CN104311559A - Synthetic method of optically pure chiral annular N, N-acetal - Google Patents

Synthetic method of optically pure chiral annular N, N-acetal Download PDF

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CN104311559A
CN104311559A CN201410461487.3A CN201410461487A CN104311559A CN 104311559 A CN104311559 A CN 104311559A CN 201410461487 A CN201410461487 A CN 201410461487A CN 104311559 A CN104311559 A CN 104311559A
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alkyl
aryl
thiazolinyl
alkynyl
cycloalkyl
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邱立勤
何宇伟
程楚瑜
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Sun Yat Sen University
National Sun Yat Sen University
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National Sun Yat Sen University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Abstract

The present invention discloses a synthetic method of optically pure chiral annular N, N-acetal; chiral Br Nsted acid or chiral dioxazoline/ metal salt is used as a catalyst, in the presence or no presence of a molecular sieve, in-series asymmetric imine condensation-addition-amidation reaction of N substituent aliphatic diamine and o-formyl benzoate is performed for synthesis of the target compound. The method is high in reaction yield, good in enantiomeric selectivity, mild in condition, simple in operation, and friendly to environment. At the same time the substrate has the characteristics of wide applicable range, is applicable to all types of substituted o-formyl benzoate compounds and various chain substituted aliphatic diamine and aromatic diamine with various chain lengths, and is very suitable for synthesis of medicines and intermediates.

Description

One class optical homochiral cyclic n nitroso compound, the synthetic method of N-acetal
Technical field
The invention belongs to chemical catalysis field, specifically, relate to asymmetry catalysis method and synthesize a class optical homochiral cyclic n nitroso compound, the synthetic method of N-acetal
Background technology
Nitrogen heterocyclic chipal compounds is the important component part of drug molecule and natural product, wherein N, N-acetal is extensively present in ocean and Lu Sheng natural product alkaloid with in Medicine small molecule with the structure of its uniqueness, this compounds often has good biological activity [(a) Zhang, M.; Huang, X.; Shen, L.; Qin, Y.J.Am.Chem.Soc.2009,131,6013. (b) Zi, W.; Xie, W.; Ma, D.J.Am.Chem.Soc.2012,134,9126. (c) Horning, B.D.; MacMillan D.W.C.J.Am.Chem.Soc.2013,135,6442. (d) Wang, Q.Z.; Liang, J.Y.; Feng, X.Chin.Chem.Lett.2010,21,596. (e) Snider, B.B.; Zeng, H.Org.Lett.2000,2,4103. (f) Shao, C.-L.; Xu, R.-F.; Wei, M.-Y.; She, Z.-G.; Wang, C.-Y.J.Nat.Prod.2013,76,779. (g) Sharma, M.; Chauhan, K.; Shivahare, R.; Vishwakarma, P.; Suthar, M.K.; Sharma, A.; Gupta, S.; Saxena, J.K.; Lal, J.; Chandra, P.; Kumar B.; Chauhan, P.M.S.J.Med.Chem.2013,56,4374.].In molecule, asymmetric N, N-acetalation efficiently can build N as one, the organic reaction of N-acetal, has extremely important status and apply [(a) Chinigo, G.M. widely in drug molecule synthesis; Paige, M.; Grindrod, S.; Hamel, E.; Dakshanamurthy, S.; Chruszcz, M.; Minor, W.; Brown, M.L.J.Med.Chem.2008,51,4620.].Such as, in the molecule reported in recent years, asymmetric N, N-acetalation can use chirality acid is as catalyzer, but successfully example is only only limitted to anthranilamide and derivative thereof as substrate [(a) Cheng, X.; Vellalath, S.; Goddard, R.; List, B.J.Am.Chem.Soc.2008,130,15786. (b) Rueping, M.; Antonchick, A.P.; Sugiono, E.; Grenader, K., Angew.Chem.Int.Ed.2009,48,908-910. (c) Cheng, D.-J.; Tian, Y.; Tian, S.-K.Adv.Synth.Catal.2012,354,995.].Meanwhile, be only form Lewis acid by chiral oxazoline and metal directly to catalyze and synthesize [Prakash, M. by an example; Kesavan, V.Org.Lett.2012,14,1896.], but substrate is also be only limitted to anthranilamide as substrate.Literature search finds, up to now, aliphatic diamine only only has two example report [(a) Katritzky, A.R. as N, N-acetalation asymmetric in the molecule of substrate; He, H.-Y.; Verma, A.K.Tetrahedron:Asymmetry2002,13,933-938. (b) Yamada, S.; Takahashi, Y.Tetrahedron Lett.2009,50,5395.], and be all by introducing chiral auxiliary group in the structure of aliphatic diamine, metering asymmetric reaction generates chiral ring N, N-acetal product.And by the asymmetric N of direct catalysis, N-acetalation synthesizes the example of this compounds, and there is not been reported.It is reported, the cyclic n nitroso compound of isoindolone structure, N-acetal has anti-inflammatory (anti-inflammatory), spasmolytic (spasmolytic), cough-relieving (antitussive), rheumatism (rheumatism), analgesia (analgesic), biological activity [(a) Geigy, J. widely such as calm (sedative), hypotensive (blood pressure lowering) etc.; R.Neth.Appl.6,613,264,1967; Chem.Abstr.1967,67,82204q. (b) Graf, W.Swiss 481,123,1969; Chem.Abstr.1970,72,100709t. (c) Graf, W.Swiss 481,124,1969; Chem.Abstr.1970,72,100710m.]; Also be a kind of compound of good anti HIV-1 virus, and the activity of AntiHIV1 RT activity depend on N, configuration [Mertens, the A. of N-acetal chiral centre; Zilch, H.; Koenig, B.; Schaefer, W.; Poll, T.; Kampe, W.; Seidel, H.; Leser, U.; Leinert, H.J.Med.Chem.1993,36,2526.].And, there is the cyclic n nitroso compound of isoindolone structure, lead compound [(a) Nielsen, T.E. that N-acetal is still very important; Quement, S.L.; Meldal, M.Org.Lett.2005,7,3601. (b) Mizutani, N.; Chiou, W.-H.; Ojima, I.Org.Lett.2002,4,4575. (c) Vink, M.K.S.; Schortinghuis, C.A.; Mackova-Zabelinskaja, A.; Fechter, M.; Pochlauer, P.; Castelijns, A.M.C.F.; Van Maarseveen, J.H.; Hiemstra, H.; Griengl, H.; Schoemaker, H.E.; Rutjes, F.P.J.T.Adv.Synth.Catal.2003,345,483.].The cyclic n nitroso compound of optical purity isoindole-5-ketone structure in the past, N-acetal is all obtained by metering method of asymmetric synthesis, up to now, also do not apply the cyclic n nitroso compound that asymmetry catalysis method obtains optical purity isoindolone structure, the report of N-acetal, we have invented the cyclic n nitroso compound that optical purity isoindolone structure is prepared in a kind of efficient catalysis asymmetric synthesis, the method for N-acetal for this reason.
Summary of the invention
The object of the present invention is to provide a kind of asymmetry catalysis synthesis of chiral cyclic n nitroso compound efficiently, the method for N-acetal.
To achieve these goals, the present invention adopts following technical scheme:
One class optical homochiral cyclic n nitroso compound, the synthetic method of N-acetal, comprises the following steps: having or do not having or under molecular sieve existent condition, temperature of reaction is in the organic solvent of-85-100 DEG C, the aliphatic diamine replaced with adjacent formylbenzoate ester and N-for raw material, with chirality acid catalyst or chiral oxazoline/metal-salt carry out condensation reaction as catalyzer, generate and atom N to occur in molecule to imines addition amidated cascade reaction simultaneously after imines, react after 5 minutes to 72 hours, separation obtains product, and the mol ratio of the aliphatic diamine that described adjacent formylbenzoate ester, N-replace and chiral catalyst is 1:1.2-2:0.02-0.2;
Synthesized optical purity cyclic n nitroso compound, N-acetal compound has following general structure:
N=0 in structural formula, 1, 2, 3, when 4, compound represents 1-respectively and replaces-2, 3-dihydro-1H-imidazoles [2, 1-a] and isoindole-5-ketone, 1-replaces-1, 3, 4, 10b-tetrahydropyrimidine [2, 1-a] isoindole-6 (2H)-one compound, 1-replaces-2, 3, 4, 5-tetrahydrochysene-1H-[1, 3] phenodiazine Zhuo [2, 1-a] isoindole-7 (11bH)-one, 1-replaces-1, 3, 4, 5, 6, 12b-six hydrogen-[1, 3] the pungent cycloalkanes [2 of diaza, 1-a] isoindole-8 (2H)-one, 1-replaces-2, 3, 4, 5, 6, 7-octahydro-1H-[1, 3] diaza cycloalkanes in the ninth of the ten Heavenly Stems [2, 1-a] isoindole-9 (13bH)-one, R 1be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, C2-C16 carbonyl, aryl, aromatic heterocycle, substituted benzyl,
R 2, R 3, R 4, R 5be selected from H, F, Cl, Br, I, C1-C16 alkyl, C1-C16 alkoxyl group, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, C2-C16 cyano group, NO 2, CF 3, SO 3h, aldehyde radical, hydroxyl, carboxyl, amino, amide group, aryl, aromatic heterocycle, substituted benzyl;
R 6, R 7, R 8, R 9be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, oxygen alkyl carbonyl, cyano group, substituted benzyl;
R 10be selected from H, C1-C16 alkyl, C3-C16 thiazolinyl, C3-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, aryl, aromatic heterocycle, substituted benzyl;
Wherein R 11, R 12, R 13, R 14, R 15be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, cyano group, NO 2, CF 3, SO 3h, aldehyde radical, hydroxyl, carboxyl, amino, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, and described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10;
The structure of described adjacent acyl group benzoic ether is: r 16for being selected from arbitrarily C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is selected from the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10; Described N-replaces aliphatic diamine structural formula: wherein n=0,1,2,3,4;
Described chiral catalyst structure is selected from: (R or S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R or S) (R or S) (R or S) (R or S)
(R, R) or (S, S) (R or S) (R or S) (R or S) (R or S) (R or S) tartrate; Described Shou bisoxazoline ligand structure is selected from: (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R, R) or (S, S, S) (R a, R, R) or (S a, S, S) (R a, R, R) or (S a, S, S) (R p, R, R) or (S p, S, S) (R, R) or (S, S) metal-salt used is: Sc (OTf) 3, Yb (OTf) 3, La (OTf) 3, Y (OTf) 3, Cu (OTf) 2or Zn (OTf) 2;
Wherein R 17be selected from H, C1-C16 alkyl, three (C1-C16 alkyl) are silica-based or three virtues are silica-based; R 18for being selected from arbitrarily H, F, Cl, Br, I, C1-C16 alkyl, three (C1-C16 alkyl) are silica-based or three virtues are silica-based; R 19for being selected from OH, NH arbitrarily 2, NHSO 2r 20, NHPO (R 20), NHPO (OR 20), wherein R 20for being selected from arbitrarily H, C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10; R 21for being selected from, C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10.
In above-mentioned synthetic method, described organic solvent is preferably benzene,toluene,xylene, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin, sherwood oil, normal hexane, tetrahydrofuran (THF), dimethyl formamide, N,N-DIMETHYLACETAMIDE, ether, hexanaphthene, normal heptane, Skellysolve A, dioxane, glycol dimethyl ether, methyl tertiary butyl ether or acetonitrile, solvent can be wherein a kind of or two or more mixed solvent.
In above-mentioned synthetic method, the product obtained is separated by recrystallization, column chromatography, thin-layer chromatography or underpressure distillation.
In above-mentioned synthetic method, the mol ratio of the aliphatic diamine that described adjacent formylbenzoate ester, N-replace and chiral catalyst is 1:1.2-2:0.02-0.2.
In above-mentioned synthetic method, the product obtained be configured as R or S.
Compared with prior art, the present invention has following beneficial effect: the present invention is with chirality acid or Shou bisoxazoline/metal-salt, as catalyzer, are being with or without under molecular sieve existent condition, and N substituting group aliphatic diamine is connected with adjacent formylbenzoate ester asymmetric imines condensation-addition-amidate action, synthesising target compound.Reaction yield is high, and enantioselectivity is good, and mild condition is simple to operate, environmental friendliness.Simultaneously substrate has the feature of wide accommodation, is applicable to the adjacent formylbenzoate ester compound of all kinds of replacement and various chain replaces and the aliphatic diamine of chain length and aromatic diamines, is very suitable for the synthesis of medicine and intermediate thereof.
Embodiment
The following example contributes to the understanding of the present invention, but does not limit content of the present invention.
Embodiment 1: preparation N 1-alkyl replacement-1，2-diaminoethane
By N 1-tertbutyloxycarbonyl replacement-1，2-diaminoethane (30mmol) and equimolar aldehyde are dissolved in 100mL methyl alcohol, stir lower reflux water-dividing reaction 0.5-4h, then cool to room temperature, add NaBH 4(30mmol), reaction 1-5h, reaction terminates rear 50mL dichloromethane extraction three times, anhydrous magnesium sulfate drying, concentrating under reduced pressure, and column chromatography obtains product (elutriant: ethyl acetate/methanol).Be dissolved in by the pure products obtained and absorb in ethyl acetate that HCl gas reaches capacity, stirring at room temperature 2-8h, adds acid in sodium hydroxide He excessive, extraction into ethyl acetate.Anhydrous magnesium sulfate drying, concentrating under reduced pressure is dry obtains substrate N 1-alkyl replacement-1，2-diaminoethane.
Embodiment 2: the acid catalyzed N of chiral phosphorus 1in-alkyl-1，2-diaminoethane and adjacent acyl radical methyl benzoate generation molecule, N, N-acetalation is prepared optical purity 1-and is replaced-2,3-dihydro-1H-imidazoles [2,1-a] and isoindole-5-ketone compound
Add high-temperature activation in the reaction tubes of drying after molecular sieve (50mg), the toluene of adjacent acyl radical methyl benzoate (0.1mmol) and catalyzer (0.01mmol) and 1mL drying, ice bath adds N under stirring 1-(2,6-di-isopropyl benzyl)-1，2-diaminoethane, react and disappear to raw material with TLC monitoring, column chromatography (elutriant: petrol ether/ethyl acetate) obtains product.The chiral phosphoric acid catalyzer used when the present embodiment is:
Chirality 1-replaces-2,3-dihydro-1H-imidazoles [2,1-a] and isoindole-5-ketone product 1:
31.1mg,(Flash?column?chromatography?eluent,petroleum?ether:ethyl?acetate＝10:1),white?solid:m.p.119.0-120.1℃； 89％yield,96％ee；HPLC?Analysis:Daicel?Chiralpak?OD-H?columm，n-heptane:i-PrOH＝95:5,flow?rate?1.0mL/min,λ＝225nm，t major＝9.74min,t minor＝10.75min。 1h NMR (300MHz, CDCl 3) δ: 7.84-7.82 (m, 1H), 7.54-7.51 (m, 5H), 4.90 (s, 1H), 4.13 (d, J=12.3Hz, 1H), 3.87 (d, J=12.3Hz, 1H), 3.69-3.63 (m, 1H), 3.47-3.21 (m, 4H), 3.06-2.91 (m, 1H), 1.11 (d, J=6.9Hz, 6H), 1.05 (d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 173.4,148.7,143.6,133.8,131.7,130.5,129.5,127.9,124.4,123.6,123.0,81.20,54.8,46.9,41.9,28.7,24.5,23.7; High resolution mass spectrum (ESI) m/z calculated value C 23h 29n 2o [M+H] +324.2280, measured value 324.2290.
34.0mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.121.3-122.1 DEG C; 93%yield, 95%ee; HPLC Analysis:Daicel Chiralpak OD-H columm:n-heptane:i-PrOH=99:1, flow rate:1.0mL/min, λ=225nm:t major=16.13min, t minor=14.76min; 1h NMR (300MHz, CDCl 3) δ: 7.47 (d, J=7.2Hz, 1H), 7.28-7.10 (m, 5H), 4.90 (s, 1H), 4.13 (d, J=12.3Hz, 1H), 3.87 (d, J=12.3Hz, 1H), 3.69-3.64 (m, 1H), 3.46-3.21 (m, 4H), 3.05-2.97 (m, 1H), 1.11 (d, J=6.9Hz, 6H), 1.07 (d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 172.0 (d, J=3.0Hz), 163.5 (d, J=247.6Hz), 148.5,139.3 (d, J=2.5Hz), 136.1 (d, J=8.4Hz), 130.4,128.1,124.9 (d, J=8.3Hz), 123.1,119.0 (d, J=23.3Hz), 111.1 (d, J=23.1Hz), 80.7,54.9,47.2,41.8,28.8,24.5,23.7; High resolution mass spectrum (ESI) calculated value C 23h 28n 2oF [M+H] +367.2180, measured value 367.2188. 35.0mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.93.7-94.2 DEG C; 92%yield, 92%ee; HPLC Analysis:Daicel Chiralpak OD-H columm:n-heptane:i-PrOH=99:1, flow rate:1.0mL/min, λ=225nm:t major=15.94min, t minor=14.27min; 1h NMR (300MHz, CDCl 3) δ: 7.78 (d, J=1.8Hz, 1H), 7.47-7.43 (m, 1H), 7.28-7.23 (m, 1H), 7.11 (d, J=7.8Hz, 3H), 4.90 (s, 1H), 4.12 (d, J=12.6Hz, 1H), 3.87 (d, J=12.6Hz, 1H), 3.66 (d, J=9.9,8.1Hz, 1H), 3.46-3.20 (m, 4H), 3.06-3.02 (m, 1H), 1.11 (d, J=6.9Hz, 6H), 1.08 (d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 171.8,148.5,141.9,135.8,135.7,131.8,130.4,128.1,124.6,124.5,123.1,80.9,55.0,47.3,41.9,28.8,24.5,23.8; High resolution mass spectrum (ESI) m/z calculated value C 23h 28n 2oCl [M+H] +383.1885, measured value 383.1889.
39.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.97.9-98.8 DEG C; (c=2.0, CHCl 3); 93%yield, 92%ee; HPLC Analysis:Daicel Chiralpak OD-H columm:n-heptane:i-PrOH=99:1, flow rate:1.0mL/min, λ=225nm:t major=17.36min, t minor=15.11min; 1h NMR (300MHz, CDCl 3) δ: 7.94 (s, 1H), 7.60 (d, J=8.1Hz, 1H), 7.26-7.23 (m, 1H), 7.12-7.03 (m, 3H), 4.89 (s, 1H), 4.12 (d, J=12.3Hz, 1H), 3.87 (d, J=12.3Hz, 1H), 3.72-3.63 (m, 1H), 3.46-3.21 (m, 4H), 3.02 (dd, J=17.7,9.9Hz, 1H), (1.11 d, J=6.6Hz, 6H), (1.08 d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 171.5,148.4,142.3,135.8,134.5,130.3,128.1,127.4,124.9,123.5,123.1,80.9,54.9,47.3,41.7,28.8,24.5,23.8; High resolution mass spectrum (ESI) m/z calculated value C 23h 28n 2oBr ([M+H] +) 427.1379, measured value 427.1386.
39.2mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.148.5-149.8 DEG C; 92%yield, 96%ee; HPLC Analysis:Daicel Chiralpak OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=10.30min, t minor=16.91min; 1h NMR (300MHz, CDCl 3) δ: 7.63 (s, 1H), 7.35-7.22 (m, 3H), 7.11 (d, J=7.8Hz, 3H), 4.90 (s, 1H), 4.15 (d, J=12.3Hz, 1H), 3.83 (d, J=12.3Hz, 1H), 3.65 (dd, J=18.0,9.9Hz, 1H), 3.45-3.39 (m, 1H), 3.32-3.23 (m, 3H), 3.00 (dd, J=17.7,9.3Hz, 1H), 2.47 (s, 3H), 1.13 (d, J=6.6Hz, 6H), 1.06 (d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 173.6,148.5,140.9,139.6,134.0,132.6,130.6,128.0,124.6,123.0,81.1,54.8,46.9,41.8,28.7,24.6,23.8,21.4; High resolution mass spectrum (ESI) m/z calculated value C 24h 31n 2o ([M+H] +) 363.2436, measured value 363.2438.
34.0mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=5:1), white solid:m.p.154.5-155.8 DEG C; 90%yield, 94%ee; HPLC Analysis:Daicel Chiralpak OJ-H columm:n-heptane:i-PrOH=90:10, flow rate:1.0mL/min, λ=225nm:t major=21 .28min, t minor=15.49min; 1h NMR (300MHz, CDCl 3) δ: 7.30-7.04 (m, 6H), 4.87 (s, 1H), 4.12 (d, J=12.6Hz, 1H), 3.87-3.80 (m, 4H), 3.63 (dd, J=18.0,9.0Hz, 1H), 3.45-3.39 (m, 1H), 3.29-3.23 (m, 3H), 3.03-2.95 (m, 1H), 1.12 (d, J=6.6Hz, 6H), 1.06 (d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 173.3,160.9,148.5,136.0,135.4,130.6,127.9,124.1,123.0,119.7,107.1,80.9,55.6,54.8,46.9,41.8,28.7,24.5,23.7; High resolution mass spectrum (ESI) m/z calculated value C 23h 28n 2o 2[M+H] +379.2380, measured value 379.2391.
35.4mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=5:1), white solid:m.p.165.8-166.5 DEG C; 90%yield, 91%ee; HPLC Analysis:Daicel Chiralpak AS-H columm:n-heptane:i-PrOH=90:10, flow rate:1.0mL/min, λ=225nm:t major=17.81min, t minor=13.79min; 1h NMR (300MHz, CDCl 3) δ: 8.59 (s, 1H), 8.29 (dd, J=8.4,1.8Hz, 1H), 7.31-7.26 (m, 1H), 7.14-7.07 (m, 3H), 5.02 (s, 1H), 4.18 (d, J=12.6Hz, 1H), 3.98 (d, J=12.6Hz, 1H), 3.81-3.72 (m, 1H), 3.53-3.39 (m, 2H), 3.31-3.22 (m, 2H), 3.13-3.04 (m, 1H), (1.11 d, J=6.6Hz, 6H), (1.08 d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 170.40,149.3,149.0,148.5,135.5,130.1,128.4,126.5,124.7,123.3,119.6,80.8,55.4,47.9,41.9,28.9,24.4,23.8; High resolution mass spectrum (ESI) m/z calculated value C 23h 28n 3o 3[M+H] +394.2125, measured value 394.2132.
34.4mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.127.8-128.7 DEG C; 94%yield, 96%ee; HPLC Analysis:Daicel Chiralpak OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=12.99min, t minor=17.18min; 1h NMR (300MHz, CDCl 3) δ: 7.78 (dd, J=8.4,5.1Hz, 1H), 7.30-7.11 (m, 4H), 6.79 (dd, J=8.4,1.8Hz, 1H), 4.90 (s, 1H), 4.13 (d, J=12.3Hz, 1H), 3.89 (d, J=12.3Hz, 1H), 3.70-3.64 (m, 1H), 3.46-3.23 (m, 4H), 3.02 (dd, J=14.7,9.3Hz, 1H), (1.11 d, J=6.9Hz, 6H), (1.08 d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 172.3,165.1 (d, J=251.0Hz), 148.5,146.2 (d, J=9.3Hz), 130.4,129.7 (d, J=2.1Hz), 128.2,126.2 (d, J=9.6Hz), 123.1,117.0 (d, J=23.2Hz), 111.1 (d, J=24.4), 80.7,55.2,47.4,41.9,28.9,24.5,23.8; High resolution mass spectrum m/z calculated value C 23h 28n 2oF [M+H] +367.2180 measured value 367.2183.
35.1mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.175.2-175.8 DEG C; 92%yield 96%ee; HPLC Analysis:Daicel Chiralpak OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=10.13min, t minor=15.72min; 1h NMR (300MHz, CDCl 3) δ: 7.72 (d, J=8.1Hz, 1H), 7.47 (d, J=8.1Hz, 1H), 7.30-7.25 (m, 1H), 7.14-7.06 (m, 3H), 4.91 (s, 1H), 4.14 (d, J=12.6Hz, 1H), 3.89 (d, J=12.6Hz, 1H), 3.74-3.65 (m, 1H), 3.46-3.20 (m, 4H), 3.47-3.22 (m, 4H), 3.07-2.98 (m, 1H), (1.12 d, J=6.9Hz, 6H), (1.09 d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 172.3,148.5,145.3,138.2,132.1,130.3,129.9,128.3,125.4,124.1,123.1,80.6,55.3,47.5,41.9,28.8 .24.4,23.8; High resolution mass spectrum m/z calculated value C 23h 28n 2oCl [M+H] +383.1885, measured value 383.1889.
39.2mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.179.6-180.8 DEG C; 92%yield, 96%ee; HPLC Analysis:Daicel Chiralpak OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=10.30min, t minor=16.91min; 1h NMR (300MHz, CDCl 3) δ: 7.67-7.61 (m, 2H), 7.28-7.12 (m, 4H), 4.91 (s, 1H), 4.14 (d, J=12.6Hz, 1H), 3.89 (d, J=12.6Hz, 1H), 3.74-3.65 (m, 1H), 3.47-3.22 (m, 4H), 3.08-2.99 (m, 1H), 1.12 (d, J=7.2Hz, 6H), 1.09 (d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 172.4,148.5,145.5,132.8,132.5,130.3,128.3,127.1,126.5,125.6,123.1,80.6,55.3,47.5,41.9,28.8,24.4,23.8; High resolution mass spectrum m/z calculated value C 23h 28n 2oBr ([M+H] +) 427.1379, measured value 427.1386.
37.8mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.177.4-179.2 DEG C; cHCl 3); 91%yield, 92%ee; HPLC Analysis:Daicel Chiralcel OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=7.81min, t minor=11.83min; 1h NMR (300MHz, CDCl 3) δ: 7.90 (d, J=8.1Hz, 1H), 7.78 (d, J=7.8Hz, 1H), 7.30-2.25 (m, 2H), 7.12 (d, J=7.8Hz, 2H), 5.00 (s, 1H), 4.18 (d, J=12.3Hz, 1H), 3.94 (d, J=12.3Hz, 1H), 3.80-3.71 (m, 1H), 3.53-3.41 (m, 2H), 3.30-3.21 (m, 2H), 3.13-3.04 (m, 1H), (1.08 d, J=6.6Hz, 12H); 13c NMR (100MHz, CDCl 3) δ: 171.6,148.4,144.3,137.0,133.6 (q, J=32.3Hz), 130.2,128.4,126.7 (d, J=3.7Hz), 124.7,123.6 (q, J=271.2), 123.2,120.92 (q, J=3.8Hz); High resolution mass spectrum m/z calculated value C 24h 28n 2oF 3([M+H] +) 417.1950, measured value 417.1948.
34.4mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=5:1), white solid:m.p.201.5-203 DEG C; cHCl 3); 91%yield, 90%ee; HPLC Analysis:Daicel ChiralpakAS-H columm:n-heptane:i-PrOH=90:10, flow rate:1.0mL/min, λ=225nm:t major=23.81min, t minor=10.78min; 1h NMR (300MHz, CDCl 3) δ: 7.72 (d, J=8.4Hz, 1H), 7.27-7.22 (m, 1H), 7.13 (d, J=7.5Hz, 2H), 7.02 (dd, J=8.4,2.1Hz, 1H), 6.79 (d, J=2.1Hz, 1H), 4.89 (s, 1H), 4.16 (d, J=12.3Hz, 1H), 3.87-3.82 (m, 4H), 3.71-3.61 (m, 1H), 3.43-3.26 (m, 4H), 3.05-2.96 (m, 1H), (1.13 d, J=6.9Hz, 6H), (1.08 d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 173.3,160.9,148.5,136.0,135.4,130.6,127.9,124.1,123.0,119.7,107.1,81.0,55.6,54.8,46.9,41.8,28.7,24.5,23.7; High resolution mass spectrum m/z calculated value C 24h 31n 2o 2([M+H] +) 379.2380, measured value 379.2376.
32.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:m.p.156.2-158.0 DEG C; 90%yield, 92%ee; HPLC Analysis:Daicel Chiralcel OJ-H columm:n-heptane:i-PrOH=98:2, flow rate:1.0mL/min, λ=225nm:t major=10.68min, t minor=14.45min; 1h NMR (300MHz, CDCl 3) δ: 7.69 (d, J=7.5Hz, 1H), 7.32-7.22 (m, 2H), 7.12-7.08 (m, 3H), 4.89 (s, 1H), (4.16 d, J=12.6Hz, 1H), (3.84 d, J=12.6Hz, 1H), 3.71-3.62 (m, 1H), 3.45-3.23 (m, 4H), 3.05-2.96 (m, 1H), 2.42 (s, 3H), 1.11 (d, J=6.6Hz, 6H), 1.06 (d, J=6.6Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 173.8,148.5,144.1,142.4,131.1,130.7,130.3,127.9,124.0,123.9,123.0,81.1,55.1,47.1,41.9,28.7,24.5,23.7,21.8; High resolution mass spectrum m/z calculated value C 24h 31n 2o ([M+H] +) 363.2430, measured value 363.2431.
The chiral phosphoric acid catalyzer used when the present embodiment is:
The product that obtains obtains product: 36.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:90%yield, 50%ee; HPLCAnalysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t major=9.74min, t minor=10.75min.
The chiral phosphoric acid catalyzer used when the present embodiment is:
Institute obtains product: 36.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:90%yield, 52%ee; HPLC Analysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t major=9.74min, t minor=10.75min.
The chiral phosphoric acid catalyzer used when the present embodiment is:
The product that obtains obtains product: 37.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:91%yield, 65%ee; HPLC Analysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t major=9.74min, t minor=10.75min.
The chiral phosphoric acid catalyzer used when the present embodiment is:
Institute obtains product
The product that obtains obtains product: 35.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:89%yield, 70%ee; HPLC Analysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t major=9.74min, t minor=10.75min.
Embodiment 3: chiral oxazoline/acid catalyzed N of metal Lewis 1in-alkyl-1，2-diaminoethane and adjacent acyl radical methyl benzoate generation molecule, N, N-acetalation is prepared optical purity 1-and is replaced-2,3-dihydro-1H-imidazoles [2,1-a] and isoindole-5-ketone compound
Add high-temperature activation in the reaction tubes of drying after molecular sieve (50mg), adjacent acyl radical methyl benzoate (0.1mmol) and chiral oxazoline part (0.01mmol), Sc (OTf) 3with the toluene of 1mL drying, under stirring at normal temperature, add N 1-(2,6-di-isopropyl benzyl)-1，2-diaminoethane, react and disappear to raw material with TLC monitoring, column chromatography (elutriant: petrol ether/ethyl acetate) obtains product.The chiral oxazoline part that the present embodiment is used is:
The product obtained is:
26.8mg,(Flash?column?chromatography?eluent,petroleum?ether:ethyl?acetate＝10:1),white?solid:77％yield,62％ee；HPLC?Analysis:Daicel?Chiralpak?OD-H?columm，n-heptane:i-PrOH＝95:5,flow?rate?1.0mL/min,λ＝225nm，t minor＝9.74min,t major＝10.75min。
Embodiment 4: chiral thiourea catalyzing N 1n, N-acetalation in-alkyl-1，2-diaminoethane and adjacent acyl radical methyl benzoate generation molecule, prepare optical purity 1-and replace-2,3-dihydro-1H-imidazoles [2,1-a] and isoindole-5-ketone compound:
Add high-temperature activation in the reaction tubes of drying after molecular sieve (50mg), the toluene of adjacent acyl radical methyl benzoate (0.1mmol) and chiral thiourea (0.01mmol) and 1mL drying, adds N under stirring at normal temperature 1-(2,6-di-isopropyl benzyl)-1，2-diaminoethane, react and disappear to raw material with TLC monitoring, column chromatography (elutriant: petrol ether/ethyl acetate) obtains product.The chiral thiourea catalyzer that the present embodiment uses is:
The product obtained is: 36.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:93%yield, 70%ee; HPLC Analysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t major=9.74min, t minor=10.75min.
Embodiment 5: the N of chiral squaric acid amide catalysis 1in-alkyl-1，2-diaminoethane and adjacent acyl radical methyl benzoate generation molecule, N, N-acetalation is prepared optical purity 1-and is replaced-2,3-dihydro-1H-imidazoles [2,1-a] and isoindole-5-ketone compound:
Add high-temperature activation in the reaction tubes of drying after molecular sieve (50mg), the toluene of adjacent acyl radical methyl benzoate (0.1mmol) and chiral squaric acid amide (0.01mmol) 1mL drying, adds N under stirring at normal temperature 1-(2,6-di-isopropyl benzyl)-1，2-diaminoethane, react and disappear to raw material with TLC monitoring, column chromatography (elutriant: petrol ether/ethyl acetate) obtains product.The chiral squaric acid amide that the present embodiment uses is: (S)
The product obtained is: 35.5mg, (Flash column chromatography eluent, petroleum ether:ethyl acetate=10:1), white solid:91%yield, 68%ee; HPLC Analysis:Daicel Chiralpak OD-H columm, n-heptane:i-PrOH=95:5, flow rate 1.0mL/min, λ=225nm, t minor=9.74min, t major=10.75min.
Embodiment 6: the acid catalyzed N of chiral phosphorus 1in-alkyl-1,2-propylene diamine and adjacent acyl radical methyl benzoate generation molecule, N, N-acetalation is prepared optical purity 1-and is replaced-2,3,4,5-tetrahydrochysene-1H-[1,3] phenodiazine Zhuo [2,1-a] isoindole-7 (11bH)-one compound:
Add high-temperature activation in the reaction tubes of drying after molecular sieve (50mg), the toluene of adjacent acyl radical methyl benzoate (0.1mmol) and catalyzer (0.01mmol) and 1mL drying, ice bath adds N under stirring 1-(2,6-di-isopropyl benzyl)-1,3-propylene diamine, react and disappear to raw material with TLC monitoring, column chromatography (elutriant: petrol ether/ethyl acetate) obtains product.The chiral phosphoric acid catalyzer that the present embodiment is used is:
Chirality 1-replaces-2,3,4,5-tetrahydrochysene-1H-[1,3] phenodiazine Zhuo [2,1-a] isoindole-7 (11bH)-one product
32.5mg,(Flash?column?chromatography?eluent,petroleum?ether:ethyl?acetate＝10:1),white?solid:m.p.126.0-128.1℃； 89％yield,66％ee；HPLC?Analysis:Daicel?Chiralpak?OD-H?columm，n-heptane:i-PrOH＝95:5,flow?rate?1.0mL/min,λ＝225nm，t major＝7.28min,t minor＝9.75min。 1h NMR (300MHz, CDCl 3) δ: 7.92-7.89 (m, 1H), 7.62-7.50 (m, 3H), 7.23-7.20 (m, 1H), 5.06 (s, 1H), 4.53-4.47 (m, 1H) 4.08 (d, J=12.3Hz, 1H), 3.57 (d, J=12.3Hz, 1H), 3.59-3.08 (m, 3H), 2.92 (d, J=12.3Hz, 1H), 2.74-2.65 (m, 1H), 1.87-1.70 (m, 1H), 1.77-1.55 (m, 1H) 1.11 (d, J=6.9Hz, 6H), (1.05 d, J=6.9Hz, 6H); 13c NMR (100MHz, CDCl 3) δ: 165.9,148.9,141.7,133.5,130.7,130.6,129.1,127.6,124.1,123.9,122.7,76.7,48.3,44.3,38.9,28.7,24.5,24.0,22.4; High resolution mass spectrum (ESI) m/z calculated value C 23h 29n 2o [M+H] +363.2436, measured value 363.2455.

Claims (5)

1. a class optical homochiral cyclic n nitroso compound, the synthetic method of N-acetal, is characterized in that comprising the following steps: having or do not having or under molecular sieve existent condition, temperature of reaction is in the organic solvent of-85-100 DEG C, the aliphatic diamine replaced with adjacent formylbenzoate ester and N-for raw material, with chirality acid catalyst or chiral oxazoline/metal-salt carry out condensation reaction as catalyzer, generate and atom N to occur in molecule to imines addition amidated cascade reaction simultaneously after imines, react after 5 minutes to 72 hours, separation obtains product, and the mol ratio of the aliphatic diamine that described adjacent formylbenzoate ester, N-replace and chiral catalyst is 1:1.2-2:0.02-0.2;
Synthesized optical purity cyclic n nitroso compound, N-acetal compound has following general structure:
N=0 in structural formula, 1, 2, 3, when 4, compound represents 1-respectively and replaces-2, 3-dihydro-1H-imidazoles [2, 1-a] and isoindole-5-ketone, 1-replaces-1, 3, 4, 10b-tetrahydropyrimidine [2, 1-a] isoindole-6 (2H)-one compound, 1-replaces-2, 3, 4, 5-tetrahydrochysene-1H-[1, 3] phenodiazine Zhuo [2, 1-a] isoindole-7 (11bH)-one, 1-replaces-1, 3, 4, 5, 6, 12b-six hydrogen-[1, 3] the pungent cycloalkanes [2 of diaza, 1-a] isoindole-8 (2H)-one, 1-replaces-2, 3, 4, 5, 6, 7-octahydro-1H-[1, 3] diaza cycloalkanes in the ninth of the ten Heavenly Stems [2, 1-a] isoindole-9 (13bH)-one, R 1be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, C2-C16 carbonyl, aryl, aromatic heterocycle, substituted benzyl,
R 2, R 3, R 4, R 5be selected from H, F, Cl, Br, I, C1-C16 alkyl, C1-C16 alkoxyl group, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, C2-C16 cyano group, NO 2, CF 3, SO 3h, aldehyde radical, hydroxyl, carboxyl, amino, amide group, aryl, aromatic heterocycle, substituted benzyl;
R 6, R 7, R 8, R 9be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, oxygen alkyl carbonyl, cyano group, substituted benzyl;
R 10be selected from H, C1-C16 alkyl, C3-C16 thiazolinyl, C3-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, aryl, aromatic heterocycle, substituted benzyl;
Wherein R 11, R 12, R 13, R 14, R 15be selected from H, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, cyano group, NO 2, CF 3, SO 3h, aldehyde radical, hydroxyl, carboxyl, amino, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, and described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10;
The structure of described adjacent acyl group benzoic ether is: r 16for being selected from arbitrarily C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is selected from the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10; Described N-replaces aliphatic diamine structural formula: wherein n=0,1,2,3,4;
Described chiral catalyst structure is selected from: (R or S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R or S) (R or S) (R or S) (R or S) (R, R) or (S, S) (R or S) (R or S) (R or S) (R or S) (R or S) tartrate; Described Shou bisoxazoline ligand structure is selected from: (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R) or (S, S) (R, R, R) or (S, S, S) (R a, R, R) or (S a, S, S) (R a, R, R) or (S a, S, S) (R p, R, R) or (S p, S, S) (R, R) or (S, S) metal-salt used is: Sc (OTf) 3, Yb (OTf) 3, La (OTf) 3, Y (OTf) 3, Cu (OTf) 2or Zn (OTf) 2;
Wherein R 17be selected from H, C1-C16 alkyl, three (C1-C16 alkyl) are silica-based or three virtues are silica-based; R 18for being selected from arbitrarily H, F, Cl, Br, I, C1-C16 alkyl, three (C1-C16 alkyl) are silica-based or three virtues are silica-based; R 19for being selected from OH, NH arbitrarily 2, NHSO 2r 20, NHPO (R 20), NHPO (OR 20), wherein R 20for being selected from arbitrarily H, C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10; R 21for being selected from, C1-C16 perfluoroalkyl, C1-C16 alkyl, C2-C16 thiazolinyl, C2-C16 alkynyl, C3-C16 cycloalkyl, C3-C16 cycloalkenyl group, C3-C16 cycloalkynyl radical, fragrant heterocycle, aryl or conjugation aromatic ring, described aryl is substituted-phenyl, described conjugation aromatic ring is phenanthryl and anthryl; Described fragrant heterocycle is the heterocyclic group of nitrogenous, sulphur, the Sauerstoffatom of C5-C10.
2. synthetic method as claimed in claim 1, it is characterized in that, described organic solvent is benzene,toluene,xylene, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin, sherwood oil, normal hexane, tetrahydrofuran (THF), dimethyl formamide, N,N-DIMETHYLACETAMIDE, ether, hexanaphthene, normal heptane, Skellysolve A, dioxane, glycol dimethyl ether, methyl tertiary butyl ether or acetonitrile, solvent is wherein a kind of or two or more mixed solvent.
3. synthetic method as claimed in claim 1, it is characterized in that, the product obtained is separated by recrystallization, column chromatography, thin-layer chromatography or underpressure distillation.
4. synthetic method as claimed in claim 1, is characterized in that, the mol ratio of the aliphatic diamine that described adjacent formylbenzoate ester, N-replace and chiral catalyst is 1:1.2-2:0.02-0.2.
5. synthetic method as claimed in claim 1, is characterized in that, the product obtained be configured as R or S.
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