Figure 1: Family tree of Organocatalysis

Organocatalysis

Over the decades, organic synthesis was predominantly operated by two classes of catalytic systems including transition metal catalysis and biocatalysis. However, this concept is being altered, with completely organic catalysts appearing as the third pillar of potent catalysts in organic synthesis. The small organic molecules designed as organocatalysts where an inorganic element is not part of the active transitions can activate the substrate or reagents mainly two-ways either through strong interaction like covalent or weak interactions like van der Waals forces or hydrogen bonding (non-covalent). The existence of organocatalysts has led to a revolution in the synthesis of molecular diversity and complexity in an asymmetric and non-asymmetric manner via several activation modes. It has turned into one of the most important hot topics of current research in terms of synthetic efficiency and green chemistry point of view.

Inspired by these, our group is mainly focused on the development of diverse organocatalytic strategies based on different modes of activation that direct selective synthesis of bio-active molecules and natural product mimics.

Covalent Organocatalysis by Iminium Ion and Enamine Ion Catalysis

In general, both primary and secondary amine catalysts are used as effective catalysts in iminium catalysis which can form iminium ions from reversible condensation with aldehydes or ketones. But primary amines are prone to undergo deprotonation, whereas deprotonation with a secondary amine to form imine is quite impossible. Consequently, secondary amine catalysts completely dominated this field over primary amines. The increased electrophilic character of the so-called formed iminium ions as compared to carbonyl groups is proposed to facilitate various reactions such as Knoevenagel condensation, nucleophilic and cycloaddition reactions, etc. Similarly, the reversible reaction between an amine and carbonyl compound was proposed to form the enamine ion that can then undergo various nucleophilic reactions.

Asymmetric Organocatalysis

The stereo-divergent construction of a chiral complex molecular structure of potential therapeutic interest represents an increasingly promising field in organic chemistry. However, controlling the selectivity of the desired product in a simple, efficient manner from readily available raw materials while minimizing hazardous chemicals is scientifically challenging but demanding. After the transition-metal and bio-based catalysis, the emergence of the third pillar of asymmetric catalysis based on small organic molecules exceptionally provides an outstanding area for constructing structurally functionalized molecules with high selectivity in organic chemistry. At present, organocatalysis has become the backbone of modern asymmetric synthesis for constructing morphologically intricate and enantiomerically pure compounds that may serve as potential building blocks/intermediates of many steroids, natural products, and commercial drugs.

To address the existing dark space of chemical reactions, our group is mainly involved in developing various asymmetric organocatalytic strategies for constructing chiral molecules of potential therapeutic interest. Our study will allow the scouting of large building blocks for rapid evaluation of synthetic viability, chemical space, and limitations of the work, exemplifying a platform for reaction discovery inconsistent with sustainability to endorse succeeding investigations.