Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C–C Couplings via Hydrogen Transfer

Abstract

Experimental and computational studies illuminating the factors that guide metal-centered stereogenicity and, therefrom, selectivity in transfer hydrogenative carbonyl additions of alcohol proelectrophiles catalyzed by chiral-at-metal-and-ligand octahedral d 6 metal ions, iridium(III) and ruthenium(II), are described. To augment or invert regio-, diastereo-, and enantioselectivity, predominantly one from among as many as 15 diastereomeric-at-metal complexes is required. For iridium(III) catalysts, cyclometalation assists in defining the metal stereocenter, and for ruthenium(II) catalysts, iodide counterions play a key role. Whereas classical strategies to promote selectivity in metal catalysis aim for high-symmetry transition states, well-defined lowsymmetry transition states can unlock selectivities that are otherwise difficult to achieve or inaccessible.

β-Hydroxy Esters as Malonic Semialdehyde Proelectrophiles in Enantioselective Butadiene-Mediated Crotylation: Total Synthesis of Octalactins A and B

“…Fragment A is potentially accessible via iterative butadiene-mediated anti -crotylation of 2a . Fragment B was envisioned to arise via enantioselective iridium-catalyzed allylation of isobutanol followed by cross-metathesis of the resulting homoallylic alcohol with vinylpinacolboronate followed by iodination of the carbon–boron bond …”

“…The preparation of Fragment B began with the π-allyliridium- C , O -benzoate-catalyzed allylation of isobutanol to provide homoallylic alcohol 6 in 88% yield with high levels of enantiocontrol (94% ee) (Scheme ). Exposure of homoallylic alcohol 6 to (2-propenyl)­pinacolboronate in the presence of the Hoveyda–Grubbs II catalyst (added via syringe pump addition), effected cross-metathesis with complete ( Z )-stereoselectivity .…”