Expanding the Redox-Relay Strategy: Accessing Carbonylated Compounds from Alkenyl Silyl and Methyl Ethers by Heck Arylations

The redox-relay strategy occurring in the Heck reactions1 consists in the migration of a palladium hydride intermediate through successive migratory insertions along the carbon chain, followed by a terminal redox process, usually converting an alcohol into the corresponding aldehyde or ketone (Scheme 1, R1 = H). This redox scenario allows access to distal functionalised aryl ketones. Recently, we reported a novel variant of this reaction2 converting methyl and silyl-protected alkenols into the corresponding aryl ketones under Heck- Matsuda arylation conditions in excellent yields. Careful analysis of the reaction allowed us to isolate TBDPSOMe and TBDPSF derivatives as by-products. Kinetic data by in situ 1H NMR indicated that methanolysis and fluoride mediated deprotection occurs concomitantly, while fluoride ions from BF4 – convert TBSPSOMe into the TBDPSF derivative (Scheme 2). These finds suggest that the alkenyl silyl ethers, and presumably methyl ethers, undergo either a nucleophilic-assisted redox-relay process (Scheme 1, path a), or an anchimeric-assisted palladium reductive elimination (Scheme 1, path b), followed by methanolysis and/or fluorination of the silyl/methyl group bound to a putative oxonium intermediate. Both pathways would lead to the formation of the carbonylated product and regeneration of Pd(0). DFT calculations for alkenyl methyl ether redox-relay step favour the transition state through path a (Scheme 1) instead of the oxonium hypothesis.