Trapping of thermally generated ortho- and para-quinone methides by imidazoles and pyrazoles: a simple route to green synthesis of benzopyrone-azole hybrids and their evaluation as α-glucosidase inhibitors.

An efficient green approach for the trapping of in situ generated ortho-and para-quinone methide intermediates by imidazoles and pyrazoles has been developed. A wide range of quinone methide precursors based on simple phenols are compatible with the experimental protocol under mild thermal conditions. This methodology was demonstrated to be suitable for the synthesis of methylene-linked benzopyrone-azole hybrids using naturally occurring coumarin and chromone Mannich bases. In most cases, the products were isolated in good to excellent yields without chromatographic purification. In vitro studies showed that some of the synthesized compounds exhibit inhibitory activity towards α-glucosidase.

Rapid synthetic approaches to libraries of diversified 1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones and 3-(2-hydroxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-ones.

An efficient and practical synthetic procedure for libraries of diversified 1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones using a multicomponent process is presented. A convenient synthetic procedure for obtaining functionalized 3-(2-hydroxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-ones via ring-opening strategy has also been developed. This protocol was found to be compatible with a wide range of substituents and paves the way for the practical synthesis of title compounds with a broad range of substituents under mild condition. The products can be easily isolated by crystallization without the use of chromatography.

Third Generation Buchwald Precatalysts with XPhos and RuPhos: Multigram Scale Synthesis, Solvent-Dependent Isomerization of XPhos Pd G3 and Quality Control by 1H- and 31P-NMR Spectroscopy.

The third generation Buchwald precatalysts Pd(ABP)(Phos)(OMs) (also known as Phos Pd G3)) with XPhos and RuPhos were prepared in multigram scale by a modified procedure (ABP = fragment of C-deprotonated 2-aminobiphenyl, XPhos = 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, RuPhos = 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, OMs- = CH3SO3-). The 1H- and 31P-NMR spectra of the title complexes and some impurities, measured by various 1D and 2D techniques, were analyzed in detail. The solvent-dependent isomerization of Pd(ABP)(XPhos)(OMs) was studied by NMR, and the X-ray structures of two isomers were determined. The impurities in precatalysts, such as Pd(ABP)(HABP)(OMs) (HABP-neutral 2-aminobiphenyl coordinated to Pd2+ in N-monodentate mode) and PdCl2(XPhos)2, were identified and characterized by single crystal X-ray diffraction. A simple method for the quick quality control (QC) of the precatalysts, suitable for routine use, was proposed. The method was based on the assessment of the impurity content on the basis of the 1H-NMR spectra analysis.

Photochemical [2 + 2] Cycloaddition of Alkenyl Boronic Derivatives: An Entry into 3-Azabicyclo[3.2.0]heptane Scaffold.

The synthesis of 3-azabicyclo[3.2.0]heptyl boropinacolates and trifluoroborates via the [2 + 2] photocycloaddition of the corresponding alkenyl boronic derivatives and maleimides or maleic anhydride is described. Optimization of the reaction conditions (i.e., wavelength, concentration of the reagents, photosensitizer) was carried out, and the scope and limitations of the method were studied. Alkenyl boronic acid pinacolates were found to be more suitable for the [2 + 2] cycloaddition, providing better reaction outcomes compared to the trifluoroborates. The utility of this approach was shown by the preparation of bi- and trifunctional building blocks (21 examples), which could be easily synthesized on up to 60 g scale. These cycloadducts provide a convenient entry into the 3-azabicyclo[3.2.0]heptane scaffold through the C-C coupling or oxidative deborylation reactions.