Copper‐Catalyzed ortho‐Functionalization of Quinoline N‐Oxides with Vinyl Arenes

Abstract

An efficient copper-catalyzed regioselective CÀH alkenylation and borylative alkylation of quinoline N-oxides with vinyl arenes in the presence of pinacol diborane has been developed. The reaction proceeds through the borylcupration of the vinyl arenes followed by nucleophilic attack of the resulting alkyl copper species to the quinoline N-oxides. Benzoquinone and KO t Bu were identified as the necessary additives at the second step of the reaction that are crucial for the success of the reaction. A wide range of C2-functionalizaed quinolines were obtained with good functional group tolerance, which may find utilities in pharmaceuticals and synthetic chemistry.

Quinoline N‐Oxide: A Versatile Precursor in Organic Transformations

“…In 2020, copper‐catalyzed regioselective both alkenylation and alkylation of quinoline N‐oxides using vinyl arenes in the existence of pinacol diborane was proposed by Hui Hu and coworkers [22] . In the additional step, the applications of the additives have a significant role for the generation of desired products, thus the use of oxidant gives a 1,1’‐disubstistuted alkene and use of base gives the borylated alkyl selectively (Scheme 15).…”

“…As for example, the compound 45 could be used Pd‐catalyzed cross coupling arylation with aryl bromide to form the product 46 , reaction with Grignard reagent to generate the product 47 and the reaction between borane 45 (Scheme 18). [22] Also, the reaction of the compound 45 with ClCH 2 Br in n ‐BuLi provided the product 48 [23] …”

Pd-catalyzed Intermolecular Dehydrogenative Heck Reactions of Six-membered Heteroarenes

“…Liu's team carried out the olefination of isoquinoline and quinoline N-oxides using catalytic PdCl 2 in DMSO [69,77]. These substrates being prototypical oxygen atom transfer reagents [78], the reactions arose under external-oxidant-free conditions leading to 1-substituted isoquinolines (Eq.…”

Gold-Catalyzed Regio- and Stereoselective Alkenylation of Quinoline N-Oxides with Allenamides

“…For instance, C2-alkenylation of pyridine/quinoline N -oxides with electron-deficient alkenes or styrenes has been demonstrated via Pd-, I 2 -, or Brønsted acid-catalyzed reactions. Our group developed a copper-catalyzed C2-alkenylation or -alkylation of quinoline N -oxides with alkenes and C2-alkenylation with alkynes in the presence of diborane and a base. A nickel-catalyzed C2-alkenylation of pyridine N -oxides with alkynes has been reported by Hiyama et al (Scheme a).…”