Ruthenium‐Catalyzed Stereo‐ and Site‐Selective ortho‐ and meta‐C−H Glycosylation and Mechanistic Studies

Abstract

C-aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium-catalyzed highly stereo-and site-selective ortho-and meta-C Ar À H glycosylation is described. A series of C-aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N-heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho-C Ar À H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta-CÀ H glycosylation was mediated by σ-activation. Density functional theory calculations also showed that the high stereoselectivity of meta-C Ar À H glycosylation was due to steric hindrance.

Stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals

“…Subsequently, G-α is received through OA (oxidative addition) and RE (reductive elimination) steps. The DFT calculations revealed that the OA proceeds via a concerted three-membered cyclic transition state ( 4-TS ), which directly leads to the form of the d -mannofuranosyl Pd(IV) intermediate ( F-α ) without the formation of oxocarbenium 26 , 56 (Supplementary Figs. 5 and 10 ).…”

“…This is expected given the considerable challenges posed by multifunctional, sterically hindered sugar substrates and the additional need to control the diastereoselectivity of C (alkenyl) –C (anomeric) bond formation. Following our continuous interest in Catellani-type reactions and carbohydrate chemistry 2 , 48 , 49 , 56 – 58 , we questioned whether modular and stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals.…”

Synthesis of heteroaryl C-glycosides via Ru-catalyzed C–H activation/cyclization: dioxazolone glycogen designs and applications

“…To our delight, the desired product 1 was obtained in 92% yield (Scheme 3) in the presence of [Ru ( p-cymene)Cl 2 ] 2 (5 mol%), AgNTf 2 (20 mol%), and NaOAc (50 mol%) in DCE (0.1 M) at 80 °C under nitrogen for 12 h. Subsequently, under the optimized conditions, C-nucleoside analogs (Scheme 3) were synthesized from benzimidates and dioxazolone glycogen anomers. This approach was applicable to many substituted alkyl benzimidates containing electronneutral (5,6,16,17), electron-withdrawing (2-4, 9-15), and electron-donating (7,8,19) groups, resulting in the corresponding 2-glycosyl-quinazolines in moderate to excellent yields. It is noteworthy that esters (9-11), halogens (2-4, 13, 14), and benzyloxy (7) groups exhibited tolerance, thereby providing promising prospects for subsequent functionalizations.…”

Ruthenium-Catalyzed Ligand-Enabled Regiodivergent Difluoroallylation of Aryl C–H Bonds

“…Functionalizing organic molecules through transition-metal-catalyzed C–H bond activation is a convenient and promising strategy. , In recent years, significant progress has been made in ruthenium-catalyzed chelation-assisted C–H bond activation. − However, studies on Ru-catalyzed ortho / meta switchable C–H functionalization are limited due to different mechanistic processes involved. − Therefore, there is a high demand for a switchable method of ruthenium-catalyzed C–H bond activation that can provide both ortho - and meta -functionalized arenes.…”