Science of Synthesis

Lee, D.; Reddy Sabbasani, V., Science of Synthesis: Metal-Catalyzed Cyclization Reactions, (2016) 2, 671.

Ring-closing metathesis (RCM) has emerged as one of the most powerful synthetic methods to form cyclic molecular frameworks including small, medium, and large carbo- and heterocycles as illustrated by the selected examples above. Due to the compatibility and differential reactivity of alkenes and alkynes relative to other polar functional groups in the substrate, the ring-closure step can be introduced flexibly in the synthetic sequence. Over the past two decades, significant conceptual and technological advances have been achieved in all three metathesis classes (alkene, enyne, and alkyne metathesis). The limitations of ring-closing metathesis, such as Z-selective diene ring-closing metathesis, chemo- and sequence-selective enyne ring-closing metathesis, and the availability of reactive yet user-friendly and functional group tolerant catalysts for diyne ring-closing metathesis, have been addressed in remarkable fashion although further improvements are yet to be realized. Continued development of fundamentally new concepts and investigations to address the shortcomings of current ring-closing metathesis technology will certainly make ring-closing metathesis part of the state-of-the-art synthetic arsenal for the preparation of a variety of cyclic molecules including natural products and pharmaceuticals.