Palladium-catalyzed enantioselective Heck alkenylation of trisubstituted allylic alkenols: a redox-relay strategy to construct vicinal stereocenters

In a Heck reaction using multi-substituted alkenes, the initial syn-carbopalladation sets two vicinal stereocenters by virtue of the migratory insertion process. Unfortunately, the resultant Pd–alkyl undergoes facile b-hydride elimination, which generally eliminates the stereochemistry imparted by migratory insertion. Recently, we have reported a modern variant of the Heck reaction, wherein the directionality and stereochemical delity of b-hydride elimination can be controlled and, thus, the initial stereochemical consequence of migratory insertion is not lost. Termed redox-relay Heck reactions, the unsaturation of the alkene is conserved as it is transferred to a different position on the alkyl chain, most commonly by oxidation of an alcohol to a carbonyl. These reactions have been rendered enantioselective and are effective on both disubstituted alkenes to form tertiary stereocenters and trisubstituted alkenes to form quaternary stereocenters (Scheme 1A). However, the potential power of the syn migratory insertion has not been realized as only a single stereocenter has been set. Therefore, we set out to investigate if vicinal centers can be forged through the use of trisubstituted alkenols of type 2 in enantioselective redox-relay Heck reactions (Scheme 1B). In this case, such stereocenters could be strategically constructed if we took advantage of the propensity for the alkenyl electrophile (1) to add at the alkene carbon distal to the alcohol functionality, producing a new