Cobalt‐Catalyzed Regio‐, Diastereo‐ and Enantioselective Reductive Coupling of 1,3‐Dienes and Aldehydes

Catalytic regio‐, diastereo‐ and enantioselective reductive coupling of 1,3‐dienes and aldehydes through regio‐ and enantioselective oxidative cyclization followed by regio‐ and diastereoselective protonation promoted by a chiral phosphine–cobalt complex is presented. Such processes represent an unprecedented reaction pathway for cobalt catalysis that enable selective transformation of the more substituted alkene in 1,3‐dienes, affording a broad scope of bishomoallylic alcohols without the need of pre‐formation of stoichiometric amounts of sensitive organometallic reagents in up to 98% yield, >98:2 regioselectivity, >98:2 dr and 98:2 er. Application of this method to construction of axial stereogenicity and deuterated stereogenic center provided a wide range of multifunctional chiral building blocks that are otherwise difficult to access. DFT calculations revealed the origin of regio‐ and stereoselectivity as well as a unique oxidative cyclization mechanism for cobalt catalysis.