Visible-Light-Induced Pd-Catalyzed Radical Strategy for Constructing C-Vinyl Glycosides

Abstract

A novel visible-light-induced palladium-catalyzed Heck reaction for bromine sugars and aryl olefins with high regioand stereochemistry selectivity for the preparation of C-glycosyl styrene is described. This reaction takes place in one step at room temperature by using a simple and readily available starting material. This protocol can be scaled up to a wide range of glycosyl bromide donors and aryl olefin substrates. Mechanistic studies indicate that a radical addition pathway is involved.C-Glycosides, in which the glycosidic oxygen is replaced by a carbon atom, have received a great deal of attention 1 because of the crucial roles of carbohydrates in resisting metabolic degradation and biological activities. 2 Compared with N-or Oglycosides, C-glycosides show an obvious enhancement in both in vitro and in vivo stability. Despite the significant methods available for constructing C-glycosides, a stereoselective and efficient method is still challenging and lags far behind that for O-or N-glycosides. 3 Over the past few decades, synthetic methods for C-glycosides have mainly concentrated on transition-metal-catalyzed 4 cross-coupling reactions. In particular, the construction of aryl C-glycosides 5 has undergone remarkable development. In 2008, Gagnéand co-workers reported a Ni-catalyzed Negishi cross-coupling approach for the synthesis of C-alkyl and C-aryl glycosides 6 (Scheme 1, Gagne's work). Recently, an efficient and stereoselective synthesis via palladium-catalyzed C−H glycosylation of Caryl glycosides was reported by Chen and co-workers. 7 In addition, the groups of Gagne, Cossy, and Nakamura also explored nickel-, 8 cobalt-, 9 and iron-catalyzed 10 cross-coupling reactions through generation of glycosyl radical intermediates to synthesize C-aryl glycosides.Although synthetic routes for C-aryl glycosides have been widely explored, the C-glycosyl styrenes, which are versatile starting compounds for, e.g., varitriol, 11 C-glycosyl aldehydes, 12 UDP sugar derivatives, 13 pyranopyran carbohydrate amino acids, 14 and some natural products, 15 remain challenging. At the outset, an intramolecular radical cyclization strategy was applied to prepare C-glycopyranosyl styrenes. In 1991, Stork and co-workers 16 demonstrated a temporary silicon connection for constructing C-glycopyranosyl styrenes that undergo an intramolecular radical process. Soon afterward, the Beau group 17 used a similar strategy to realize samarium iodidepromoted radical cyclization for the formation of the Cglycopyranosyl bond. Over the past few years, some other

Visible-light-driven palladium-catalyzed Dowd–Beckwith ring expansion/C–C bond formation cascade

“…Based on the above results and literature, 11 a plausible mechanism for this ring-expansion/alkenylation reaction is proposed (Scheme 2). Firstly, the L n Pd 0 complex is photoexcited to form an excited state L n Pd 0 * species upon irradiation, which promotes a single-electron transfer event with 1a to generate the putative Pd I species and a primary alkyl radical I .…”

“…Inspired by the pioneering works on visible-light induced Pd-catalyzed alkyl-Heck coupling reactions, 11 we envisioned that photoirradiation might facilitate the SET event between Pd(0) complex and Dowd–Beckwith halides to initiate the ring expansion process. The interaction of the tertiary radical species and Pd( i ) complex generated in situ would provide opportunities for further transformation (Scheme 1, eqn b).…”

Stereoselective Synthesis of C‐Vinyl Glycosides via Palladium‐Catalyzed C−H Glycosylation of Alkenes

“…Gong reported a nickel‐catalyzed reductive coupling of glycosyl bromides and vinyl chlorides using zinc reductant [6b] . More recently, Liang reported a palladium‐catalyzed radical‐mediated Heck coupling of glycosyl bromides and aryl olefins under visible light irradiated conditions [6c] . Glycosyl radical intermediates were invoked in the all above reaction systems.…”

Blue light enhanced Heck arylation at room temperature applied to allenes

“…34 Moreover, visible-light Pd(0) catalysis was used for the radical cross-coupling of C(sp 3 )–H bonds with non-activated bromides, 35 in an intermolecular Nasaka–Heck reaction via the photoactivation of N–O bonds 36 and for the synthesis of C -glycoside styrenes. 37 In the above-mentioned transformations, a radical mechanism was generally hypothesised, involving a barrierless oxidative addition of the substrate ( e.g. alkyl halides) to a photoexcited Pd(0) complex.…”