α‐Hydroxylation of Enolates and Silyl Enol Ethers

Abstract

The autoxidation of enolizable carbonyl compounds was reported as early as 1871, and the accelerating action of base is well documented. The products of these reactions, however, were usually mixtures of compounds resulting from decomposition of the unstable alpha‐hydroperoxy intermediates. It was not recognized until the 1960s that these intermediates can be reduced to alpha‐hydroxy compounds with zinc dust. This observation laid the foundation for what has become on of the simplest and most widely used strategies for introducing a hydroxyl group adjacent to a carbonyl group, namely the oxidation of metal enolates. The alpha‐hydroxy carbonyl array not only occurs in many biologically active molecules, but also serves as an important building block for synthesis. While the oxygenation of enolates still play an important role in the synthesis of alpha‐hydroxy carbonyl compounds, a variety of new, more convenient oxididizing agents, including chiral nonracemic ones, have been introduced. In addition, sily enol ethers and silyl ketene acetals can serve as educts for alpha‐hydroxycarbonyl compounds. This chapter covers the literature of alpha‐hydroxylation of metal enolates and silyl enol ethers up to the end of 2000. Nitriles and aza‐enolates are included. The related alpha‐alkoxylation, alpha‐acyloxylation, and alpha‐sulfonyloxylation of metal enolates are briefly discussed.

Copper-Catalyzed Vinylogous Aerobic Oxidation of Unsaturated Compounds with Air

“…14 In the classic oxidation of steroids, α -hydroxylation has been possible using molecular oxygen as an oxidant: 15 generation of an enolate in the presence of a strong base (e.g., lithium diisopropylamide (LDA)), nucleophilic attack of oxygen by the enolate, and reduction of the newly formed peroxide by a trialkyl phosphite. 16 Phase-transfer catalysis has also been applied for aerobic oxidation of ketones and 2-oxindoles.…”

The Direct Introduction of Carbonates α to Carbonyl Groups

“…The reaction worked well in both polar and non-polar solvents at room temperature, but consistently cleaner transformations were achieved using either DMSO or THF as the reaction medium, which led to their adoption in our standard protocol (see typical procedure for experimental details cyclohexanone with one equivalent of 7 in DMSO at room temperature for 16 hours gave the a-functionalised product 12 in 82% yield after purification by chromatography (Scheme 3). 10 We believe the reaction proceeds via condensation of the reagents to give an enamine which undergoes a [3,3]-sigmatropic rearrangement to provide an afunctionalised imine which is hydrolysed in situ to furnish the observed product 12. Reaction of cyclohexanone with the ethyl 8, benzyl 9 and allyl 10 reagents, also gave the expected products 13-15 in good yields.…”

“…We postulated this reaction was progressing though the enamine intermediate 34, followed by a concerted[3,3]sigmatropic rearrangement to give the a-functionalised imine 35; however, the increased leaving group ability of…”

Iodobenzene Dicarboxylates as Transferrable Oxygen Sources: Synthesis of α-Oxygenated Ketones from Terminal Aryl Alkynes

“…To date, many procedures have been developed to prepare α-oxygenated ketones, such as α-oxygenation of enolates, [1] epoxidation, [2] dihydroxylation, [3] aminoxylation [4] of preformed enol ethers, enolates and enamines, and reduction of diketones. [5] In the past decade, the application of hypervalent iodine(III) reagents in organic synthesis has attracted intense interest due to their intriguing oxidizing properties, low toxicity, mild reactivity, ease of handling and ready availability.…”