文献类型：期刊文献

英文题名：Practical synthesis of C1 deuterated aldehydes enabled by NHC catalysis

作者：Geng, Huihui[1,2];Chen, Xiaobei[1,2];Gui, Jingjing[3,4];Zhang, Yueteng[5,6];Shen, Zuyuan[1,2];Qian, Pengfei[1,2];Chen, Junwei[1,2];Zhang, Shilei[3,4];Wang, Wei[1,2,5,6]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioengn Reactor, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[3]Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis, Suzhou, Jiangsu, Peoples R China;[4]Soochow Univ, Coll Pharmaceut Sci, Suzhou, Jiangsu, Peoples R China;[5]Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA;[6]Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA

年份：2019

卷号：2

期号：12

起止页码：1071

外文期刊名：NATURE CATALYSIS

收录：;EI(收录号：20194607666065);WOS:【SCI-EXPANDED(收录号:WOS:000502586500007)】；

基金：Financial support was provided by the NIH (5R01GM125920-03), the National Natural Science Foundation of China (21702058 and 21202112), East China University of Science and Technology, the '111' Project and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD).

语种：英文

外文关键词：Reaction intermediates - Cost effectiveness - Condensation reactions - Deuterium - Catalysis

摘要：The recent surge in applications of deuterated pharmaceutical agents has created an urgent demand for synthetic methods that efficiently generate deuterated building blocks. Here, we show that N-heterocyclic carbenes promote a reversible hydrogen-deuterium exchange reaction with simple aldehydes, which leads to a practical approach to synthetically valuable C1 deuterated aldehydes. The reactivity of the well-established N-heterocyclic carbene-catalysed formation of Breslow intermediates from aldehydes is reengineered to overcome the overwhelmingly kinetically favourable benzoin condensation reaction and achieve the critical reversibility to drive the formation of desired deuterated products when an excess of D2O is employed. Notably, this operationally simple and cost-effective protocol serves as a general and truly practical approach to all types of 1-D-aldehydes including aryl, alkyl and alkenyl aldehydes, and enables chemoselective late-stage deuterium incorporation into complex, native therapeutic agents and natural products with uniformly high levels (>95%) of deuterium incorporation for a total of 104 tested substrates.