Oxyarylation and oxidative cycloaddition of Phenols on oxygenated 2H-chromens. Targeting the synthesis of bioactive natural pterocarpans and derivatives

Pterocarpan 1a was isolated at the UFCe and showed antiproliferative effect on cancer cell lines.[1] A series of 5-carba-pterocarpans (2a,b), isosters of 1, was synthesized by our group.[2] Unfortunately, 2a was less active than 1a but 2b showed a strong and selective antiproliferative effect in SF-295 cells (Glioblastome).
The first approach studied for the synthesis of 1 involved an oxyarylation of 2H-chromens (3) with o-iodophenols (4a,b)3 (Figure 2). Better yields were obtained for o-Iodo-phenol bearing aldehydes at the aromatic (~50-60%).Natural product 1a and some analogues were obtained in lower yields (~25%).
The second synthetic approach, an oxidative cycloadition of 2H-chromens (3) with phenols 5c,d (Figure 3), was studied with available oxygenated 2H-chromens (3). These reactions led to pterocarpans core skeleton in just one step (1c,d), expanding the scope of the original publication.[4] Late functionalization on 1c,d to introduce a new phenol or alcoxi group at the D-ring is under investigation.