Ruthenium-Catalyzed Annulation of N-Cbz Hydrazones via C–H/N–N Bond Activation for the Rapid Synthesis of Isoquinolines

Abstract

In this work, N-Cbz hydrazone has been employed as a rarely explored directing group for the synthesis of isoquinolines by annulation with internal alkynes via C–H/N–N activation using Ru catalyst. Additive as well as external oxidant-free rapid protocol has been established for the synthesis of isoquinolines using microwave strategy. Use of non-volatile and biodegradable PEG as a green solvent with lower catalyst loading makes the proposed protocol environmentally benign. Further, higher functional group tolerance and wide substrate scope has been observed under the stated methodology with higher yields.

Revolutionizing C–H Activation Reactions: Harnessing Green Solvents for Sustainable Catalysis

“…Bhanage and co-workers have utilized N-Cbz hydrazone as a directing group in their research to synthesize isoquinolines through annulation with internal alkynes. 40 This approach involves the C-H/N-N activation using a Ru catalyst. Remarkably, they've created a quick process for making isoquinolines without the need for any additives or external oxidants, making the process more efficient.…”

The Application of Microwaves, Ultrasounds, and Their Combination in the Synthesis of Nitrogen-Containing Bicyclic Heterocycles

“…As compared to the previously reported synthetic procedures based on conventional heating [ 106 ], this protocol represented an environmentally friendly approach due to a shortened time of reaction, a reduced time of purification and no external oxidants or transition metals being involved.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…The method was in compliment with previous reports (Scheme 258). [266] Sarathkumar et al reported the microwave-assisted Ru(II)-catalyzed synthesis of 4-aryl-3-(aryl/alkylthio) isoquinolin-1(2H)-one 421 via CÀ H/NÀ O activation of N-methoxybenzamides 82 with phenyl(phenylethynyl) sulfane 419. Using the developed reaction conditions wide range of 4-aryl-3-(aryl/alkylthio)isoquinolin-1 (2H)-one 421 were synthesized in moderate to good yields.…”