Enantioselective synthesis of α-perfluoroalkylated cyclic amino acids and their derivatives was elaborated using the organocatalytic Strecker reaction with 5-7 membered cyclic ketimines. The prepared amino nitriles could be transformed into chiral Rf-prolines and their 6,7-membered homologues as well as their corresponding amides and diamines (yields up to 99%, up to >99% ee).
Enantioselective synthesis of thiazole‐containing α‐perfluoroalkylated cyclic amines was elaborated. Organocatalytic Strecker reaction with 5–7 membered cyclic ketimines was used as a key step of sequence. The prepared chiral amino nitriles bearing CF3‐ or C2F5‐group in the alpha position were transformed into the corresponding chiral thioamides by the reaction with hydrogen sulfide. Subsequent reaction with alpha bromo‐ or chloro‐substituted carbonyls allowed obtaining perfluoroalkylated analogues of natural thiazole‐containing cyclic amines in high isolated yield and up to > 99 % ee.
A general route to alpha‐substituted cyclic amino acids was elaborated. The approach is based on Strecker reaction with cyclic ketimines. The influence of ring size and substituent at the alpha‐position of cyclic ketimine on the hydrocyanation was studied. It was found that five‐membered aminonitriles have a tendency to eliminate HCN very easily, especially in the case of aryl‐substituted derivatives. A series of 5–7 membered amino nitriles with different substituents was prepared. Subsequent hydrolysis allows the preparation of alpha‐substituted pipecolic acids. In the case of seven‐membered derivatives, it was necessary to use a formylation‐hydrolysis sequence. Synthesis of alpha‐substituted prolines and their amides was elaborated starting from the corresponding five‐membered ketimines through a benzylation‐hydrolysis‐hydrogenation sequence.
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