134746-23-9Relevant articles and documents
Asymmetric Synthesis of Protected Unnatural α-Amino Acids via Enantioconvergent Nickel-Catalyzed Cross-Coupling
Freas, Dylan J.,Fu, Gregory C.,Yang, Ze-Peng
supporting information, p. 8614 - 8618 (2021/06/28)
Interest in unnatural α-Amino acids has increased rapidly in recent years in areas ranging from protein design to medicinal chemistry to materials science. Consequently, the development of efficient, versatile, and straightforward methods for their enanti
Enantioselective Synthesis of α-Allyl Amino Esters via Hydrogen-Bond-Donor Catalysis
Bendelsmith, Andrew J.,Kim, Seohyun Chris,Wasa, Masayuki,Roche, Stéphane P.,Jacobsen, Eric N.
supporting information, p. 11414 - 11419 (2019/08/20)
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.
Synthesis and Reactivity of α-Haloglycine Esters: Hyperconjugation in Action
Samanta, Shyam S.,Roche, Stéphane P.
, p. 6597 - 6605 (2019/11/03)
A general and efficient synthesis of α-haloglycine esters from commercially available feedstock chemicals, in a single step, is reported. The reactivity of these α-haloglycine esters with various nucleophiles was studied as surrogates of α-iminoesters upon activation with hydrogen-bond donor catalysts. DFT calculations on the α-haloglycine structures (X = F, Cl, Br) accompanied by an X-ray characterization of the α-bromoglycine ester support the existence of a “generalized” anomeric effect created by hyperconjugation. This peculiar hyperconjugative effect is proposed to be responsible for the enhanced halogen nucleofugality leading to a facile halogen abstraction by hydrogen-bond donor catalysts. This reactivity was exploited with thiourea catalysts on several catalytic transformations (aza-Friedel–Crafts and Mannich reactions) for the synthesis of several types of non-proteinogenic α-amino esters.
In Situ-Generated Glycinyl Chloroaminals for a One-Pot Synthesis of Non-proteinogenic α-Amino Esters
Samanta, Shyam S.,Roche, Stéphane P.
, p. 8514 - 8526 (2017/08/23)
An acetyl chloride-mediated cascade transformation involving a primary carbamate, ethyl glyoxylate, and various types of nucleophiles is reported for the synthesis of orthogonally protected α-amino esters. These reactions proceeded rapidly to afford the pivotal α-chloroglycine intermediate in excellent yields, which can be directly functionalized in situ with various types of nucleophiles. A mild and unique AcOH(cat.)/AcCl system was found to promote an autocatalytic-like condensation and facilitate the multicomponent assembly of non-proteinogenic α-amino esters. To better understand this one-pot transformation and the orchestration of the components' condensations, the investigation of a broader scope of nucleophiles and some kinetic studies are presented. Our findings suggest that the halogenation step toward the formation of α-chloroglycine is the rate-determining step likely proceeding through the formation of N-carbamoyl iminium. Also, the initial kinetic profiling for the nucleophilic substitution supports an SN1-like (SN2C+) mechanism in which nucleophiles add to the iminium-chloride tight ionic pair. These results lead ultimately to the design of a new protocol in which an achiral hydrogen bond donor thiourea catalyst was utilized to enhance the reaction scope and enable silylated nucleophiles to be efficiently exploited to synthesize novel non-proteinogenic α-amino esters.
Autocatalytic one pot orchestration for the synthesis of α-arylated, α-amino esters
Roche, Stephane P.,Samanta, Shyam S.,Gosselin, Marine M. J.
supporting information, p. 2632 - 2634 (2014/03/21)
A novel acetyl chloride-mediated cascade transformation involving three components (benzyl carbamate, ethyl glyoxylate and arene nucleophiles) is reported. Aryl orthogonally protected α-amino acids are obtained in a one pot cascade, using a mild AcOH-AcCl system, via a critical autocatalytic dehydration-activation step ensuring an original and efficient Friedel-Crafts orchestration. The Royal Society of Chemistry 2014.
Asymmetric Mannich synthesis of α-amino esters by anion-binding catalysis
Wasa, Masayuki,Liu, Richard Y.,Roche, Stéphane P.,Jacobsen, Eric N.
supporting information, p. 12872 - 12875 (2016/10/06)
We report a scalable, one-pot Mannich route to enantioenriched α-amino esters by direct reaction of α-chloroglycine ester as a practical imino ester surrogate. The reaction is promoted by a chiral aminothiourea, which is proposed to operate cooperatively
