Enantioselective Synthesis of Cyclopenta[b]benzochalcogenanes

Flavaglins are a class of natural products characterized by a cyclopenta[b]benzofuran scaffold. They have already shown broad potential for pharmacological applications, including anticancer and antiviral activity. Beraprost was the first approved drug containing a cyclopenta[b]benzofuran.
However, literature on higher chalcogen variations in this cyclic system is limited, with only a few sulfurcontaining examples reported and no selenium or tellurium analogues described. Therefore, our objective is to develop methodologies to access cyclopenta[b]benzocalcogenane derivatives.
Our current proposal is based on the methodology described by Jørgensen, starting from orthosubstituted cinnamaldehydes which is subjected to a base-catalyzed asymmetric Michael addition followed by a NHC-catalyzed benzoin condensation, leading to the desired tricyclic product after a double cyclization.
The synthetic precursor was prepared via a Wittig reaction on 2-bromobenzaldehyde, followed by acetalization. A Halogen-Magnesium exchange, subsequent reaction with an elemental chalcogen and a SN2 displacement on α-bromoacetophenones should yield the desired intermediates. This step is currently on going.