Catalytic Approaches to Multicomponent Reactions: A Critical Review and Perspectives on the Roles of Catalysis

Abstract

In this review, we comprehensively describe catalyzed multicomponent reactions (MCRs) and the multiple roles of catalysis combined with key parameters to perform these transformations. Besides improving yields and shortening reaction times, catalysis is vital to achieving greener protocols and to furthering the MCR field of research. Considering that MCRs typically have two or more possible reaction pathways to explain the transformation, catalysis is essential for selecting a reaction route and avoiding byproduct formation. Key parameters, such as temperature, catalyst amounts and reagent quantities, were analyzed. Solvent effects, which are likely the most neglected topic in MCRs, as well as their combined roles with catalysis, are critically discussed. Stereocontrolled MCRs, rarely observed without the presence of a catalytic system, are also presented and discussed in this review. Perspectives on the use of catalytic systems for improved and greener MCRs are finally presented.

Hf(OTf)4-Catalyzed Three-Component Synthesis of N-Carbamate-Protected β-Amino Ketones

“…Multicomponent reactions (MCRs), which employ three or more reactants to yield a product derived from all the starting materials in a one-pot manner, have long been recognized as a powerful tool to enrich molecular diversity in natural product synthesis and medicinal chemistry [ 33 , 34 , 35 ]. However, the revelation of the reaction mechanisms of MCRs, which is crucial for condition optimization and the manipulation of stereochemistry outcomes, has always been a challenging task due to the multiple potential reaction pathways and the difficulty of capturing key intermediates [ 35 , 36 , 37 ]. To elucidate the reaction pathway for the three-component synthesis of β-carbamate ketones, we separately tested the reactivity of each component to another under solvent-free conditions.…”

Six‐Component Reactions and Beyond: The Nuts and Bolts

“…A wide range of reviews and book chapters in recent years on isocyanides articulate this peculiar transition new entrants to the field experience. [88][89][90][91][92][93][94][95][96] In summary, we collectively hold the view that isocyanide chemistry is far from exhausted, and many new developments are expected in the field. At the end of the 20th century, the renaissance of isocyanide chemistry was driven by a lack of innovation and productivity in the pharmaceutical sector which led to a need for library compatible methodologies that could feasibly afford a broad spectrum of heterocyclic scaffolds, pseudopeptide structures and subsequent biologically active compounds.…”

Solvent Screening Is Not Solvent Effect: A Review on the Most Neglected Aspect of Multicomponent Reactions

“…A recent review has discussed the role of catalysis to improve yields and selectivities, to lower reaction temperature, and to avoid excess reagents for improved MCRs conditions. [11] In another example, advances in the use of organocatalysts for multicomponent transformations has been presented and discussed. [12] Reactions performed with metal-free catalysis have also been analyzed in a recent review.…”

“…The large number of recent reviews [7–10] describing several features, types, applications, and drawbacks associated with these reactions underlines the growth and prominence of MCRs. A recent review has discussed the role of catalysis to improve yields and selectivities, to lower reaction temperature, and to avoid excess reagents for improved MCRs conditions [11] . In another example, advances in the use of organocatalysts for multicomponent transformations has been presented and discussed [12] .…”