Highly Substrate‐Selective Macrocyclic Ring Closing Metathesis

A selective ring‐closing metathesis (RCM) reaction for the formation of large macrocycles by using latent sulfur chelated ruthenium iodide benzylidenes, readily activated by thermal and photochemical (UV‐A and visible light) stimuli, is reported. For dienes having one terminal alkene and one internal double bond, the specific affinity of diiodo ruthenium alkylidenes for the unhindered terminus, combined with their reluctance to react with internal olefins, favors RCM over oligomerization, providing high macrocyclic yields even at relatively high concentrations. Alternatively, for substrates containing two internal double bonds, a sacrificial methylene donor can be used to obtain the desired products. With this methodology, lactones, lactams, and macrocyclic ketones ranging from 13‐ to 22‐membered rings could be synthesized in moderate to high yields. In addition, synthetic applications for a one‐pot cyclization/reduction sequence to produce Exaltolide, a natural macrolide (commercial musk), Dihydrocivetone, and other saturated macrocycles have been explored. Thus, we disclose herein an important advantage for diiodo ruthenium benzylidene catalysts over their less selective dichloro counterparts and provide a more profound understanding of the mechanisms that provide the enhanced cyclization outcome.