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Enantioselective Synthesis of ?-Allyl Amino Esters via Hydrogen-Bond-Donor Catalysis.

ABSTRACT: We report a chiral-squaramide-catalyzed enantio- and diastereoselective synthesis of ?-allyl amino esters. The optimized protocol provides access to N-carbamoyl-protected amino esters via nucleophilic allylation of readily accessible ?-chloro glycinates. A variety of useful ?-allyl amino esters were prepared, including crotylated products bearing vicinal stereocenters that are inaccessible through enolate alkylation, with high enantioselectivity (up to 97% ee) and diastereoselectivity (>10:1). The reactions display first-order kinetic dependence on both the ?-chloro glycinate and the nucleophile, consistent with rate-limiting C-C bond formation. Computational analysis of the uncatalyzed reaction predicts an energetically inaccessible iminium intermediate, and a lower energy concerted SN2 mechanism.

SUBMITTER: Bendelsmith AJ

PROVIDER: S-EPMC7293823 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Enantioselective Synthesis of α-Allyl Amino Esters via Hydrogen-Bond-Donor Catalysis.

Bendelsmith Andrew J AJ Kim Seohyun Chris SC Wasa Masayuki M Roche Stéphane P SP Jacobsen Eric N EN

Journal of the American Chemical Society 20190711 29

We report a chiral-squaramide-catalyzed enantio- and diastereoselective synthesis of α-allyl amino esters. The optimized protocol provides access to <i>N</i>-carbamoyl-protected amino esters via nucleophilic allylation of readily accessible α-chloro glycinates. A variety of useful α-allyl amino esters were prepared, including crotylated products bearing vicinal stereocenters that are inaccessible through enolate alkylation, with high enantioselectivity (up to 97% ee) and diastereoselectivity (>1 ...[more]

PMID: 31280564

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