Stereoselective synthesis of spirocyclic derivatives of functionalized 2,3,4,7-tetrahydro-1H-azepines

Abstract

A simple and effective stereoselective synthesis of unique azaspirocyclic 2,3,4,7-tetrahydro-1H-azepine derivatives, namely, 7-azaspiro[4.6]undec-9-ene and 8-azaspiro[5.6]- dodec-10-ene, from simple commercially available reagents was accomplished. Their key 1,2-epoxy derivatives as individual diastereomers were obtained in nine steps with 31–32% overall yields. The possibility of synthesizing a library of small spiroheterocyclic molecules was exemplified by the N-Boc-protected (1RS,2SR,6RS)-1,2-epoxy-8-aza- spiro[5.6]dodec-10-ene scaffold through simple chemical modifications of its epoxide function.