Promising system to reduce epimerization

Abstract

Development of new system which could minimize the epimerization of the a-center at the a-amido radical stage is presented. To study the behaviour of this system, stereoselective synthesis of a-amino compounds via generating a-amido radicals of this system was attempted. The system was prepared by condensation of L-serin methyl ester with methyl phthaladehydate in the presence of triethyl amine. The desired system (tricyclic lactam) was formed in 70% yield and only as the exo isomer. This is the thermodynamically more stable "bowl-like" conformation. The a-alkylated derivative of this tricyclic lactam was prepared via enolate alkylation. The a-alkylated compound was formed in 30% yield and only as the endo isomer. This endo alkylation could be the result of the attack of alkyl group preferentialy from concave face of the "bowl-like" tricyclic lactam. Then methyl esters of tricyclic lactams were directly converted into selenoesters, the radical precursors and radical reactions were carried out via generating a-amido radicals under standared radical reaction conditions. The radical reductions a-unsubstituted system with Bu3SnH and Bu3SnD gave reduced and deuterated products respectively in good yield with higher selectivity favouring exo-isomer while similar reactions with asubstituted system produced reduced and deuterated products also with higher selectivity but favouring endo-isomer. These higher selectivities for the radical reactions could be attributed to the stereoelectronic effect of novel tricyclic system used. The difference of the selectivities between a-substituted and aunsubstituted stage could be rationalized by considering pyramidalization of the tertiary radical center in the transition state of the a-substituted stage.