ASYMMETRIC ELECTROPHILIC ALPHA-AMIDOALKYLATION .10. A NEW CAMPHORIMIDE DERIVED CHIRAL AUXILIARY FOR THE ASYMMETRIC-SYNTHESIS WITH N-ACYLIMINIUM IONS - PREPARATION OF ARACEMIC 2-SUBSTITUTED PIPERIDINES

[摘要] Compound 5 is a new alpha-amidoalkylation reagent for the asymmetric synthesis of 2-substituted piperidines. Its chiral auxiliary 3 is derived from camphoric acid and designed for an asymmetric induction mechanism featuring precomplexation as the decisive step for stereodifferentiation. Reagent 5 can smoothly be alkylated with various organometallic reagents after is activation by HCl-addition which presumably results in alpha-chloroamide 6. Organozinc and organoaluminum compounds appear to give the best results with the highest diastereoselectivities being 97.8/2.2 for the ethylation (7a/8a), 87.7/12.3 for the methylation (7b/8b), 96.5/3.5 for the butylation (7c/8c) and 90.4/9.6 for the phenylation (7d/8d) of 5. From the alpha-amidoalkylation products 7a-d the corresponding optically active 2-substituted piperidinium chlorides 9a-d can be obtained by removal of the chiral auxiliary which removal may be accomplished either through reduction with LiAlH4 or by hydrolysis with KOH.

[发布日期] 1994-03-07

[关键词] ASYMMETRIC SYNTHESIS;ALPHA-AMIDOALKYLATION;2-SUBSTITUTED PIPERIDINES;PRECOMPLEXATION