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

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.

Accelerated SuFEx Click Chemistry for Modular Synthesis

Click chemistry is a method for the rapid synthesis of functional molecules with desirable properties. We report the development of accelerated SuFEx, a powerful click reaction for the efficient coupling of aryl and alkyl alcohols directly with SuFExable hubs catalyzed by 2-<i>tert</i>-butyl-1,1,3,3-tetramethylguanidine (BTMG, Barton's base). The new method circumvents the need to synthesize silyl ether substrates while allowing the use of sub-stoichiometric catalyst loadings. This is made possible through a synergistic effect between BTMG and hexamethyldisilazane (HMDS) additive. The powerful combination drives the <i>in situ</i> formation of reactive TMS-ether intermediates while exploiting the silicon-fluoride bond formation's thermodynamic driving force. Comparatively, the required BTMG base's catalyst loading is generally low (1.0–20 mol%) compared to the dominant SuFEx catalyst, DBU (10–30 mol%). In line with click chemistry principles, the scalable reaction only requires simple evaporation of the volatile side products (NH₃, Me₃Si-F, TMS-OH, BTMG) under reduced pressure instead of extensive purification. The new SuFEx protocol is tolerant of a wide selection of functional groups and meets all the demands of a click reaction, thereby dramatically shortening reaction times and delivering products in excellent yield.

Accelerated SuFEx Click Chemistry for Modular Synthesis

Click chemistry is a method for the rapid synthesis of functional molecules with desirable properties. We report the development of accelerated SuFEx, a powerful click reaction for the efficient coupling of aryl and alkyl alcohols directly with SuFExable hubs catalyzed by 2-<i>tert</i>-butyl-1,1,3,3-tetramethylguanidine (BTMG, Barton's base). The new method circumvents the need to synthesize silyl ether substrates while allowing the use of sub-stoichiometric catalyst loadings. This is made possible through a synergistic effect between BTMG and hexamethyldisilazane (HMDS) additive. The powerful combination drives the <i>in situ</i> formation of reactive TMS-ether intermediates while exploiting the silicon-fluoride bond formation's thermodynamic driving force. Comparatively, the required BTMG base's catalyst loading is generally low (1.0–20 mol%) compared to the dominant SuFEx catalyst, DBU (10–30 mol%). In line with click chemistry principles, the scalable reaction only requires simple evaporation of the volatile side products (NH₃, Me₃Si-F, TMS-OH, BTMG) under reduced pressure instead of extensive purification. The new SuFEx protocol is tolerant of a wide selection of functional groups and meets all the demands of a click reaction, thereby dramatically shortening reaction times and delivering products in excellent yield.