ABSTRACT
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 delta-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.
Subject(s)
Benzene/chemistry , Indoles/chemistry , Quinolizines/chemistry , Alkaloids/chemistry , Cyclization , Molecular Structure , Phenylalanine/analogs & derivatives , Phenylalanine/chemistry , Quinolizines/chemical synthesis , Stereoisomerism , Tryptophan/analogs & derivatives , Tryptophan/chemistryABSTRACT
A straightforward procedure for the synthesis of enantiopure polysubstituted piperidines is reported. It involves the direct generation of chiral non-racemic oxazolo[3,2-a]piperidone lactams that already incorporate carbon substituents on the heterocyclic ring and the subsequent removal of the chiral auxiliary. The key step is a cyclocondensation reaction of (R)-phenylglycinol or other amino alcohols with racemic or prochiral delta-oxo (di)acid derivatives in highly stereoselective processes involving dynamic kinetic resolution and/or desymmetrization of diastereotopic or enantiotopic ester groups.
Subject(s)
Piperidines/chemical synthesis , Ethanolamines , Glycine/analogs & derivatives , Glycine/chemistry , Kinetics , Lactams/chemistry , StereoisomerismABSTRACT
[reaction: see text] Racemic oxodiester 1 undergoes stereoselective cyclocondensation with (S)-tryptophanol, (S)-(3,4-dimethoxyphenyl)alaninol, or the corresponding amino acids, in a process involving a tandem dynamic kinetic resolution/desymmetrization of diastereotopic groups, to give bicyclic lactams, which are cyclized to substituted indolo[2,3-a]- and benzo[a]quinolizidines.
Subject(s)
Biological Products/chemical synthesis , Indole Alkaloids/chemical synthesis , Iridoids/chemistry , Amino Acids/chemistry , Biological Products/chemistry , Cyclization , Indole Alkaloids/chemistry , Iridoid Glucosides , Lactams/chemical synthesis , Molecular Structure , Quinolizines/chemistry , StereoisomerismABSTRACT
Cyclocondensation reactions of aminoalcohols and with racemic or prochiral delta-oxoacid derivatives provide polysubstituted lactams with high enantioselectivity in a process that involves dynamic kinetic resolution and/or desymmetrization of enantiotopic or diastereotopic ester groups.
