Microbiological oxygenation of bridgehead azabicycloalkanes

被引:29
作者
Davis, CR
Johnson, RA
Cialdella, JI
Liggett, WF
Mizsak, SA
Marshall, VP
机构
[1] Research Laboratories, Pharmacia and Upjohn, Inc., Kalamazoo
[2] Department of Chemistry, Augustana College, Rock Island
关键词
D O I
10.1021/jo962192f
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A series of N-substituted bridgehead azabicycloalkanes has been prepared and examined as substrates for microbiological oxygenation using the fungi Beauveria bassiana, Rhizopus nigricans, Aspergillus ochraceus, and Rhizopus arrhizus. Oxygenation using B. bassiana of N-tosyl-7-azabicyclo[2.2.1]heptane gave N-[p-(hydroxymethyl)benzenesulfonyl]-7-azabicyclo[2.2.1]heptane (56% yield), of N-(phenyloxycarbonyl)-7-azabicyclo[2.2.1]heptane 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-azabicyclo[3.2.1]octane gave the S-endo-ol, and of N-(phenyloxycarbonyl)-9-azabicyclo[3.3.1]nonane gave the 3-exo-ol(30%) and 3-one(16%). Oxygenation using R. nigricans of N-BOC-7-azabicyclo[2.2.1]heptane gave the 2-endo-ol (62% yield, 28% ee) and the 2-exo-ol (27% yield, 42% ec). Oxidation 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%).
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页码:2244 / 2251
页数:8
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