Display options
Cite
Volonterio A, Vergani B, Crucianelli M, et al. (R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes. J Org Chem. 1998;63(21):7236-7243doi: 10.1021/jo980602p.
Volonterio, A., Vergani, B., Crucianelli, M., Zanda, M., & Bravo, P. (1998). (R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes. The Journal of organic chemistry, 63(21), 7236-7243. https://doi.org/10.1021/jo980602p
Volonterio, Alessandro, et al. "(R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes." The Journal of organic chemistry vol. 63,21 (1998): 7236-7243. doi: https://doi.org/10.1021/jo980602p
Volonterio A, Vergani B, Crucianelli M, Zanda M, Bravo P. (R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes. J Org Chem. 1998 Oct 16;63(21):7236-7243. doi: 10.1021/jo980602p. PMID: 11672366.
Copy Download .nbib Format: NLM
Share it on

J Org Chem. 1998 Oct 16;63(21):7236-7243. doi: 10.1021/jo980602p.

(R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes.

The Journal of organic chemistry

Alessandro Volonterio, Barbara Vergani, Marcello Crucianelli, Matteo Zanda, Pierfrancesco Bravo

Affiliations

  1. C.N.R.-Centro di Studio per le Sostanze Organiche Naturali, Via Mancinelli 7, I-20131 Milano, Italy.

PMID: 11672366 DOI: 10.1021/jo980602p

Abstract

A new, efficient, and stereoselective two-step approach to stereochemically defined chiral nonracemic gamma-tri- and gamma-difluoro beta-amino alcohols (70% to >95% ee) is described, using tri- and difluoropyruvaldehyde N,S-ketals (R)-1a,b as starting materials. Addition of Grignard reagents to (R)-1 occurs with moderate to excellent anti-stereocontrol, depending on the nature of the organomagnesium halides, providing the beta-p-tolylthio beta-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 NaBH(4)/pyridine system, probably via the corresponding intermediate transient imines 13, providing sulfur-free gamma-tri- and gamma-difluorinated beta-amino alcohols 7 with high levels of anti-stereoselectivity. A considerable shift toward syn-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).

Publication Types