Asymmetric synthesis of alpha,alpha-difluoro-beta-amino acid derivatives from enantiomerically pure N-tert-butylsulfinimines.
Addition of the Reformatsky reagent derived from ethyl bromodifluoroacetate to alkyl- and aryl-substituted N-tert-butylsulfinimines furnishes beta-tert-butylsulfinamyl-beta-substituted alpha,alpha-difluoroproponiates in diastereomeric ratios ranging from 80:20 to 95:5. The diastereomers are easily separated and the enantiomerically pure, protected beta-amino esters are readily transformed to the corresponding acid, amide, and amine derivatives as useful synthons for medicinal chemistry targets.
Staas
Donnette D
DD
Merck Research Laboratories, West Point, Pennsylvania 19486, and Merck Research Laboratories, Rahway, New Jersey 07065, USA. donnette_staas@merck.com
Savage
Kelly L
KL
Homnick
Carl F
CF
Tsou
Nancy N
NN
Ball
Richard G
RG
D000596:Amino Acids / Q000138:chemical synthesis*; D005461:Fluorine; D007097:Imines; D013237:Stereoisomerism; D013449:Sulfonamides / Q000737:chemistry
D000596:Amino Acids; D007097:Imines; D013449:Sulfonamides; C408993:tert-butylsulfonamide; D005461:Fluorine