Enantioselective synthesis of (-)-gilbertine via a cationic cascade cyclization

被引:70
作者
Jiricek, J [1 ]
Blechert, S [1 ]
机构
[1] Tech Univ Berlin, Inst Chem, D-10623 Berlin, Germany
关键词
D O I
10.1021/ja0399021
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Described is the first enantioselective synthesis of (-)-gilbertine (2), a member of the uleine-type family, and the determination of the absolute configuration of this natural product is reported. The key step employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and the construction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reaction to build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivative was achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol was used successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole (20). Furthermore, an unexpected behaviour of this 2,3-disubstituted cyclohexanone derivative during an epimerization process was investigated, resulting in different chemical behaviour of the enantiomers and the racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstrating the versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving (-)-gilbertine in 5.5% overall yield.
引用
收藏
页码:3534 / 3538
页数:5
相关论文
共 34 条
[1]  
ALVAREZ M, 1994, MONOTERPENOID IN 4 S, V25, pCH6
[2]   SHORT FORMAL SYNTHESES OF INDOLE ALKALOIDS OF THE ULEINE AND STRYCHNOS GROUPS [J].
AMAT, M ;
SATHYANARAYANA, S ;
HADIDA, S ;
BOSCH, J .
TETRAHEDRON LETTERS, 1994, 35 (38) :7123-7126
[3]   Palladium(0)-catalyzed heteroarylation of 2- and 3-indolylzinc derivatives. An efficient general method for the preparation of (2-pyridyl)indoles and their application to indole alkaloid synthesis [J].
Amat, M ;
Hadida, S ;
Pshenichnyi, G ;
Bosch, J .
JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (10) :3158-3175
[4]  
BLECHERT S, 1985, LIEBIGS ANN CHEM, P2073
[5]  
BLECHERT S, 1997, ANGES CHEM, V109, P1516
[6]  
BOATMAN S, 1968, C R ORG SYNTH, V48, P40
[7]  
BUCHI G, 1971, J AM CHEM SOC, V93, P2492
[8]   NEW METHOD FOR CONTROLLED HYDROXYMETHYLATION OF KETONES [J].
COREY, EJ ;
CANE, DE .
JOURNAL OF ORGANIC CHEMISTRY, 1971, 36 (20) :3070-&
[9]   TOTAL SYNTHESIS OF (+/-)-DASYCARPIDONE, (+/-)-EPIDASYCARPIDONE, AND (+/-)-EPIULEINE [J].
DOLBY, LJ ;
BIERE, H .
JOURNAL OF ORGANIC CHEMISTRY, 1970, 35 (11) :3843-&
[10]   Tetrathiafulvalene-mediated stereoselective synthesis of the tetracyclic core of Aspidosperma alkaloids [J].
Fletcher, R ;
Kizil, M ;
Lampard, C ;
Murphy, JA ;
Roome, SJ .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1998, (15) :2341-2351