Mechanism and Stereochemistry of Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Ene–Vinylcyclopropanes and Carbon Monoxide Revealed by Visual Kinetic Analysis and Quantum Chemical Calculations

Abstract

Previously, we developed a rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene−vinylcyclopropanes (ene−VCPs) and carbon monoxide to synthesize eight-membered carbocycles. The efficiency of this reaction can be appreciated from its application in the synthesis of several natural products. Herein we report the results of a 15-year investigation into the mechanism of the [5 + 2 + 1] cycloaddition by applying visual kinetic analysis and high-level quantum chemical calculations at the DLPNO-CCSD(T)//BMK level. According to the kinetic measurements, the resting state of the catalyst possesses a dimeric structure (with two rhodium centers) whereas the active catalytic species is monomeric (with one rhodium center). The catalytic cycle consists of cyclopropane cleavage (the turnover-limiting step), alkene insertion, CO insertion, reductive elimination, and catalyst transfer steps. Other reaction pathways have also been considered but then have been ruled out. The steric origin of the diastereoselectivity (cis versus trans) was revealed by comparing the alkene insertion transition states. In addition, how the double-bond configuration of the VCPs (Z versus E) affects the substrate reactivity and the origins of chemoselectivity ([5 + 2 + 1] versus [5 + 2]) were also investigated. The present study will provide assistance in understanding other carbonylative annulations catalyzed by transition metals.

Why [4 + 2 + 1] but Not [2 + 2 + 1]? Why Allenes? A Mechanistic Study of the Rhodium-Catalyzed [4 + 2 + 1] Cycloaddition of In Situ Generated Ene–Ene–Allenes and Carbon Monoxide

“…We cannot get the equilibrium constant K in Figure f, so we cannot compare this measured value with the computed one, considering that k obs = k cat K 0.5 . The kinetic process of the present [4 + 2 + 1] reaction is similar to the [5 + 2 + 1] reaction reported by our group …”

“…Geometry optimization of all of the minima and transition states was carried out with the BMK functional at 298 K in the gas phase, and the def2-SVP basis set was used for all atoms. The BMK functional performed well in our previous benchmark study of the [Rh­(CO) 2 Cl] 2 -catalyzed [5 + 2 + 1] cycloaddition of ene–VCPs and CO and was chosen in the present study as well . Vibrational frequencies were computed at the same level to check whether each optimized structure was an energy minimum or a transition state.…”

Rh(i)-catalyzed dimerization of ene-vinylidenecyclopropanes for the construction of spiro[4,5]decanes and mechanistic studies

“… 5 In the metal-catalyzed domino cyclization reaction, the formation of multiple C–C bonds can be controlled by choosing different metals ( e.g. , Rh, 6 Co, 7 Ni, 8 etc. 9 ) and ligands to control the chemo-, regio- and stereo-selectivity, involving interesting mechanisms.…”

Six-Step Total Synthesis of Isohirsut-4-ene through [5+2+1] Cycloaddition and Transannular Epoxide–Alkene Cyclization

“…In addition to the aim described above, we were also interested in developing a general [5+2+1] reaction-based transannular strategy for linear triquinanes with a bridgehead quaternary carbon at position C-7, like that in the natural product of isohirsut-4-ene. Previously, we have developed a [5+2+1] cycloaddition/aldol reaction strategy to achieve a linearly fused 5/5/5 tricyclic skeleton with a quaternary carbon at position C-3 (Figure b). , Several linear triquinanes such as hirsutene, hirsutic acid C, and 1-desoxyhypnophilin have been produced using this strategy .…”

“…Following the retrosynthetic plan, we started our process by synthesizing the known compound 2 (Scheme ), DEC tethered ene-vinylcyclopropane (ene-VCP), in one step from the commercial compounds on a gram scale (7.35 g, 35% yield). Then we carried out the [5+2+1] reaction on a 5 mmol scale using the previously optimized conditions {0.2 atm of CO, 80 °C, dioxane as the solvent, 5 mol % catalyst [Rh­(CO) 2 Cl] 2 }. The desired 5/8 bicyclic product 3 was obtained in 64% yield as a single diastereomer.…”