Origin of Regiochemical Control in Rh(III)/Rh(V)-Catalyzed Reactions of Unsaturated Oximes and Alkenes to Form Pyrdines

Abstract

The Rh(III)-catalyzed reactions of α,β-unsaturated oximes with alkenes are versatile methods for the synthesis of pyridines. Density functional theory (DFT) calculations reported here reveal the detailed mechanism and origins of selectivity in this reaction. The Rh(III)/Rh(V)/Rh(I) catalytic cycle was found to be more favorable than the previously proposed Rh(III)/Rh(I)/ Rh(III) catalytic cycle. The Rh(III)/Rh(V)/Rh(I) catalytic cycle involves C−H activation, alkene insertion, deprotonation, oxime migratory oxidative addition, nitrene insertion, 1,5-hydrogen shift, and β-hydride elimination to give the pyridine product and form a Rh(I) species. Subsequent oxidation by Ag+ regenerates the Rh(III) catalyst. Reductive elimination from a alkyl-Rh(III) species is predicted to be difficult, so that the Rh(III)/Rh(I)/ Rh(III) catalytic cycle can be excluded. The reactivities of oxime ethers and oxime esters are compared. The oxime ester acts as both a directing group and an internal oxidant. In this reaction, the N−O bond is activated by the pivalate, and migratory oxidative addition onto the Rh(III) species generates the corresponding Rh(V) nitrene complex. However, in the absence of the pivalate on the oxime ether, the activation energy for oxidative addition is much higher. The reactivity was analyzed by NPA charge calculations, comparison of the N−O bond orders, and the bond dissociation energies. The calculations also explain the regioselectivity of alkene insertion, which is shown to be an electronic effect rather than a steric effect.

α-Arylation of Silyl Enol Ethers via Rhodium(III)-Catalyzed C–H Functionalization

“…The lack of reactivity observed suggests that Rh(III) species are incapable of promoting the α-arylation of silyl enol ether 1a with benzamide 2b. Taken together with the complementary regio-outcome when compared with enol ethers, 24,33 we believe that a different mechanism is operative, one in which AgOAc enables a Rh(III)/(V)/(III) pathway 46,47 that facilitates an otherwise difficult C(sp 2 )−C(sp 3 ) bondforming process. AgOAc-mediated oxidations of some Ir(III) and Rh(III) complexes to higher valent species, which have been achieved in the Rohde laboratory, 48 and recent investigations of oxidatively induced reductive eliminations by the Chang laboratory provide support for this proposal.…”

Mechanistic Insights into the Dual Directing Group-Mediated C–H Functionalization/Annulation via a Hydroxyl Group-Assisted MIII-MV-MIII Pathway

“…Nevertheless, a more detailed reaction mechanism is still unclear and thus it should be systematically expounded, since such a DDG-assisted strategy has emerged as a straightforward and powerful method for the target compound synthesis in current C–H activation reactions. Considering the significance of the DDG-assisted C–H functionalization and based on the previous density functional theory (DFT) calculations for TM-catalyzed C–H activation/annulation reactions, , herein, systematic DFT calculations and the designed proof-of-concept experimental study have been accordingly carried out by using the catalytic coupling of oximes and propargyl alcohols as the effectors, which give detailed insight into the DDG-enabled mechanism, and thus, it also provides some key inspiration on how to achieve the high chemoselectivity in the future C–H functionalization reactions.…”

Electrochemical Rhodium-Catalyzed C–H Cyclodimerization of Alkynes to Access Diverse Functionalized Naphthalenes: Involvement of RhIV/V and RhI Dual Catalysis

“…Furthermore, the reaction would be halted without electricity, while the reaction continued by switching the electric current back on. These results evidenced that the electrochemistry played an important role in this transformation through accelerating the generation of active Rh I and Rh IV/V species . Finally, the employment of TEMPO or BHT did not lead to a significant decrease in the efficiency, implying that a radical pathway might not be involved in the reaction.…”