Research and Development of an Efficient Synthesis of Hexahydrofuro[2,3-b]furan-3-ol Moiety—A Key Component of the HIV Protease Inhibitor Candidates

A highly efficient method for synthesizing racemic hexahydrofuro[2,3- b ]furan-3-ol has been developed utilizing a lanthanide catalyst, such as Yb(fod) 3, to promote condensation of 2,3-dihydrofuran and glycolaldehyde dimer. Access to either optically enriched enantiomer of bisfuran alcohol can be obtained by using this method employing chiral ligands with the lanthanide catalyst. In support of Gilead Sciences’ protease inhibitor project, this method has been demonstrated to be a robust and scalable process with potential application for the construction of a variety of furo[2,3- b ]furan derivatives.