Enantioselective Oxy‐Heck–Matsuda Arylations: Expeditious Synthesis of Dihydrobenzofuran Systems and Total Synthesis of the Neolignan (−)‐Conocarpan

This work discloses the first examples of an effective enantioselective oxy‐Heck–Matsuda reaction using a variety of styrenic olefins to generate chiral dihydrobenzofurans. The reaction proceeds in moderate to good yields, with high trans diastereoselectivity (up to 20:1) in enantioselectivities up to 90:10 using the N,N‐ligand pyrimidine‐bisoxazoline (PyriBox). The oxy‐Heck–Matsuda reactions were carried out under mild conditions and rather low catalyst loadings. The feasibility and practicality of the process is demonstrated by a concise total synthesis of the neolignan (−)‐conocarpan. X‐ray diffraction of an advanced brominated intermediate in the route to (−)‐conocarpan has allowed the unequivocal assignment of the absolute stereochemistry of the oxy‐Heck–Matsuda aryldihydrobenzofuran products. A rationale for the mechanism operating in these enantioselective oxy‐Heck–Matsuda reactions is also presented. magnified image