Recent advances for the catalytic asymmetric construction of medium-sized rings

Abstract

The synthesis of enantioenriched medium-sized rings has been recognized as a long-standing challenge. Typical strategies referring to “head-to-tail” cyclization approaches rely on using stoichiometric chiral substrates in most cases, and these limit quick access to these target scaffolds. Asymmetric catalysis provides a new insight for the assembly of enantiopure medium-sized ring scaffolds. In this manner, optically pure compounds are generated from achiral substrate by using a small quantity of chiral catalyst. Over the past few decades, catalytic asymmetric synthesis of medium-sized rings has seen remarkable progress. A series of protocols, such as transition-metal catalysis and organocatalysis, have proven to be practical for assembling medium-sized ring systems. In this review, we provide a concise overview of the most recent breakthroughs in catalytic asymmetric synthesis of medium-sized rings. By summarizing these elegant strategies, we aim to inspire chemists to develop more efficient approaches for the asymmetric synthesis of medium-sized rings. Medium-sized rings are widely presented in natural products with diverse biological activity. However, they are less commonly encountered among clinical drugs and small-molecule screening libraries owing to challenges associated with the synthesis of these scaffolds. The development of new approaches for construction of medium-sized rings in an asymmetric version has become a fascinating area of study. A number of processes have proven to be practical to assemble the medium-sized ring systems. Nevertheless, the current established protocols are restricted to a handful of activation models, of which the transition-metal-catalyzed asymmetric annulation is the primary strategy. Particularly, the use of organocatalysts for asymmetric synthesis of medium rings remains a formidable challenge at present. In the future, there will likely be a focus on asymmetric organo-catalytic systems involving ring-expansion and -rearrangement reactions. This review provides a concise overview of the most recent breakthroughs in catalytic asymmetric synthesis of medium-sized rings. Strategies involving transition-metal catalysis and organocatalysis are discussed, with a particular interest in the proposed catalytic cycle. The aim of this review is to inspire further innovation for the asymmetric construction of medium-sized rings.