Carboxylic Esters as Bifunctional Reagents in Decarboxylative Cross-Coupling Reactions and Alkene Functionalizations

Transition-metal catalyzed cross-coupling reactions have transformed carbon-carbon bond formation in complex organic molecules, revolutionizing fields like pharmaceutical and agrochemical industries, polymers, and natural product synthesis. Despite their vast applications, these reactions heavily rely on toxic organic halides and organometallic reagents that require multiple preparation steps and often lack stability. Carboxylic esters (RCOOE) offer a promising alternative as they are readily available, potentially bio-sourced, and can serve as bifunctional partners in cross-coupling reactions. The ester’s R and E groups can act as nucleophiles and electrophiles upon carbon dioxide extrusion, forming carbon-carbon bonds (R–E) by recombination in an exergonic transformation. However, unlocking the full potential of esters faces a significant kinetic challenge due to the difficult activation of strong C–O bonds. This challenge has limited applications to reactive substrates like allyl esters (E = allyl).The DECAF project seeks to overcome these barriers by developing groundbreaking multi-catalyst cross-coupling reactions using dialkyl carboxylic esters (RCOOE with R, E = alkyl) as versatile and bifunctional reagents under visible-light irradiation. In the first Strand, DECAF will focus on generating reactive intermediates from the cleavage of ester C–O bonds. Their potential as cross-coupling partners will be demonstrated through the example of Heck-type couplings with alkenes. The second Strand will introduce an electron-borrowing strategy to enable the decarboxylative recombination of esters. This unified mechanistic approach will extend the application of carboxylic esters as bifunctional reagents to catalytic alkene transfer dialkylations and, ultimately, decarboxylative sulfonylations.