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

Abstract

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.

Intramolecular rhodium-catalysed [2 + 2 + 2] cycloaddition of linear chiral N-bridged triynes: straightforward access to fused tetrahydroisoquinoline core

“…Regarding the mechanism, formation of compounds 9 can be understood through a catalytic cycle analogous to others previously proposed for Rh-catalysed [2 + 2 + 2] cycloaddition of triynes. 17 Given that previous studies revealed that solvent effects attributed to toluene in similar Rh-catalysed [2 + 2 + 2] cycloadditions are minor, solvent effects were not included in the present computational study. The overall process from model triyne 7 to afford the merged symmetrical tetrahydroisoquinoline 9 is exergonic by 118.3 kcal mol −1 , very similar to that calculated for a chiral triyne 6a (Δ G R = −119.43 kcal mol −1 ).…”

Recent Advances on the Development of Synthetic Strategies to Access Dibenzoxepine Derivatives

“…In 2018, Ojima and co-workers reported rapid access to allocolchicinoid derivatives 123 in good to excellent yields by the [2+2+2] cycloaddition of o -phenylenetriynes 122 using [Rh(COD)Cl] 2 (catalyst) and DPPP (ligand) under microwave conditions (Scheme 50 ). 49 The reaction tolerated various functional groups and heteroatoms to access fused 6-7-6-5 tetracyclic 5,7-dihydrodibenzo[ c , e ]oxepine derivatives in a single step.…”

Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings

“…The use of oxygen and/or nitrogen in the linkers could be tolerated as well, leading to heterocylic 6‐6‐7‐5 scaffolds. Later on, Ojima and co‐workers disclosed the [2+2+2+1] cycloaddition between o ‐phenylenetriynes and CO to form the 6‐7‐7‐5 fused tetracyclic scaffold of colchicinoids in good yield (Scheme 3, bottom) [9b] …”