A Gallium-Catalyzed Cycloisomerization/Friedel−Crafts Tandem

Under noble (Au, Pt, Ru) and group 13 (Ga, In) metals catalysis, 1,6-arenynes rearrange to give 1,2-dihydronaphthalenes in a high yielding, regiocontrolled fashion. When the reaction is carried out in the presence of electron-rich arenes (anisole, phenol, indole derivatives), Friedel−Crafts addition may follow the cycloisomerization step. Only GaX3 salts proved able to catalyze these two C−C bond formation events. This specificity of gallium has been exploited for the synthesis of valuable polycyclic compounds that would be very difficult to prepare otherwise. For instance, tetrahydroisoquinolines and tetrahydrobenzoazepines have been obtained by selective 6-exo-dig or 7-endo-dig cyclization of N-tethered 1,6-arenynes. DFT calculations were carried out to shed light on the mechanism and provide a rationale for this regiodivergency. Computations also reveal the fundamental role of the tether in the stabilization of carbocationic species. Differential reactivities of other types of substrates in gallium- and gold-catalyzed cascades are also exposed, showing that the two approaches are complementary. In particular, bimolecular Friedel−Crafts additions are facilitated under gallium catalysis.

在贵金属（Au、Pt、Ru）及第13族金属（Ga、In）催化下，1,6-芳炔可发生重排反应，以高产率、区域可控的方式生成1,2-二氢萘。当反应在富电子芳烃（苯甲醚、苯酚、吲哚衍生物）存在下进行时，环异构化步骤后可伴随傅-克（Friedel−Crafts）加成反应。仅三卤化镓（GaX₃）盐被证实可催化这两次碳-碳键形成过程。镓的这一独特催化特性被用于合成极具制备难度的高价值多环化合物。例如，通过氮连接臂修饰的1,6-芳炔的选择性6-外式-dig（6-exo-dig）或7-内式-dig（7-endo-dig）环化，可得到四氢异喹啉与四氢苯并氮杂䓬。研究人员开展了密度泛函理论（DFT）计算以阐明反应机理，并为该区域发散性反应提供理论解释。计算结果还揭示了连接臂在稳定碳正离子物种过程中的关键作用。此外，研究还阐明了其他类型底物在镓催化与金催化级联反应中的反应活性差异，表明两种催化策略具有互补性；尤其在镓催化体系下，双分子傅-克加成反应更易进行。