A Concise and Versatile Double‐Cyclization Strategy for the Highly Stereoselective Synthesis and Arylative Dimerization of Aspidosperma Alkaloids

Abstract

The monoterpene indole alkaloids represent the largest family of alkaloid natural products whose more than 2,000 members display a broad range of chemical diversity and potent biological activity.1 The structural challenges presented by this family have long been a source of interest, resulting in the development of a variety of inventive synthetic strategies to access various family members. The biogenetically related natural alkaloids N-methylaspidospermidine (1), N-methylquebrachamine (2), and tabernaebovine (3) represent the aspidosperma subfamily of monoterpene indole alkaloids (Figure 1).2-5 The dimeric alkaloid 3, isolated from Tabernaemontana bovina in 1998,2e has a fascinating molecular constitution that exhibits a unique C2–C15′ linkage between two pentacyclic aspidosperma skeletons. While elegant strategies for synthesis of other dimeric monoterpene indole alkaloids have been reported,5 no synthetic solution to the distinctive C2–C15′ union present in 3 exists. As an outgrowth of our laboratory's studies concerning electrophilic amide activation,6 we report a concise and convergent strategy for the enantioselective synthesis of alkaloids (–)-1, (+)-2, and dimeric (+)-dideepoxytabernaebovine (4).