Water-promoted Synthesis of Stereoselective Oxazoline-fused Saccharides and Construction for 1, 2-cis Glycosylamines of Multi-modifications of Polyhydroxyl groups

The multi-modifications of polyhydroxyl groups and the stereoselective formation of 1,2-cis glycosidic bonds are difficult in glycochemistry. Herein we disclosed a concise synthesis of the oxazoline-fused saccharides (oxazolinoses) from acetyl saccharides and benzonitriles under acidic conditions promoted by the stoichiometric water. The oxazolinoses can be easily converted into 1,2-cis glycosylamines with differentiated modifications at 2,3-positions on the saccharide ring in few steps and the 1-NH2 can further be simply transformed to the 1-OH. Oxazolinoses can also be directly used to synthesize complex chiral molecules such as schisandrins. Saccharides screening have shown that the oxazolinoses could be synthesized from various monosaccharides and oligosaccharides. Accordingly, 1-α- or 1-β-1,2-cis glycosylamines can be obtained from different oxazolinoses which are 1,2-cis stereoselectivity controlled by neighboring group participation. The density functional theory (DFT) calculations have revealed the origin of the stereoselectivity and the key role of water.

Revisiting the ‘Phenonium Phenomenon’: Regiodivergent Opening of Nonsymmetrical Phenonium Ions with Halide Nucleophiles

Formation of phenonium ions through anchimeric assistance (neighboring-group participation) of aryl rings has been known since 1949. Although these reactive intermediates have been studied extensively by physical organic chemists, their potential as control elements in synthesis is underutilized. Presented here are our laboratory’s recently reported first examples of regiodivergent openings of nonsymmetrical phenonium ions with chloride nucleophiles. The selectivity of these processes is under reagent control. The reactions are operationally simple and permit the stereospecific synthesis of complex chiral building blocks from readily accessible epoxide starting materials.1 Introduction2 Select Examples of Phenonium Ion Methodology3 Regiodivergent Opening of Nonsymmetrical Phenonium Ions4 Summary and Outlook

Characterization of Glycosyl Dioxolenium Ions and Their Role in Glycosylation Reactions

Controlling the chemical glycosylation reaction remains the major challenge in the synthesis of oligosaccharides. Though 1,2-<i>trans</i> glycosidic linkages can be installed using neighboring group participation, the construction of 1,2-<i>cis</i> linkages is difficult and has no general solution. Long-range participation (LRP) by distal acyl groups may steer the stereoselectivity, but contradictory results have been reported on the role and strength of this stereoelectronic effect. It has been exceedingly difficult to study the bridging dioxolenium ion intermediates because of their high reactivity and fleeting nature. Here we report an integrated approach, using infrared ion spectroscopy, DFT calculations and a systematic series of glycosylation reactions to probe these ions in detail. Our study reveals how distal acyl groups can play a decisive role in shaping the stereochemical outcome of a glycosylation reaction and opens new avenues to exploit these species in the assembly of oligosaccharides and glycoconjugates to fuel biological research

Characterization of Glycosyl Dioxolenium Ions and Their Role in Glycosylation Reactions

Controlling the chemical glycosylation reaction remains the major challenge in the synthesis of oligosaccharides. Though 1,2-<i>trans</i> glycosidic linkages can be installed using neighboring group participation, the construction of 1,2-<i>cis</i> linkages is difficult and has no general solution. Long-range participation (LRP) by distal acyl groups may steer the stereoselectivity, but contradictory results have been reported on the role and strength of this stereoelectronic effect. It has been exceedingly difficult to study the bridging dioxolenium ion intermediates because of their high reactivity and fleeting nature. Here we report an integrated approach, using infrared ion spectroscopy, DFT calculations and a systematic series of glycosylation reactions to probe these ions in detail. Our study reveals how distal acyl groups can play a decisive role in shaping the stereochemical outcome of a glycosylation reaction and opens new avenues to exploit these species in the assembly of oligosaccharides and glycoconjugates to fuel biological research

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

An iodine-mediated hydration reaction of alkynes serves as a green alternative to metal-catalyzed procedures. Previous work has shown that this method works well with terminal alkynes on keto-functionalized scaffolds, including 1,3-dicarbonyls and their heteroatom analogues. It was hypothesized that the reaction proceeds through a 5-exo-dig neighboring group participation (NGP) cyclization and an α-iodo intermediate. The work described herein probes the existence of the intermediate through NMR investigations and explores the scope of the hydration process with internal alkynes. The NMR experiments confirm the existence of the α-iodo intermediate, and methodology studies demonstrate that alkyl-capped, asymmetric, internal alkynes undergo a regiospecific hydration, also via the 5-exo-dig NGP pathway.