Chiral N-acyl-tert-butanesulfinamides: The "safety-catch" principle applied to diastereoselective enolate alkylations

Diastereoselective enolate alkylation reactions of N-acylsulfinamides and c onversion of the alkylation products to a variety of enantiopure products a re reported. Several sulfinamides were prepared in solution followed by acy lation to provide N-acylsulfinamides, The N-acylsulfinamides were then eval uated in diastereoselective enolate alkylation reactions. Of the sulfinamid es evaluated, tert-butanesulfinamide provided the highest diastereoselectiv ity.;To establish the potential utility of sulfinamides as versatile auxili aries, methods were developed for (1) the racemization-free acylation of te rt-butanesulfinamide to prepare optically pure N-acyl-tert-butanesulfinamid es, (2) the diastereoselective C-alkylation of N-acyl-tert-butanesulfinamid es, (3) the conversion of the N-acyl-tert-butanesulfinamides to the active ester equivalent by N-alkylation and S-oxidation, and (4) the cleavage of t he N-alkyl-N-acyl-tert-butanesulfonamides to give chiral alcohol, ester, am ide, and carboxylic acid target compounds. These studies provide the ground work for the development of sulfinamides as dual chiral auxiliaries and lin kers for the multistep solid-phase synthesis of enantioenriched compounds.