MICROBIOLOGICAL OXYGENATION OF BRIDGEHEAD AZABICYCLOALKANES

A series of N-substituted bridgehead azabicycloalkanes has been prepar ed and examined as substrates for microbiological oxygenation using th e fungi Beauveria bassiana, Rhizopus nigricans, Aspergillus ochraceus, and Rhizopus arrhizus. Oxygenation using B. bassiana of N-tosyl-7-aza bicyclo[2.2.1]heptane gave methyl)benzenesulfonyl]-7-azabicyclo[2.2.1] heptane (56% yield), of N-(phenyloxycarbonyl)-7-azabicyclo[2.2.1]hepta ne gave the 2-endo-ol (56% yield, 51% ee), of N-BOC-7-azabicyclo[2.2.1 ]heptane gave the 2-endo-ol (10% yield), of N-Cbz-7-azabicyclo- [2.2.1 ]heptane gave the 2-endo-ol (28%), of N-(phenyloxycarbonyl)-8-azabicyc lo[3.2.1]octane gave the S-endo-ol, and of N-(phenyloxycarbonyl)-9-aza bicyclo[3.3.1]nonane gave the 3-exo-ol(30%) and 3-one(16%). Oxygenatio n using R. nigricans of N-BOC-7-azabicyclo[2.2.1]heptane gave the 2-en do-ol (62% yield, 28% ee) and the 2-exo-ol (27% yield, 42% ec). Oxidat ion of the N-BOC-7-azabicyclo [2.2.1]heptan-2-ols gives the a-ketone, a synthetic intermediate useful for conversion to the natural product, epibatidine. Oxygenation of N-(phenyloxycarbonyl)-7-azabicyclo[2.2.1] heptane using EE. arrhizus gives the a-endo-ol (5% yield, 31% ee) and the 2-exo-ol (18% yield, 22% ec). Oxygenation of N-(phenyloxycarbonyl) -8-azabicyclo[3.2.1]octane using A. ochraceous gives the 3-endo-ol (36 %) and the 3-one (4%).