<i>p</i>‑Chlorobenzyl Ether: A <i>p</i>‑Methoxybenzyl Ether in Disguise

In the chemistry of polyfunctionalized organic compounds, protecting groups that can undergo mild and selective cleavage while still being stable during the entire synthetic sequence are often required. In this work, we present a straightforward conversion of the robust <i>p</i>-chlorobenzyl ether into the more labile and well-described <i>p</i>-methoxybenzyl ether using palladium catalysis. This reaction was demonstrated to be high yielding and compatible with a wide range of functionalities, thereby providing a useful supplement to the conventional ether protecting groups

Effect of 2‑<i>O</i>‑Benzoyl para-Substituents on Glycosylation Rates

From a series of competition experiments, we have explored the degree to which various para-substituents (CN, Br, H, OMe, pyrrolidino) of a 2-<i>O</i>-benzoyl functionalized glucosyl donor of the thioglycoside type affect the rate of glycosylation under <i>N</i>-iodosuccinimide/triflic acid activation. As expected, electron-withdrawing groups were found to decrease the rate of glycosylation, whereas electron-donating groups resulted in the opposite outcome, underscoring the influence on the reaction rate exerted by a participating group. On this basis, a Hammett linear free-energy relationship was established (<i>R</i>² = 0.979, ρ = 0.6), offering fundamental insight into the magnitude of anchimeric assistance in glycosylation chemistry

Remote Electronic Effects by Ether Protecting Groups Fine-Tune Glycosyl Donor Reactivity

It was established that <i>para</i>-substituted benzyl ether protecting groups affect the reactivity of glycosyl donors of the thioglycoside type with the <i>N</i>-iodosuccinimide/triflic acid promoter system. Having electron donating <i>p</i>-methoxybenzyl ether (PMB) groups increased the reactivity of the donor in comparison to having electron withdrawing <i>p</i>-chloro (PClB) or <i>p</i>-cyanobenzyl ether (PCNB) protecting groups, which decreased the reactivity of the glycosyl donor relative to the parent benzyl ether (Bn) protected glycosyl donor. These findings were used to perform the first armed-disarmed coupling between two benzylated glucosyl donors by tuning their reactivity. In addition, the present work describes a highly efficient palladium catalyzed multiple cyanation and methoxylation of <i>p</i>-chlorobenzyl protected thioglycosides. The results of this paper regarding both the different electron withdrawing properties of various benzyl ethers and the efficient and multiple protecting group transformations are applicable in general organic chemistry and not restricted to carbohydrate chemistry

3‑(Dimethylamino)-1-propylamine: A Cheap and Versatile Reagent for Removal of Byproducts in Carbohydrate Chemistry

Inexpensive 3-(dimethylamino)-1-propylamine (DMAPA) was found to be effective in anomeric deacylation reactions giving 1-<i>O</i> deprotected sugars in high yield as precursors for the formation of imidate glycosyl donors. DMAPA was also found to be useful for removing excess reagents such as benzoyl chloride, tosyl chloride, and 2,2,2-trifluoro-<i>N</i>-phenylacetimidoyl chloride. The deacylation reaction could be conducted in moist THF and did not require chromatographic purification since an acidic wash was sufficient to remove excess reagent and the formed byproduct

Vinyl Grignard-Mediated Stereoselective Carbocyclization of Lactone Acetals

A novel Ferrier-type carbocyclization is reported. It involves a carbohydrate-derived lactone acetal synthesized from methyl α-d-glucopyranoside, which upon treatment with excess vinylmagnesium bromide provides a highly substituted carbocyclic product as a single stereoisomer. The yield is greatly increased when <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylenediamine is added to the reaction mixture. Optimized reaction conditions have been applied to lactone acetals derived from other carbohydrates. Based on the obtained results, a possible reaction mechanism has been proposed. Furthermore, scalability of the reaction up to 15 g scale and derivatization of the carbocyclic product has been demonstrated, including the formation of a rare <i>trans</i>-bicyclo­[4.3.0]­nonene scaffold via a ring-closing metathesis. The structure of this and all carbocyclic products were confirmed by X-ray crystallographic analysis

A Protocol for Metal Triflate Catalyzed Direct Glycosylations with GalNAc 1‑OPiv Donors

Herein we report on the development of novel glycosylation methodology for the concise synthesis of naturally occurring glycoconjugate motifs containing <i>N</i>‑acetylgalactosamine (GalNAc) from the cheaper and commercially available <i>N</i>‑acetylglucosamine (GlcNAc). The stereoselective glycosylations proceed with catalytic amounts of a promoter and without the need for <i>N</i>-protection other than the biologically relevant <i>N</i>-acetyl group. Among the catalysts explored, both Bi­(OTf)₃ and Fe­(OTf)₃ were found to be highly active Lewis acids for this reaction. It was also found that other less reactive metal triflates such as those of Cu­(II) and Yb­(III) can be beneficial in glycosylation reactions on more demanding glycosyl acceptors. We have furthermore demonstrated that it is possible to control the anomeric stereoselectivity in the glycosylation via postglycosylation in situ anomerization to obtain good yields of α-galactosides. The present protocol was used to prepare important naturally occurring carbohydrate motifs, including a trisaccharide fragment of the naturally occurring marine sponge clarhamnoside

Aarhus Sensor Green: A Fluorescent Probe for Singlet Oxygen

A tetrafluoro-substituted fluorescein derivative covalently linked to a 9,10-diphenyl anthracene moiety has been synthesized, and its photophysical properties have been characterized. This compound, denoted Aarhus Sensor Green (ASG), has distinct advantages for use as a fluorescent probe for singlet molecular oxygen, O₂(a¹Δ_g). In the least, ASG overcomes several limitations inherent to the use of the related commercially available product called Singlet Oxygen Sensor Green (SOSG). The functional behavior of both ASG and SOSG derives from the fact that these weakly fluorescent compounds rapidly react with singlet oxygen via a _π2 + _π4 cycloaddition to irreversibly yield a highly fluorescent endoperoxide. The principal advantage of ASG over SOSG is that, at physiological pH values, both ASG and the ASG endoperoxide (ASG-EP) do not themselves photosensitize the production of singlet oxygen. As such, ASG better fits the requirement of being a benign probe. Although ASG readily enters a mammalian cell (i.e., HeLa) and responds to the presence of intracellular singlet oxygen, its behavior in this arguably complicated environment requires further investigation

Designer Titania-Supported Au–Pd Nanoparticles for Efficient Photocatalytic Hydrogen Production

Photocatalytic hydrogen evolution may provide one of the solutions to the shift to a sustainable energy society, but the quantum efficiency of the process still needs to be improved. Precise control of the composition and structure of the metal nanoparticle cocatalysts is essential, and we show that fine-tuning the Au–Pd nanoparticle structure modifies the electronic properties of the cocatalyst significantly. Specifically, Pd_shell–Au_core nanoparticles immobilized on TiO₂ exhibit extremely high quantum efficiencies for H₂ production using a wide range of alcohols, implying that chemical byproducts from the biorefinery industry can be used as feedstocks. In addition, the excellent recyclability of our photocatalyst material indicates a high potential in industrial applications. We demonstrate that this particular elemental segregation provides optimal positioning of the unoccupied d-orbital states, which results in an enhanced utilization of the photoexcited electrons in redox reactions. We consider that the enhanced activity observed on TiO₂ is generic in nature and can be transferred to other narrow band gap semiconductor supports for visible light photocatalysis