Expanding the Chemical Space of 1,2-Difunctionalized Cyclobutanes.

An efficient approach to the synthesis of previously unavailable or hardly accessible 1,2-difunctionalized cyclobutanes (mostly with NH2/NHBoc, OH, SH, or SO2F groups attached to the carbocycle either directly or via a CH2 unit) relying on the divergent strategy is described. This class of compounds provides sp3-enriched and conformationally restricted building blocks that are of special demand for medicinal chemistry. The target compounds were prepared not only as pure racemic (±)-cis- and (±)-trans-diastereomers but in some cases also as single enantiomers. The developed procedures are readily scaled up and allow obtaining the target compounds on an up to hundred-gram scale. On the basis of the results of 20 X-ray diffraction experiments, structural characterization of the 1,2-difunctionalized cyclobutane core was performed using the extended Cremer-Pople puckering parameters and exit vector (EVP) plots.

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.

Reactions of 3-Arylisocoumarins with N-Nucleophiles - A Route to Novel Azaheterocycles.

This review highlights the promising science that has arisen from the synthesis of novel azaheterocycles from isocoumarins. Specific topics include their synthesis and biological activity. Isocoumarins (1H-isochromen-1-ones) are promising synthons, in particular due to the presence of a deoxybenzoin fragment which opens up wide possibilities for synthetic transformations. The deoxybenzoin cycle is highly susceptible to the action of various nucleophilic agents; its oxygen atom participates in recyclization reactions under the action of N-nucleophiles where it is replaced by a nitrogen atom, making it possible to obtain isoquinolones via a reaction with ammonia, primary amines, hydroxylamine and benzodiazepinones via a reaction with hydrazine. We systematize literature data, including patents (about 60 publications in all), demonstrate the routes of 3- arylisocoumarins modification under the action of N-nucleophiles - ammonia and primary amines, diamines, secondary amines, (het)arylamines, hydroxylamine, and hydrazines, and discuss the practical importance of these studies for medicinal chemistry.