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Probing Catalyst Speciation in Pd-MPAAM-Catalyzed Enantioselective C(sp3)–H Arylation: Catalyst Improvement via Destabilization of Off-Cycle Species

Chiral monoprotected aminoethyl amine (MPAAM) ligands were recently reported to facilitate enantioselective Pd-catalyzed arylation of strong cyclopropane C­(sp3)–H bonds. Herein, we describe detailed experimental and theoretical investigations into the influence of MPAAM ligands, L1 and L2, as well...

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Bibliographic Details
Published in:ACS catalysis 2021-09, Vol.11 (17), p.11040-11048
Main Authors: Hao, Wei, Bay, Katherine L, Harris, Caleb F, King, Daniel S, Guzei, Ilia A, Aristov, Michael M, Zhuang, Zhe, Plata, R. Erik, Hill, David E, Houk, K. N, Berry, John F, Yu, Jin-Quan, Blackmond, Donna G
Format: Article
Language:English
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Summary:Chiral monoprotected aminoethyl amine (MPAAM) ligands were recently reported to facilitate enantioselective Pd-catalyzed arylation of strong cyclopropane C­(sp3)–H bonds. Herein, we describe detailed experimental and theoretical investigations into the influence of MPAAM ligands, L1 and L2, as well as a monoprotected aminoethyl thioether (MPAThio) ligand, L3, on the reaction kinetics, product enantioselectivity, and turnover number. We show an unusual negative nonlinear effect in ligand enantiopurity on rate and ee that has not been shown previously in CH activation reactions, along with a negative dependence of the ligand concentration on the reaction rate. NMR titrations, kinetic modeling, crystal structures, and DFT calculations implicate the concentration-dependent formation of stable, off-cycle, homoleptic Pd­(L)2 species in the presence of L1 or L3. However, in the L2 system, the results suggest that only the catalytically active, monosubstituted [Pd­(L)­(OAc)] species is formed, regardless of ligand concentration, demonstrating the subtle influence of the ligand structure on the reaction kinetics and mechanism. The effect of these mechanistic findings on ligand design is demonstrated by the results for a new ligand in the MPAAM family, L2, which exhibits higher reaction rates.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.1c02805