Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives
- Creators
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Kalek, Marcin
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Fu, Gregory C.
Abstract
Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.
Additional Information
© 2015 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: May 28, 2015. Publication Date (Web): July 20, 2015. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences: R01-GM57034) and the Swedish Research Council (fellowship for M.K.: Dnr 350-2012-6645). We thank Dr. Nathan D. Schley, Dr. Michael K. Takase (X-ray Crystallography Facility; a Bruker KAPPA APEX II X-ray diffractometer was purchased via NSF CRIF:MU Award CHE-0639094), Dr. David G. VanderVelde (NMR Facility), Dr. Scott C. Virgil (Center for Catalysis and Chemical Synthesis, supported by the Gordon and Betty Moore Foundation), and Dr. Daniel T. Ziegler for assistance. The authors declare no competing financial interest.Attached Files
Published - jacs.5b05528.pdf
Supplemental Material - ja5b05528_si_001.cif
Supplemental Material - ja5b05528_si_002.pdf
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Additional details
- PMCID
- PMC4577964
- Eprint ID
- 59023
- Resolver ID
- CaltechAUTHORS:20150728-084201151
- NIH
- R01-GM57034
- Swedish Research Council
- Dnr 350-2012-6645
- NSF
- CHE-0639094
- Gordon and Betty Moore Foundation
- Created
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2015-07-28Created from EPrint's datestamp field
- Updated
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2022-05-26Created from EPrint's last_modified field