SYNTHETIC ASPECTS OF AN ASYMMETRIC NITROGEN-INSERTION PROCESS - PREPARATION OF CHIRAL, NON-RACEMIC CAPROLACTAMS AND VALEROLACTAMS - TOTAL SYNTHESIS OF (-)-ALLOYOHIMBANE

The conversion of a series of prochiral ketones to the corresponding ring-expanded lactams is described. The key step is a stereoelectronically controlled photochemical rearrangement reaction that is carried out on axially dissymmetric oxaziridines derived from the ketone substrates. The stereochemically enriched oxaziridine substrates are prepared by a strategy that utilizes a combination of intraannular and extraannular stereochemical control features. A model for the asymmetric induction imparted by the chiral substituent on nitrogen has been described, and the effect of using various achiral and chiral amines (including double diastereoselectivity) has been assessed. The intrinsic stereoselectivity of the photochemical oxaziridine to lactam rearrangement reaction has been determined for several oxaziridines, including several derived from meso five-membered-ring ketones. The direction of stereoselectivity for the rearrangement reaction in all cases examined was found to depend only on the axial chirality of the substrate oxaziridine and not on stereochemical or conformational factors. The stereoselectivity of the reaction was unambiguously demonstrated for the first time in cyclopentanone derivatives. Finally, an overall scheme for the practical preparation of a series of chiral caprolactams in enantiomerically homogeneous form is described, resulting in overall selectivities ranging from 54:46 to 88:12. This methodology was applied to the synthesis of a key intermediate in benzomorphinan synthesis and to the total synthesis of (-)-alloyohimbane. © 1990, American Chemical Society. All rights reserved.