The application of the most representative and up-to-date examples of homogeneous asymmetric organocatalysis to the synthesis of molecules of interest in medicinal chemistry is reported. The use of different types of organocatalysts operative via noncovalent and covalent interactions is critically reviewed and the possibility of running some of these reactions on large or industrial scale is described. A comparison between the organo- and metal-catalysed methodologies is offered in several cases, thus highlighting the merits and drawbacks of these two complementary approaches to the obtainment of very popular on market drugs or of related key scaffolds. 1. Introduction Over the past ten years, the field of enantioselective organocatalysis has had a significant impact on chemical synthesis [1, 2]. Currently, asymmetric organocatalysis is recognized [3] as an independent synthetic tool besides asymmetric metallic catalysis and enzymatic catalysis for the synthesis of chiral organic molecules. Multiple advantages compared with the other two catalytic domains are the reasons for the rapid growth and acceptance of organocatalysis. In general, organocatalysts are air- and moisture-stable and, thus, inert-equipments such as vacuum lines or glove boxes are not necessary. They are easy to handle even on large scale and relatively less toxic compared to transition metals. Moreover, frequently the reactions are conducted under mild conditions and high concentrations thus avoiding the use of large amounts of solvents and minimizing waste. The organocatalysts can be classified by means of their interactions with the substrate or “mode of action” as covalent or noncovalent catalysts (Figure 1). Figure 1: General classification of the activation mode of several representative classes of molecules in organocatalysis. In covalent organocatalysis, a new covalent bond between the catalysts and the substrate is formed as in the case of aminocatalysis [4] and carbenes [5], leading to a strong interaction between the substrate and the reagent in the reaction. In the case of noncovalent interactions between the substrate and the catalyst, the activation of the substrate occurs via weak binding exemplified by hydrogen bonding [6] or ionic interaction as in the case of phase transfer catalysis [7]. The field of asymmetric organocatalysis has enjoyed phenomenal growth in the past 15 years [8–10] and during the “golden age” [11] of organocatalysis many researchers from academia and chemical industry were involved in this field, with most efforts focused on the development of
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