Asymmetric Organocatalysis-A Powerful Technology Platform for Academia and Industry: Pregabalin as a Case Study

Enantioselective organocatalysis has quickly established itself as the third pillar of asymmetric catalysis. It is a powerful technology platform, and it has a tremendous impact in both academic and industrial settings. By focusing on pregabalin, as a case study, this Perspective aims to show how a process amenable to industry of a simple chiral molecule can be tackled in several different ways using organocatalysis

Asymmetric Organocatalysis Accelerated via Self-Assembled Minimal Structures

Self-assembling minimalistic peptides embedded with an organocatalytic moiety were designed. By controlling the formation of fibrils via external intervention, it was shown that the activation is accelerated when the organocatalyst is in its supramolecular state. The effect of the accelerated catalysis was demonstrated in a Michael benchmark reaction

Continuous-Flow Synthesis of Arylthio-Cyclopropyl Carbonyl Compounds

The straightforward, continuous-flow synthesis of cyclopropyl carbaldehydes and ketones has been developed starting from 2-hydroxycyclobutanones and aryl thiols. This acid-catalyzed mediated procedure allows access to the multigram and easily scalable synthesis of cyclopropyl adducts under mild conditions, using reusable Amberlyst-35 as a catalyst. The resins, suitably ground and used for filling steel columns, have been characterized via TGA, ATR, SEM and BET analyses to describe the physical-chemical properties of the packed bed and the continuous-flow system in detail. To highlight the synthetic versatility of the arylthiocyclopropyl carbonyl compounds, a series of selective oxidation reactions have been performed to access sulfoxide and sulfone carbaldehyde cyclopropanes, oxiranes and carboxylic acid derivatives

Catalytic Asymmetric Benzidine Rearrangement

A chiral Brønsted acid catalyzes the asymmetric benzidine rearrangement of N,N′‐dinaphthylhydrazines. Different electronically and structurally diverse axially chiral 2,2′‐binaphthyl diamine (BINAM) derivatives are obtained with high enantioselectivity

Towards High-Performance Lewis Acid Organocatalysis

The combination of Lewis acid organocatalysis and internal hydrogen-bond assistance was used to develop a new type of highly active disulfonimide catalyst. The increased Lewis acidity was documented by activity comparisons as well as theoretical investigations. Finally, the potential of the hydrogen-bond-assisted disulfonimide catalyst was demonstrated by its application in an enantioselective transformation

Asymmetric Organocatalysis—A Powerful Technology Platform for Academia and Industry: Pregabalin as a Case Study

Enantioselective organocatalysis has quickly established itself as the third pillar of asymmetric catalysis. It is a powerful technology platform, and it has a tremendous impact in both academic and industrial settings. By focusing on pregabalin, as a case study, this Perspective aims to show how a process amenable to industry of a simple chiral molecule can be tackled in several different ways using organocatalysis

Organocatalytic Asymmetric Conjugate Additions of Oxindoles and Benzofuranones to Cyclic Enones

The asymmetric catalytic synthesis of densely functionalized molecules that contain vicinal quaternary and tertiary stereocenters is a challenge for modern chemical methodology. Here we show that a chiral primary amine, derived from natural molecules, efficiently catalyzes the stereoselective conjugate addition of oxindoles to cyclic enones, leading directly to valuable chiral scaffolds. Proof-of-concept for extending the method to benzofuranone derivatives is also provide