Pd-catalyzed regio-, diastereo- and enantioselective cross-coupling reactions of dihydrofurans

The objective of this thesis was the development of new enantioselective intermolecular Pd-catalyzed cross-coupling transformations using 2,3-dihydrofuran derivatives and readily available electrophiles. In Chapter 2 the arylation of 5-alkyl-2,3-dihydrofurans is presented. The well established complementary reactivity of homo and heterotopic bidentate ligands in the Heck reaction allowed us to develop a single set of experimental reaction conditions. The use of a chiral (P,P) or (P,N) ligand afforded the corresponding 2-alkyl-2-aryl-2,3-dihydrofurans or 2-alkyl-2-aryl-2,5-dihydrofurans in good yield and high levels of regio- and enantiocontrol. In Chapter 3 and 4 the carboetherification and carboamination of 2,3-dihydrofuran derivatives by 2-bromophenol and mesyl protected 2-bromoanilines are disclosed. These fully intermolecular heterocarbofunctionalization methodologies give direct access to the highly valuable tetrahydrofurobenzofuran and tetrahydrofurofuroindoline scaffolds. In Chapter 5, the isolation and characterization of reactive intermediates allowed us to rationalize the factors that govern the regioselectivity of the arylation in these new transformations