CaltechAUTHORS
  A Caltech Library Service

Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides

Wang, Zhaobin and Yang, Ze-Peng and Fu, Gregory C. (2021) Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides. Nature Chemistry, 13 (3). pp. 236-242. ISSN 1755-4330. https://resolver.caltech.edu/CaltechAUTHORS:20210111-120204779

[img] PDF - Supplemental Material
See Usage Policy.

20Mb
[img] Crystallographic Info File (CIF) (Crystallographic data for compound 13. CCDC reference 1958912) - Supplemental Material
See Usage Policy.

1050Kb
[img] Crystallographic Info File (CIF) (Crystallographic data for compound 80. CCDC reference 1965146) - Supplemental Material
See Usage Policy.

428Kb
[img] Crystallographic Info File (CIF) (Crystallographic data for compound 81. CCDC reference 1958913) - Supplemental Material
See Usage Policy.

397Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20210111-120204779

Abstract

The development of efficient methods, particularly catalytic and enantioselective processes, for the construction of all-carbon quaternary stereocentres is an important (and difficult) challenge in organic synthesis due to the occurrence of this motif in a range of bioactive molecules. One conceptually straightforward and potentially versatile approach is the catalytic enantioconvergent substitution reaction of a readily available racemic tertiary alkyl electrophile by an organometallic nucleophile; however, examples of such processes are rare. Here we demonstrate that a nickel-based chiral catalyst achieves enantioconvergent couplings of a variety of tertiary electrophiles (cyclic and acyclic α-halocarbonyl compounds) with alkenylmetal nucleophiles to form quaternary stereocentres with good yield and enantioselectivity under mild conditions in the presence of a range of functional groups. These couplings, which probably proceed via a radical pathway, provide access to an array of useful families of organic compounds, including intermediates in the total synthesis of two natural products, (–)-eburnamonine and madindoline A.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41557-020-00609-7DOIArticle
https://rdcu.be/cdn3APublisherFree ReadCube access
https://www.ccdc.cam.ac.uk/structuresRelated ItemCambridge Crystallographic Data Centre
ORCID:
AuthorORCID
Wang, Zhaobin0000-0001-7934-2879
Yang, Ze-Peng0000-0003-0248-1963
Fu, Gregory C.0000-0002-0927-680X
Additional Information:© 2020 Nature Publishing Group. Received 12 January 2020; Accepted 18 November 2020; Published 11 January 2021. This paper is dedicated to the memory of Professor Jonathan Williams (University of Bath). Support has been provided by the NIGMS (R37-GM62871) and the Dow Next Generation Educator Fund (grant to Caltech). We thank S.M. Batiste, L.M. Henling, H. Huo, F. Schneck, M.K. Takase, S.C. Virgil and W. Zhang for assistance and helpful discussions. Data availability: The data that support the findings of this study are available in the Supplementary Information (experimental procedures and characterization data). Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 1958912 (13), 1958913 (81), and 1965146 (80). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Author Contributions: Z.W. and Z.-P.Y. performed all experiments. Z.W. and G.C.F. wrote the manuscript. All authors contributed to the analysis and the interpretation of the results. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
NIHR37-GM62871
Dow Next Generation Educator FundUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20210111-120204779
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210111-120204779
Official Citation:Wang, Z., Yang, ZP. & Fu, G.C. Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides. Nat. Chem. 13, 236–242 (2021). https://doi.org/10.1038/s41557-020-00609-7
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107393
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Jan 2021 20:34
Last Modified:03 Mar 2021 18:03

Repository Staff Only: item control page