N-Tosylhydrazone directed annulation via C–H/N–N bond activation in Ru(ii)/PEG-400 as homogeneous recyclable catalytic system: a green synthesis of isoquinolines

Abstract

A green and sustainable methodology for the synthesis of isoquinolines using Ru(ii)/PEG-400 as a homogeneous recyclable catalytic system has been demonstrated. N-Tosylhydrazone, a rarely explored directing group, has been successfully employed for an annulation type of reaction with alkynes via C-H/N-N activation. A short reaction time with a simple extraction procedure, a wide substrate scope with high yields of products, easily prepared substrates, biodegradable solvent, and scalability up to the gram level enhance the efficiency and sustainability of the proposed protocol. Further, the expensive ruthenium-based homogeneous catalytic system could be reused up to a fourth consecutive cycle without any loss in its activity.

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…Deshmukh and Bhanage designed a Ru‐catalyzed N ‐tosylhydrazone 9 e directed annulation towards the synthesis of isoquinolines 74 h [260] . The method was similar to the previous reported method by Zhang et al [202] .…”

“…Benzimidates and diazo compounds of different substitution were successfully converted into isoquinoline derivatives in good yields (Scheme 252). [259] Deshmukh and Bhanage designed a Ru-catalyzed N-tosylhydrazone 9 e directed annulation towards the synthesis of isoquinolines 74 h. [260] The method was similar to the previous reported method by Zhang et al [202] in 2015 using Rh-catalysis (Scheme 253).…”

Rapid and Atom Economic Synthesis of Isoquinolines and Isoquinolinones by C–H/N–N Activation Using a Homogeneous Recyclable Ruthenium Catalyst in PEG Media

“…6‐Chloro‐1,7‐dimethyl‐3,4‐diphenylisoquinoline (3ma): [19b] Slightly yellow solid; m.p. 158–160 °C; 1 H NMR (500 MHz, CDCl 3 ) δ = 8.19 (d, J = 3.6 Hz, 1H), 7.50 (d, J = 3.4 Hz, 1H), 7.36–7.26 (m, 5H), 7.24–7.13 (m, 5H), 3.05 (s, 3H), 2.46 (s, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ = 156.56, 149.69, 141.72, 139.25, 137.19, 134.81, 133.73, 131.28, 130.97, 129.30, 128.31, 127.63, 127.53, 127.32, 127.12, 125.89, 125.66, 22.40, 21.00; GC–MS (EI 70 eV) m/z (% rel.…”

“…On account of this, an attempt was made for their synthesis using atom economic directing groups, homogeneous recyclable catalytic media and microwave strategy. Continuing our work in the synthesis of N‐heterocycles, herein we report microwave assisted, external oxidant free synthesis of isoquinolines and isoquinolinones by annulation of ketazines and dibenzoylhydrazines with internal alkynes using Ru catalyst in PEG‐400 solvent, a homogeneous reusable catalytic system. Furthermore, the proposed strategy worked efficiently in significantly short time with no silver salt or acid additives.…”

Synthesis of Isoquinoline Derivatives via Palladium‐Catalyzed C−H/C−N Bond Activation of N‐Acyl Hydrazones with α‐Substituted Vinyl Azides

“…In recent years, several aromatic hydrazones (N-Tos, N-Cbz, N-Boc, and N-pyridine, etc.) have been explored in rhodium(III), [10] cobalt(III), [11] cobalt(II), [12] and ruthenium(II) [13] -catalyzed annulations with al-kynes through CÀ H/NÀ N bond activation to afford 1,3,4-trisubstituted isoquinolines, along with NÀ N bond cleavage of hydrazones (Scheme 1a). To the best of our knowledge, palladium-catalyzed CÀ H functionalization using aryl ketone hydrazones as directing groups for the synthesis of isoquinolines have never been reported to date.…”