Semipinacol

Semipinacol rearrangement is a class of rearrangement reactions in organic chemistry in which an adjacent substituent migrates in response to activation of a hydroxyl-bearing center, typically transforming a vicinal diol, an epoxy alcohol, or a related motif into a carbonyl-containing product with a rearranged skeleton. The process is driven by the formation of a cationic or oxocarbenium intermediate adjacent to the migrating group, and the migration stabilizes this center through a 1,2-shift, accompanied by collapse to a carbonyl compound.

Mechanistically, activation of a leaving group on the carbon bearing or adjacent to the hydroxyl initiates the sequence. A neighboring group (usually an alkyl, aryl, or heteroatom substituent) migrates by a 1,2-shift to the cationic center, generating a more stabilized oxocarbenium species. Collapse of this intermediate yields a carbonyl compound—often an aldehyde or ketone—with the migrating group's position correspondingly rearranged. Substrate motifs frequently include vicinal diols, epoxides, or adjacent alcohols that can participate in orbital alignment and stabilization. The reaction can occur intramolecularly and is frequently exploited to effect ring contractions or expansions, enabling complex skeleton construction.

Scope and selectivity vary with the substrate and activation conditions; migration aptitude typically follows aryl and tertiary alkyl > secondary > primary substituents, and the outcome can be influenced by stereochemistry and neighboring group effects. Variants employ different activating reagents and catalysts, and can be combined with subsequent nucleophilic capture to furnish diverse products.

Semipinacol rearrangements have been employed in natural product synthesis and in the construction of contorted carbonyl frameworks, offering a strategic tool for reorganizing carbon skeletons adjacent to hydroxyl-bearing centers. See also pinacol rearrangement, 1,2-shift chemistry.