The α‐Hydroxy Ketone (α‐Ketol) and Related Rearrangements†

Abstract

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.

Gold(III)‐ and Platinum(II)‐Catalyzed Domino Reaction Consisting of Heterocyclization and 1,2‐Migration: Efficient Synthesis of Highly Substituted 3(2H)‐Furanones

“…The intermediate oxonium ion is expected to trigger an irreversible 1,2-shift analoguous to a formal a-ketol rearrangement. [8] In contrast to the related pinacol rearrangements, [9] oxonium ion rearrangements have not been used to terminate cationic cyclizations. The overall sequence provides an efficient and flexible access to 3(2H)-furanones 2, which are structural elements in many natural products [10] and pharmaceutically active substances.…”

3.16 The Semipinacol Rearrangements

“…185,186 3.16.6 Rearrangement of a-Hydroxy Ketones and a-Hydroxy Imines Rearrangement of a-hydroxy ketones and imines is also called 'a-ketol rearrangement' or 'acyloin rearrangement,' which has been well documented (Scheme 8). 8 This rearrangement is an isomeric process of a-hydroxy ketone or imine through 1,2-migration of alkyl or aryl group. It can be promoted by acid, base, or heat.…”

“…This reaction is also known as the 'acyloin rearrangement' or 'a-ketol rearrangement', 8 wherein the electrophilic carbon center becomes the carbonyl or imine carbon. Because of the presence of tertiary a-hydroxy ketone or imine moieties, the isomerization involving an enolization/ protonation procedure is unavailable.…”

Reduction of Alkynyl α‐Hydroxy Esters: Stereoselective α‐Ketol Rearrangement

“…[1][2][3] Under these conditions, both isomers are in equilibrium, and the more stable α-hydroxy carbonyl compound is formed. This transformation, called α-ketol or acyloin rearrangement, has been applied to the synthesis of many polycyclic compounds.…”