Methodology and heterocycles

Methodological studies in heterocyclic chemistry

Access to bioactive molecules and/or natural products

Team leader: Professor Isabelle GILLAIZEAU

Dr. Pascal BOUYSSOU

 

The development of efficient methodologies to generate biologically relevant molecules constitutes an essential area to create libraries by varying functional groups, building blocks, stereochemistry and molecular frameworks in order to obtain molecular diversity. To this end, particular attention is paid to identify improved methods for heterocyclic synthesis focusing on two aspects: reaction economy and selectivity (chemo-, regio- and stereoselectivity) that call for the development of more efficient and also eco-friendly procedures.

 

Enamides : a valuable tool in organic synthesis …

 

Over the past decade, enamides have emerged as a relevant functional group that has been involved in a variety of new synthetic transformations including natural product and bioactive molecule syntheses. Enamides are stable enamine surrogates and provide key intermediates for the synthesis of small but complex nitrogen-containing compounds. The π-donating ability of the nitrogen atom renders enamides more electron-rich than simple alkenes and they afford a means of activating carbon-carbon double bonds, giving them both nucleophilic and electrophilic properties.

 

Among the available methodologies for the preparation of enamides or enecarbamates, the palladium catalyzed cross-coupling reaction of the corresponding enol ether appears as a very fruitful approach. We described a powerful methodology from lactam- and imide-derived vinyl phosphates which represent versatile intermediates for the preparation of original (N-, O-) heterocyclic compounds. This methodology has allowed us to prepare a range of original privileged heterocyclic structures (e.g. 1,4-dihydropyridines, 1,4-oxazines, 1,4-dihydropyrazines, benzodioxines, benzoxazines…).

 

Metal Catalyzed Regioselective Functionalization of Enamide …An access to molecular diversity ...

 

Recently, we focused our interest onto transition metal-catalyzed C-C bond formation via C-H bond functionalization. Suitable conditions (i.e. metal catalysis) for high control of regio- and chemoselectivity was studied.