Regiocontrolled Remote C−H Olefination of Small Heterocycles

Abstract

Achieving site-selective C-H functionalization of arene is a fundamental challenge, as it is mainly controlled by the electronic nature of the molecules. A chelation-assisted C-H functionalization strategy overcomes the selectivity issues by utilizing distance and geometry of covalently attached directing groups (DGs). This strategy requires stoichiometric DG installation/removal and a suitable functional group on which to tether the DG. Such strategies are ineffective for small heterocycles unless suitable functional groups are added. Moreover, heterocycles are not the judicious choice as substrates owing to the possibilities of catalyst deactivation. Inspired by recent developments, this work demonstrates the utilization of a chelating template backbone bearing covalently attached directing groups, which enables site-selective remote C-H functionalization of heterocycles. The observed selectivity is the outcome of non-covalent interactions between the heterocycles and bifunctional template backbone.

Beyond hydrogen bonding: recent trends of outer sphere interactions in transition metal catalysis

“…164 It is relevant to note that transition metal-catalyzed distal C-H bond activations are typically ensured by directing groups, which impose issues associated to the introduction and removal of the directing group, besides the extensive efforts devoted to trial-and-error screening to search for the optimal catalytic system. Such methodology was corroborated by Maiti's group using C 2 -symmetric templates 168 and further expanded to thiazole substrates (Scheme 39). 169 The same group employed allylic alcohols as coupling partners for the palladium-catalyzed C-H bond alkylation at the C-5 position of quinoline and thiazole derivatives, and at the C-7 position for benzothiazole and benzoxazole, respectively.…”

“…Furthermore, it is possible to recycle and recover the template by treatment with 4dimethylaminopyridine, which coordinates stronger to the palladium template than the substrates and the products, followed by a mild acidification. [167][168][169][170][171] It is relevant to note that the success of these strategies relies also on the non-negligible roles of mono-protected amino acids co-ligands, silver salts and hexafluoroisopropanol as solvent.…”

Recent development in transition metal-catalysed C–H olefination

“…Shortly after, a similar remote C–H olefination of small heterocycles using a modified bifunctional template (T) was reported by our group ( Scheme 50 ). 57 We synthesized a symmetrical covalently attached nitrile-based tridentate template for the site-selective remote C–H olefination of heterocycles 104 in improved yield and selectivity. A variety of substituted quinolines and other heterocycles such as benzoxazole and benzothiazole were employed under the reaction conditions to afford products 105 in good yield and selectivity.…”

Bimetallic anchoring catalysis for C-H and C-C activation

“…Inspired by this strategy, Maiti's group designed a series of similar bifunctional ligands (Scheme 15), and applied them to develop various types of selective alkenylation or alkylation reactions of quinolones [24], pyridyl-arenes [25] and thiazoles [26] with acrylates or allylic alcohols, achieving good yields and up to excellent site selectivity. These results further demonstrate that bimetallic anchoring catalysis is a powerful strategy for non-directed selective C-H activation.…”