Trifluoroalanine dipeptides

Guo, Y., Fujiwara, K. and Uneyama, K. (2006) A novel route to dipeptides via noncondensation of amino acids 2-Aminoperfluoropropene as a synthon for trifluoroalanine dipeptides. Org. Lett., 8, 827-829. 

The third reaction pattern in nucleophilic reaction to difluoroalkenes is addition. Protic nucleophiles such as amines and alcohols add sometimes to the difluoroalkenes in a manner of 1,2-addition to the double bond where both nucleophilic moiety and proton are incorporated into the double bond (Scheme 2.27). A difluoromethylene moiety is potentially a carbonyl synthon and a difluoroalkylidene moiety is a synthon of an amide [17] and an ester (53) [18]. l,l-Difluoro-2-aminoalkenes (52) (R1 = amino moiety) would be transformed to dipeptides (53) (RX = amino ester, R1 = amino moiety) on reacting with amino esters. This idea was realized by the reaction of 60 with a variety of amino esters, leading to a practical synthesis of trifluoroalanine dipeptides (62) as shown in Scheme 2.27 [ 19]. 

H N C00R= Alanine, leucine, serine, tyrosine, methionine, proline, etc. Figure 5.5 Synthesis of trifluoroalanine-containing dipeptides. 

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