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We report a novel and highly stereoselective electro-2-deoxyglycosylation from glycals. This method features excellent stereoselectivity, scope, and functional-group tolerance. This process can also be applied to the modification of a wide range of natural products and drugs. Furthermore, a scalable synthesis of glycosylated podophyllotoxin and a one-pot trisaccharide synthesis through iterative electroglycosylations were achieved.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective preparation of the challenging β- C-glycosyl arenes by the anomerization of α- C-glycosides using HBF4 is also described. This protocol has a broad substrate scope and a wide functional-group tolerance. It can be used for the gram-scale preparation of 3-oxo- C-glycosides, which are versatile substrates for the preparation of many biologically important C-glycosides.

Stereo-controllable glycosylation reactions of 2,3-oxazolidinone protected glucosamine thioglycoside donor with different phenol acceptors based on preactivation protocol, are described. It was found that BF3·Et2O worked as α-directing additive, while TTBP acted as β-directing additive. Simply by altering additives, either α-aryl glycosides or β-aryl glycosides were achieved in a stereoselective manner. The additives were also applied to the stereoselective glycosylation reactions of 2,3-oxazolidinone protected galactosamine donor with phenol substrates.

A new approach for the synthesis of phenolic glycosides via aromatic O-glycosylation of 1,2-anhydrosugar and aryl boronic acids was disclosed. This method is characterized by the use of aryl boronic acid as the aryl source and produces phenolic glycosides in a stereoselective manner. This reaction provides an alternative approach to the synthesis of phenolic glycosides. It also represents a new application of aryl boronic acids as versatile reagents in organic synthesis.

A new "ring-opening-ring closure" strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α- or β-preferred aryl-C-Δ(2,3)-glycosides, respectively. Furthermore, β-D-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-D-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective manner.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

The multifaceted biological importance of carbohydrates has made them very popular targets in modern synthetic chemistry. Great progress has been made in stereoselective glycosylation methods and the construction of complex oligosaccharides. This Focus Review highlights the versatile applications of preactivation strategies in stereoselective glycosylation and oligosaccharide synthesis. Recent advances in synthetic methods, such as 4,6-O-benzylidene-acetal-directed β-mannosylation, the 1,2-cis-glycosylation mediated by a chiral auxiliary, the use of an oxazolidinone or carbonate protecting group, and glycosylation with participating additives, are described. Various examples of sequential glycosylation based on preactivation protocols for efficient oligosaccharide assembly are also summarized.

A mild and convenient transformation for the synthesis of nitro-polyols is described. The nitro-polyol derivatives were prepared either from 2-nitroglycals via a pyridine-promoted scission of the carbon–carbon double bond or from glycals via a sequential nitration–scission procedure. The generated nitro-polyols could undergo a stereoselective Michael addition reaction. The utility of the addition products was exemplified by the concise synthesis of (−)-hyacinthacine A1 and 7a-epi-(−)-hyacinthacine A1.

A new sialyl donor, N,N-dibenzyl-protected p-toluenethiosialoside, was synthesized and its sialylation reaction was investigated. This reaction proceeded in a preactivation manner and preferred to provide b-anomeric coupling products. The b-selectivity was rationalized based on the assumption that N,N-dibenzylamino group could serve as an oriented group to activate the hydroxyl group of acceptor from b-face.

Based on a pre-activation protocol, the stereoselectivity of oxazolidinone-protected amino sugar thioglycoside donors towards glycosylations can be controlled by additives. Either α- or β-selectivity could be obtained by changing additives. 2,4,6-Tri-tert-butylpyrimidine (TTBP) was the best β-directing additive, while thiophene worked as the best α-directing additive. The bifunctional additives such as tetrabutyl ammonium iodide (TBAI) afforded either α- or β-selectivity depending on the amount added. Poor α-­selectivity of some glycosylations without any additives was greatly improved by adding TBAI or thiophene.

A new sialyl donor, N , N -acetyl, benzoyl- O -perbenzoyl-protected p -toluenethiosialoside, was synthesized and its sialylation reaction was investigated. This reaction proceeded in dichloromethane and β anomeric selectivity was achieved when NIS–TfOH was used as promoter. This method may be employed to construct the unnatural β-linked sialosides.

Oxidative Heck-type C-glycosylations of glycals with various arylboronic acids using Pd(OAc)(2) as catalyst in the presence of oxidant were developed. The corresponding ketone, enol ether, and enone types of C-glycosides were predictably obtained with benzoquinone (BQ), Cu(OAc)(2)/O(2), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as oxidants, respectively. This method provides a simple, mild, and stereoselective synthesis of aryl 2-deoxy-C-glycosides.

Diverse 2,3-oxazolidinone protected 2-amino-2-deoxy- d -glucose thioglycosides were prepared and studied as glycosyl donors at low temperature by BSM/Tf2O pre-activation protocol before the addition of glycosyl acceptors. The stereochemistry outcomes of a series of glycosylations were investigated. Different stereoselectivities of the coupling reactions were obtained, arising from the different protecting groups in the oxazolidinone donors. 4,6-Di-O-benzyl-N-benzyl-oxazolidinone protected thioglycoside donor 1c underwent glycosylation with general β-anomeric selectivity and the stereoselectivity could be also affected by glycosylation conditions.

An efficient ‘one-pot’ approach to the synthesis of 1,6-dideoxy- N -alkylated nojirimycin derivatives in good yields and with high stereoselectivity was developed. It was found that the synthetic N -alkylated iminosugars showed inhibitory effects on the release of the cytokines IFN-γ and IL-4 from the mouse splenocytes. The preliminary structure–activity relationship was deduced from the activities of N -substituted iminosugars. Apart from the cytokine inhibitory activities, a series of glycosidase inhibitory activities were also examined. The present experimental data demonstrated that synthetic iminosugars might hold potential as immunosuppressive agents.

A new “ring-opening–ring closure” strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α- or β-preferred aryl-C-Δ2,3-glycosides, respectively. Furthermore, β-d-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-d-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective ma...

The multifaceted biological importance of carbohydrates has made them very popular targets in modern synthetic chemistry. Great progress has been made in stereoselective glycosylation methods and the construction of complex oligosaccharides. This Focus Review highlights the versatile applications of preactivation strategies in stereoselective glycosylation and oligosaccharide synthesis. Recent advances in synthetic methods, such as 4,6-O-benzylidene-acetal-directed β-mannosylation, the 1,2-cis-glycosylation mediated by a chiral auxiliary, the use of an oxazolidinone or carbonate protecting group, and glycosylation with participating additives, are described. Various examples of sequential glycosylation based on preactivation protocols for efficient oligosaccharide assembly are also summarized.

Catalytic or stoichiometric amounts of Lewis acids were found to be very effective α-directing additives in the stereoselective glycosylations of diverse 2,3-O-carbonate-protected glucose and galactose thioglycoside donors by preactivation protocol. The poor stereoselectivities of 4,6-di-O-acetyl-2,3-O-carbonate protected thioglycoside donors in glycosyl coupling reactions were greatly improved, and excellent α-stereoselectivities were achieved by the addition of 0.2 equiv of BF(3)·OEt(2). On the other hand, the β-selectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected thioglucoside donor toward glycosylations were reversed completely to the α-selectivities by the use of 1 equiv of SnCl(4), making the stereoselectivity controllable. Furthermore, the poor stereoselectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected thiogalactoside donor in glycosylations were also improved by using SnCl(4) as additive.

Saccharides are polyhydroxy compounds, and their synthesis requires complex protecting group manipulations. Protecting groups are usually used to temporarily mask a functional group which may interfere with a certain reaction, but protecting groups in carbohydrate chemistry do more than protecting groups usually do. Particularly, protecting groups can participate in reactions directly or indirectly, thus affecting the stereochemical outcomes, which is important for synthesis of oligosaccharides. Herein we present an overview of recent advances in protecting groups influencing stereoselectivity in glycosylation reactions, including participating protecting groups, and conformation-constraining protecting groups in general.

A facile, versatile and stereoselective synthesis of bicyclic polyhydroxylated alkaloids as castanospermine analogues is described. The synthetic route started from methyl pyranosides. The key steps involved a high-yielding expeditious one-pot tandem reaction from alkenes to N-substituted delta-lactams. The delta-lactams were stereoselectively vinylated to give the dienes, which were followed by the ring-closing metathesis to produce the cyclized products. The functional group transformations of the resulting bicyclic compounds furnished diverse polyhydroxylated alkaloids in good yields.

Oxidative Heck-type C-glycosylations of glycals with various arylboronic acids using Pd(OAc)2 as catalyst in the presence of oxidant were developed. The corresponding ketone, enol ether, and enone types of C-glycosides were predictably obtained with benzoquinone (BQ), Cu(OAc)2/O2, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as oxidants, respectively. This method provides a simple, mild, and stereoselective synthesis of aryl 2-deoxy-C-glycosides.

Under pre-activation glycosylation conditions, the 4,6-di-O-acetyl-N-acetyloxazolidinone protected donor afforded either excellent β- or α-stereoselectivity simply by means of the addition of hindered base TTBP or the absence of base, leading to the controllable stereochemistry of coupling reactions.

Under pre-activation glycosylation conditions, the 4,6-di-O-acetyl-N-acetyloxazolidinone protected donor afforded either excellent beta- or alpha-stereoselectivity simply by means of the addition of hindered base TTBP or the absence of base, leading to the controllable stereochemistry of coupling reactions.