Catalyst-controlled doubly enantioconvergent coupling of racemic alkyl nucleophiles and electrophiles
Abstract
Stereochemical control in the construction of carbon-carbon bonds between an alkyl electrophile and an alkyl nucleophile is a persistent challenge in organic synthesis. Classical substitution reactions via S_N1 and S_N2 pathways are limited in their ability to generate carbon-carbon bonds (inadequate scope, due to side reactions such as rearrangements and eliminations) and to control stereochemistry when beginning with readily available racemic starting materials (racemic products). Here, we report a chiral nickel catalyst that couples racemic electrophiles (propargylic halides) with racemic nucleophiles (β-zincated amides) to form carbon-carbon bonds in doubly stereoconvergent processes, affording a single stereoisomer of the product from two stereochemical mixtures of reactants.
Additional Information
© 2020 American Association for the Advancement of Science. This is an article distributed under the terms of the Science Journals Default License. Received 4 September 2019; accepted 26 November 2019. We thank S. H. Jungbauer, S. C. Virgil, L. M. Henling, D. G. Vander Velde, H. Yin, D. J. Freas, W. Zhang, and Z. Yang for assistance and discussions. Funding: Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences, R37-GM62871). H.H. thanks the Resnick Sustainability Institute at Caltech for fellowship support. Author contributions: H.H. and B.J.G. performed all experiments. H.H. 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. Data and materials availability: The data that support the findings of this study are available in the paper, in its supplementary materials (experimental procedures and characterization data), and from the Cambridge Crystallographic Data Centre (CCDC) (www.ccdc.cam.ac.uk/structures; crystallographic data are available free of charge under CCDC reference numbers 1935944 and 1935945).Attached Files
Accepted Version - nihms-1566755.pdf
Supplemental Material - aaz3855_Huo_SM.pdf
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Additional details
- Alternative title
- Catalyst-controlled asymmetric substitution reactions by racemic nucleophiles: From singly to doubly enantioconvergent processes
- PMCID
- PMC7566878
- Eprint ID
- 101007
- Resolver ID
- CaltechAUTHORS:20200130-135407173
- NIH
- R37-GM62871
- Resnick Sustainability Institute
- Created
-
2020-01-30Created from EPrint's datestamp field
- Updated
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2022-02-09Created from EPrint's last_modified field
- Caltech groups
- Resnick Sustainability Institute