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Reaction Mechanism, Origins of Enantioselectivity, and Reactivity Trends in Asymmetric Allylic Alkylation: A Comprehensive Quantum Mechanics Investigation of a C(sp³)–C(sp³) Cross-Coupling

Cusumano, Alexander Q. and Stoltz, Brian M. and Goddard, William A., III (2020) Reaction Mechanism, Origins of Enantioselectivity, and Reactivity Trends in Asymmetric Allylic Alkylation: A Comprehensive Quantum Mechanics Investigation of a C(sp³)–C(sp³) Cross-Coupling. Journal of the American Chemical Society, 142 (32). pp. 13917-13933. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20200710-102850852

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Abstract

We utilize quantum mechanics to evaluate a variety of plausible mechanistic pathways for the entirety of the catalytic cycle for asymmetric decarboxylative allylic alkylation of allyl β-ketoesters. We present a mechanistic picture that unites all current experimental observations, including enantioinduction, reaction rate, catalyst resting state, enolate crossover experiments, water tolerance, and the effects of solvation on inner- and outer-sphere mechanisms. Experiments designed to evaluate the fidelity and predictive power of the computational models reveal the methods employed herein to be highly effective in elucidating the reactivity of the catalytic system. On the basis of these findings, we highlight a computational framework from which chemically accurate results are obtained and address the current limitations of the decarboxylative asymmetric allylic alkylation reaction.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.0c06243DOIArticle
ORCID:
AuthorORCID
Cusumano, Alexander Q.0000-0002-2914-2008
Stoltz, Brian M.0000-0001-9837-1528
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2020 American Chemical Society. Received: June 9, 2020; Published: July 8, 2020. We thank the NIH (R01 GM080269) and Caltech for financial support. We further thank Dr. Michael Bartberger (1200 Pharma) for insightful discussion. W.A.G. received support from ONR (ONR N00014-18-1-2155). The Caltech High Performance Computing (HPC) center is acknowledged for support of computational resources. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHR01 GM080269
CaltechUNSPECIFIED
Office of Naval Research (ONR)N00014-18-1-2155
Other Numbering System:
Other Numbering System NameOther Numbering System ID
WAG1383
Issue or Number:32
Record Number:CaltechAUTHORS:20200710-102850852
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200710-102850852
Official Citation:Reaction Mechanism, Origins of Enantioselectivity, and Reactivity Trends in Asymmetric Allylic Alkylation: A Comprehensive Quantum Mechanics Investigation of a C(sp3)–C(sp3) Cross-Coupling. Alexander Q. Cusumano, Brian M. Stoltz, and William A. Goddard. Journal of the American Chemical Society 2020 142 (32), 13917-13933; DOI: 10.1021/jacs.0c06243
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104322
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Jul 2020 18:16
Last Modified:17 Aug 2020 20:46

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