Di Marco Lorenzo, Hans Morgan, Delaude Lionel, Monbaliu Jean-Christophe M
Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, 4000, Liège, Belgium.
Laboratory of Organometallic Chemistry and Homogeneous Catalysis, Department of Chemistry, University of Liège, 4000, Liège, Belgium.
Chemistry. 2016 Mar 18;22(13):4508-14. doi: 10.1002/chem.201505135. Epub 2016 Feb 16.
Two methods were assessed for the generation of common N-heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous-flow setups with either a heterogeneous inorganic base (Cs2CO3 or K3PO4) or a homogeneous organic base (KN(SiMe3)2). In-line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC-catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N-Boc-glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous-flow organocatalysis with NHCs.
评估了两种方法，用于从稳定的咪唑（啉）盐前体生成常见的N-杂环卡宾（NHC），采用方便直接的连续流动装置，使用非均相无机碱（碳酸铯或磷酸钾）或均相有机碱（双（三甲基硅基）氨基钾）。用二硫化碳在线猝灭表明，均相策略对于制备一个小型NHC库最为有效。接下来，将游离亲核卡宾的生成与两个基准NHC催化反应相结合；即乙酸乙烯酯与苯甲醇的酯交换反应以及N-Boc-甘氨酸甲酯与乙醇胺的酰胺化反应。两种有机催化转化均完全转化，萃取后获得了优异的产率，展示了NHC连续流动有机催化的首个实例。
