| The use of short peptides (3–8 amino acids in length) as catalysts for the asymmetric acylation reaction is described. A combination of mechanism-based design principles and combinatorial screening techniques are utilized for catalyst discovery. Highly selective catalysts that exhibit k rel (= kfast/kslow ) >50 in the acylation of certain secondary and tertiary alcohols are described. The most selective catalysts exhibit enantiomer specific rate acceleration. We propose a mechanism for this rate acceleration involving substrate-catalyst contacts and evidence to support this mechanism is presented. The suitability of short peptides as asymmetric catalysts has been demonstrated and foreshadows their use in a wide variety of transformations, including site-selective transformations. Preliminary studies along these lines are presented. |
