biostudies-literatureJoshi CNIGMS NIH HHSNIH HHS2959-2966https://www.ebi.ac.uk/biostudies/studies/S-EPMC10168682biostudies-literatureUnknown12(5)Experimental and theoretical ¹³C kinetic isotope effects (KIEs) are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh₃)₄-catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd-(PPh₃)). This is based on the congruence of the experimental KIE for the carbon attached to bromine (KIE_C-Br = 1.020) and predicted KIE_C-Br for the transition state for oxidative addition to the Pd(PPh₃) complex (1.021). For aryl iodides, the near-unity KIE_C-I of ~1.003 suggests that the first irreversible step in the catalytic cycle precedes oxACS catalysisIsotope Effects Reveal the Catalytic Mechanism of the Archetypical Suzuki-Miyaura Reaction.PMC10168682S10 OD026746R01 GM126283Kim SIzzo JAHirschi JSMacharia JMVetticatt MJJoshi CWambua VfalseIsotope Effects Reveal the Catalytic Mechanism of the Archetypical Suzuki-Miyaura Reaction.Experimental and theoretical ¹³C kinetic isotope effects (KIEs) are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh₃)₄-catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd-(PPh₃)). This is based on the congruence of the experimental KIE for the carbon attached to bromine (KIE_C-Br = 1.020) and predicted KIE_C-Br for the transition state for oxidative addition to the Pd(PPh₃) complex (1.021). For aryl iodides, the near-unity KIE_C-I of ~1.003 suggests that the first irreversible step in the catalytic cycle precedes ox2022-01-01T00:00:00Z2022 Mar2025-04-18T13:57:23.318Z2025-04-06T23:50:06.924ZS-EPMC101686823716865010.1021/acscatal.1c05802