Autocatalytic Cycles in a Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction.

This work describes the autocatalytic copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between tripropargylamine and 2-azidoethanol in the presence of Cu(II) salts. The product of this reaction, tris-(hydroxyethyltriazolylmethyl)amine (N(C3N3)3), accelerates the cycloaddition reaction (and thus its own production) by two mechanisms: (i) by coordinating Cu(II) and promoting its reduction to Cu(I) and (ii) by enhancing the catalytic reactivity of Cu(I) in the cycloaddition step. Because of the cooperation of these two processes, a rate enhancement of >400× is observed over the course of the reaction. The kinetic profile of the autocatalysis can be controlled by using different azides and alkynes or ligands (e.g., ammonia) for Cu(II). When carried out in a layer of 1% agarose gel, and initiated by ascorbic acid, this autocatalytic reaction generates an autocatalytic front. This system is prototypical of autocatalytic reactions where the formation of a product, which acts as a ligand for a catalytic metal ion, enhances the production and activity of the catalyst.

Nickel-Catalyzed Enantioselective Pyridone C-H Functionalizations Enabled by a Bulky N-Heterocyclic Carbene Ligand.

Annulated pyridones are an important scaffold found in many biologically active compounds. A Ni(0)-catalyzed C-H functionalization of 2- and 4-pyridones is disclosed, providing access to annulated pyridones via enantioselective intramolecular olefin hydroarylation. Key to the success of the transformation was the development of a sterically hindered and tunable N-heterocyclic carbene ligand resembling a chiral version of IPr. This ligand allows for mild reaction temperatures, and leads to the annulated pyridones in excellent yields and enantioselectivities.

1,3-syn-Diaxial Repulsion of Typical Protecting Groups Used in Carbohydrate Chemistry in 3-O-Substituted Derivatives of Isopropyl d-Idopyranosides.

The strength of 1,3-syn-diaxial repulsion was evaluated for main types of protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate chemistry. As molecular probes for this study, derivatives of isopropyl 2-O-benzyl-4,6-O-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and tert-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from p-methoxyphenyl d-galactopyranoside. The equilibrium between OS2 and 4C1 conformations in these compounds was investigated using 3JH,H and 3JC,H coupling constants that were determined from 1D 1H NMR and 2D J-resolved HMBC spectra in various solvents. The analysis of the corresponding coupling constants calculated using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers in the equilibrium revealed the highest repulsion between the 3-allyloxy group and the isopropoxy aglycon and its dependence on the solvent polarity. Differences in the conformational behavior of 3-O-allyl and 3-O-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-syn-diaxial repulsion. 3-O-TBDPS derivative existed mainly in 4C1 conformation. The attenuation of the 1,3-syn-diaxial repulsive interaction indicates that TBDPS has stereoelectronic properties that may have significance in context of fixing unnatural pyranoside conformation with the help of silyl groups but have been disregarded until now.