Deconstructive Cyanomethylation Enabled by Radical Cross‐Coupling through Multiple C−C Bond and C−H Bond Cleavage

Abstract Being in its infancy, radical cross‐coupling is highly efficient for C−C bond construction, though suffers from selectivity problems and limited reaction types. New methodologies to realize radical cross‐coupling selectively are highly desired. Herein, an iron catalyzed deconstructive cyanomethylation of unstrained cyclic and linear alcohols with acetonitrile has been developed through radical cross‐coupling. The unprecedented method enables a ring‐opening functionalization of cyclohexanols to produce α‐cyanomethyl ketones. Notably, the highly challenging reaction involves twice C−C single bond cleavage through β‐scission of alkoxyl radical intermediates, and twice C( sp 3 )−H bond transformation via hydrogen atom transfer (HAT) procedures, resulting in two carbon radical species that realize a radical cross‐coupling process to form a new C( sp 3 )−C( sp 3 ) bond selectively. α‐arylketo and α‐aryl substituted tertiary alcohols can also be applied as substrates, leading to terminal cyano‐functionalized linear products, with ketone as the leaving fragment. Mechanistically, a new procedure to generate alkoxyl radical with chlorine radical through the in‐situ formed intermediate cycloalkyl hypochlorite was suggested. magnified image