Synthesis of 2,3-Dihydropyrroles by Rhodium(II)-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles: Diversity Generation by One-Pot Methodologies.

A versatile one-pot strategy for the generation of compounds of synthetic interest has been presented, promoting the development of practical processes. First, the transannulation of N-sulfonyltriazoles through alkenes and rhodium catalysis was described, giving 2,3-dihydropyrroles in 13-76% yield. As contributions of the strategy, the evaluation of alkenes with different properties, and the use of only drops of solvent (0.40 M) was highlighted. In addition, we described a methodology for the modulation of the N-sulfonyltriazoles, to obtain selectively cyclopropyl tosylimines or 2,3-dihydropyrroles. For the latter products, neat conditions were also included. Finally, the potential of the methodology was demonstrated by the synthesis of six structurally different analogues starting from the same substrates and late-stage transformation of bioactive molecules. These compounds were generated in 38-63% yield, after two or more conversion steps carried out in the same reaction vessel.

Synthesis of propargylamines via the A3 multicomponent reaction and their biological evaluation as potential anticancer agents.

Propargylamines have gained importance in the area of anticancer research. We synthesized 1-substituted propargylic tertiary amines using the A3-coupling as the key step. Both, solution and solid-phase protocols, were used to provide a library of 1-substituted propargylic tertiary amines with interesting structural diversity. The triple negative breast cancer subtype is the most aggressive and it lacks effective therapeutic options, while pancreatic cancer is one of the neoplasms with worse prognosis and limited therapeutic possibilities. The development of tumor-selective drugs has always been a major challenge in cancer treatment. From our library, two propargylamines displayed a high degree of cytotoxic selectivity. These levels of selectivity give a very interesting perspective for further development of 1-substituted propargylic tertiary amines as new potential chemotherapeutic antitumor agents.

Design of a Selective Ring-Closing Enyne Metathesis-Reduction for the Generation of Different Synthetic Scaffolds.

A tandem process of ring-closing enyne metathesis (RCEYM)-reduction using modern ruthenium catalysts and a hydrogen donor is described. This straightforward methodology is useful for C(sp3) generation under mild reaction conditions. Variables such as solvent, catalyst, hydride source, and temperature were adjusted toward the exclusive formation of different products.