Cyanohydrins Blaise reaction

The reaction of a nitrile with a Reformatsky reagent is known as the Blaise reaction and when applied to (9-trimethylsilyl cyanohydrins leads to the formation of tetronic acids with high ee [79]. By working-up the Blaise reaction with ammonium chloride it is possible to isolate... 

Duffield, J.J. and Regan, A.C. (1996) Asymmetric synthesis of tetronic acids by Blaise reaction of protected optically active cyanohydrins. Tetrahedron Asymmetry, 7, 663-666. 

Syed, J., Forster, S. and Effenberger, F. (1998) Application of the Blaise reaction stereoselective synthesis of (4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates from (R)-cyanohydrins. Tetrahedron Asymmetry, 9, 805-815. 

Tetronic acids (Scheme 18) are of great interest because their derivatives are widespread in nature. The Blaise reaction (addition of the zinc derivative of an a-bromo ester to a nitrile) has been applied to optically active 0-protected cyanohydrins. Isolation of the tetronic acids was achieved, in moderate yields, by acid hydrolysis and cyclization of the intermediate imines [94]. Better results were obtained in an optimized reaction sequence [141] (Scheme 18). 

A partial reduction of O-protected chiral cyanohydrins is also possible by reaction with Reformatsky reagents (Blaise reaction). The primarily formed imino intermediates can be hydrolyzed under very mild conditions to give the enamines ( )-15, which yield by treatment with strong acids the tetronic acids (R)-16 (Scheme 9) [39,40]. 

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