Mechanistic and Synthetic Aspects of the Benzilic Acid and Ester Rearrangements

Abstract

Since its discovery the Benzilic acid rearrangement has been the subject of a number of mechanistic studies and successfully employed in key steps in the synthesis of a number of important target molecules. In this review we look at the advances that have been made over the last 20 years in understanding the mechanism of this rearrangement (including the stereochemical aspects), whilst reviewing some important syntheses where this particular rearrangement was used as a key step.

Direct Visualization of a Mechanochemically Induced Molecular Rearrangement

“…This step has been suggested to precede the rate-determining step involving a phenyl migration (Scheme 1 b). [7,8] Nonetheless, alternative mechanisms for the rearrangement of benzil (1) with hydroxide ions in solution have been proposed, in which, for example, the migration of the phenyl group and the proton transfer are concurrent rather than sequential. [16] Similarly, the involvement of single-electron-transfer (SET) processes in the Figure 2.…”

“…Since its discovery by Liebig in 1838, [6] the benzil-benzilic acid rearrangement has been in the focus of exhaustive experimental [7] and theoretical studies. [8] It is generally assumed that in solution this rearrangement occurs through the initial reversible addition of a hydroxide ion to benzil, followed by an irreversible [1,2]-phenyl migration and a subsequent proton exchange (Scheme 1 b).…”

Direct Visualization of a Mechanochemically Induced Molecular Rearrangement

“…As previously mentioned, solution‐based experiments and computational work on the benzil–benzilic acid rearrangement have suggested an initial reversible addition of hydroxide ion to benzil that would give rise to an intermediate such as A (Scheme b). This step has been suggested to precede the rate‐determining step involving a phenyl migration (Scheme b) . Nonetheless, alternative mechanisms for the rearrangement of benzil ( 1 ) with hydroxide ions in solution have been proposed, in which, for example, the migration of the phenyl group and the proton transfer are concurrent rather than sequential .…”

“…This step has been suggested to precede the rate-determining step involving a phenyl migration (Scheme 1 b). [7,8] Nonetheless, alternative mechanisms for the rearrangement of benzil (1) with hydroxide ions in solution have been proposed, in which, for example, the migration of the phenyl group and the proton transfer are concurrent rather than sequential. [16] Similarly, the involvement of single-electron-transfer (SET) processes in the 1and KOH (2.0 equiv), and b) benzil (1) and KOH (1.0 equiv) at 30 Hz.…”

“…Since its discovery by Liebig in 1838, [6] the benzil-benzilic acid rearrangement has been in the focus of exhaustive experimental [7] and theoretical studies. [8] It is generally assumed that in solution this rearrangement occurs through the initial reversible addition of a hydroxide ion to benzil, followed by an irreversible [1,2]-phenyl migration and a subsequent proton exchange (Scheme 1 b).…”