电子匹配亲核1,6-共轭加成在合成领域得到了广泛的研究和应用。相比之下,亲核1,5-缀合物添加代表电子禁止过程并且被认为是不可行的。这里,我们描述了通过氢化钯催化的1,5-共轭加成反应的模块化方案。开发了钯和协同Pd/有机催化剂体系来催化1,5-共轭反应,然后是分子间或分子内[3+2]环化。建立了一个可迁移的1,5-添加协议,以证实该umpolung概念的可行性。1,5-加成产物可以方便地转化为一系列特权的对映体富集基序,包括多取代的四氢呋喃,二氢呋喃,环丙烷,环丁烷,氮杂环丁烷,氧杂环丁烷,硫杂环丁烷,螺环和桥接环。初步机理研究证实了氢化钯催化的参与。
Electronically matched nucleophilic 1,6-conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5-conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5-conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5-conjugate reaction, followed by inter- or intramolecular [3+2] cyclization. A migratory 1,5-addition protocol is established to corroborate the feasibility of this
umpolung concept. The 1,5-addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis.