Optically active 1,10-bi-2-naphthol (BINOL, 1) and its derivatives have found many applications, ranging from chiral ligands of catalysts for asymmetric reactions to hosts for molecular recognition and enantiomer separation, to the intermediates for the synthesis of chiral materials. Several protocols have been developed for the access to its enantiopure form, including classical crystallization of diastereoisomeric derivatives, enantioselective formation of inclusion crystals with chiral host molecules, enzymatic hydrolysis of esters, and asymmetric coupling of 2-naphthol derivatives. So far, the enantioselective formation of inclusion crystals with chiral host molecules is one of the most practical methods because of its very high efficiency and the ready availability of the racemic BINOL (Fig. 1).
Molecular complexation has proven to be one of the most effective methods for the resolution of chiral organic molecules. In particular, chiral ammonium salts were reported to be effective host molecules for the resolution of racemic phenol derivatives by Toda's group. In the case of BINOL, N-benzylcinchonidinium chloride (2) readily forms inclusion crystals with its R-enantiomer, which precipitate from the solution and the (S)-enantiomer remains in the mother liquid. With the improvement of this procedure by Pu and Cai, both the (R) and (S) enantiomers can be obtained efficiently in >99% ee. However, the commercially available N-benzylcinchonidinium chloride (2) is expensive and its preparation seems difficult because of long reaction time and poor reproducibility of the procedure. Therefore, we investigated the use of N-benzylcinchoninium chloride (3), an epimer of 2, as the chiral host for the resolution of BINOL. One reason is that 3 can be readily prepared in 85% yield via an improved procedure through the reaction of cinchonine (4) with benzyl chloride in dimethylformamide (DMF) at 80oC for 3 h as shown in
Scheme 1. It was found that racemic BINOL can also be effectively resolved with N-benzylcinchoninium chloride through molecular complexation.