Transition-metal-catalyzed C-H bond functionalizations: feasible access to a diversity-oriented β-carboline library.

Diversification of the -carboline skeleton has been demonstrated to assemble a -carboline library starting from the tetrahydro--carboline framework. This strategy affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkynyl-substituted -carbolines at the C1, C3, or C8 position through three categorically different types of transition-metal-catalyzed CC bond-forming reactions, in the presence of multiple potentially reactive positions. These site-selective functionalizations include; 1) the Cu-catalyzed C1/C3-selective decarboxylative Csp3Csp2 and Csp3C(sp) coupling of hexahydro--carboline-3-carboxylic acid with a CH bond of a heteroarene or terminal alkyne; 2) the chelation-assisted Pd-catalyzed C1/C8-selective CH arylation of hexahydro--carboline with aryl boron reagents; and 3) the chelation-assisted Pd-catalyzed C1/C3-selective oxidative CH/CH cross-coupling of -carboline-N-oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro--carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and perlolyrine. We believe that these strategies could provide inspiration for late-stage diversifications of bioactive core scaffolds.