Asymmetric Synthesis of Biaryl Diols via Dynamic Kinetic Resolution

We have developed a protocol incuding dynamic kinetic resolution as the key step for the asymmetric synthesis of biaryl diol stereoisomers. The two aryl alkanols as the starting materials were cross-coupled by palladium catalysis to give dl- and meso-diol, which were then subject to chemoenzymatic dynamic kinetic resolution (DKR) for the transformation into single stereoisomeric diol diester. Diol diester was finally deacylated to give the corresponding biaryl diol stereoisomer. The chemoenzymatic DKR was performed with a ruthenium-based racemization catalyst and a (R)-selective lipoprotein lipase. Total 17 (R,R)-diols including 7 C-2-symmetric diols were synthesized with excellent enantiopurities (>99% ee).