Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

Abstract

A metal- and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.

Destabilizing Predictive Copper‐Catalyzed Click Reactions by Remote Interactions with a Zinc‐Porphyrin Backbone

“…[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Consequently, and in view to obtain supramolecular ligands featuring different substitution patterns in the triazolopyridine site, we envisioned an alternative route that also involves copper-catalyzed click chemistry, but this time, relying on the treatment of 1 with tosyl azide and further stoichiometric reaction with pyridine N-oxides (Scheme 1, bottom). [44][45][46] However, as it is herein presented, the copper-catalyzed click reaction involving the alkyne zinc-porphyrin 1 with tosyl azide did not afford the expected compound 1' but delivered products resulting from nucleophile addition such as sulfonyl imidates or sulfonyl amides (2). Together with observations found in a number of control experiments, it appears that the zinc-porphyrin unit plays a key role in order to stabilize otherwise inaccessible reaction intermediates leading to the unexpected compounds.…”

“…However, the access to 2‐azidopyridine derivative reagents is not trivial due to tautomerism and many functional groups are not tolerated during the synthesis process starting from 2‐bromopyridine derivatives [24–43] . Consequently, and in view to obtain supramolecular ligands featuring different substitution patterns in the triazolopyridine site, we envisioned an alternative route that also involves copper‐catalyzed click chemistry, but this time, relying on the treatment of 1 with tosyl azide and further stoichiometric reaction with pyridine N ‐oxides ( Scheme 1, bottom) [44–46] . However, as it is herein presented, the copper‐catalyzed click reaction involving the alkyne zinc‐porphyrin 1 with tosyl azide did not afford the expected compound 1′ but delivered products resulting from nucleophile addition such as sulfonyl imidates or sulfonyl amides ( 2 ).…”

Quinoline N‐Oxide: A Versatile Precursor in Organic Transformations

“…In 2021, Geetanjali S. Sontakke and team proposed a process of deoxygenative heteroarylation of quinoline N‐oxide at C‐2 position using N‐sulfonyl‐1,2,3‐triazoles [37] . The optimized conditions are evaluated to be quinoline N‐oxide (0.1 mmol), 1‐sulfonamyl‐1,2,3‐triazole (0.12 mmol) in 1,2‐dichloroethane (DCE) at rt for 15–20 minutes.…”

“…In 2021, Geetanjali S. Sontakke and team proposed a process of deoxygenative heteroarylation of quinoline N-oxide at C-2 position using N-sulfonyl-1,2,3-triazoles. [37] The optimized conditions are evaluated to be quinoline N-oxide (0.1 mmol), 1sulfonamyl-1,2,3-triazole (0.12 mmol) in 1,2-dichloroethane (DCE) at rt for 15-20 minutes. The screening of different additives showed that the À OÀ , À SÀ and À N-linked triazoles reacted under standard reaction conditions very well giving good to high yields of products (Scheme 44).…”

Allenes: Versatile Building Blocks in Cobalt-Catalyzed C–H Activation

“…To our delight, 2-triazolyl quinolines 11 were obtained in excellent yields by reaction with N-sulfonyl triazoles 10 under metal-free conditions. 29 Furthermore, dienylated quinolines 8 and 11, obtained by reduction or triazolylation, respectively, were tested in a Diels-Alder reaction and in catalytic hydrogenation (Scheme 10b).…”