The a-Hydroxy Ketone (α-Ketol) and Related Rearrangements

Paquette, Leo A.; Hofferberth, John E.


Treatment of suitable alpha-hydroxy aldehydes and ketones with a base, a Bronsted or Lewis acid, or simply with heat has long been know to induce the 1,2-shift of an alkyl or aryl substituent to form an isomeric product. The synthetic utility of the process was considerably expanded when applied to steroidal D-ring homoannulations, and has more recently encompassed novel ring expansion to numerous complex target ring systems. The classical alpha-ketol rearrangement shares, in common with other base-promoted ketogenic isomerizations, the property of advancing from an alkoxide to a carbonyl group as the migrating center relocates its bonding electrons to the adjacent trigonal center. A distinctive feature of the title reaction, however, is its reversibility, such that the more stable alpha-hydroxy carbonyl isomer is favored. The process has sometimes been termed the acyloin rearrangement.

This chapter focuses on the isomerization of alpha-hydroxy ketones, aldehydes, and imines under various reaction conditions exclusive of photochemical activation. The literature coverage extends to 2000.

Since many of the steroidal transformations were carried out in early days when products were not always adequately characterized; errors in structural assignment were occasionally made. Experimental detail was sometimes lacking. To alleviate this problem, we have included only experiments that lead to reasonably pure products of established structure.