BINOL enantiomer through resolution

- Jan 03, 2018 -

1,1'-Bi-2-naphthol (BINOL) is an organic compound that is often used as a ligand for transition-metal catalysed asymmetric synthesis. BINOL has axial chirality and the two enantiomers can be readily separated and are stable toward racemisation. The specific rotation of the two enantiomers is +/- 35.5° (c=1 in THF). BINOL is a precursor for another chiral ligand called BINAP.

   The organic synthesis of BINOL is not a challenge as such but the preparation of the individual enantiomers is.

    Racemic BINOL can also be produced using iron(III) chloride as an oxidant. The mechanism involves complexation of iron(III) into the hydroxyl, followed by a radical coupling reaction of the naphthol rings initiated by iron(III) reducing into iron(II).

    Currently, producing larger quantity of both enantiomers through resolution is more economic and effective way. Previously reported resolutions include: 1) making a cyclic phosphate of binaphthol, then resolution and subsequent reduction to release the pure binaphthol; 2) using enzymatic hydrolysis of the diester of binaphthol;  and 3) forming inclusion complexes with suitable compounds. The use of N-benzylcinchonidinium chloride to make inclusion complexes was reported by Tanaka and co-workers for obtaining one enantiomer of binaphthol. Using acetonitrile as solvent, in which the inclusion complex has very low solubility, allows for the isolation of both enantiomers with high enantiomeric excess. This simple and efficient procedure represents a much better resolution for 1,1'-bi-2-naphthol.

   Both enantiomers of 1,1'-bi-2-naphthol are widely used for various applications: 1) chiral inducing agents for catalytic, asymmetric reactions such as the Diels-Alder reaction, ene reaction, or as Lewis acids; 2) enantioselective reduction of ketones; 3) synthesis of chiral macrocycles and other interesting compounds.