Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenative couplings

• Published in: Chinese chemical letters Vol. 35; no. 9; p. 109495
• Main Authors: Tang, Kun, Su, Fen, Pan, Shijie, Lu, Fengfei, Luo, Zhongfu, Che, Fengrui, Wu, Xingxing, Chi, Yonggui Robin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2024
• Subjects: Aryl radical; Cross dehydrogenative coupling; Enones; Hydrogen atom transfer; N-Heterocyclic carbene; Cross dehydrogenative coupling; Aryl radical; Hydrogen atom transfer; Enones; N-Heterocyclic carbene
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2024.109495

Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery. The development of synthetic strategies for highly efficient preparation of enones thereby receives intense attention, in particular through the transition metal-catalyzed coupling reactions. Here, we describe a carbene-catalyzed cross dehydrogenative coupling (CDC) reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives. Mechanistically, the in situ generated aryl radical is pivotal to “activate” the alkene by forming an allyl radical through intermolecular hydrogen atom transfer (HAT) pathway and thus forging the carbon-carbon bond formation with aldehyde as the acyl synthon. Notably, our method represents the first example on the enone synthesis through coupling of “non-functionalized” aldehydes and alkenes as coupling partners, and offers a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations. A carbene-catalyzed cross dehydrogenative coupling (CDC) reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives is disclosed. Mechanistically, the in situ generated aryl radical is pivotal to “activate” the alkene by forming an allyl radical through intermolecular hydrogen atom transfer (HAT) pathway, thus forging the direct carbon-carbon bond formation with aldehyde and offering a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations. [Display omitted]