The main goal of this thesis was the development of new stereo- and enantio-selective catalytic methodologies taking advantage of the intrinsic reactivity of functionalized cyclic carbonates and related heterocycles (e.g., nonstrained lactones) and use them as starting materials for the synthesis of more complex stereodefined organic targets, by means of transition-metal (TM) catalysis (specifically Pd and Cu). Three main research projects are collected in this thesis:
Firstly, a new methodology aiming at the stereoselective synthesis of highly functionalized (Z)-configured allylic thioethers and their corresponding sulfones has been developed. This protocol based on a Pd-catalyzed thiolation of vinyl cyclic carbonate substrates features good yields and high (Z)-selectivity.
Secondly, we targeted the enantioselective construction of tertiary propargylic sulfones. These building blocks are of significant importance in organic synthesis and medicinal chemistry. The recently introduced alkyne-functionalized cyclic organic carbonates inspired us to pursue a Cu-catalyzed asymmetric propargylic sulfonylation reaction of these precursors by using versatile sulfinate salts. This practical method provided a new approach targeting the construction of sulfur-containing, tetrasubstituted carbon stereocenters featuring high enantioselectivity and wide functional group diversity. The applicability of the transformation was demonstrated by various functionalization reactions of the tertiary sulfone building blocks.
Finally, we discover a new protocol that enables the efficient assembly of biologically relevant gamma-amino acids bearing quaternary stereocenters. Notably, in this project, we took advantage of the catalytic formation of copper-allenylidene intermediates that can be intercepted by a series of amine nucleophiles in an enantioselective fashion allowing the ring-opening aminolysis of nonstrained, alkyne-substituted lactones.