Asymmetric Ruthenium-Catalyzed Carbonyl Allylations by Gaseous Allene via Hydrogen Auto-Transfer: 1° versus 2° Alcohol Dehydrogenation for Streamlined Polyketide Construction

Iodide-bound ruthenium–JOSIPHOS complexes catalyze the redox-neutral C–C coupling of primary alcohols 2a–2r with the gaseous allene (propadiene) 1a to form enantiomerically enriched homoallylic alcohols 3a–3r with complete atom efficiency. Using formic acid as the reductant, aldehydes dehydro-2a and dehydro-2c participate in reductive C–C coupling with allene to deliver adducts 3a and 3c with comparable levels of asymmetric induction. Deuterium labeling studies corroborate a mechanism in which alcohol dehydrogenation triggers allene hydroruthenation to form transient allylruthenium–aldehyde pairs that participate in carbonyl addition. Notably, due to a kinetic preference for primary alcohol dehydrogenation, chemoselective C–C coupling of 1°,2°-1,3-diols occurs in the absence of protecting groups. As illustrated by the synthesis of C7–C15 of spirastrellolide B and F (7 vs 17 steps), C3–C10 of cryptocarya diacetate (three vs seven or nine steps) and a fragment common to C8′–C14′ of mycolactone F (one vs four steps) and C22–C28 marinomycin A (one vs nine steps), this capability streamlines type I polyketide construction.