Synthesis of Furan-Annelated BINOL Derivatives: Acid-Catalyzed Cyclization Induces Partial Racemization

In this account, we describe the
synthesis of a series of BINOL-based
bis- and trisphosphoric acids 11d/e/f, which commonly feature an unusual phosphoric acid monoester
motif. This motif is generated by an acid-catalyzed 5-endo-dig cyclization of the 3-alkynyl-substituted BINOL
precursors to give the corresponding Furan-annelated derivatives,
followed by phosphorylation of the remaining phenolic alcohols. In
the cyclization reaction, we observed an unexpected partial racemization
in the bis- and tris-BINOL scaffolds, leading to mixtures of diastereomers
that were separated and characterized spectroscopically and by X‑ray
crystal structure analyses. The cyclization and racemization processes
were investigated both experimentally and by DFT-calculations, showing
that although the cyclization proceeds faster, the barrier for the
acid-catalyzed binaphthyl-racemization is only slightly higher.