Amino-acids reaction with hexafluoroacetone

Piperazine-2,5-diones can be symmetric or asymmetric. Symmetric DKPs are readily obtained by heating amino acid esters,1179-181 whereas asymmetric DKPs are obtained directly from the related dipeptides under basic or, more properly, acid catalysis, or by cyclocondensation of dipeptide esters.1182-185 As an alternative procedure hexafluoroacetone can be used to protect/activate the amino acid for the synthesis of symmetric DKPs or of the second amino acid residue for synthesis of the dipeptide ester and subsequent direct cyclocondensation to DKPs.1186 The use of active esters for the cyclocondensation is less appropriate since it may lead to epimerization when a chiral amino acid is involved as the carboxy component in the cyclization reaction. Resin-bound DKPs as scaffolds for further on-resin transformations are readily prepared using the backbone amide linker (BAL) approach, where the amino acid ester is attached to the BAL resin by its a-amino group and then acylated with a Fmoc-protected amino acid by the HATU procedure, N -deprotection leads to on-resin DKP formation1172 (see Section 6.8.3.2.2.3). 

Substituted oxazolidin-5-ones are produced by the reaction of amino acids with substituted acetone. Simmons and Wiley [267] applied 1,3-dichlorotetrafluoroacetone, and it is this reagent that has been most often used for the preparation of oxazolidinones [268] (Scheme 5.27). The use of hexafluoroacetone as a reagent is limited as it is gaseous, expensive and the derivatives of the simplest amino acids are too volatile. The former reagent is therefore preferred for cyclizations. 

These derivatives are readily formed by the reaction of hexafluoroacetone with the amino acid. ... 

Cyanoformamidines, exhibiting nucleophilic and electrophilic properties in the 1,3-positions, react with hexafluoroacetone forming five-membered heterocycles (86CB2127). This ability to form five-membered heterocycles is the major characteristic of hexafluoroacetone, which is also inherent in some perfluorinated and partially fluorinated ketones, aldehydes, and imines in their reactions with a-functional derivatives of carboxylic acids, as well as w-amino, a-N-alkylamino,... 

In a novel approach, an enantiomerically pure derivative of 2-amino-4,4,4- trifluorobutanoic acid was synthesized via nucleophilic trifluoromethylation (Figure 3) (5). In the key step. Gamer s aldehyde (2) (6), an oxazolidine derived from L-serine, reacted with the Ruppert-Prakash reagent, TMS-CF3 (a trifluoromethide equivalent) (7) and tetrabutylammonium fluoride. (S) - 5,5,5,5, 5, 5 - Hexafluoroleucine (3) (88% ee) was prepared in 18% overall yield from hexafluoroacetone and ethyl bromopyruvate in seven steps (8). The highly enantioselective reduction of the keto carbonyl group of 4 to the hydroxyester 5 either by baker s yeast and sucrose (91% ee) or by catecholborane and an oxazaborolidine catalyst (99% ee) was the pivotal reaction of the sequence. These workers (9) also prepared (-)-(R)- 4,4,4,4, 4, 4 -hexafluorovaline (6) (98% ee). The key step was the separation of the tosylate salts of the diastereomers formed by anti-Michael addition of (+)-(R)-... 

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