Sulfinic acids and their salts have recently emerged as versatile coupling partners to efficiently access a wide variety of hetero- and carbocyclic compounds, under relatively mild conditions. Their growing importance is attributable to their dual capacity for acting as nucleophilic or electrophilic reagents. This report summarizes recent advances in the preparation and use of sulfinates in organic synthesis.

The synthesis and structure-activity relationships associated with a series of 1,1-diarylethylene tubulin polymerization inhibitors 3 and 4 are described. The key step for their preparation involves a palladium-catalyzed coupling of N-arylsulfonylhydrazones with aryl halides, thus providing flexible and convergent access to tri- and tetrasubstituted 1,1-diarylolefins 3 and 4 related to isocombretastatin A-4 (isoCA-4). These compounds have been evaluated for tubulin polymerization inhibitory activity as well as for cytotoxic activity. The most potent compounds are 1,1-diaryl-2-methoxyethylenes 4b, 4d and 4e having a trisubstituted double bond. They exhibited good antiproliferative activity against various human cancer cell lines (GI(50) = 8-80 nM). Compounds 4b and 4e strongly inhibited tubulin polymerization with IC(50) values of 2 and 3 μM, respectively, and induced cell cycle arrest in the G(2)/M phase in the K562 cell line. Docking studies in the colchicine binding site of tubulin allowed identification of residues most likely to interact with these inhibitors and explain their potent anti-tubulin activity.

Aromatic enynes can be transformed into arylnaphthalenes or benzofulvenes depending on the reaction conditions. Under gold(I) catalysis, exclusive or major 6-endo-dig cyclization took place leading to arylnaphthalenes. However, a catalytic system based on palladium iodide/1,3-bis(diphenylphosphino)propane, in the presence of cesium carbonate as a base was necessary to furnish exclusively 5-exo-dig cycli-zation pattern, regardless of the electronic effects of the substituents. In the latter transformation, a mechanistic study (kinetic isotopic effect, density functional theory) involving a C À H activation is suggested for the exclusive formation of benzofulvenes.

The use of sulfinic acids and their salts continue to be extensively developed in organic chemistry. This is attributable to their dual capacity for acting as nucleophilic or electrophilic reagents,...

We report the the copper(II) acetoacetonate [Cu(acac)2]/BINAP‐catalyzed synthesis of arylamines from N‐tosylhydrazones and anilines. A fine tuning of the reaction conditions was required to accomplish the cross‐coupling successfully, including the ligands effect and the addition of small amounts of water. The characteristic feature of this protocol is its functional group compatibility and its chemoselectivity when various aminophenol derivatives were used. Taking into consideration the interest for this copper‐reductive coupling in which no stoichiometric metal hydride reagent is employed, this can be considered as an alternative to the conventional reductive amination.magnified image

International audienceAn original formation of one C-N bond and one C-C bond on the same carbenic center has been developed. This approach involves a copper-catalyzed cross-coupling reaction between 2’-bromo-biaryl-N-tosylhydrazones and different amines leading to 9H-fluoren-9-amine derivatives. This reaction proceeds under mild conditions in glycerol, an inexpensive and environmentally friendly solvent without adding any external ligand

This report highlights the recent advances in direct C–H bond functionalization of 5,5- and 6,5-fused heterocycles containing at least two nitrogen atoms. Besides C–C bond formation, C–N, C–S, C–P, and C–Si bonds can also be created via a metal-catalyzed process. Some examples, where a C–H functionalization approach was applied for the synthesis of drug candidates, will be presented as well.1 Introduction2 C–H Functionalization Reactions of N-Containing Heterocycles2.1 Imidazo[1,2-a]pyridines2.2 Pyrrolo[1,2-a]pyrazines2.3 Imidazo[1,2-b]pyrazoles2.4 Imidazo[1,2-a]pyrimidines2.5 Imidazo[1,2-a]pyrazines and Imidazo[1,5-a]pyrazines2.6 Imidazo[1,2-b]pyridazines2.7 Imidazo[4,5-b]pyridines and Imidazo[4,5-c]pyridines2.8 Pyrazolo[3,4-b]pyridines2.9 Pyrazolo[1,5-a]pyrimidines2.10 Pyrrolo[2,3-d]pyrimidines and Pyrrolo[3,2-d]pyrimidines2.11 Imidazo[1,2-b][1,2,4]triazines2.12 Imidazo[1,2-b][1,2,4,5]tetrazines3 Outlook4 Conclusion

C2 direct alkynylation of 3H-imidazo[4,5-b]pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe2 or Cu(OAc)2), a phosphine ligand (DPEphos) and a base (LiOtBu) in 1,4-dioxane at 120 °C. This C-H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and gem-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3H-imidazo[4,5-b]pyridines, a valuable scaffold in drug design.