title: Carbamoyl anion addition to N-sulfinyl imines: highly diastereoselective synthesis of α-amino amides.
abstract: Carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl aldimines and ketimines to provide α-amino amides. The methodology enables the direct introduction of a carbonyl group without the requirement of unmasking steps as with other nucleophiles. The products may be converted to α-amino esters or 1,2-diamines. Iterative application of the reaction enabled the stereoselective synthesis of a dipeptide. Spectroscopic and computational studies support an anion structure with η(2) coordination of lithium by the carbonyl group.
authors.affiliation: Chemical Development and Analytical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road/P.O. Box 368, Ridgefield, Connecticut 06877-0368, USA. jonathan.reeves@boehringer-ingelheim.com
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Reeves
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Tan
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Herbage
authors.forename: Zhengxu S
authors.initials: ZS
authors.lastname: Han
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Marsini
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Li
authors.forename: Guisheng
authors.initials: G
authors.lastname: Li
authors.forename: Yibo
authors.initials: Y
authors.lastname: Xu
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fandrick
authors.forename: Nina C
authors.initials: NC
authors.lastname: Gonnella
authors.forename: Scot
authors.initials: S
authors.lastname: Campbell
authors.forename: Shengli
authors.initials: S
authors.lastname: Ma
authors.forename: Nelu
authors.initials: N
authors.lastname: Grinberg
authors.forename: Heewon
authors.initials: H
authors.lastname: Lee
authors.forename: Bruce Z
authors.initials: BZ
authors.lastname: Lu
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000577:Amides; D004151:Dipeptides; D007097:Imines