Yang, Ze-Peng and Freas, Dylan J. and Fu, Gregory C. (2021) Asymmetric Synthesis of Protected Unnatural α-Amino Acids via Enantioconvergent Nickel-Catalyzed Cross-Coupling. Journal of the American Chemical Society, 143 (23). pp. 8614-8618. ISSN 0002-7863. PMCID PMC8351905. doi:10.1021/jacs.1c03903. https://resolver.caltech.edu/CaltechAUTHORS:20210604-111535270
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Abstract
Interest in unnatural α-amino acids has increased rapidly in recent years in areas ranging from protein design to medicinal chemistry to materials science. Consequently, the development of efficient, versatile, and straightforward methods for their enantioselective synthesis is an important objective in reaction development. In this report, we establish that a chiral catalyst based on nickel, an earth-abundant metal, can achieve the enantioconvergent coupling of readily available racemic alkyl electrophiles with a wide variety of alkylzinc reagents (1:1.1 ratio) to afford protected unnatural α-amino acids in good yield and ee. This cross-coupling, which proceeds under mild conditions and is tolerant of air, moisture, and a broad array of functional groups, complements earlier approaches to the catalytic asymmetric synthesis of this valuable family of molecules. We have applied our new method to the generation of several enantioenriched unnatural α-amino acids that have previously been shown to serve as useful intermediates in the synthesis of bioactive compounds.
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Additional Information: | © 2021 American Chemical Society. Received: April 14, 2021; Published: June 3, 2021. This paper is dedicated to Professor David A. Evans on the occasion of his 80th birthday. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences; grant R01-GM062871), the National Science Foundation Graduate Research Fellowship Program (grant DGE-1745301), and the Dow Next-Generation Educator Fund (grant to Caltech). We thank Lawrence M. Henling and Dr. Michael K. Takase (Caltech X-Ray Crystallography Facility), Dr. Asik Hossain, Dr. Paul H. Oyala (Caltech EPR Facility), Dr. Felix Schneck, Dr. David G. VanderVelde (Caltech NMR Facility), and Dr. Scott C. Virgil (Caltech Center for Catalysis and Chemical Synthesis) for assistance and helpful discussions. Author Contributions. Z.-P.Y. and D.J.F. contributed equally. The authors declare no competing financial interest. Accession Codes. CCDC 2072620 contains the supplementary crystallographic data for this paper. | |||||||||
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Subject Keywords: | Reagents, Enantioselective synthesis, Electrophiles, Alkyls, Cross coupling reaction | |||||||||
Issue or Number: | 23 | |||||||||
PubMed Central ID: | PMC8351905 | |||||||||
DOI: | 10.1021/jacs.1c03903 | |||||||||
Record Number: | CaltechAUTHORS:20210604-111535270 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210604-111535270 | |||||||||
Official Citation: | Asymmetric Synthesis of Protected Unnatural α-Amino Acids via Enantioconvergent Nickel-Catalyzed Cross-Coupling. Ze-Peng Yang, Dylan J. Freas, and Gregory C. Fu. Journal of the American Chemical Society 2021 143 (23), 8614-8618; DOI: 10.1021/jacs.1c03903 | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 109385 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | George Porter | |||||||||
Deposited On: | 07 Jun 2021 15:38 | |||||||||
Last Modified: | 12 Jul 2022 20:03 |
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