Regioselective Metal-Free Cross-Coupling of Quinoline N-Oxides with Boronic Acids

Abstract

A novel and operationally simple one-step C-H bond functionalization of quinoline N-oxides to 2-substituted quinolines was developed. This approach enables the regioselective functionalization under external oxidant- and metal-free conditions. The developed transformation represents the first application of the Petasis reaction in functionalization of heterocycles.

Regioselective Cyanation of Six‐Membered N‐Heteroaromatic Compounds Under Metal‐, Activator‐, Base‐ and Solvent‐Free Conditions

“…[33] Stepwise CÀ H bond functionalization of 3-bromoquinoline was carried out using cross-dehydrogenative coupling followed by N-oxidation and cyanation. [33] Stepwise CÀ H bond functionalization of 3-bromoquinoline was carried out using cross-dehydrogenative coupling followed by N-oxidation and cyanation.…”

Reaction of Quinoline N‐Oxides and Pyridine N‐Oxides with Arylzinc Reagents: Synthesis of 2‐Arylquinolines and 2‐Arylpyridines

“…of Ac 2 O. The sealed reaction tube was heated at 120°C for 1 h to afford 2-(p-tolyl)quinoline in 36% yield ( [7][8][9][10][11]. The reaction in toluene gave markedly higher yield (Table 1, entry 12).…”

“…In the reaction of pyridine N-oxides with aryl Grignard reagents Kellogg et al demonstrated that the products were dienal oximes (6) [6a] rather than 2-aryl-N-hydroxydihydro-pyridines (7) proposed by kato and Yamanaka (Scheme 1). [5] We found that reaction of quinoline N-oxide with p-MeC 6 H 4 ZnCl at 100°C in the absence of TFAA afforded 3 a along with 2-(p-tolyl) quinolin-1(2H)-ol (8) (Scheme 2a).…”

“…Unfortunately, pyridine N-oxides were not compatible with the protocol. [7] Transition-metal-free cross-dehydro-genative coupling of quinoline N-oxides with 1,3-azoles was also performed in the presence of LiOtBu or N(SiMe 3 ) 3 /NMe 4 F. [8] We are interested in the CÀ C bond construction using arylzinc reagents in the presence or absence of transition metal catalysts. [9,10] Organozinc reagents exhibit higher reactivity than organoboron reagents and better compatibility of functional groups than Grignard reagents.…”

Stereospecific Coupling of Boronic Esters with N-Heteroaromatic Compounds

“…Some of the common methods include addition− elimination reactions 2,3 (Scheme 1A), Stille 4 /Kumada 5 /Negishi 6 /Suzuki−Miyaura 7 cross-coupling (Scheme 1B), and C− H activation followed by addition to an alkene/alkyne or aryl halide (Scheme 1C, D). 8,9 In most cases sp 2 −sp 2 bonds are created, limiting the methodology to achiral (flat) molecules. However, recent awareness of the greater clinical success of sp 3 -rich heteroaromatic compounds has fueled demand for methods that create chiral molecules bearing heterocyclic motifs.…”