Development of Multi‐Catalytic Strategies Based on the Combination between Iron‐/Copper‐ and Organo‐Catalysis

Abstract

Despite the latest advances in catalysts efficiency, using one single catalytic activation mode can lead to considerable limitations. To overcome reactivity or selectivity issues, multi-catalytic combinations can represent interesting alternatives. This manuscript reviews the recent transformations developed in my group through the combination between cheap iron or copper complexes and organocatalysis. Combining these activation modes enables considerable synthetic economies inconceivable by using one single catalyst. The strategies developed to combine efficiently different catalysts as well as the resulting synthetic applications are discussed.

Copper Catalyzed Decarboxylative Functionalization of Ketoacids

“…Indeed, in recent years, considerable progress was obtained through the appropriate merging of complementary metal-and organo-catalysis. [3] Among all the co-catalysts tested, we discovered that addition of simple iron or copper Lewis acids could considerably improve both reactivity and selectivity. Notably, using 6 mol% of Cu(i-BuCOO) 2 , 3 a could be isolated in 50 % yield and > 98 % ee, indicating that the copper complex was involved in the rate and enantio-determining step of the process.…”

“…In addition, in order to bypass the inherent selectivity and reactivity issues associated with these catalysts, when necessary, we also often took advantage of multicatalytic combination with organocatalysis. [3] In addition to the rapid preparation of natural product fragments, cascade incorporation of fluorine also provided new type of synthetic analogues of improved properties in a broad range of applications.…”

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

“…Nucleophilic attack on to the 1,3-dicarbonyl occurs stereoselectively, and subsequent hydrolysis of the imine affords a ketone intermediate that is reduced by iron. This work has since been extended by the same group, who have published various reviews on the subject. , Wang and colleagues employed dual ruthenium/copper catalysis toward alcohol functionalization in 2022, combining ruthenium-catalyzed in situ oxidation with copper-catalyzed asymmetric Michael addition (Scheme b) . Ketimine esters were utilized as Michael acceptors in this transformation, generating highly functionalized δ-hydroxyesters with high diastereo- and enantioselectivity.…”

Cinchona‐Based Hydrogen‐Bond Donor Organocatalyst Metal Complexes: Asymmetric Catalysis and Structure Determination

“…[36][37][38][39][40][41][42][43][44][45] This way, multicomponent or multistep reactions could take place that cannot be realized without their combined application. [46][47][48][49][50][51][52][53][54][55][56][57] Consequently, based on our previous work, procuring the corresponding knowledge in the field of organocatalysis, we aimed to combine cinchona (thio)squaramide and thiourea organocatalysts with copper(II), nickel(II), and silver(I) salts in reactions that are relevant in pharmaceutical aspects, such as Michael addition, Friedel-Crafts reaction and A 3 coupling reaction. Furthermore, we have found explanations for the formation and activity of the prepared organocatalyst-metal complexes via the applied quantum chemical calculations linked to analytical techniques.…”

“…Transition metals combined with organocatalysts can merge their superior qualities to promote reaction systems that can lead to new transformations [36–45] . This way, multicomponent or multistep reactions could take place that cannot be realized without their combined application [46–57] …”