Straightforward Methodology for the Enantioselective Synthesis of Benzo[a]- and Indolo[2,3-a]quinolizidines

• Published in: Journal of organic chemistry 2007-07, Vol.72 (14), p.5193-5201
• Main Authors: Amat, Mercedes, Santos, Maria M. M, Bassas, Oriol, Llor, Núria, Escolano, Carmen, Gómez-Esqué, Arantxa, Molins, Elies, Allin, Steven M, McKee, Vickie, Bosch, Joan
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Benzene - chemistry; Chemistry; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Indoles - chemistry; Molecular Structure; Organic chemistry; Phenylalanine - analogs & derivatives; Phenylalanine - chemistry; Preparations and properties; Quinolizines - chemical synthesis; Quinolizines - chemistry; Stereoisomerism; Tryptophan - analogs & derivatives; Tryptophan - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo070539g

An enantioselective two-step route to substituted benzo[a]- and indolo[2,3-a]quinolizidines has been developed. It consists of (i) a stereoselective cyclocondensation of a racemic or prochiral δ-oxo(di)ester with either (S)-(3,4-dimethoxyphenyl)alaninol or (S)-tryptophanol in a process involving a dynamic kinetic resolution and/or the differentiation of enantiotopic or diastereotopic ester groups, and (ii) a subsequent stereocontrolled cyclization on the aromatic ring taking advantage of the masked N-acyl iminium ion present in the resulting oxazolopiperidone lactams.