Chiral Diketopiperazines as Catalysts

The first catalytic asymmetric Strecker reaction was reported by the Upton group using the cyclic dipeptide 5 as an organocatalyst [4, 5, 15]. This diketopiperazine 5 was prepared starting from (S)-phenylalanine and (S)-a-amino-y-guanidinobutyric 

Asymmetric Organocatalysis. Albrecht Berkessel and Harald Groger Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30517-3 

The catalytic properties of the dipeptide were very sensitive to conditions such as solvent viscosity, enantioselective autocatalysis, and the method of crystallization of the catalyst. The last of these is particularly surprising, because 5 does not act as a heterogeneous catalyst but is soluble under the reaction conditions. 

It should be added that attempts to perform a direct Stacker reaction starting from benzaldehyde, ammonia, and hydrocyanide in the presence of the organocatalyst 5 were also made by the Lipton group [4]. The resulting amino nitrile, however, was found to be racemic [4]. 

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