Mechanisms and origins of the switchable regioselectivity of FeBr3-catalyzed [1,2]-aryl and [1,2]-alkyl shifts of α-aryl aldehydes

Abstract

With the aid of DFT calculations, the FeBr₃-catalyzed skeletal rearrangements of 2-cyclohexanal,2-p-C₆H₄OMe-propylaldehyde (1A) and 2-phenyl,2-p-C₆H₄OMe-propylaldehyde (1B) were investigated theoretically. As compared to mono-FeBr₃ as a catalyst, the bis-FeBr₃ serving as a catalyst is found to be not only enhancing the catalytic efficiency but also improving the product selectivity. For the reaction starting from 1A, the [1,2]-group shift (first step) is rate-determining, and why the Cy shift is the most favored is rationalized in comparison with the p-C₆H₄OMe and Me shifts. For the reaction starting from 1B, the [1,2]-H shift (second step) is rate-determining although the [1,2]-p-C₆H₄OMe shift is favored over the [1,2]-phenyl shift. In contrast to the experimental proposal, the newly established H₂O/Br⁻ joint-assisted H-shift mechanism explains the partial α-H source of the [1,2]-Cy shift product. In addition, we discussed the inherent mechanism that explains why both the [1,2]-p-C₆H₄OMe and [1,2]-p-C₆H₄CF₃ shifts are more facile than the [1,2]-phenyl shift although the substituents –OMe and –CF₃ have opposite electronic behaviors.