Synthesis of bridged bicyclic hydrazines via endocyclic N-acylhydrazonium intermediates: A novel route to the 1-Azatropane skeleton

Abstract

Bicyclic molecules with the I ,7 -dia2a-6 ,6-dimethylbicyclo[2 .2 .llheptane and l,8-diaza-7,7-dimethylbicyclo[3.11Joctane (l-aza-7/Mimethyltropane) skeleton are shown to be efficiently synthesized via cyclization reactions of endocyclic tf-acylhydrazonium intermediates. By using a protected p-ketoester as the internal nucleophile, azacocaine analogues are also accessible via this methodology.

Synthesis of Cyclic Hydrazino α-Carboxylic Acids

“…Similar conversions with other N-acylhydrazonium species have also been reported. 80,81 Scheme 14 Intramolecular cyclizations of hydrazonium ions Cyclic hydrazonium ions may be generated from the appropriate hydrazone precursors and can be subsequently converted into a-nitrilo hydrazines by addition of cyanide. Following this general strategy, 1,2-pyrazolidine 102a and 1,2-piperazine 102b have been Cbz-protected and oxidized to give pyrazoline intermediates 103 in good yields.…”