Proline and its Derivatives as Organocatalysts for Multi‐ Component Reactions in Aqueous Media: Synergic Pathways to the Green Synthesis of Heterocycles

• Published in: Advanced synthesis & catalysis Vol. 362; no. 1; pp. 87 - 110
• Main Authors: Vachan, B. S., Karuppasamy, Muthu, Vinoth, Perumal, Vivek Kumar, Sundaravel, Perumal, Subbu, Sridharan, Vellaisamy, Menéndez, J. Carlos
• Format: Journal Article
• Language: English
• Published: Heidelberg Wiley Subscription Services, Inc 07.01.2020
• Subjects: Agrochemicals; Aqueous environments; Aqueous solutions; Derivatives; green chemistry; heterocycles; Organic chemistry; organocatalysis; Proline; water as solvent
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201900558

Proline is a non‐toxic and inexpensive natural amino acid that is readily available in both enantiomeric forms and was one of the very first compounds to be studied as an organocatalyst. Proline can engage in several modes of organocatalysis, as it can behave both as a Brønsted acid or a Brønsted base, and it can also easily generate the iminium or enamine intermediates that are typical of covalent organocatalysis. In view of the importance of diminishing the generation of residues formed by volatile organic solvents, the development of synthetically useful reactions that can be performed in aqueous environments is of increasing significance. The synergic combination of the advantages of water as a reaction medium with the efficiency associated to reactions that are able to generate several bonds in one operation is particularly relevant from the point of view of sustainable chemistry. In this review we critically summarize the use of proline and proline derivatives as catalysts of multi‐component reactions performed in aqueous media and leading to synthetically and biologically relevant heterocycles, a very important class of compounds that constitutes over 60% of drugs and agrochemicals.