Bioinspired organocatalytic asymmetric reactions

Abstract

Several small organic molecule catalysts are reminiscent of natural enzymes in their mode of action and substrate interaction/activation. This striking similarity has been a great source of inspiration for the development of new organocatalytic asymmetric processes. A few representative examples, mostly dealing with catalysts interacting through multiple hydrogen-bonds (synthetic oxyanion holes), are highlighted in this perspective.

Enolate chemistry with anion–π interactions

“…In this report, we demonstrate that anion-p interactions can stabilize the most important anionic reactive intermediates and transition states in chemistry 31,32 and biology 33,34 . Enolates, the initial reactive intermediate of all these transformations, can be stabilized by DDG RI ¼ 4.7 kJ mol À 1 on isolated, unoptimized p-acidic surfaces, thus increasing the acidity of the conjugate enols by DpK a ¼ 1.9.…”

“…The significance of the stabilization of enolate 6 by anion-p interactions for enolate chemistry was evaluated first with the Michael addition to enone 7 (Fig. 2a), a classical reaction of general interest in the community 31,32,37 . The reaction kinetics were determined by NMR spectroscopy for a 50 mM solution of 5 and 7 in CD 3 CN/CDCl 3 1:1 in the presence of 5 mM DBU (1,8-diazabicycloundec-7-ene; Supplementary Fig.…”

“…Core-substituted analogues (RaH, Fig. 1) 1,23,24,42 as well as tweezers and macrocycles 1,4,21 are currently being prepared to elaborate on these expectations and initiate studies on asymmetric enolate chemistry 31,32,42 .…”

“…However, as soon as transmembrane transport with anion-p interactions has finally been confirmed, it was immediately clear that they should also be capable of stabilizing anionic transition states 1 . Building on an introductory study on catalysis of the Kemp elimination with anion-p interactions 23,24 , we here report that anion-p interactions can accelerate the reactions that are most central in chemistry 31,32 and biology 33,34 , that is, enolate chemistry.…”

Toward Ideal Asymmetric Catalysis

“…The characteristic function of the oxyanion hole is to stabilize a high-energy tetrahedral intermediate or transition state featuring a negatively charged oxygen by the simultaneous donation of two or more hydrogen bonds in the active sites [69]. A good example to demonstrate the powerfulness of the oxyanion hole is the chorismate mutases mediated [3,3]-sigmatropic Claisen rearrangement of chorismate to prephenate (Figure 1.5), which is a part of the Shikimate pathway [70].…”