Catalytic Ugi reactions: Current advances, future challenges – Part 2
Multicomponent reactions (MCRs) are a very important class of reactions that are considerably useful in the quest for new medicines and, within this category, the Ugi-MCR holds a special place. In part 2 of this series (the first was previously published) we discuss advances in the catalytic 3- and 4-component Ugi reactions (U-3-CR and U-4-CR, respectively) as regards to nanocatalysis, biocatalysis, asymmetric catalysis with organocatalysts, as well as continuous manufacturing methods such as, continuous-flow processes. Again, in this review there is a strong focus on green and sustainable versions of this important reaction. To conclude this report, the operation and implications (both presently and in the future) of this versatile and enabling reaction in the pharmaceutical industry are discussed.
In our previous review we discussed the history and development of this important multicomponent reaction (MCR) since its inception in the laboratory of Ivar Ugi at the Central Research Laboratories of Bayer AG in 1959 to more recent discoveries with novel metal and non-metal catalytic systems (1). In this second part, we continue our assessment of this reaction, principally in regard to the use of novel nanocatalytic systems, enzymatic catalysis, enantioselective catalysis (with chiral organocatalysts), with continuous flow systems and also, we weigh up the current state of this reaction in connection to API production and its exploitation by the pharmaceutical industry.
As stated previously; there are two types of Ugi MCR; the 3- and the 4-component Ugi MCR reaction (U-3-CR and U-4-CR, respectively) (1).
A major break-through took place in 2018, with the first demonstration of a highly enantioselective version by Zhang and coworkers who developed an asymmetric phosphoric acid-catalyzed U-4-CR (2) (the capacity to run this reaction with high enantioselectivit ...