From Stoichiometric to Catalytic E–H Functionalization by Non-Metallocene Zirconium Complexes─Recent Advances and Mechanistic Insights

Abstract

The chemistry of group 4 elements has historically been dominated by the use of metallocene complexes in stoichiometric transformations. While this area continues to be widely explored, the development of non-cyclopentadienyl-based ligands has substantially contributed to the increase in applicability of group 4 metals in catalysis during the last 15 years. In addition to their application in polymerization catalysis, zirconium complexes supported by nitrogen-based anionic ligands have been useful as catalysts for a variety of E–H functionalization reactions. Two particular zirconium systems, (1) bis(ureate)-supported zirconium complexes reported by the Schafer group and (2) tripodal triamidoamine-supported zirconium complexes employed by the Waterman group, promote a variety of E–E′ bond-forming catalytic processes upon E/E′–H activation. The former system has been exploited for catalytic hydroamination, hydroaminoalkylation, and hydroalkynylation (alkyne dimerization) reactions, and the latter system has been used in hydrophosphination and dehydrocoupling reactions. This Perspective focuses on the bountiful reactivity of these catalytic systems with an emphasis on mechanistic insights of these transformations gained from a combination of kinetic analyses, isolation of reaction intermediates, stoichiometric reactivity studies, and computational calculations. The insights generated from this approach have revealed a series of features that enable catalytic E–E′ bond formation and that can contribute to guided efforts in early transition-metal ligand design. For the zirconium bis(ureate) system, the expanded coordination sphere promoted by the multidentate ligand facilitates the coordination of neutral amine donors that are essential for realizing innersphere E–H bond formation in hydrofunctionalization catalysis. For the triamidoamine-supported zirconium complexes, the noninnocent tripodal ligand mediates E–H bond formation/activation during catalysis. For both zirconium systems, the highly ionic nature of the chelating ligands has been shown to induce significant polarization of reactive Zr–E bonds (E = N, C, P). This bond polarization translates into exceptionally reactive Zr–E bonds, akin to those of rare earth metals, enabling σ-bond insertion reactions for E–E′ bond formation. The goal of this Perspective is to highlight examples where compelling evidence has been gathered demonstrating ligand design effects to promote zirconium catalysis. Lessons learned from the featured zirconium systems aim to highlight ligand design features that will advance new directions in early transition-metal catalysis.

Understanding mechanism driven regioselectivity in zirconium-catalysed hydroaminoalkylation: homoallylic amines from conjugated dienes

“…Rigorous characterization of zirconium complexes supported by L1 have previously afforded insightful crystalline samples of isolated catalytic intermediates. 59 Thus, stoichiometric reactions were pursued to isolate the putative allyl zirconium intermediates ( Scheme 4 ). Known alkyl amido complex 6-Si 48 was dissolved in C 6 D 6 and treated with 1 equiv.…”

Mechanistic Investigation of Zirconium-Catalyzed Hydroaminoalkylation of Alkynes: Substrate and Ligand Effects

“…Previous work from our group has shown that bis­(ureate) proligand L1 facilitates the isolation of intermediates in catalysis. This approach has been used to obtain mechanistic insights of related C–C and C–N bond-forming reactions catalyzed by bis­(ureate)-supported zirconium complexes . Accordingly, to understand the source of the contrasting reactivity between N -benzylaniline and N -(trimethylsilyl)­benzylamine in alkyne hydroaminoalkylation, we undertook stoichiometric reactivity studies using these two different amine substrates.…”

“…This approach has been used to obtain mechanistic insights of related C−C and C−N bond-forming reactions catalyzed by bis(ureate)-supported zirconium complexes. 35 Accordingly, to understand the source of the contrasting reactivity between N-benzylaniline and N-(trimethylsilyl)benzylamine in alkyne hydroaminoalkylation, we undertook stoichiometric reactivity studies using these two different amine substrates. Alkylamido complexes such as 3 are reliable precursors for accessing bis(ureate) supported zirconaaziridine intermediates in situ (4, Scheme 3).…”

Jumping in the Chiral Pool: Asymmetric Hydroaminations with Early Metals

“…The thusly formed nitrogen-containing compounds including N -heterocycles offer diverse applications not only in material sciences, but also in natural product synthesis and pharmaceutical chemistry. One synthetic concept in the mostly applied preparation of such molecules is the hydroamination reaction [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”