Theoretical Perspectives in Organocatalysis

Abstract

It is clear that the field of organocatalysis is continuously expanding during the last decades. With increasing computational capacity and new techniques, computational methods have provided a more economic approach to explore different chemical systems. This review offers a broad yet concise overview of current state-of-the-art studies that have employed novel strategies for catalyst design. The evolution of the all different theoretical approaches most commonly used within organocatalysis is discussed, from the traditional approach, manual-driven, to the most recent one, machine-driven.

Keywords: asymmetric organocatalysis; computational design; computationally-led catalyst design; organocatalysts; prediction.

Scheme 1

Evolution and historical highlights of organocatalysis.

Figure 1

Evolution of the number of papers over time regarding organocatalysis (blue) and computational organocatalysis (red).

Figure 2

General workflow for the traditional approach (top) and computational rational design (bottom) in catalyst optimisation.

Figure 3

(A) Comparative study of two possible mechanisms of action for the asymmetric addition of oxazolones to activated 1,3‐enynes catalysed by Brønsted acid catalysts: the enol‐type (red pathway) and Münchnone‐type (blue pathway) of mechanism of action. (B) Reaction scheme of the enantioselective cyclisation of benzothiazolomines using a styrene‐based organocatalyst, showing both the control and the rationally designed catalyst as well as the main interactions within the TS using either.

Figure 4

General workflow for automatic approach of catalyst design.

Figure 5

(A) Computational evaluation of the [5,5] bicyclic guanidine catalysed asymmetric cycloaddition reaction of anthrones. (B) automated stereoselectivity assessment of 18 axially chiral bipyridine NN’‐dioxide allylation catalysts.

Figure 6

Workflow for the most usual procedure carried out in ML approaches.