The Wittig reaction – transforming aldehydes or ketones into olefins - is a very fundamental reaction, which holds significant importance in various fields of applied synthetic chemistry. Traditionally, executing this reaction demands a meticulous reaction setup and often involves highly reactive reagents like butyl lithium. Yet, achieving synthetically useful yields often proves challenging due to the sensitivity of the reactive phosphonium ylide species, commonly requiring cooling (-70 to 0 °C) and the strict exclusion of air and moisture. After sequential addition of the aldehyde or ketone substrate to the pre-formed ylide, the olefination frequently needs elevated temperature to proceed. This advanced handling is prone to errors and thus diminished yields.
We herein present a remarkably simple and environmentally friendly solvent-free mechanochemical approach to Wittig olefination with an astonishing short overall reaction time of just 30 seconds. Here, the need for pre-formed ylide species and sequential substrate addition is eliminated. Instead, all reagents are combined in a Teflon milling vessel and ground at a frequency of 36 Hz for 30 seconds under ambient atmosphere using a mixer mill device.
This novel protocol not only accelerates the reaction but also features an easy-to-handle solid base (KOtBu), excellent functional group tolerance, high overall yields, and eliminates the need for solvents. Demonstrating its versatility, we successfully applied this method for the olefination of various natural and bioactive compounds, including menthone, vanillin, and estrone.
With its potential to streamline chemical processes, particularly in the pharmaceutical industry, this approach represents a significant step towards safer and more sustainable practices.
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Research facilities:
Zentrum für Kernspinresonanzspektroskopie
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Project title:
Entwicklung von i-BM in der Direkten Kupfer Mechanokatalyse: J 4922 (FWF - Österr. Wissenschaftsfonds)
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Research Areas:
Sustainable Production and Technologies: 80% Beyond TUW-research focus: 20%