214852-75-2Relevant academic research and scientific papers
CR-trifluoro- and difluoropyruvaldehyde AT,S-ketals: Chiral synthetic equivalents of β-trifluoro and β-difluoro α-amino aldehydes
Volonterio, Alessandro,Vergani, Barbara,Crucianelli, Marcello,Zanda, Matteo,Bravo, Pierfrancesco
, p. 7236 - 7243 (1998)
A new, efficient, and stereoselective two-step approach to stereochemically defined chiral nonracemic γ-tri- and γ-difluoro β-amino alcohols (70% to >95% ee) is described, using tri- and difluoropyruvaldehyde W,S-ketals (R)-la,b as starting materials. Addition of Grignard reagents to (R)-l occurs with moderate to excellent anfi-stereocontrol, depending on the nature of the organomagnesium halides, providing the β-p-tolylthio β-benzyloxycarbonylamino secondary carbinols 5. The stereochemical outcome of these reactions can be rationalized by means of a chelated Cram's cyclic model, where the NCbz group is the chelating ligand and the p-tolylthio residue acts as the stereocontrolling "large" group. Reductive displacement of the 2-p-tolylthio substituent of 5 efficiently takes places by means of the NaBH4pyridine system, probably via the corresponding intermediate transient imines 13, providing sulfur-free γ-tri- and γ-difluorinated β-amino alcohols 7 with high levels of anii-stereoselectivity. A considerable shift toward syra-stereoselectivity was obtained performing the reaction on the corresponding phenylacetates 8. Cleavage and reduction of the NHCbz moiety of 7 provided tri- and difluoro analogues of, respectively, norephedrine (11) and ephedrine (12).
