Divergent Asymmetric Total Syntheses of (-)-Alloaristoteline and (+)-Aristoteline via Directed Indolization Strategies

Abstract

We have previously demonstrated that ene-hydrazides prepared from enol triflates in regiochemically defined form may undergo Fischer indolization reactions without regiochemical scrambling. As a part of our ongoing research on the regiocontrolled indolization strategy toward indole alkaloid synthesis, we present a new synthetic approach to (-)-alloaristoteline and (+)-aristoteline via directed Fischer indolization strategies. The key common intermediate, doubly-bridged enol triflate, was prepared via a set of reactions including enantioselective deprotonation-silylation and intramolecular Mukaiyama Michael addition. It was successfully bifurcated to complete the first completely synthetic routes to the titled natural alkaloids using late-state directed indolization strategies.