Ni-catalyzed enantioselective three-component reductive alkylacylation of alkenes: modular access to structurally complex α-amino ketones.

Chiral alpha-amino ketones have found extensive applications as functional molecules. A nickel-catalyzed, enantioselective, and fully intermolecular three-component 1,2-alkylacylation of -acyl enamides has been realized with tertiary alkyl bromides and carboxylic acid-derived electrophiles as the coupling reagents. This reductive coupling strategy is operationally simple, exhibiting broad substrate scope and excellent functional group tolerance using readily available starting materials and allowing rapid access to structurally complex α-amino ketone derivatives in high enantioselectivity.

Nickel-Catalyzed Defluorinative Coupling of Aliphatic Aldehydes with Trifluoromethyl Alkenes.

A simple procedure is reported for the nickel-catalyzed defluorinative alkylation of unactivated aliphatic aldehydes. The process involves the catalytic reductive union of trifluoromethyl alkenes with aldehydes using a nickel complex of a 6,6'-disubstituted bipyridine ligand with zinc metal as the terminal reductant. The protocol is distinguished by its broad substrate scope, mild conditions, and simple catalytic setup.

Nickel-Catalyzed Decarboxylative Coupling of Redox-Active Esters with Aliphatic Aldehydes.

The addition of alkyl fragments to aliphatic aldehydes is a highly desirable transformation for fragment couplings, yet existing methods come with operational challenges related to the basicity and instability of the nucleophilic reagents commonly employed. We report herein that nickel catalysis using a readily available bioxazoline (BiOx) ligand can catalyze the reductive coupling of redox-active esters with aliphatic aldehydes using zinc metal as the reducing agent to deliver silyl-protected secondary alcohols. This protocol is operationally simple, proceeds under mild conditions, and tolerates a variety of functional groups.