Enantioselective Carbonyl Crotylation of Alcohol Proelectrophiles via Ruthenium-Catalyzed Hydrogen Autotransfer: Innovation Inspired by Polyketide Total Synthesis

From the first report of 1,3-butadiene-mediated carbonyl crotylation in 2008 to the recent development of a simple ruthenium-JOSIPHOS catalyst derived from inexpensive, air-stable RuHCl(CO)(PPh3)3, the discovery and evolution of 1,3-butadiene-mediated carbonyl crotylation is reviewed. The key role of iodide counterions in guiding metal-centered stereogenicity and, therefrom, regio-, stereo-, and site-selectivity is highlighted, as are applications in polyketide total synthesis. These methods are unique in their ability to affect crotylation of primary alcohol proelectrophiles in the presence of free secondary hydroxyl groups and offer an atom-efficient alternative to classical protocols for aldehyde crotylation that rely on premetalated reagents.