Radical α–alkylation of ketones with unactivated alkenes under catalytic and sustainable industrial conditions

The industrially–viable aerobic α–alkylation of cyclic and acyclic ketones with allyl and alkyl alkenes in the presence of catalytic amounts of Mn2+, under homo– and heterogeneous conditions, is achieved here. The substitution of organic peroxides by Mn2+ either as a simple soluble salt or supported in zeolites, in air, generates in–situ peracid radicals and circumvents the aggressiveness of current industrial protocols, to pave the way for the design of sustainable aerobic catalytic systems. Combined reactivity and mechanistic studies show that large cyclic ketones stabilize a radical in the α–position due to a higher polarizability, steric hindrance and no proximity effects. As a proof of concept, the gram–scale synthesis of the industrial fragrance exaltolide is carried out with the Mn2+ catalysts in air, which clearly improves any other previously reported method not only in safety and environmental terms but also in number of synthetic steps and overall yield.