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

Abstract

Herein, we report an atom‐efficient, rapid, green, and sustainable approach to synthesize isoquinolines and isoquinolinones using a homogeneous recyclable ruthenium catalyst in PEG Media assisted by microwave energy. Dibenzoylhydrazine was used for C–H/N–N activation reactions for the first time in combination with ketazine as oxidizing directing groups for annulation reactions with internal alkynes. The developed protocol is environmentally benign due to significantly shortened times with an easy extraction method, higher atom economy, external oxidant and silver or antimony salt free conditions, applicability to a gram scale synthesis, use of biodegradable solvent and wide substrate scope with higher product yields. Moreover, it is worth noting that the established methodology allowed reuse of the catalytic system for up to five successive runs with minimal loss in activity.

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

“…In 2019, Deshmukh et al developed a new method for the synthesis of isoquinolines assisted by microwave energy [ 105 ]. This strategy used polyethylene glycol (PEG) as a green, non-volatile, and biodegradable solvent.…”

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis

“…Isoquinoline derivatives 218 can be prepared by the annulation reaction of 2,3-diaza-1,3-butadienes 219 with alkynes via sequential C-H/N-N bond activation. Recently a ruthenium catalyst in PEG media with microwave radiation [ 102 ] and an air-stable cobalt catalyst in trifluoroethanol with NaOAc as an additive [ 103 ] was used in this reaction. Diazadienes 219 derived from acetophenone with electron-donating and electron-withdrawing groups at different positions of the phenyl ring were well tolerated for the reaction with various alkynes to afford the corresponding isoquinolines 218 in good to excellent yields, regardless of the catalyst used ( Scheme 48 ).…”

C−H Functionalized Molecules: Synthesis, Reaction Mechanism, and Biological Activity

“…[14][15][16] The catalytic CÀ H activation has also appealed great attention for intermolecular and intramolecular synthesis because of its significant efficacy in atom economy, environmental sustainability, and lesser steps over conventional synthetic techniques. [17] This field has reached the point where researchers can now achieve selective CÀ H bond activation even in the presence of other active bonds for the synthesis of novel complex organic molecules that would not have been possible using traditional methods. Further, these novel organic molecules could act as intermediates for the formation of synthetic targets with varied bioactivities.…”

“…Advancement in the field of organometallic chemistry has led to the synthesis of new promising metal catalysts resulting in direct C−H bond activation [14–16] . The catalytic C−H activation has also appealed great attention for intermolecular and intramolecular synthesis because of its significant efficacy in atom economy, environmental sustainability, and lesser steps over conventional synthetic techniques [17] . This field has reached the point where researchers can now achieve selective C−H bond activation even in the presence of other active bonds for the synthesis of novel complex organic molecules that would not have been possible using traditional methods.…”