Continuous Flow Synthesis of N-Sulfonyl-1,2,3-triazoles for Tandem Relay Cu/Rh Dual Catalysis

Abstract

The continuous flow synthesis of N-sulfonyl-1,2,3-triazoles, which are convenient reactive azavinyl carbene precursors, for tandem relay Cu/Rh dual catalysis has been developed. Most reactions readily proceeded at 75 °C in a short residence time of 13.09 min in the presence of 2.5 mol % of CuTC. The scope of the reactions was explored by synthesizing diversely functionalized N-sulfonyl and sulfamoyl triazoles in yields ranging from 92 to 98%. To demonstrate the scalability of the process, the reaction was conducted on a 5.4 mmol scale with residence and collection times of 13.09 and 60 min, respectively. Furthermore, a series of controlled experiments were performed to investigate the compatibility of Cu and Rh in a batch or a continuous flow system. Finally, the first integrated flow system using the azavinyl carbene intermediate under the tandem relay Cu/Rh dual catalysis was developed for the synthesis of various cis-diamino enones from alkynes and sulfonyl azides.

Copper-Catalyzed Continuous-Flow Transfer Hydrogenation of Nitroarenes to Anilines: A Scalable and Reliable Protocol

“…Despite progress in this domain, the development of simple, green, efficient, and practical catalytic transfer hydrogenation systems for nitroarene reduction is still highly desirable. In the drive to develop selective catalysts that are able to suppress the use of undesired noble metals, copper has received much attention in recent decades, and its efficient application in catalyzed continuous-flow synthetic processes is reported in the literature. − Very few literature refers to Cu-catalyzed continuous hydrogenation, − and it focuses on the reduction of 5-HMF; only one example has reported copper-catalyzed transfer hydrogenation in-flow in the presence of a huge excess of NaBH 4 …”