Practical Method for Transforming Alkynes into α-Diketones
Zhonghui Wan,* Chauncey D. Jones, David Mitchell, John Y. Pu and Tony Y. Zhang
*Global Chemical Process Research and Development, Eli Lilly and Company,
Lilly Corporate Center, Indianapolis, Indiana 46285, wanzh
lilly.com
Z. Wan, C. D. Jones, D. Mitchell, J. Y. Pu, T. Y. Zhang, J. Org. Chem., 2006, 71, 826-828.
DOI: 10.1021/jo051793g
Abstract
Oxidation of alkynes to α-dicarbonyl derivatives through a convenient one-pot procedure via a Brønsted acid-promoted "hydration" and a DMSO-based oxidation sequence has been achieved in high yields.
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proposed mechanism
Details
The document describes a practical method for transforming alkynes into α-diketones using a one-pot procedure involving Brønsted acid-promoted hydration and DMSO-based oxidation. This method is efficient, high-yielding, and avoids the use of stoichiometric inorganic oxidants and toxic transition-metal catalysts. The process involves hydrating alkynes to monoketones using formic acid, followed by oxidation with DMSO and a catalytic amount of HBr. Various strong Brønsted acids were tested, with methanesulfonic acid emerging as the most effective promoter. The method was successfully applied to a range of alkynes, yielding the corresponding α-dicarbonyl derivatives in good to excellent yields. The reaction mechanism involves the formation of vinyl formate, which decomposes to monoketone, followed by DMSO oxidation to the dicarbonyl compound. Efficient removal of dimethyl sulfide is crucial for high yields. The procedure is exemplified by the synthesis of 1-(4-fluorophenyl)-2-(4-trifluoromethylphenyl)-ethane-1,2-dione, achieving a 93% yield. The study highlights the method's practicality, efficiency, and environmental benefits, making it a valuable approach for synthesizing α-dicarbonyl derivatives.
Key Words
1,2-Diketones, Formic Acid, DMSO
ID: J42-Y2006-200
