Pd-Catalyzed Dual-?-1,1-C(sp3)-H Activation of Free Aliphatic Acids with Allyl-O Moieties

Allyl alcohols represent a unique class of coupling partners in C-H functionalization reactions. In this work, we report a simple strategy that involves dual-1,1-C(sp(3))-H activation of free aliphatic acids, leading to the direct synthesis of gamma-lactones that contain alpha,beta-unsaturated groups at the gamma-position. Various allyl alcohols including primary, secondary, tertiary, etc., have been used as suitable coupling partners to generate a diverse range of gamma-lactones. A number of aliphatic acids including the long-chain ones have been used as substrates in the protocol. A mechanistic investigation has been carried out and suggests C-H activation to be the rate-determining step and a subsequent allylic C-H activation in the reaction. The synthesized lactones having alpha,beta-unsaturated fragments attached are expected to be useful in the synthesis of complex molecules via further synthetic manipulation.

Automated summary

Allyl alcohols are used as unique coupling partners in C-H functionalization reactions. This study presents a simple strategy for the synthesis of gamma-lactones through dual-1,1-C(sp(3))-H activation of free aliphatic acids. Various allyl alcohols and aliphatic acids, including long-chain ones, have been used to generate a diverse range of gamma-lactones. The rate-determining step is identified as C-H activation, followed by allylic C-H activation in the reaction. The synthesized lactones with alpha,beta-unsaturated fragments can be useful in the synthesis of complex molecules through further synthetic manipulation.