Andrew J Bendelsmith1, Seohyun Chris Kim1, Masayuki Wasa1, Stéphane P Roche2, Eric N Jacobsen1. 1. Department of Chemistry & Chemical Biology , Harvard University , Cambridge , Massachusetts 02138 , United States. 2. Department of Chemistry & Biochemistry , Florida Atlantic University , Boca Raton , Florida 33431 , United States.
Abstract
We report a chiral-squaramide-catalyzed enantio- and diastereoselective synthesis of α-allyl amino esters. The optimized protocol provides access to N-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 (>10:1). The reactions display first-order kinetic dependence on both the α-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.
We report a chiral-squaramide-catalyzed enantio- and diastereoselective synthesis of α-allyl n class="Chemical">aminoesters. The optimized protocol provides access to N-carbamoyl-protected amino esters via nucleophilic allylation of readily accessible α-chloro glycinates. A variety of useful α-allyl aminoesters 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 α-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.