Applications of asymmetric organocatalysis in medicinal chemistry

Abstract

In the last decade, organocatalysis, the use of small chiral organic molecules as catalysts, has proven to be a valuable and attractive tool for the synthesis of enantiomerically enriched molecules. A number of organocatalysts and processes, such as one-pot, tandem, cascade or multicomponent reactions, have been reported to date. Furthermore, the many advantages of organocatalysis - robust, non-toxic, affordable, inert atmosphere, easy reaction manipulation, etc. - allow the preparation of bioactive compounds using simple and metal-free procedures, thus avoiding false positives in the biological evaluation. This mini-review focuses on medicinal chemistry programs that have synthesized biologically active compounds using one or more organocatalytic steps. In this respect, the potential of organocatalytic methods for enabling the chemical synthesis of important medicinal targets will be highlighted.

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

“…[1][2][3][4][5][6][7][8][9][10][11][12] Since the pioneering work in this area by the groups of MacMillan, [13] and Barbas, [14] numerous publications have appeared in which the design, synthesis and uses of a variety of organocatalysts is described. Today, one of the biggest challenges in the synthesis of organic compounds is the implementation of procedures that are more friendly to the environment.…”

“…[22,23] The Michael addition is considered as one of the most powerful tools for the formation of C-C bonds. [1][2][3][4][5][6][7][8][9][10][11][12] In recent years, the number of publications on the study of this organocatalytic reaction has increased considerably. [1] In 1980, Seebach and coworkers reported the reaction of achiral enamines with β-nitrostyrene with good yields and excellent diastereoselectivities.…”

Organocatalytic Asymmetric α-Chlorination of 1,3-Dicarbonyl Compounds Catalyzed by 2-Aminobenzimidazole Derivatives

“…Due to the potential of these compounds, their catalytic asymmetric synthesis has been intensively investigated in the past few years [5][6][7]. Despite the breakthrough asymmetric organocatalysis has experienced during the last fifteen years, not only from a synthetic point of view [8], but also as a strategy for the preparation of natural-occurring and pharmaceutically active compounds [9][10][11], only a few privileged catalysts have been shown to be highly selective in the electrophilic α-chlorination of carbonyl compounds. In 2004, MacMillan [12], Lectka [13], and Jørgensen [14] reported the first catalytic highly enantioselective α-chlorination of aldehydes, acid chlorides, and ketones, respectively, using perchloroquinones and N-chlorosuccinimide (NCS) as chlorination reagents.…”

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

“…Over the past decade, asymmetric organic catalysis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], quite powerful for synthesizing various heterocyclic molecules, has formed the basis of several elegant approaches to construct chiral single-heterocycle piperidine skeletons with high efficiency and low toxicity under environmentally friendly conditions . In contrast, relatively few organocatalytic methods have been described to stereo-selectively form spirocyclic piperidine derivatives [30][31][32][33][34][35][36], particularly ones with a quaternary stereocenter [37][38][39].…”