The Cyclic Dipeptide cyclo as a Catalyst for Asymmetric Addition of Hydrogen Cyanide to Aldehydes

Article abstract of DOI:10.1021/jo00288a030

cyclo<(S)-Phenylalanyl-(S)-histidyl> (cyclo<(S)-Phe-(S)-His>, 1) catalyzes the addition of hydrogen cyanide to benzaldehyde in toluene at -20 deg C to afford (R)-mandelonitrile with enantiomeric excess of 97 percent in high yield. cyclo<(R)-Phenylalanyl-(R)-histidyl> gives (S)-mandelonitrile. cyclo<(S)-Phe-(S)-His> (1) exhibits a broad substrate specificity, and a variety of aldehydes (3a-r) such as m-methoxybenzaldehyde (3c), 6-methoxy-2-naphthaldehyde (3k), and isobutyraldehyde (3o) similarly afforded the corresponding cyanohydrins with high enantiopurities (97 percent ee for 3c, 93 percent ee for 3k, 71 percent ee for 3o). (R)-Mandelonitrile thus obtained was successfully converted to various chiral synthons such as mandelic acid (7), methyl mandelate (8), and 2-amino-1-phenylethanol (9) without any racemization.