Palladium-Catalyzed Alkenylation of Quinoline-N-oxides via C−H Activation under External-Oxidant-Free Conditions

Abstract

The direct cross-coupling of quinoline-N-oxides with olefin derivatives has been realized using palladium acetate as the catalyst in the absence of external ligand and oxidant to give the corresponding 2-alkenylated quinolines and 1-alkenylated isoquinolines chemo- and regioselectively in 27−95% yield. The catalytic process is proposed to proceed via direct C−H bond activation of the quinoline-N-oxide with Pd(OAc)2 followed by Heck coupling with the olefin. The resultant N-oxide of the alkenylated quinoline can oxidize the reduced Pd(0) to regenerate the Pd(II) active species and simultaneously release the 2-alkenylated quinoline without using any external oxidants and reductants.

Halogen-Bonded Co-Crystals of Aromatic N-oxides: Polydentate Acceptors for Halogen and Hydrogen Bonds

“…The C−H···O contacts are attractive, and are rather site acidity-dependent. For example, the C2-proton acidity in pyridine N-oxides for ortho-C−H functionalization in organic synthesis [19][20][21][22][23][24][25], and in crystal engineering for C−H···O−N interactions is well studied [51][52][53][54]. However, to the best of our knowledge, the combination of C−H···O−N and C−I···O−N interactions through the N−O group, giving rise to supramolecular assemblies, has not been extensively studied.…”

“…Aromatic N-oxides have been long known in heterocyclic chemistry for functionalized pyridines syntheses [19][20][21][22][23][24][25]. Besides being valuable synthetic intermediates, the dipolar neutral N⁺−O − group exhibits a push-pull property towards aromatic rings, enabling it to undergo both electrophilic and nucleophilic substitution reactions, categorizing these compounds as promising building blocks in supramolecular chemistry [26,27].…”

Unexpected Course of the Reaction of 2‐Unsubstituted 1H‐Imidazole 3‐Oxides with Ethyl Acrylate

“…Despite the potential importance of ethenylations of aromatic N-oxides, there are, to the best of our knowledge, only two reports known on Pd-catalyzed reactions of this type (Scheme 2). In one case, pyridine N-oxides 2 were converted regioselectively into 3-(pyridin-2-yl) propenoates 3 with a preserved N-oxide group in high yield [8]. The second reaction reported is the transformation of quinoline N-oxides 4 into the propenoates 5.…”

“…Prompted by the results described in [7] and [8], we decided to study the reaction of ethyl acrylate with 2-unsubstituted imidazole 3-oxides 1 both in the presence and in the absence of a catalytic amount of Pd(AcO) 2 .…”

Title Pages

“…Palladium(II)-catalyzed direct arylation (with arylboronic acids) or acetoxylation of 2-aryloxypyrimidines provides a facile route to phenol derivatives via a temporary directing group 16 . Palladium(II)-catalyzed 2(1)-vinylation of (iso)quinoline-N-oxides with olefins proceeds in the absence of external ligand and oxidant via concomitant N-deoxygenation 17 . Continuing with the theme of palladium catalysis, alkylarenes (including those bearing functional groups) may be obtained simply in water at room temperature by cross-coupling of alkyl iodides and aryl bromides under catalysis by Pd(0) [generated from PdCl 2 (Amphos) 2 ] in the presence of zinc powder, aided by TMEDA and the vitamin E-based PTS as nonionic amphiphile 18 .…”