Xiang Jia-Chen, Wang Jia-Wei, Yuan Peng, Ma Jin-Tian, Wu An-Xin, Liao Zhi-Xin
Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering and Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
J Org Chem. 2022 Nov 18;87(22):15101-15113. doi: 10.1021/acs.joc.2c01591. Epub 2022 Nov 8.
Precise control of the chemoselectivity of the halogenation of a substrate equipped with multiple nucleophilic sites is highly demanding and challenging. Most reported chlorinations of methyl ketones show poor compatibility or even exclusive selectivity toward electron-rich arene, olefin, and alkyne residues. This is attributed to the direct or in situ employment of electrophilic Cl/Cl species. Here, we reported that, even bearing those competitive residues, methyl ketones can still undergo dichlorination to afford α,α-dichloroketones in a chemo-specific manner. Enabled by the I-dimethyl sulfoxide catalytic system, in which hydrochloric acid only acts as a nucleophilic Cl donor, this straightforward dichlorination reaction is safe and operator-friendly and has high atomic economy, giving access to structurally diverse α,α-dichloroketones in good yields and with good functional-group tolerance.
精确控制具有多个亲核位点的底物卤化反应的化学选择性极具要求且具有挑战性。大多数已报道的甲基酮氯化反应对富电子芳烃、烯烃和炔烃残基的兼容性较差，甚至具有排他性选择性。这归因于亲电Cl/Cl物种的直接使用或原位生成。在此，我们报道，即使带有那些竞争性残基，甲基酮仍能以化学特异性方式进行二氯化反应，生成α,α-二氯酮。在碘-二甲基亚砜催化体系的作用下，其中盐酸仅作为亲核Cl供体，这种直接的二氯化反应安全且操作简便，具有高原子经济性，能够以良好的产率和官能团耐受性获得结构多样的α,α-二氯酮。
