Horizons in Asymmetric Organocatalysis: En Route to the Sustainability and New Applications

Abstract

Nowadays, the development of new enantioselective processes is highly relevant in chemistry due to the relevance of chiral compounds in biomedicine (mainly drugs) and in other fields, such as agrochemistry, animal feed, and flavorings. Among them, organocatalytic methods have become an efficient and sustainable alternative since List and MacMillan pioneering contributions were published in 2000. These works established the term asymmetric organocatalysis to label this area of research, which has grown exponentially over the last two decades. Since then, the scientific community has attended to the discovery of a plethora of organic reactions and transformations carried out with excellent results in terms of both reactivity and enantioselectivity. Looking back to earlier times, we can find in the literature a few examples where small organic molecules and some natural products could act as effective catalysts. However, with the birth of this type of catalysis, new chemical architectures based on amines, thioureas, squaramides, cinchona alkaloids, quaternary ammonium salts, carbenes, guanidines and phosphoric acids, among many others, have been developed. These organocatalysts have provided a broad range of activation modes that allow privileged interactions between catalysts and substrates for the preparation of compounds with high added value in an enantioselective way. Here, we briefly cover the history of this chemistry, from our point of view, including our beginnings, how the field has evolved during these years of research, and the road ahead.

Greener Synthesis of Pyrroloquinazoline Derivatives: Recent Advances

“…Since the pioneer works of List and MacMillan, approximately 20 years ago, a number of impressive contributions has been made in this area [62] . The principal characteristics of organocatalysis are the possibility to perform enantioselective reactions in a metal free medium, in general in mild reaction conditions, and the use of natural products or derivatives as catalysts [63] . Despite this, only one example of the use of organocatalysis for the green synthesis of pyrroloquinazoline derivatives has been described so far.…”

Construction of Chemoenzymatic Linear Cascades for the Synthesis of Chiral Compounds

“…The quest for green, environmentally friendly, synthetic procedures, is one of the most challenging tasks of contemporary organic chemistry. Organocatalysis, the use of small molecules to catalyse chemical transformations, has proven to be an excellent tool in asymmetric synthesis, providing access to a variety of functional groups under sustainable conditions [57] . In 2000, seminal works by MacMillan [58] and List [59] inspired the development of this field, for which they have been awarded the 2021 Nobel Prize in Chemistry .…”

“…Organocatalysis, the use of small molecules to catalyse chemical transformations, has proven to be an excellent tool in asymmetric synthesis, providing access to a variety of functional groups under sustainable conditions. [57] In 2000, seminal works by MacMillan [58] and List [59] inspired the development of this field, for which they have been awarded the 2021 Nobel Prize in Chemistry . Despite the relatively late development when compared with other modalities of catalysis, the field has greatly expanded in the last 15 years and has proved to be a useful tool for asymmetric CÀ C bond formation under a variety of reaction conditions, showing high reactivity and selectivity.…”

Enzyme Kits to Facilitate the Integration of Biocatalysis into Organic Chemistry – First Aid for Synthetic Chemists

“…[6,7] More refined synthetic strategies such as protecting group-free [8] and biomimetic total syntheses, [9] diversity-oriented compound generation, [10,11] inert CÀ H activation, [12,13] early-or late-stage modifications, [14,15] and biocatalysis in general, [16,17] are boosting the synthetic elegance by reducing the number of steps required, increasing the atom economy, and ultimately making chemical reactions more environmentally friendly and sustainable. [18] The recent Nobel prizes in chemistry for 'asymmetric organocatalysis' [19,20] in 2021 [21] and for the 'directed evolution of enzymes' [22,23] in 2018 [24] symbolise such efforts.…”