Nickel-catalyzed reductive coupling of unactivated alkyl bromides and aliphatic aldehydes

A mild, convenient coupling of aliphatic aldehydes and unactivated alkyl bromides has been developed. The catalytic system features the use of a common Ni(ii) precatalyst and a readily available bioxazoline ligand and affords silyl-protected secondary alcohols. The reaction is operationally simple, utilizing Mn as a stoichiometric reductant, and tolerates a wide range of functional groups. The use of 1,5-hexadiene as an additive is an important reaction parameter that provides significant benefits in yield optimizations. Initial mechanistic experiments support a mechanism featuring an alpha-silyloxy Ni species that undergoes formal oxidative addition to the alkyl bromide via a reductive cross-coupling pathway.

Aliphatic aldehydes and alkyl bromides are reductively coupled using nickel catalysis. A BiOX ligand and 1,5-hexadiene paired with a silyl chloride and Mn as the terminal reductant are important features of the process.