jo8b01608_si_001.pdf (12.68 MB)

Synthesis of Colchicinoids and Allocolchicinoids through Rh(I)-Catalyzed [2+2+2+1] and [2+2+2] Cycloadditions of o‑Phenylenetriynes with and without CO

Download (12.68 MB)
journal contribution
posted on 21.08.2018, 00:00 by Chih-Wei Chien, Yu-Han Gary Teng, Tadashi Honda, Iwao Ojima
The nonbenzenoid aromatics, tropones and tropolones, are found in various natural products such as colchicine and hinokitol, which possess significant biological activities. The traditional methods to construct the tropone skeletons include oxidation of cycloheptatriene and [4+3] cycloadditions. In addition, the total synthesis of colchicine and its analogues requires laborious organic transformations in the formations of 6–7–7 fused-ring systems. Transition metal-catalyzed carbocyclization and cycloaddition reactions have proven to be among the most efficient methods for constructing complex polycyclic systems. On the basis of our recent discovery of the Rh-catalyzed carbonylative [2+2+2+1] cycloaddition of triynes to the formation of a fused tropone system, we report here the application of this methodology to the one-step formation of the 6–7–7–5 fused tetracyclic scaffold of colchicinoids based on the [2+2+2+1] cycloaddition of o-phenylenetriynes with CO. In addition, the one-step formation of allocolchicinoids bearing the 6–7–6–5 fused tetracyclic system through the Rh-catalyzed [2+2+2] cycloaddition of o-phenylenetriynes is also described.