Timothy T. Curran

Implementation of the Dakin-West reaction for the preparation of an α-amino-pentafluoroethyl ketone

Abstract We have successfully implemented the Dakin-West reaction to prepare 4-(carbamoyl- or benzoylamino)-5-methyl-1,1,1,2,2-pentaffuorohexan-3-one ( 3, 7a and 7b ). We also isolated and characterized the impurities obtained from this Dakin-West reaction. Although we were successful in the literature-described conversion of 3 to 4 , we have been unsuccessful at benzamide cleavage of 7a or 7b under a variety of conditions, presumably owing to the presence of an electrophilic pentafluoroethyl ketone moiety. We illustrated that 5-pentafluoroethyl oxazole 15 can be derived from N -benzoyl-pentafluoroethyl ketone 7a and that oxazole 15 is also resistant to ring opening.

A convenient synthesis of peptidyl perfluoroalkyl ketones

Abstract A convenient method is described for the preparation of α-amino perfluoroalkyl ketones via direct nucleophilic perfluoroalkylation of the corresponding peptide ester. This method was used to prepare dehydrovaline pentafluoroethyl ketone 2 from the corresponding N -Boc-protected dehydrovaline methyl ester 3 . Similar α-amino esters, N -Boc-valine methyl ester 4 , Boc-Valyl-prolyl-dehydrovaline methyl ester 8a and Boc-valyl-prolyl-valine methyl ester 8b were also converted directly to the corresponding pentafluoroethyl ketones 6 , 9a and 9b . The method was also applied to the synthesis of heptafluoropropyl- and nonafluorobutyl peptidyl ketones 11a and 11b from their corresponding esters, albeit in lower yield. These amino ketones are useful as intermediates in the preparation of peptidyl perfluoroalkyl ketones which have been shown to be potent inhibitors of human neutrophil elastase.