Diastereoselective addition of diethyl difluoromethylphosphonate to enantiopure sulfinimines:: synthesis of α,α-difluoro-β-aminophosphonates, phosphonic acids, and phosphonamidic acids

Addition of diethyl lithiodifluoromethylphosphonate to enantiomerically pure aromatic, heteroaromatic, and aliphatic aldehydederived sulfinimines afforded N-sulfinyl alpha,alpha-difluoro-beta-aminophosphonates with generally good enantioselectivity and in high yield. The reaction with acetophenone-derived sulfinimine resulted in the formation of the addition product with high diastereoselectivity and in only moderate yield. A two-step deprotection involving treatment of diastereomerically pure N-sulfinyl alpha, alpha-difluoro-beta-aminophosphonates with trifluoroacetic acid in EtOH followed by refluxing with 10 N HCl provided enantiopure alpha,alpha-difluoro-beta-aminophosphonates and alpha,alpha-difluoro-beta-aminophosphonic acids. The N-Cbz derivative of (R)-2-amino-1,1-difluoro-2-phenylethylphosphonate was a convenient starting point for the preparation of corresponding difluorophosphonate monoester, difluorophosphonic acid, and difluorophosphonamidic acid. At 21 degrees C difluorophosphonamidic acid was stable in aqueous solution at pH above 5. (c) 2006 Elsevier Ltd. All rights reserved.