Premium
Synthesis of 1‐azabicyclic systems by double cyclization
Author(s) -
Oka Mitsuru,
Baba Kunihisa,
Hamajima Hitoshi,
Unno Ryoichi,
Matsumoto Yukiharu,
Nakamura Kensuke,
Dong Lulu
Publication year - 2003
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570400126
Subject(s) - chemistry , nonane , octane , decane , diastereomer , ring (chemistry) , bicyclic molecule , stereochemistry , double bond , medicinal chemistry , organic chemistry
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.