The evolution of methods for carbonyl allylation and crotylation of alcohol proelectrophiles culminating in the design of iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric carbonyl allylation and its relevance to polyketide construction. Using gaseous allene or butadiene as precursors to allyl- or crotylruthenium nucleophiles, respectively, new capabilities for carbonyl allylation and crotylation have been unlocked, including stereo- and site-selective methods for the allylation and crotylation of 1,3-diols and related polyols.1 Introduction and Historical Perspective2 Ruthenium-Catalyzed Conversion of Lower Alcohols into Higher Alcohols3 Conclusion and Future Outlook

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.

The first correlation between metal-centered stereogenicity and regioselectivity in a catalytic process is described. Alternate pseudo-diastereomeric chiral-at-ruthenium complexes of the type RuX(CO)[η 3 -prenyl][(S)-SEGPHOS] form in a halidedependent manner and display divergent regioselectivity in catalytic C−C couplings of isoprene to alcohol proelectrophiles via hydrogen autotransfer. Whereas the chloride-bound ruthenium-SEGPHOS complex prefers a trans-relationship between the halide and carbonyl ligands and delivers products of carbonyl secprenylation, the iodide-bound ruthenium-SEGPHOS complex prefers a cis-relationship between the halide and carbonyl ligands and delivers products of carbonyl tert-prenylation. The chlorideand iodide-bound ruthenium-SEGPHOS complexes were characterized in solution and solid phase by 31 P NMR and X-ray diffraction. Density functional theory calculations of the iodide-bound catalyst implicate a Curtin−Hammett-type scenario in which the transition states for aldehyde coordination from an equilibrating mixture of sec-and tert-prenylruthenium complexes are rate-and product-determining. Thus, control of metal-centered diastereoselectivity has unlocked the first catalytically enantioselective isoprene-mediated carbonyl tert-prenylations.

A new family of stabilized benzylic nucleophiles for the palladium-catalyzed decarboxylative allylic alkylation reaction has been developed. Allyl esters derived from 3-carboxyphthalides were found to undergo palladium-catalyzed deallylation and decarboxylation under mild reaction conditions, a process facilitated by the formation of a stabilized aromatic anion. The regioselective allylic coupling of this intermediate afforded a variety of functionalized phthalides in 73−96% yields.