Catalytic Ugi reactions: current advances, future challenges – part 1
Multicomponent reactions (MCRs) are a very important class of reactions that are used with ever increasing frequency in the hunt for new medicinal compounds. Among these reactions, the Ugi reaction holds a special place, as it can be catalyzed by various types of catalysts. As part 1 of a two series short review (the second to be published in a later review) we discuss advances in the catalytic 3- and 4-component Ugi reactions (U-3-CR and U-4-CR, respectively) using metal and non-metal catalytic systems (in the second review we discuss: nano-catalytic systems, biocatalysis and the progress that has been made to date in the development of the catalytic asymmetric version, as well as the application of continuous flow systems and the industrial application of this exciting reaction). In this review a strong emphasis is placed on sustainable and non-conventional methods, such as microwaves, unconventional solvents (such as water and deep-eutectic-solvents) and ball-milling, etc..
INTRODUCTION AND HISTORY Multicomponent reactions (MCRs) have become essential tools for the rapid exploration of chemical space and in the quest for newer and more efficient medicines (1). Furthermore, they constitute intrinsically sustainable synthetic processes, since many of their features overlap and resonate with Green Chemistry principles, and many efforts over the last number of years have being focused on these reactions essentially with greater product diversity as the key priority (2). Among these reactions, which include the Biginelli, Passerini and Petasis reactions, the Ugi reaction holds a special place as it allows access to peptide-like products, through both Ugi-3 (U-3-CR) or Ugi-4 (U-4-CR) component reactions. The Ugi reaction is relatively new, it was discovered by Ivar Ugi working at the Central Research Laboratories of Bayer AG in 1959 and essentially involves the condensation of a primary amine, a carbonyl compound, a carboxylic acid (which can function as the catalyst) and an isocyanide to form dipeptide products (Scheme 1) (3) (the reaction has 1931 hits on Web of Science; 670 hits from 2015-pres ...