Divergent Asymmetric Total Synthesis of (−)‐Voacafricines A and B

Abstract

AbstractA divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst‐controlled asymmetric Pictet–Spengler reaction of 6‐methoxytryptamine with a chiral α‐ketoester affording a 1,1‐disubstituted tetrahydro‐β‐carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5‐disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8‐alkyl octahydro‐2H‐5,8‐methanofuro[2,3‐b]azepin‐8‐ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.