Scope and mechanism of C-H bond functionalization with binuclear rhodium and ruthenium catalysts

Abstract

The development of “new-to-nature” C-H bond functionalization including alkylation and amination catalyzed by metal complexes, particularly dirhodium paddlewheel catalysts, via metal-carbene and metal-nitrene/imido intermediates has attracted widespread and increasing attention. An appealing strategy is to quest for metal catalysts that can generate coordinated organic radicals, such as metal-carbene/nitrene radical anion species, due to the high reactivity of these open-shell intermediates. This thesis focuses on exploration of C-H bond functionalization using second-row transition metal bimetallic catalysts via the open-shell intermediates as a radical variant of the long-standing dirhodium paddlewheel-catalyzed analogues, and describes novel dirhodium and diruthenium catalysts which exhibit high/unusual activity/selectivity in C–H bond functionalization via unprecedented rhodium-carbene radical anion or ruthenium-nitrene radical anion species.

Dirhodium catalyst Rh2(tBuPC)2 (H2tBuPC = 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine) was synthesized and characterized by spectroscopic techniques including NMR, MALDI-TOF, and UV-Vis, and also by cyclic voltammetry. This catalyst, compared with literature-reported metal catalysts including dirhodium paddlewheel catalysts, is more effective in catalyzing light alkane alkylation with donor-acceptor diazo compound. For linear alkanes, tunable primary to secondary site-selective alkylation was achieved, both with up to 93% selectivity. The alkylation protocol is applicable to small molecule and bio-active substrates with yield up to 95%. Gram-scale reaction using fed-batch system resulted in turnover number of up to 71830. Mechanistic studies reveal the dissociation of Rh-Rh bond upon addition of diazo compound leading to formation of a monomeric RhIII-carbene radical anion species, as evidenced by radical trapping experiments and EPR and FT-IR spectroscopy, together with DFT calculations. Based on mechanistic studies and DFT calculations, a concerted mechanism for the C–H alkylation by the RhIII-carbene radical anion species is proposed.

The Rh2(tBuPC)2 catalyst was also applied to sequential bond activation reactions involving pre-activation of Rh2(tBuPC)2 by PPh3 or N-heterocyclic carbene to give metalloradicals and use of strained rings (e.g. bicyclo[4.1.0]heptadiene) as a carbene or alkyl source (via C-C bond activation by metalloradicals) for generation of metal-carbene/metal-alkyl radical intermediates, which resulted in the alkylation of C-H and X-H bonds (X = N, O) in up to 91% yield. By electrochemical reductions, diruthenium catalyst Ru2(tBuPC)2 was applicable as a supplement for the dirhodium counterpart. The electrocatalytic reactions using commercially available cyclopropane rings for alkylation of nucleophilic X-H bonds (X = N or O) gave product yields of up to 70% under stoichiometric ratios. Mechanistic studies lend evidence to the pre-cycle electrochemical reduction of Ru2(tBuPC)2 to generate RuI-metalloradical anion species. The electronic structure and reaction profile of such metalloradical intermediate were investigated by DFT calculations.

A series of hydrogen-bond template diruthenium paddlewheel catalysts supported by formamidine ligands were synthesized for enantioselective amination of C–H bonds, giving enantioselectivity of up to 96:4 e.r. (outperforming commercially available dirhodium catalysts). Screening of ligands and hydrogen-bond template revealed that halogen-halogen shielding ligands and flexibility of template are critical for high enantioselectivity. The hydrogen-bond template increases the KIE of the amination reaction. Mechanistic studies by MALDI-TOF, FT-IR, and EPR spectroscopy and DFT calculations point to a stepwise mechanism involving RuIII-nitrene radical anion intermediate.