Bimetallic catalysis represents an alternative paradigm for coupling chemistry that complements the more traditional single-site catalysis approach. In this perspective, recent advances in bimetallic systems for catalytic C–C and C–X coupling reactions are reviewed. Behavior which complements that of established single-site catalysts is highlighted. Two major reaction classes are covered. First, generation of catalytic amounts of organometallic species of e.g. Cu, Au, or Ni capable of transmetallation to a Pd co-catalyst (or other traditional cross-coupling catalyst) has allowed important new C–C coupling technologies to emerge. Second, catalytic transformations involving binuclear bond-breaking and/or bond-forming steps, in some cases involving metal–metal bonds, represent a frontier area for C–C and C–X coupling processes.

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Bimetallic catalysis for C–C and C–X coupling reactions

Computational chemistry provides a versatile toolbox for studying mechanistic details of catalytic reactions and holds promise to deliver practical strategies to enable the rational in silico catalyst design. The versatile reactivity and nontrivial electronic structure effects, common for systems based on 3d transition metals, introduce additional complexity that may represent a particular challenge to the standard computational strategies. In this review, we discuss the challenges and capabilities of modern electronic structure methods for studying the reaction mechanisms promoted by 3d transition metal molecular catalysts. Particular focus will be placed on the ways of addressing the multiconfigurational problem in electronic structure calculations and the role of expert bias in the practical utilization of the available methods. The development of density functionals designed to address transition metals is also discussed. Special emphasis is placed on the methods that account for solvation effects and the multicomponent nature of practical catalytic systems. This is followed by an overview of recent computational studies addressing the mechanistic complexity of catalytic processes by molecular catalysts based on 3d metals. Cases that involve noninnocent ligands, multicomponent reaction systems, metal-ligand and metal-metal cooperativity, as well as modeling complex catalytic systems such as metal-organic frameworks are presented. Conventionally, computational studies on catalytic mechanisms are heavily dependent on the chemical intuition and expert input of the researcher. Recent developments in advanced automated methods for reaction path analysis hold promise for eliminating such human-bias from computational catalysis studies. A brief overview of these approaches is presented in the final section of the review. The paper is closed with general concluding remarks.

Computational Approach to Molecular Catalysis by 3d Transition Metals: Challenges and Opportunities

Transition metals can assemble to form multinuclear complexes by engaging in direct metal-to-metal interactions. Metal–metal covalent bonds provide a large perturbation in electronic structure, relative to mononuclear metal ions, and the unique properties of these dinuclear fragments can be harnessed in a broad range of applications—for example, as chromophores in photochemical processes, redox centers in molecular electronics, or structural elements in metal–organic materials. There is a growing body of evidence that metal–metal bonds may also be formed under conditions relevant to catalysis and play a key role in transformations that were previously assumed to only involve mononuclear species. These findings have stimulated interest in characterizing multinuclear reaction pathways and developing well-defined multinuclear platforms as catalytic active sites. In this Perspective, we present case studies in this emerging area of catalysis research, emphasizing the impact of metal–metal bonding in either en...

Metal–Metal Bonds in Catalysis

An emerging area of homogeneous catalysis is the use of catalysts featuring two closely associated metal sites. This approach complements the traditional focus on single-site catalysts and makes available new parameters with which to optimize catalytic behavior. Single-site catalysts are optimized through changing 1) the identity of the metal, and 2) the steric and electronic properties of the ligands. Bimetallic catalysts introduce new optimization parameters such as 3) catalyst nuclearity (mononuclear vs. binuclear), and 4) bimetallic pairing (relative compatibility of two metal sites). In order to harness these new optimization parameters in developing systems, it is necessary to first understand the origin of bimetallic selectivity effects that already have been documented. This Concept article highlights bimetallic effects on the chemo-, regio-, and stereoselectivity of catalytic transformations, using selected case studies from the recent literature as illustrative examples.

Selectivity Effects in Bimetallic Catalysis

The reaction mechanism of the Pd-catalyzed benzyl/allyl coupling of benzyl chloride with allyltributylstannan, resulting in the dearomatization of the benzyl group, was studied using density functional theory calculations at the B3LYP level. The calculations indicate that the intermediate (η3-benzyl)(η1-allyl)Pd(PH3) is responsible for the formation of the kinetically favored dearomatic product. Reductive elimination of the dearomatic product from the intermediate occurs by coupling the C-3 terminus of the η1-allyl ligand and the para-carbon of the η3-benzyl ligand in (η3-benzyl)(η1-allyl)Pd(PH3). For comparison, various C−C coupling reaction pathways have also been examined.

DFT Studies on the Mechanism of Allylative Dearomatization Catalyzed by Palladium

Experiments and density functional calculations were used to quantify the impact of the Pd–Ti interaction in the cationic heterobimetallic Cl2Ti(NtBuPPh2)2Pd(η3-methallyl) catalyst 1 used for allylic aminations. The catalytic significance of the Pd–Ti interaction was evaluated computationally by examining the catalytic cycle for catalyst 1 with a conformation where the Pd–Ti interaction is intact versus one where the Pd–Ti interaction is severed. Studies were also performed on the relative reactivity of the cationic monometallic (CH2)2(NtBuPPh2)2Pd(η3-methallyl) catalyst 2 where the Ti from catalyst 1 was replaced by an ethylene group. These computational and experimental studies revealed that the Pd–Ti interaction lowers the activation barrier for turnover-limiting amine reductive addition and accelerates catalysis up to 105. The Pd–Ti distance in 1 is the result of the NtBu groups enforcing a boat conformation that brings the two metals into close proximity, especially in the transition state. The turno...

Origin of Fast Catalysis in Allylic Amination Reactions Catalyzed by Pd–Ti Heterobimetallic Complexes

Allylic aminations with hindered secondary amine nucleophiles catalyzed by heterobimetallic Pd-Ti complexes.

Phosphinoamide-scaffolded heterobimetallic palladium–titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts in situ and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles.

Diana L. Anderson

Papers

Origin of Fast Catalysis in Allylic Amination Reactions Catalyzed by Pd–Ti Heterobimetallic Complexes

Allylic aminations with hindered secondary amine nucleophiles catalyzed by heterobimetallic Pd-Ti complexes.

Allylic Aminations with Hindered Secondary Amine Nucleophiles Catalyzed by Heterobimetallic Pd—Ti Complexes.