Peptide-catalysed aldol reactions

In this chapter, remarkable advances in the research devoted to peptide catalysed alcohol esterifications, 1,4-conjugate additions, aldol reactions, Strecker synthesis, asymmetric cyanohydrin synthesis and alkene epoxida-tion are discussed. 

Scheme 13.21 Aldol reactions catalysed by N-terminal prolyl peptides 32 and 33.

The group of Zhang designed a series of L-proline-based dipeptides eom-prising a C-terminal amino-piperidyl pyridine moiety (Scheme 13.22a). The asymmetric aldol reaction between various aldehydes and cyelie ketones, catalysed by peptide 34 in 10 mol% loading, was performed in brine since... 

Scheme 13.23 Aldol reactions catalysed by supported N-terminal prolyl peptides 37-40.

Since the introduction of the first peptide organocatalyst in the 1980s, a considerable number of new peptide frameworks have been developed that are able to effectively catalyse several important transformations including alcohol esterifications, 1,4-conjugate additions, aldol reactions, Strecker synthesis, asymmetric cyanohydrin synthesis and alkene epoxidation are discussed. A few successful examples of solid-supported peptides and reactions in ball milling under solvent-free conditions have been demonstrated. These methods combine the advantages of being economically and environmentally friendly processes. 

Small peptides - simple di- and tri-peptides with a primary amine at the N-terminus -catalyse the aqueous aldol between unmodified ketones and aldehydes with up to 86% ee.121 This is dramatically different from the corresponding amino acid-catalysed reaction, suggesting that peptide formation may have been significant in the evolution of asymmetric synthesis. Addition of a-cyclodextrin raised the ee further through the hydrophobic effect. 

---