How Strain-Release Determines Chemoselectivity: A Mechanistic Study of Rhodium-Catalyzed Bicyclo[1.1.0]butane Activation

Abstract

Bicyclo[1.1.0]butane (BCB) derivatives are versatile coupling partners, and various reaction modes for their activation and transformation have been proposed. In this work, three BCB-activation modes in Rh-catalyzed BCB transformations that construct diastereoselective α-quaternary β-lactones were investigated by density functional theory calculations. Our results show that, compared with C1−C3 insertion and C−C3 oxidative addition, C2−C3 oxidative addition is more favorable. The whole catalytic cycle involves five main steps: C−H activation, oxidative addition, β-C elimination/reductive elimination, Rh walking, and aldehyde insertion/protonation. Independent gradient model, intrinsic reaction coordinate, distortion−interaction energy, and Laplacian electron-density analyses were carried out to investigate the mode of BCB activation. Our calculation also showed that aldehyde-insertion is the diastereoselectivity determining step, which is controlled by the steric effect between the ligand, methyl group, and aldehyde.

DFT Insight into a Strain-Release Mechanism in Bicyclo[1.1.0]butanes via Concerted Activation of Central and Lateral C–C Bonds with Rh(III) Catalysis

“…Consequently, the overall barrier of the reaction is calculated to be 21.0 kcal/mol. The distinguishing feature of the calculated catalytic cycle, setting it apart from previous reports, 14,15 is its simultaneous cleavage of both the central and lateral C−C bonds in the BCB ester. This concurrent cleavage results in the formation of a Rh-carbene intermediate.…”

“…The calculated results are shown in Figure 1. Initially, oxime ether 1 coordinates to the catalytically active cationic species, 15 Cp*Rh(OAc) + , labeled with symbol A, giving rise to intermediate IM1. Following that, the C−H bond activation occurs according to a concerted metalation deprotonation (CMD) mechanism via TS1 with a barrier of 15.7 kcal/mol, delivering rhodacycle intermediate B.…”

“…The strain-release-driven transformations utilizing BCBs, developed by Glorius et al, 14 which a protodemetalation process delivers the final product, α-quaternary β-lactone (4), regenerating the catalyst. While the mechanisms proposed by Glorius et al 14 and Bai et al 15 are informative, there are still some unsolved problems, including the reason for the perfect E-selectivity and diastereoselectivity of the product. This leads us to conduct additional computational studies on the strain-release-driven three-component reactions.…”

“…XXXX, XXX, XXX−XXX the C2−C3 bond to the Rh(III) center. The resulting rhoda(V)-cycle intermediate E is subsequently converted into D via TS4, which was described as a transition state involving concerned reductive elimination and β-C elimination 15. The relative Gibbs energies of TS3 and TS4 are 25.2 and 29.6 kcal/mol, respectively.…”

One-Pot Synthesis of Difluorobicyclo[1.1.1]pentanes from α-Allyldiazoacetates

“…20a and 20b afforded the desired 2,2-difluorobicyclo[1.1.1]­pentane products 22a and 22b but in low yield, whereas 20c gave none of the desired product. Interestingly, 22a and 22b were generated as single diastereomers which suggests that the addition of difluorocarbene to the bicyclo[1.1.0]­butane is controlled by the orientation of the substituents set during the intramolecular cyclopropanation. ,,− …”