Enantiopure N-acyldihydropyridones as synthetic intermediates: Asymmetric synthesis of (-)-septicine and (-)-tylophorine

被引:71
作者
Comins, DL
Chen, XH
Morgan, LA
机构
[1] Department of Chemistry, North Carolina State University, Raleigh
关键词
D O I
10.1021/jo9711495
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A concise asymmetric synthesis of(-)-septicine (1) and (-)-tylophorine (2) was accomplished with a high degree of stereocontrol in eight and nine steps, respectively. Addition of 4-(1-butenyl)magnesium bromide to 1-acylpyridinium salt 3, prepared in situ from 4-methoxy-3-(triisopropylsilyl)pyridine and the chloroformate of (-)-trans-2-(alpha-cumyl)cyclohexanol, gave a 91% yield of diastereomerically pure dihydropyridone 7. Oxidative cleavage of 7 and subsequent reduction provided alcohol 6 in 81% yield. Conversion of 6 to the chloride followed by treatment with sodium methoxide gave indolizidinone 9 in high yield. Bromination and conjugate reduction of 9 with L-Selectride, and trapping the intermediate enolate with N-(5-chloro-2-pyridyl)triflimide, provided bromovinyl triflate 11. Palladium-catalyzed cross-coupling of excess (3,4-dimethoxyphenyl)zinc bromide and 11 gave (-)-septicine (1). On the basis of this synthesis, (-)-1 was assigned the R configuration. Reaction of 1 with vanadium(V) trifluoride oxide in TFA/CH2Cl2 effected oxidative coupling to give a 68% yield of(-)-tylophorine (2).
引用
收藏
页码:7435 / 7438
页数:4
相关论文
共 39 条
[1]   PHENANTHROINDOLIZIDINE ALKALOIDS FROM TYLOPHORA-TANAKAE [J].
ABE, F ;
IWASE, Y ;
YAMAUCHI, T ;
HONDA, K ;
HAYASHI, N .
PHYTOCHEMISTRY, 1995, 39 (03) :695-699
[2]  
[Anonymous], 1996, Adv. Nitrogen Heterocycl
[3]   ALPHA-AMINO-ACIDS AS CHIRAL EDUCTS FOR ASYMMETRIC PRODUCTS - CHIRALLY SPECIFIC SYNTHESES OF TYLOPHORINE AND CRYPTOPLEURINE [J].
BUCKLEY, TF ;
RAPOPORT, H .
JOURNAL OF ORGANIC CHEMISTRY, 1983, 48 (23) :4222-4232
[4]   SYNTHESIS OF PHENANTHROINDOLIZIDINES .2. SYNTHESIS OF (+/-)-TYLOCREBRINE, (+/-)-TYLOPHORINE, (+/-)-ANTOFINE, AND (+/-)-2,3-DI ETHOXYPHENANTHROINDOLIZIDINE [J].
CHAUNCY, B ;
GELLERT, E .
AUSTRALIAN JOURNAL OF CHEMISTRY, 1970, 23 (12) :2503-&
[5]   A unified strategy for the synthesis of phenanthroizidine alkaloids: Preparation of sterically congested pyridines [J].
Ciufolini, MA ;
Roschangar, F .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (48) :12082-12089
[6]   CHIRAL DIHYDROPYRIDONES AS SYNTHETIC INTERMEDIATES - ASYMMETRIC-SYNTHESIS OF (+)-ELAEOKANINE-A AND (+)-ELAEOKANINE-C [J].
COMINS, DL ;
HONG, H .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (17) :6672-6673
[7]   Anionic cyclizations of chiral 2,3-dihydro-4-pyridones: A five-step, asymmetric synthesis of indolizidine 209D [J].
Comins, DL ;
Zhang, YM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (48) :12248-12249
[8]   N-ACYLDIHYDROPYRIDONES AS SYNTHETIC INTERMEDIATES - A SHORT SYNTHESIS OF (+/-)-INDOLIZIDINE-209B [J].
COMINS, DL ;
ZELLER, E .
TETRAHEDRON LETTERS, 1991, 32 (42) :5889-5892
[9]   N-ACYLDIHYDROPYRIDONES AS SYNTHETIC INTERMEDIATES - SYNTHESIS OF (+/-)-SEPTICINE AND (+/-)-TYLOPHORINE [J].
COMINS, DL ;
MORGAN, LA .
TETRAHEDRON LETTERS, 1991, 32 (42) :5919-5922
[10]   Asymmetric addition of Grignard reagents to chiral 1-acylpyridinium salts: A chiral auxiliary study [J].
Comins, DL ;
GuerraWeltzien, L .
TETRAHEDRON LETTERS, 1996, 37 (22) :3807-3810