The application of C–H bond functionalization in the total syntheses of indole natural products

Abstract

The direct functionalization of unactivated C–H bonds has been a rapidly growing field in organic chemistry in recent years because of its indisputable advantages in bond forming reactions in terms of step and atom-economy. On the other hand, indole natural products compose a major family of natural products which attract synthetic chemists because of their intriguing structural features and diverse biological properties. Over the past two decades, important advances have been achieved in the synthesis of natural products including indole natural products by strategically applying C–H functionalization tactics, which enabled bond formation previously not possible and ultimately improved markedly the synthetic efficiency. Progress before 2016 in this area has been overviewed in several elegant review articles. With the methodology development since 2016, many more challenging indole natural products have been synthesized using C–H functionalization as a key transformation. This review will focus on the application of C–H bond functionalization in the total synthesis of indole natural products from the beginning of the year 2016 to Sep. 2021. We first summarize the synthesis of several indole natural alkaloids through the functionalization of C(sp²)–H bonds. Subsequently, the utilization of C(sp³)–H bond functionalization for the synthesis of some indole natural products is described.