环烷烃惰性sp3 C-H键活化构筑C-X ( X = C, O, S, Se ) 键及有机合成中的应用

Transition metal-catalyzed C-H activation has recently emerged as the most powerful and straightforward tool for the functionalization of organic molecules. Although many efforts have focused on the direct sp2 C-H activation in the past two decades. Much less research has been devoted to the activation of more inert sp3 C-H bonds, which is more challenging owing to their low reactivity and the lack of a coordination site for the transition-metal catalyst. This project mainly focused on the studies of cheap metal or metal-free catalyzed C-H bond activation of cycloalkanes to construct C-X( X = C, O, S, Se ) bonds. Firstly, a meal-catalyzed decarboxylative coupling of aryl carboxylic acids with cycloalkanes will be developed. Secondly, the first metal- catalyzed oxidative alkenylation of cycloalkanes will be achieved via cross-dehydrogenative coupling (CDC) reaction. Thirdly, a novel method for the preparation of cycloalkyl aryl sulfides and cycloalkyl aryl selenides through direct oxidation thiolation or selenylation of cycloalkanes without a metal catalyst will be developed. Lastly, a metal-catalyzed dehydrogenation-olefination and esterification of sp3 C-H bond of cycloalkanes with aromatic aldehydes will be developed, which involves four C-H bonds activation. Finally, the intramolecular C-H activation coupling will be investigated. In this project, cheap and environment-friendly cycloalkanes are used as the starting material in the C-H activation reactions, which has great academic significance and industrialization prospect.

过渡金属催化的碳氢键活化是有机合成领域中非常重要的课题。在过去的二十年间，过渡金属催化的sp2碳氢键活化反应已经得到了广泛的研究和应用。然而，过渡金属催化的sp3碳氢键活化反应研究相对较少，更具挑战性。主要是sp3碳氢键具有更高的键解离能和更低的酸性导致其难以活化；另一方面，在活化sp3碳氢键时过渡金属无法与σ-键进行耦合作用导致选择性的难以控制。本项目主要探索几种廉价的催化体系活化环烷烃 sp3 C-H键构筑C-X( X = C, O, S, Se )键。通过芳香羧酸与环烷烃的脱羧偶联反应实现环烷烃的芳基化；首次实现环烷烃与芳基烯烃的交叉偶联反应；首次发展无金属催化剂条件下的环烷烃的直接硫化与硒化反应。同时以环烷烃和芳香醛为底物，同时活化4个C-H键来合成2-环烷基芳香羧酸酯，并实现分子内关环反应研究。本项目将简单易得环烷烃作为碳氢活化反应的底物，具有重大学术价值。

本项目按照既定研究方案和相关的设计执行，通过探索廉价易得的铜、铁、镍的催化体系用于环烷烃碳氢键活化偶联反应；发展多种环烷烃碳氢活化的反应类型来构筑C–C键、C–O键、C–S键、C–Se等；同时，考察底物反应活性及反应机理研究；并将环烷烃惰性C(sp3)–H键活化构筑C-X键用于具有应用价值的天然产物中间体的制备反应中。项目执行期内取得了重要的研究成果，成功在金属催化剂的条件下实现了上述转化。主要成果集中在未活化C(sp3)–H键功能化引发的分子内关环反应，C–N键的断裂的还原偶联反应，以及自由基加成引发的不饱和酸的多步串联自由基反应，同时，在自由基多步串联反应中，发展了光催化和电催化的自由基反应，由磺酰氯以及亚磺酸形成磺酰自由基构建砜取代的环状化合物反应，溴二氟酸酯作为二氟代酯自由基和不饱和酸进行的自由基多步串联反应等，为高效构筑碳杂键提供了有效途径。