.1Hz, J2=2.9Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.14(m,10H,CH2x5),0.87(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.2,133.7, 132.1,128.6,127.7,95.5,93.7,31.8,29.4,29.3,29.2,29.1,28.6,22.7,14.1; IR(neat): ν=2923,2853,1949,1490,1463,1090,1013cm -1 ;MS(70eV,EI)m / z(%):264 (M + ( 37 Cl), 0.63), 262(M + ( 35 Cl),2.02),129(100).

[0186] Embodiment 39

[0187]

[0188] The operation is the same as in Example 1. Molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1d (333.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2q (138.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4dq (230.9 mg, 75% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.40 (d, J = 8.4 Hz, 2H, Ar-H), 7.14 (d, J = 8.4 Hz, 2H, Ar-H), 6.06 (dt, J1 = 6.3Hz, J2 = 3.1Hz, 1H, = CH), 5.56 (q, J = 6.5Hz, 1H, =CH),2.12(qd,J1=7.1Hz,J2=2.9Hz,2H,CH2),1.53-1.40(m,2H,CH2),1.40-1.14(m,10H,CH2x5),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.2,134.2,131.5,128.0,120.1,95.5,93.8,31.8,29.4,29.3,29.2,29.1, 28.6,22.7,14.1;IR(neat):ν=2922,2852,1949,1486,1462,1069,1009cm -1 ;MS (70eV, EI) m / z(%):308(M + ( 81 Br),3.73),306(M + ( 79 Br),4.13),210(100).

[0189] Embodiment 40

[0190]

[0191] The operation is the same as in Example 1. Molecular sieves (250.6 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1i (313.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2b (166.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4ib (253.8 mg, 78% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.53 (d, J = 8.0Hz, 2H, Ar-H), 7.37 (d, J = 8.0Hz, 2H, Ar-H), 6.14 (dt, J1 = 6.1Hz, J2 = 3.0Hz, 1H, = CH), 5.63 (q, J = 6.7Hz, 1H, =CH),2.14(qd,J1=7.1Hz,J2=3.1Hz,2H,CH2),1.53-1.41(m,2H,CH2),1.41-1.12(m,14H,CH2x7),0.88(t,J=6.8Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=206.2, 139.2, 128.6 (q, J= 32.2Hz), 126.6, 125.4 (q, J= 3.8Hz), 124.4 (q, J=269.6Hz),95.7,93.8,32.0,29.71,29.67,29.5,29.4,29.2,29.1,28.5,22.7,14.1; 19 F NMR (376MHz, CDCl3) δ = -62.9; IR (neat): ν = 2924, 2854, 1949, 1616, 1322, 1163, 1123, 1065cm -1 ;MS (70eV, EI) m / z (%): 324 (M + ,2.97),198(100).

[0192] Embodiment 41

[0193]

[0194] The operation is the same as in Example 1. Molecular sieves (250.3 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1o (202.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2q (138.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give allene product 4oq (201.5 mg, 86% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400MHz, CDCl3): δ = 7.27-7.21 (m, 1H, Ar-H), 7.06 (d, J = 5.2Hz, 1H, Ar-H), 7.04-6.99 (m, 1H, Ar-H), 6.18 (dt, J1 = 6.3Hz, J2 = 3.0Hz, 1H, = CH), 5.48 (q,J=6.7Hz,1H,=CH),2.10(qd,J1=7.0Hz,J2=3.0Hz,2H,CH2),1.52-1.42(m, 2H,CH2),1.40-1.12(m,10H,CH2x5),0.88(t,J=6.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ=205.4,136.5,126.2,125.6,120.0,94.2,89.1,31.8,29.4,29.3, 29.2,29.1,28.8,22.7,14.1;IR(neat):ν=2922,2852,1950,1461,1378,1233cm -1 ; MS (70eV, EI) m / z (%): 234 (M + ,1.95),135(100).

[0195] Embodiment 42

[0196]

[0197] Lithium hydroxide (18.0 mg, 0.75 mmol), allene 4km (171.3 mg, 0.5 mmol), ethanol (2.5 mL) and water (2.5 mL) were added to a reaction bottle in sequence. After the reaction bottle was placed in an oil bath at 90°C for 14 hours, water (2 mL) and aqueous hydrochloric acid solution (1M, 2 mL) were added to the reaction bottle in sequence. The mixed solution was extracted with ether (4 mL x 5). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the product 6' (151.9 mg, 93% purity, 86% yield): oily liquid; 1HNMR(400MHz, CDCl3): δ=12.00-8.60(br,1H,CO2H),7.74(d,J=8.0Hz,2H,Ar-H),7.27(d,J=7.6Hz,2H,Ar-H),6.17(dt,J1=5.9Hz,J2=2.9Hz,1H,=CH),5.57(q,J=6.5Hz, 1H,=CH),2.43(t,J=7.4Hz,2H,CH2),2.20(qd,J1=7.1Hz,J2=3.0Hz,2H, CH2),1.90-1.75(m,2H,CH2),1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ=205.8,179.8,137.7,135.0,125.9,95.3,94.0,83.7,33.3,27.8,24.78,24.75 ,23.8;IR(neat):ν=2976,1944,1701,1607,1355,1321,1245,1168,1140,1088cm -1 ;MS (FI) m / z (%): 328 (M + ( 11 B));HRMSCalcd.for C 19 H 25 O4 10 B(M + ):327.1877, found 327.1882.

[0198] Embodiment 43

[0199]

[0200] Au(SIPr)Cl (6.2 mg, 0.01 mmol), AgOTs (2.9 mg, 0.01 mmol) and chloroform (2 mL) were added to a reaction bottle in sequence. After stirring at room temperature for 15 minutes, 6' (70.1 mg, 93% purity, 0.2 mmol) and chloroform (1 mL) were added in sequence. After stirring at room temperature for 36 hours, the reaction solution was filtered through a silica gel short column, and the filter cake was washed with ethyl acetate (30 mL). After concentration, the product (E)-6 (47.9 mg, 73% yield) was obtained by rapid column chromatography purification (eluent: petroleum ether / ethyl acetate = 4 / 1): oily liquid; 1H NMR (400MHz, CDCl3): δ=7.77(d,J=8.0Hz,2H,Ar-H),7.39(d,J=8.0Hz,2H, Ar-H),6.68(d,J=16.0Hz,1H,=CH),6.27(dd,J1=15.8Hz,J2=6.2Hz,1H,=CH),5.09-4.91(m,1H,OCH),2.73-2.58(m,1H,one proton of CH2),2.58-2.46(m, 1H,one proton of CH2),2.14-2.03(m,1H,one proton of CH2),2.03-1.84(m,2H, one proton of CH2x2),1.83-1.67(m,1H,one proton of CH2), 1.34 (s, 12H, CH3x4); 13 C NMR (150MHz, CDCl3): δ=171.0,138.6,135.1,132.0,128.0,125.9,83.8,80.2, 29.6,28.4,24.824,24.816,18.3;IR(neat):ν=2977,1731,1607,1357,1233,1142,1087,1033cm -1 ;MS(FI)m / z(%):328(M + ( 11 B); HRMS Calcd.for C 19 H 25 O4 10 B (M + ):327.1877, found 327.1879.

[0201] Embodiment 44

[0202]

[0203] Au(SIPr)Cl (31.3 mg, 0.05 mmol), AgOTf (12.8 mg, 0.05 mmol) and dioxane (1.25 mL) were added to a reaction bottle in sequence. After stirring at room temperature for 15 minutes, 4km (342.0 mg, 1.0 mmol) and water (36.0 mg, 2.0 mmol) were added in sequence. After stirring at room temperature for 24 hours, the reaction solution was filtered through a silica gel short column, and the filter cake was washed with ether (30 mL). After concentration, the product (E)-7 (252.9 mg, 70% yield) was obtained by rapid column chromatography purification (eluent: petroleum ether / ethyl acetate = 4 / 1): oily liquid;1 H NMR (400MHz, CDCl3): δ=7.76 (d, J=7.6Hz, 2H, Ar-H), 7.37 (d, J=8.0Hz, 2H, Ar-H),6.59(d,J=16.0Hz,1H,=CH),6.28(dd,J1=15.6Hz,J2=6.4Hz,1H,=CH),4.36-4.24(m,1H,CH),3.67(s,3H,OCH3),2.38(t,J=7.2Hz,2H,CH2), 1.88-1.59(m,5H,CH2x2and OH),1.34(s,12H,CH3x4); 13 C NMR (100MHz, CDCl3): δ=174.0,139.3,135.0,133.1,130.3,125.7,83.7,72.4,51.5,36.5,33.7,24.8, 20.8;IR(neat):ν=3466,2978,1732,1608,1357,1142,1087cm -1 ;MS(FI)m / z(%): 360(M + ( 11 B); HRMS Calcd.forC 20 H 29 O5 10 B(M + ):359.2139, found 359.2148.

[0204] Embodiment 45

[0205]

[0206] Under argon atmosphere, Pd(PPh3)2Cl2 (7.0 mg. 0.01 mmol), potassium carbonate (55.6 mg, 0.4 mmol), 4km (68.4 mg, 0.2 mmol), 3-bromoquinoline (62.7 mg, 0.3 mmol), freshly dioxane (1 mL) and water (0.5 mL) were added to a dry reaction bottle in sequence. The reaction bottle was placed in an oil bath at 80°C for 5 hours. The reaction solution was filtered through a silica gel short column, and the filter cake was washed with ether. After concentration, it was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1) to obtain product 8 (54.3 mg, 95% purity, 75% yield): oily liquid; 11H NMR (400 MHz, CDCl3): δ = 9.19 (d, J = 2.4 Hz, 1H, Ar-H), 8.30 (d, J = 2.0 Hz, 1H, Ar-H), 8.13 (d, J = 8.4 Hz, 1H, Ar-H), 7.88 (d, J = 8.0 Hz, 1H, Ar-H), 7.76 - 7.69 (m, 1H, Ar-H), 7.67 (d, J = 8.4 Hz, 2H, Ar-H), 7.62 - 7.54 (m, 1H, Ar-H), 7.44 (d, J = 8.4 Hz, 2H, Ar-H), 6.23 (dt, J1 = 6.1 Hz, J2 = 3.0 Hz, 1H, =CH), 5.63 (q, J = 6.5 Hz, 1H, =CH), 3.68 (s, 3H, OCH3), 2.42 (t, J = 7.4 Hz, 2H, CH2), 2.29 - 2.13 (m, 2H, CH2), 1.92 - 1.80 (m, 2H, CH2); 13 13C NMR (100 MHz, CDCl3): δ = 205.6, 173.8, 149.7, 147.2, 136.1, 134.8, 133.4, 132.7, 129.25, 129.16, 128.0, 127.9, 127.5, 127.3, 126.9, 94.6, 94.3, 51.5, 33.3, 28.0, 24.2; IR (neat): ν = 2948, 1946, 1731, 1515, 1492, 1435, 1340, 1195, 1149 cm -1 ; MS (ESI) m / z (%): 344 (M+H + ); HRMS Calcd. for C 23 H 22 NO2 (M+H + ): 344.1645, found 344.1644.

[0207] Example 46

[0208]

[0209] 4km (68.8 mg, 0.2 mmol), ammonium acetate (92.6 mg, 1.2 mmol), sodium periodate (257.1 mg, 1.2 mmol), acetone (2.4 mL) and distilled water (1.2 mL) were added to a reaction bottle in sequence. After reacting at room temperature for 12 hours, the reaction solution was filtered through a silica gel short column, and the filter cake was washed with acetone (15 mL), concentrated and extracted with ether (4 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash column chromatography (eluent: dichloromethane / methanol = 80 / 1) to obtain the corresponding boronic acid (47.9 mg).

[0210] Pd(PPh3)2Cl2 (3.9 mg, 5.56 x 10 -3 mmol), potassium carbonate (76.5mg, 0.554mmol) and the above prepared boric acid (47.9mg, 0.184mmol). After the reaction tube was plugged with a rubber stopper, a carbon monoxide balloon was inserted, and a vacuum pump was connected to replace carbon monoxide three times under a carbon monoxide atmosphere. Then 1.1mL of anisole solution containing iodobenzene (41.4mg, 0.203mmol) was added. The reaction flask was placed in an 80°C oil bath and stirred for 6 hours. The reaction solution was filtered through a silica gel short column, and the filter cake was washed with ether (15mL). After concentration, it was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1) to obtain product 9 (37.3mg, 58% yield): oily liquid; 1 H NMR (400MHz, CDCl3): δ = 7.78 (t, J = 8.4Hz, 4H, Ar-H), 7.62-7.53 (m, 1H, Ar-H), 7.48 (t, J = 7.6Hz, 2H, Ar-H), 7.38 (d, J=8.4Hz,2H,Ar-H),6.22(dt,J1=6.3Hz,J2=3.1Hz,1H,=CH),5.64(q,J=6.5 Hz,1H,=CH),3.67(s,3H,OCH3),2.41(t,J1=7.4Hz,2H,CH2),2.21(qd,J1=7.1 Hz,J2=2.9Hz,2H,CH2),1.91-1.78(m,2H,CH2); 13C NMR (100MHz, CDCl3): δ=206.5,196.2,173.8,139.5,137.8,135.7,132.2,130.6,129.9,128.2,126.3,94.7, 94.6,51.6,33.3,27.8,24.1;IR(neat):ν=2949,1945,1732,1652,1599,1435,1306,1275,1174,1148cm -1 ;MS(ESI)m / z(%):321(M+H + ); HRMS Calcd.for C 21 H 21 O3(M+H + ):321.1485, found 321.1484.

[0211] Embodiment 47

[0212]

[0213] The operation is the same as in Example 1. Molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1y (382.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2p (202.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to give the allene product 4yp (255.2 mg, 64% yield) (purified by flash column chromatography (eluent: petroleum ether / ethyl acetate = 40 / 1)): white solid; mp 71.0-72.2 ° C (recrystallized from ether); 1 H NMR (400MHz, CDCl3): δ = 7.89 (d, J = 8.8Hz, 2H, Ar-H), 7.45-7.34 (m, 4H, Ar-H), 7.34-7.27 (m, 1H, Ar-H), 7.20(d,J=8.4Hz,2H,Ar-H),6.89(d,J=8.8Hz,4H,Ar-H),6.15-6.06(m,1H,= CH),5.56(q,J=6.5Hz,1H,=CH),5.03(s,2H,CH2),3.85(s,3H,OCH3),2.97(t, J=7.4Hz,2H,CH2),2.28-2.16(m,2H,CH2),1.92(quintet,J=7.1Hz,2H,CH2); 13C NMR (100MHz, CDCl3): δ=204.6,198.5,163.2,157.7,136.8,130.2,130.0, 128.4,127.8,127.6,127.31,127.28,115.0,113.5,94.30,94.25,69.9,55.3,37. 3,28.4,23.5;IR(neat):ν=2897,2840,1943,1670,1602,1577,1509,1231,1167cm -1 ;MS (70eV, EI) m / z(%):398(M + ,3.73),91(100).

[0214] Those skilled in the art will understand that within the protection scope of the present invention, it is feasible to modify, add and replace the above embodiments, and none of them exceeds the protection scope of the present invention.

Claims

1. A method for preparing 1,3-disubstituted allene compounds based on a gold carbene catalytic system at room temperature, characterized in that: Under the action of gold carbene catalyst and molecular sieve, terminal alkynes (2), aldehydes (1) and amines (3) containing different substituents react in an organic solvent to generate 1,3-disubstituted allene compounds at room temperature. The reaction process is shown in the following reaction formula (a): Among them, R 1 is a C1-C10 hydrocarbon group, a C1-C10 hydrocarbon group with a functional group, a phenyl group, an aryl group, or a heterocyclic group; R 2 is a C1-C10 hydrocarbon group, a C1-C10 hydrocarbon group with a functional group, a phenyl group, an aryl group, or a heterocyclic group; R 1 , R 2 wherein the functional group is selected from a carbon-carbon double bond, a halogen atom, a hydroxyl group, a silyl ether group, a carbonyl group, a nitrile group, an ester group and an amide group; the aromatic group is a phenyl group and a polyphenyl ring substituent group having an electron-donating or electron-withdrawing substituent at the ortho, meta or para position, the electron-donating substituent group includes a hydrocarbon group, a methoxy group, a benoxy group and a borate ester group, the electron-withdrawing substituent group includes a halogen, a nitrile group, an ester group, a trifluoromethyl group and a nitro group; the heterocyclic group is selected from a furyl group, a benzofuranyl group, a thienyl group, a pyridyl group, an indolyl group and an indazolyl group; The amine (3) is selected from morpholine (3a), piperidine (3b), pyrrolidine (3c), 1,2,3,4-tetrahydroquinoline (3d), 1,2,3,4-tetrahydroisoquinoline (3e), 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f), diethylamine (3g), diallylamine (3h), dicyclohexylamine (3i) and diisopropylamine (3j); The gold carbene catalyst is selected from one or more of the following structures Au1-Au3; wherein R is a C1-C30 hydrocarbon group, a C1-C30 hydrocarbon group with a functional group, a phenyl group, an aryl group, and a heterocyclic group; the functional group is selected from a carbon-carbon double bond, a carbon-carbon triple bond, a halogen atom, a hydroxyl group, a carboxyl group, an amino group, a silyl ether group, a carbonyl group, a nitrile group, an ester group, and an amide group; the aryl group refers to a phenyl group and a polyphenyl ring substituent group having an electron-donating or electron-withdrawing substituent in the ortho, meta, or para position; The electron-donating substituents include hydrocarbon groups, alkoxy groups and borate groups, and the electron-withdrawing substituents include halogen groups, nitrile groups, ester groups, trifluoromethyl groups and nitro groups; wherein X is a counter anion, including a halogen anion, a hydroxide anion, a bis(trifluoromethanesulfonyl)imide anion, a methanesulfonate anion, a trifluoromethanesulfonate anion, a p-toluenesulfonate anion, a perchlorate anion, a tetrafluoroborate anion, a hexafluorophosphate anion and a hexafluoroantimonate anion; 2. The method according to claim 1, characterized in that The method specifically comprises the following steps: in an argon atmosphere, a molecular sieve, a gold carbene catalyst and a certain volume of an organic solvent are sequentially added into a dry reaction tube; then, an aldehyde (1), an amine (3) and a terminal alkyne (2) are sequentially added under stirring conditions, and the mixture is reacted at room temperature for 24-72 hours; after the reaction is completed, the reaction solution is filtered through a silica gel short column and washed with a certain volume of ether; after the mixed solution is concentrated, a 1,3-disubstituted allene compound is obtained by rapid column chromatography; Wherein, the certain volume of organic solvent refers to the amount of the terminal alkyne (2) shown in formula (a) as the basis, and the amount of the organic solvent is 0.5-5mL / mmol; wherein, the room temperature refers to 10-40°C; the certain volume of diethyl ether refers to the amount of the terminal alkyne (2) shown in formula (a) as the basis, and the amount of the diethyl ether is 10-100mL / mol.

3. The method according to claim 1 or 2, characterized in that: The molecular screening Molecular sieves, Molecular sieves and Molecular sieve.

4. The method according to claim 1 or 2, characterized in that: The organic solvent is selected from one or more of 2,2,2-trifluoroethanol, 2,2,3,3-tetrafluoropropanol, 2,2,3,3,3-pentafluoropropanol and 1,1,1,3,3,3-hexafluoroisopropanol.

5. The method according to claim 1, characterized in that The molar ratio of the terminal alkyne (2), aldehyde (1), amine (3) and gold carbene catalyst is 1.0: (1.0-1.8): (1.0-1.4): (0.01-0.1); and / or, the amount of the molecular sieve is 100-500 mg / mmol, based on the amount of the terminal alkyne (2); and / or, the amount of the organic solvent is 0.5-5 mL / mmol, based on the amount of the terminal alkyne (2).

6. The method according to claim 1, characterized in that The room temperature refers to 10-60°C; the reaction time is 24-72 hours.

Images