Synthesis of 1-azabicyclic systems by double cyclization

✍ Scribed by Mitsuru Oka; Kunihisa Baba; Hitoshi Hamajima; Ryoichi Unno; Yukiharu Matsumoto; Kensuke Nakamura; Lulu Dong

• Book ID: 102339981
• Publisher: Journal of Heterocyclic Chemistry
• Year: 2003
• Tongue: English
• Weight: 138 KB
• Volume: 40
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570400126

✦ Synopsis

Abstract

5‐Cyano‐1‐azabicyclo[3.3.0]octane (1) was prepared in one step from 1,7‐dichloro‐4‐heptanone (4) under mild conditions. The application of this method for the preparation of 5‐cyano‐4,6‐dimethyl‐1‐azabicy‐clo[3.3.0]octane (11) gave two diastereomers in equilibrium. The NMR measurements of 11 and its reduced compound 15 showed that the major isomer is the cis‐exo form, and the minor isomer is the trans form. Molecular orbital calculations indicated that the cis‐exo form is more stable than the trans form, in agreement with the experimental results. Furthermore, 6‐cyano‐1‐azabicyclo[4.3.0]nonane (17) and 1‐azabicy‐clo[4.4.0]decane (19), both including a six‐membered ring, were prepared from appropriate haloketones by using this double cyclization method.