Cycle-l(S)-His-(S)-L.eu] adopts a confirmation in solution in which rhe imidazole ring is folded over the diketopiperasine ring. This is the opposite confirmation IO that deremdned for cycle-i(S)-His-(S)-Phel. and "ray explain the opposite sense of asymnaerric induction between the two catalysts.
q--
&)-Ij-(
H 0 H 0 (1) (2) Cyanohydrins are versatile, difunctional, starting materials for the preparation of a range of chemical productsl. However, the traditional methods of preparing cyanohydrins give a racemic product2 which needs to be resolved if it is to be used in the synthesis of homochiral products. Thus there has been much recent interest in the preparation of optically pure cyanohydrit$, and in particular in the use of chiral catalysts for the asymmetric synthesis of cyanohydrins from carbonyl compounds and a cyanide source4. Numerous catalysts have been investigated for this reaction including; enzyme$, polymersa, organometallic reagents7, and cyclic dipeptidesglo (diietopiperazines). Of these, the cyclic dipeptides initially discovered by Inoue et al. have been the most widely studied, with cycfo-[(S)-His-(S)-Phe] (1) catalysing the formation of (R)cyanohydrinsg, and cycle-[(S)-His-(S)-Leul (2) catalysing the formation of (S>cyanohydrinslo. Although the synthetic utility of catalysts (1) and (2) has been extensively investigated, little is known about the mechanism of this catalytic, asymmetric, carbon-carbon bond forming reaction. Mechanistic studies on these compounds have been hindered by their amorphous nature which has prevented an X-ray analysis. The conformation of catalyst (1) in solution has been investigated", as has the nature of the interaction between catalyst (1) and HCN12 and four possible transition state models have been proposed for the asymmetric induction13~t4. In