Shaohua Xiang

Direct C-Glycosylation of Organotrifluoroborates with Glycosyl Fluorides and Its Application to the Total Synthesis of (+)-Varitriol

A mild, stereoselective, and quick approach to accessing alkynyl and alkenyl C-glycosides via BF(3)·Et(2)O promoted coupling of organotrifluoroborates and glycosyl fluorides is reported. The application of this method was further demonstrated by the concise and efficient total synthesis of (+)-varitriol in only seven steps.

Practical Route to 2-Quinolinones via a Pd-Catalyzed C–H Bond Activation/C–C Bond Formation/Cyclization Cascade Reaction

Quinolinone derivatives were constructed via a Pd-catalyzed C-H bond activation/C-C bond formation/cyclization cascade process with simple anilines as the substrates. This finding provides a practical procedure for the synthesis of quinolinone-containing alkaloids and drug molecules. The utility of this method was demonstrated by a formal synthesis of Tipifarnib.

Stereoselective β‐C‐Glycosylation by a Palladium‐Catalyzed Decarboxylative Allylation: Formal Synthesis of Aspergillide A

The efficient stereoselective construction of glycosidic linkages is indubitably a principal focus in carbohydrate chemistry because it is necessary for the construction of natural glycoconjugates. Among the wide variety of glycosylation methods, the Ferrier reaction has received considerable attention as it provides convenient and direct access to 2,3unsaturated glycosides from glycals. However, the stringent requirement of glycosyl acceptors generally confines the reaction to specific nucleophiles with strong reactivity and the utilization of stoichiometric amounts of a Lewis acid is inevitable in some cases. In addition, the dominant anomeric effect leads to the stereoselective generation of a-glycosides for Ferrier-type O-glycosylation and therefore accents the rigidity of the reaction. On the other hand, most results from Ferrier C-glycosylation reactions remain mediocre as only moderate a-selectivity has been achieved. The pursuit of high b-selectivity is also extremely challenging and judging from the lack of substantial reports, the barriers surrounding this problem has not been solved. [Scheme 1, Eq. (1)]. Consequently, the combination of limitations surrounding the Ferrier reaction prompted researchers to develop other methods to synthesize 2,3-unsaturated glycosides in exclusive selectivity, especially b-selectivity. Recent demonstrations on the efficiency of palladiumcatalyzed coupling reactions have stimulated considerable interest in applying this strategy to carbohydrates, particularly for the synthesis of 2,3-unsaturated glycosides. One of the successful and prominent examples is the Heck-type glycosylation of glycals with arylboronic acids or aryl halides by transition-metal insertion and reductive elimination [Scheme 1, Eq. (2)]. The allylic feature of glycals also encouraged chemists to pursue the applicability of palladium-catalyzed allylic alkylation in glycosylation reactions [Scheme 1, Eq. (3)]. However, the formation of Pd p-allyl species in glycal systems has long been recognized as tedious and difficult. To overcome this challenge, the more activated pyranone system was generated and additional activators were employed. Following the removal of this hurdle, great strides were made in decarboxylative allylation (DcA). 10] In particular, intramolecular decarboxylative allylation has developed into an area of great potential among the transition-metal-catalyzed decarboxylative coupling reactions which have drawn considerable attention in the area of C C bond formation. The Tunge, Trost, and Stoltz groups, for instance, have reported a series of catalytic decarboxylative allylation and benzylation reactions. Inspired by these reports, we envisioned that the palladiumcatalyzed decarboxylation of the C-3 ester of glycal would be helpful in the formation of a Pd p-allyl intermediate which might accomplish the desired C-glycosylation with high stereoselectivity [Scheme 1, Eq. (4)]. In a continuation of our work on developing efficient glycosylation methods, we report herein on a palladium-catalyzed stereoand regioselective C-glycosylation by means of intramolecular decarboxylative coupling. In initial studies, the decarboxylative coupling reaction of compound 1a was carried out in the presence of a catalytic amount of [Pd(PPh3)4] in DMF at 80 8C for 12 h. To our delight, the regiospecific coupling product 2a was obtained in 50% yield with a b/a ratio of 6:1 (Table 1, entry 1). To improve the yield and selectivity, various Pd catalysts were screened with the 1,2-bis(diphenylphosphino)ethane (DPPE) ligand in DMF (Table 1, entries 2–4). We found that the reaction catalyzed by Pd(OAc)2 gave better yield and Scheme 1. Various types of glycosylation.

Reversing the Stereoselectivity of a Palladium‐Catalyzed O‐Glycosylation through an Inner‐Sphere or Outer‐Sphere Pathway

An efficient and concise method for the construction of various O-glycosidic bonds by a palladium-catalyzed reaction with a 3-O-picoloyl glucal has been developed. The stereochemistry of the anomeric center derives from either an inner-sphere or outer-sphere pathway. Harder nucleophiles, such as aliphatic alcohols and sodium phenoxides give β-products, and α products result from using softer nucleophiles, such as phenol.

β-Type Glycosidic Bond Formation by Palladium-Catalyzed Decarboxylative Allylation

Decarboxylative allylation of glycals: A β-type glycosidic bond has been constructed in high regio- and stereoselectivity by means of a palladium-catalyzed decarboxylative O-glycosylation. Various kinds of glycals with different protecting groups have been examined for this reaction to afford a diverse set of glycosylated products, including phenolic O-glycosides, thiophenolic S-glycoside, aliphatic O-glycosides, and disaccharides with excellent β-selectivity and reasonable to excellent yields.

One-pot synthesis of β-N-glycosyl imidazole analogues via a palladium-catalysed decarboxylative allylation

A concise and highly efficient strategy for the synthesis of N-glycosyl imidazole analogues is reported. This reaction is based on a palladium catalysed decarboxylative allylation and three steps, namely, carbamation, decarboxylation and allylation are involved. All the substrates can afford the desired products with excellent yields and selectivities.

Stereocontrolled O-Glycosylation with Palladium-Catalyzed Decarboxylative Allylation

The Pd-π-allyl intermediate in an electron-rich glycal system with poor reactivity is employed as an efficient glycosyl donor. Starting from glucal derived carbonate, various O-glycosides were formed via a palladium-catalyzed reaction through a tandem decarboxylation, proton abstraction, and nucleophilic addition, in good yields with excellent selectivity. Iterative glycosylation with the same strategy may provide an access to complex oligosaccharides.

Palladium-catalyzed glycosylation: novel synthetic approach to diverse N-heterocyclic glycosides.

An efficient and highly stereoselective method for the construction of N-heterocyclic glycosides is reported. This method is based on a palladium-catalyzed allylation which proceeded to provide N-heterocyclic glycosyl compounds in good-to-excellent yields with β- or α-selectivity. Various N-nucleophiles were examined for this reaction and selected N-glycosyl isatin substrates were further elaborated to bis-indole sugars which have potential as antiproliferative drugs.

Palladium-Catalyzed Decarboxylative Allylation/Wittig Reaction: Substrate-Controlled Synthesis of C-Vinyl Glycosides

A palladium-catalyzed one-pot Tsuji-Trost type decarboxylative allylation/Wittig reaction has been developed to synthesize C-vinyl glycosides. Screening of various aldehydes led to formation of β,(E)-selective C-vinyl glycosides with pyridyl group containing aldehydes and β,(Z)-selective C-vinyl glycosides with nonpyridyl aldehydes. A plausible mechanism is proposed based on the coordination effect of the aldehydes.