A Metal‐ and Azide‐free Oxidative Coupling Reaction for the Synthesis of [1,2,3]Triazolo[1,5‐a]quinolines and their Application to Construct C−C and C‐P Bonds, 2‐Cyclopropylquinolines and Imidazo[1,5‐a]quinolines

Abstract

An iodine‐promoted one‐pot cascade oxidative annulation reaction has been developed for the synthesis of [1,2,3]triazolo[1,5‐a]quinolines from methyl azaarenes and N‐tosylhydrazines. The reaction has a broad substrate scope and can be easily scaled up to gram‐scale. 1,2,3‐Triazoles are an important skeletal structure for the construction of C−C and C−P bonds, 2‐cyclopropylquinolines and imidazo[1,5‐a]quinolines, for which different synthetic applications were explored.

Progress on Pyridotriazole Chemistry: Synthesis and Transformations

“…Recently, Zhu [32] described a I 2 ‐promoted oxidative annulation of 2‐methyl quinolines 8 with tosylhydrazine to provide a straightforward synthesis of triazoloquinolines 9 in modest to high yields (Scheme 5). In this protocol, 2‐quinolinylaldehydes 10 were generated in situ via I 2 ‐assisted Kornblum oxidation.…”

“…Particularly, alkenes bearing a sulfonyl group gave the products as single diastereoisomer. Zhu and co‐workers [32] demonstrated that triazoloquinolines 111 underwent similar cyclopropanation with alkenes 112 in the presence of Co(TPP) at a higher reaction temperature (130 °C) (Scheme 36). Quinolinylcyclopropanes 113 were obtained with excellent diastereoselectivity in most cases (>20/1).…”

Asymmetric Radical Process for General Synthesis of Chiral Heteroaryl Cyclopropanes

“…Transition-metal catalyzed asymmetric cyclopropanation of alkenes with heteroaryldiazomethanes represents an appealing approach for the synthesis of valuable chiral heteroaryl cyclopropanes with the potential to control both diastereoselectivity and enantioselectivity. , In contrast to the well-precedented asymmetric cyclopropanation with other types of diazo compounds, only a few catalytic systems involving the use of heteroaryldiazomethanes have been reported . This underdevelopment is largely attributed to their inherent instability as well as high propensity for unwanted formal dimerization. , Moreover, it is known that rhodium- and other existing metal-based catalytic systems of cyclopropanation could suffer from the notorious catalyst poisoning effect in the presence of nitrogen- and sulfur-containing heterocycles. , Recently, Chattopadhyay and co-workers reported a [Co­(TPP)]-catalyzed (TPP = 5,10,15,20-tetraphenylporphyrin) metalloradical cyclopropanation with 2-pyridyldiazomethanes, which could be generated in situ from readily accessible N -tosylhydrazone precursors in the presence of base . While this in situ protocol offers a novel alternative for catalytic synthesis of 2-pyridylcyclopropanes in their racemic forms, the enantioselective variant of this transformation is an attractive process that remains elusive.…”

Iodine-Promoted Oxidative Cyclization of Methyl Azaarenes and α-Amino Ketones for One-Pot Synthesis of 2-Azaaryl-5-aryl Oxazoles

“…Moreover, the oxidative domino cyclization of methyl azaarene with α-amino ketones for oxazoles synthesis has not been reported via iodine-promoted reaction. As ongoing work for heterocycle synthesis from methyl azazrenes, herein we report an efficient method for the synthesis of 2,5-disubstituted oxazoles from readily available methyl azaarenes and α-amino ketones via iodine-promoted oxidative domino cyclization (Scheme c). We chose 4-methylquinolines 1a and 2a as model substrates for reaction condition optimization.…”