钯催化胺类化合物ε, δ位碳-氢键活化反应的研究

Functionalization of the amines at δ, ε positions to achieve carbon-carbon bond formation via palladium catalyized C-H activation is still a big challenge in organic chemistry. In this project, a series of N,O-bidentate auxiliary will be synthesized from oxalyl chloride and second amines, and tested under general arylation condition to find out the best directing group for C-H activation. The new developed directing was demonstrated to have a superior directing ability in C-H activation reactions. The primary experiments results disclosed that the new developed strong auxiliary could fuctionalize C–H bonds at both δ and γ position to achieve arylation, alkenylation reactions in mild condition via palladium as catalyst. To further expand the reaction types, the intramolecular amination through palladium-catalyzed C–H activation under mild condition at ε position was first observed. Tetrahydroquinolines and benzomorpholines were synthesized in moderate to excellent yield. Indolines from β-arylethylamine were also obtained in good to excellent yield under the mild condition. Primary mechanism was study , the intramolecular amination might go through a PdII/IV catalytic cycle by a sequence of C-H palladation, PdII/IV oxidation and C-N reductive elimination。The further experiment results will be discussed in next several years.

胺类化合物γ位的碳氢键活化及相应的碳碳成键反应已被广泛研究，但其δ, ε位碳氢键活化及相应的碳碳成键反应依然是碳氢键官能团化的难题。本项目设计具有N,O型双齿诱导中心的酰胺类化合物，期望解决胺类化合物δ, ε位的碳氢键向碳碳键转化的问题。. 通过廉价、易得的草酰氯与一分子胺作用，形成一种N,O双齿配位中心；通过改变胺基亲核试剂的结构，调控其电子效应和位阻效应，对胺类化合物δ, ε位进行定点碳氢键活化，并实现碳碳成键反应。. 通过本项目的研究，可以解决胺类化合物在δ, ε位的芳基化反应，烯基化反应；同时通过钯催化分子内胺化的方法，经过不常见的七元环钯中间体，实现六元杂环，四氢喹啉、苯并吗啉—类衍生物的合成。加深对碳氢键活化中诱导基团性质的认识，为进一步发展新的碳氢键活化反应提供新思路。

高区域选择性实现碳氢键官能团化反应，是碳氢键活化反应的重点与热点。在该基金支持下，主要研究导向基团诱导的胺类化合物碳氢键官能团化反应。发展一类N,O型双齿导向基团，成功的实现了胺类、羧酸类、醇类化合物的碳氢键官能团化反应。首先设计和发展了一种由廉价草酰氯和二异丙基胺出发得到N,O型导向基团，成功解决了胺类化合物远程碳氢键官能团的难题；随后发展一种由甘氨酸为母版的N,O型导向基团，能选择性的实现羧酸的碳氢键官能团化反应；最后通过肟醚或以草酰胺为导向基，解决芳香醇类邻位碳氢键转化反应的难题。最近本课题组发现，在没有导向基团辅助条件下，可以直接实现脂肪酸或氨基酸类化合物β位碳氢键官能团化反应。.发展的新型N,O双齿导向体系，借助于少见的七元环钯化过渡态的填补羧酸、胺类和醇类化合物远程碳氢键官能团化难以实现的空白。 这一系列成果属国际学术前沿，而且比其它导向基团更廉价易得，均具有潜在应用价值。