Probing Catalyst Speciation in Pd-MPAAM-Catalyzed Enantioselective C(sp³)–H Arylation: Catalyst Improvement via Destabilization of Off-Cycle Species
Abstract
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.
Additional Information
© 2021 American Chemical Society. Received 22 June 2021. Revised 5 August 2021. Published online 20 August 2021. Published in issue 3 September 2021. This work was supported by the National Science Foundation (USA) under the NSF Center for Selective C–H Functionalization (CHE-1700982). Computations were performed on the Hoffman2 cluster at UCLA and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI-1053575). Dr. Jason Chen and Brittany Sanchez of the Scripps Automated Synthesis Center are acknowledged for valuable discussions and guidance on analytical methods. The authors declare no competing financial interest.Attached Files
Supplemental Material - cs1c02805_si_001.pdf
Supplemental Material - cs1c02805_si_002.cif
Supplemental Material - cs1c02805_si_003.cif
Supplemental Material - cs1c02805_si_004.cif
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Additional details
- Alternative title
- Probing Catalyst Speciation in Pd-MPAAM-Catalyzed Enantioselective C(sp3)–H Arylation: Catalyst Improvement via Destabilization of Off-Cycle Species
- Eprint ID
- 111340
- DOI
- 10.1021/acscatal.1c02805
- Resolver ID
- CaltechAUTHORS:20211008-224638096
- CHE-1700982
- NSF
- OCI-1053575
- NSF
- DGE-1747503
- NSF Graduate Research Fellowship
- Created
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2021-10-11Created from EPrint's datestamp field
- Updated
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2021-10-11Created from EPrint's last_modified field