The Nazarov reaction

The Nazarov reaction involving heterocyclic compounds is the subject of a comprehensive study in our laboratory, which include also theoretical DFT calculation aimed at understanding facets such as the role of the heteroatom (N, S, O) on the reaction rate and the stereoselectivity (torquoselectivity) in the cyclopentannulation. We have developed two convenient methodologies for the preparation of heterocyclic dienones and dienone equivalents based on carbonylative and non carbonylative coupling of various boronic acids and esters with vinyl triflates (or phosphates) from lactams, lactones and thiolactones, as well as Lewis acid-catalyzed conditions for the electrocyclization process. Further studies on different approaches to get the Nazarov products are currently going on in my lab (see the "Gold-catalyzed syntheses" section).

 


 

The structural motif obtained by the Nazarov reaction recurs in several natural and biologically active compounds. We have for example carried out the formal enantioselective synthesis of roseophilin by exploiting the highly stereocontrolled cyclization of dienones in which one of the double bonds is embedded in a N-heterocyclic ring. By the same approach, and through a gold-catalyzed reaction, we have also carried out the first synthesis of bruceolline H and bruceolline I. Also, novel strigolactone analogues have been prepared by this methodology.