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.

Among the aromatic heterocycle rings, pyrazole –a five-membered ring with two adjacent nitrogen atoms in its structure– has been postulated as a potent candidate in the pharmacological context. This moiety is an interesting therapeutic target covering a broad spectrum of biological activities due to its presence in many natural substances. Hence, the potential of the pyrazole derivatives as antitumor agents has been explored in many investigations, showing promising results in some cases. In this sense, breast cancer, which is already the leading cause of cancer mortality in women in some countries, has been the topic selected for this review, which covers a range of different research from the earliest studies published in 2003 to the most recent ones in 2021.

An unprecedented enantioselective C–P bond formation has been developed through a C(sp3)–H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been successfully achieved following a one-pot strategy, starting from different benzylic alcohols and dibenzylphosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched α-hydroxy phosphonates in good to excellent yields (up to >95%) and high enantioselectivities (up to >99%). Furthermore, the use of this methodology has been successfully demonstrated to form a quaternary centre, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents a highly effective strategy for constructing chiral C–P bonds, which are of significant interest to the pharmaceutical industry. This proof of concept represents a significant breakthrough in the field of chemistry.