biostudies-literatureLalloo NNational Institute of General Medical SciencesNIGMS NIH HHS18617-18625https://www.ebi.ac.uk/biostudies/studies/S-EPMC8693446biostudies-literatureUnknown143(44)This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [R_FC(O)X] with aryl organometallics (Ar-M'). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between R_FC(O)X and Ar-M' can be avoided by using M' = boronate ester. Second, carbonyl de-insertion and Ar-R_F reductive elimination are the two sloJournal of the American Chemical SocietyDecarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis.PMC8693446R35 GM136332R35GM1361332Malapit CASanford MSLalloo NTaimoory SMBrigham CEfalseDecarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis.This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [R_FC(O)X] with aryl organometallics (Ar-M'). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between R_FC(O)X and Ar-M' can be avoided by using M' = boronate ester. Second, carbonyl de-insertion and Ar-R_F reductive elimination are the two slo2021-01-01T00:00:00Z2021 Nov2025-04-04T09:02:59.667Z2025-04-04T09:02:59.667ZS-EPMC86934463470980410.1021/jacs.1c08551