1-Azaspiro Annelation: A Synthetic Approach to Naturally Occurring Heterocyclic Spiranes

Abstract

The synthesis of 1-azaspiro[4, 4]nonans, -[4, 5]decanes and -[5, 5]undecanes has attracted considerable attention in recent years with special interest in natural products such as histrionacotoxin,¹ serratinine² and harringtonine.³ We have been investigating several synthetic approaches to these systems in hopes of developing one general approach to all such compounds. We were particularly interested in simplicity and chose to utilize a preformed, readily accessible, carbocyclic ring to which the spiro-heterocyclic or nitrogen containing ring would be attached. Illustrative of these general considerations was the approach shown in Scheme I.