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In this work we have assessed reactions of N6-([1,1’-biaryl]-2-yl)adenine nucleosides with Pd(OAc)2 and PhI(OAc)2, via a PdII/PdIV redox cycle. The substrates are readily obtained by Pd/Xantphos-catalyzed reaction of adenine nucleosides with 2-bromo-1,1’-biaryls. In PhMe, the N6-biarylyl nucleosides gave C6-carbazolyl nucleoside analogues by C–N bond formation with the exocyclic N6 nitrogen atom. In the solvent screening for the Pd-catalyzed reactions, an uncatalyzed process was found to be operational. It was observed that the carbazolyl products could also be obtained in the absence of a metal catalyst by reaction with PhI(OAc)2 in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Thus, under Pd catalysis and in HFIP, reactions proceed to provide carbazolyl nucleoside analogues, with some differences. If reactions of N6-biarylyl nucleoside substrates were conducted in MeCN, formation of aryl benzimidazopurinyl nucleoside derivatives was observed in many cases by C–N bond formation with the N1 ring nitrogen atom of the purine (carbazole and benzimidazole isomers are readily separated by chromatography). Whereas PdII/PdIV redox is responsible for carbazole formation under the metal-catalyzed conditions, in HFIP and MeCN radical cations and/or nitrenium ions can be intermediates. An extensive set of radical inhibition experiments was conducted and the data are presented.

in Wiley Online Library (wileyonlinelibrary.com).C(sp)-C(sp2) bond formation via Sonogashira cross-coupling reactions on 6-halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-ones with appropriate alkynes was explored. Optimization of reaction conditions with various catalysts, ligands, bases, and solvents was conducted. The combination of PdCl 2 (MeCN) 2 with X-Phos proved to be the best metal-ligand system for this conversion in the presence of triethylamine (Et 3 N) in tetrahydrofuran at room temperature for iodosubstrates, at 80°C for the bromosubstrates in 8 h, and also for the chlorosubstrates in 16 h. We also demonstrated synthesis of a successful diversity-oriented synthesis library of highly functionalized quinazolinones via Cu-free Sonogashira coupling of diverse aryl halides and azido-alkyne ("click") ligation reactions with substituted azides. The library exhibited significant antimicrobial activity when screened against several microorganisms.

What prompted you to investigate this topic?Reactions of nucleosides are alwaysf ull of surprises and one can learnal ot from their reactivities. Novel nucleoside-based structures, obtainedv ia contemporary methods, can be very valuableb ecause of their importance in diverse areas, from biological probes to potentialpharmaceutical entities.What are the main challengesi nthe broad area of your research?Precursors for our work are not trivial compoundsb ecause they possess multiple coordinatinga toms and are relatively sensitive. In addition, in many instances, substrates neededf or our studies have to be prepared from generally expensive commercial materials, often requiring the development of new methods. Does the research open other avenues that you would like to investigate?Indeed!T he utilities of hypervalent iodine reagents, fluorinated solvents and catalysis chemistry pose intriguing new questions, not only for nucleoside modifications, but also in ab roader context.The front cover artwork for Issue 21/2017 is provided by the Lakshman Group at The City Collegeo fN ew York (USA). The image shows the beautifully delicate architecture of Hawa Mahal, in Jaipur,a sas ymbol of the delicate balance of various factors in the describedC ÀNb ondf ormation of N 6 -([1,1'-biaryl]-2-yl)adenine nucleosides promoted by PhI(OAc) 2 under both Pd-mediated and uncatalyzed reaction conditions, which ultimately leads to relatively complex products tructures.

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