Diastereoconvergent Negishi Cross-coupling Using Functionalized Cyclohexylzinc Reagents

Highly diastereoselective Pd-catalyzed cross-coupling reactions of functionalized 2-, 3-, and 4-substituted cyclohexylzinc reagents with aryl, heteroaryl, and alkenyl iodides have been performed under mild conditions. The use of Ruphos (2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl) as a ligand as well as LiCl and N-ethylpyrrolidone (NEP) as additives leads to especially high diastereoselectivities and displays good functional group tolerance. The stereoselectivity can be explained by assuming that the intermediate palladium moiety occupies an equatorial position of the cyclohexyl ring.