康 · 学术 | Reaction of the Day No. 1425

转自：康龙化成

Deconstructive Carboxylation of Activated Alkenes with Carbon Dioxide

Pan-Feng Yuan, Zhao Yang, Shan-Shan Zhang, Can-Ming Zhu, Xiu-Long Yang, and Qing-Yuan Meng*

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China; Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education and College of Chemistry and Environmental Science, Hebei University, Baoding 071002, P.R. China.

—Angew. Chem. Int. Ed. 2023, e202313030, 10.1002/anie.202313030

Recommended by Xuemei Yao_ MC3

KEYWORDS: Photo chemistry (反应类型), Alkenes, CO2 (原料), carboxylic acids (产物), C(sp3)-C(sp2) (成键类型), 4DPAIPN(其他),

ABSTRACT: Carboxylation with carbon dioxide (CO2) represents one notable methodology to produce carboxylic acids. In contrast to carbon–heteroatom bonds, carbon–carbon bond cleavage for carboxylation with CO2 is far more challenging due to their inherent and less favorable orbital directionality for interacting with transition metals. Here we report a photocatalytic protocol for the deconstructive carboxylation of alkenes with CO2 to generate carboxylic acids in the absence of transition metals. It is emphasized that our protocol provides carboxylic acids with obviously unchanged carbon numbers when terminal alkenes were used. To show the power of this strategy, a variety of pharmaceutically relevant applications including the modular synthesis of propionate nonsteroidal anti-inflammatory drugs and the late-stage carboxylation of bioactive molecule derivatives are demonstrated.

Background and this work

Proposed Mechanism

Selected Substate Scope

Prof. Qing-Yuan Meng and co-worker have developed a photochemical strategy that realized deconstructive carboxylation of alkenes with carbon dioxide, giving carboxylic acids via π and σ bonds cleavage. Importantly, an investigation of the scope of this reaction indicates that this protocol is applicable to a broad range of styrenes and α, β-unsaturated alkenes, allowing for the late-stage carboxylation of bioactive molecule derivatives and the modular synthesis of propionate nonsteroidal anti-inflammatory drugs in a transition-metal free process. Compared with the transformation of activated internal alkenes by Wacker oxidation, our developed strategy would produce carboxylic acid products, while ketone products were generated in Wacker oxidation. Additionally, α-alkyl substituted aryl or ester alkenes would normally provide terminal aldehydes with low efficiency in Wacker oxidation. However, moderate to good yields of carboxylic acid products were obtained in our reaction. Furthermore, although oxidation of alcohols or aldehydes would generate the corresponding carboxylic acids, our method will be a good alternative especially when alcohols and aldehydes are not easy to be prepared.

（转自：康龙化成）