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.