Mesoionic Carbene (MIC)-Catalyzed H/D Exchange at Formyl Groups
Mesoionic Carbene (MIC)-Catalyzed H/D Exchange at Formyl Groups
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甲酰基上的介离子卡宾 (MIC) 催化的 H/D 交换5
DOI：
10.1016/j.chempr.2019.08.011
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发表时间：
2019-09-12
期刊：
影响因子：
23.5
通讯作者：
Yan, Xiaoyu
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhao, Liang-Liang;Yan, Xiaoyu
甲酰基上的 H/D 交换是合成氘代醛的最直接方法。铂族金属配合物已被用来催化这种转变，但具有显着的底物范围限制。尽管N-杂环卡宾也可以通过形成Breslow中间体来激活醛的C-H键，但安息香缩合和其他C-C键形成途径迄今为止已经超过了合成上有用的H/D交换。对醛与 1,2,3-三唑基反应的研究揭示了 Breslow 中间体的可逆形成以及甲醇溶剂中缩合步骤的抑制。使用氘化甲醇作为经济实惠的 D 源，1,2,3-三唑基可催化芳基、烯基和烷基醛的 H/D 交换，产率高且氘掺入水平高。这些介离子卡宾 (MIC) 的独特性质使得能够简化氘代合成中间体和药物载体的制备，这些中间体和药物载体作为机械和代谢探针具有很高的价值。
H/D exchange at formyl groups is the most direct approach for the synthesis of deuterated aldehydes. Platinum-group metal complexes have been employed to catalyze this transformation, with significant substrate scope limitations. Although N-heterocyclic carbenes can also activate the C- H bond of aldehydes through the formation of Breslow intermediates, benzoin condensation and other C-C-bond-forming pathways have so far outpaced synthetically useful H/D exchange. Investigation of the reaction of aldehydes with 1,2,3-triazolylidenes has revealed the reversible formation of Breslow intermediates and the inhibition of the condensation steps in methanol solvent. 1,2,3-Triazolylidenes catalyze the H/D exchange of aryl, alkenyl, and alkyl aldehydes in high yields and deuterium incorporation levels using deuterated methanol as an affordable D source. The unique properties of these mesoionic carbenes (MICs) enable a streamlined preparation of deuterated synthetic intermediates and pharmaco-phores that are highly valuable as mechanistic and metabolic probes.