Asymmetric Organocatalysis Combined with Metal Catalysis: Concept, Proof of Concept, and Beyond

Abstract

Asymmetric catalysis has been considered to be the most intriguing means for building collections of functionalized optically active compounds. In particular, metal and organocatalysis have been well established to allow many fundamentally different reactions. Metal catalysis has enabled the participation of a much broader scope of chemical bonds in organic transformations than are allowed by organocatalysis, while organocatalysis permits a broader scope of functional groups to undergo a diverse range of enantioselective transformations, individually, simultaneously, or sequentially. Theoretically, the combination of organocatalysts and metal complexes could probably render new transformations through the simultaneous or sequential activation and reorganization of multiple chemical bonds if the superior features of both the catalysts are adopted. In 2001, both our research group and Takemoto's group separately described an asymmetric allylation of glycine imino esters with allyl acetate catalyzed by palladium complexes and chiral ammonium salts. In these cases, the oxidative addition of palladium complexes to allyl acetate formed the π-allylic fragments, while the chiral ammonium salts were actually responsible for controlling the stereoselectivity. These reactions in fact marked the beginning of asymmetric organo/metal combined catalysis. Since then, asymmetric organocatalysis combined with metal catalysis, including cooperative catalysis, relay catalysis, and sequential catalysis, has been a versatile concept for the creation of unknown organic transformations. Sequential catalysis describes a one-pot reaction involving two or more incompatible catalytic cycles. Alternatively, cooperative and relay catalyses require high compatibility of principally distinct catalysts and will be the focus of this Account. The catalysts in cooperative catalytic reactions must be able to simultaneously and individually activate both substrates to drive a bond-forming reaction, while relay catalysis is basically defined as a cascade process in which two or more sequential bond-forming transformations are independently catalyzed by distinct catalysts. In the past decade, we have discovered a variety of binary catalytic systems consisting of metals, including Rh(II), Pd(0), Au(I), and Mg(II), and chiral organocatalysts, including chiral phosphoric acids and quinine-based bifunctional molecules, for cooperative catalysis and relay catalysis, allowing the accomplishment of many unprecedented asymmetric transformations. In this Account, these achievements will be summarized, particularly focusing on the description of the concept and proof of the concept, to demonstrate the robustness of combined organo/metal catalysis in the creation of efficient enantioselective transformations. In addition, elegant studies from other laboratories using chiral phosphoric acid/Au(I) for the establishment of asymmetric cascade reactions involving the carbon-carbon triple bond functionality and typical combined organo/metal catalytic systems, very rece...

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

“…This might be attributed to the in situ generated stoichiometric amount of HCl, which may promote both the background and side reactions, which is in agreement with our initial assumption. Given this, we surmised that the use of a stoichiometric weak basic inorganic salt would neutralize the equivalent of strong acid HCl to generate not only the relatively weaker achiral acid such as carbonic acid but also insoluble metal chloride in organic solvents; therefore, establishing a phase separation between the catalytic system (bulk solution) and the stoichiometric metal salt (solid phase)303132334142 to allow for the radical aminofluoroalkylation of alkenes in an enantioselective manner. Subsequently, we chose 1.2 equiv.…”

“…Buchwald succeeded in utilizing copper/bis(oxazoline) catalysts for asymmetric intramolecular oxytrifluoromethylation of alkenes with carboxylic acids with Togni's reagent, giving rise to good enantioselectivities (74–83% ee)2829. More recently, we discovered that a dual-catalytic system30313233 of Cu(I) and chiral phosphoric acid (CPA) could catalyse the asymmetric radical aminotrifluoromethylation of alkenes with Togni's reagent as the CF 3 radical source with excellent enantioselectivity34. Given these facts, it is still very desirable to design and develop new effective catalytic systems for efficient and general particularly challenging asymmetric radical fluoroalkylation reactions with versatile fluoroalkylating reagents.…”

Development of Synergistic, Dual Pd‐Cu@rGO Catalyst for Suzuki, Heck and Click Reactions: Facile Synthesis of Triazole or Tetrazole Containing Biaryls and Stilbenes

“…Therefore, design of dual synergistic catalyst has fascinated most chemists because it can reduce the cost of the process. The assistance of two different catalytic systems to run two catalytic cycles synchronously represents a unique property . However, the designing of such cooperatively functioning dual‐catalysis system is rather difficult.…”

“…However, the designing of such cooperatively functioning dual‐catalysis system is rather difficult. Recently, various dual catalytic systems have been accomplished by successfully combining a transition metal with organo catalyst or Lewis acids, or by combining N ‐heterocyclic carbenes with Lewis acid . However, the designing of transition metal based dual catalytic systems remain far less explored and is a challenge to most synthetic chemist .…”

Synergistic Cu/Pd Catalysis for Enantioselective Allylic Alkylation of Aldimine Esters: Access to α,α‐Disubstituted α‐Amino Acids

“…In transition metal catalyzed AAA [9b, 10] reactions,e ither the prochiral or racemic nucleophile attacks p-allyl complex from the opposite side of the chiral catalyst, and thus makes the stereocontrol of the nucleophile difficult. Inspired by the fact that metallated azomethine ylides were not only the dipoles in cycloadditions, [12] but also viable nucleophiles in Michael additions, [6d, 13] as reported by our group,w ee nvisioned that asynergistic Cu/Pd catalyst system [14][15][16] would be an ideal solution to overcome these problems.A ss hown in Scheme 1c,wereasoned that intercepting the reactive achiral allylpalladium intermediate B with the in-situ-formed asubstituted metallated azomethine ylide A,a ctivated by achiral copper(I) complex, could result in alinearly selective allylic alkylation process which permits control of the configuration of the generated a-quaternary stereogenic center. Despite considerable progress,t he construction of a,adisubstituted a-AAs through AAA reactions with high enantioselectivity is still underdeveloped.…”