Enzymatic Resolution of 3-oxodicyclopentadiene on a Decagram Scale

The chiral building block 3-oxodicyclopentadiene ( 1 ) can be readily resolved on a decagram scale by a short sequence consisting of (1) reduction to the corresponding endo -alcohol, (2) enzymatic oxidative resolution with a ketoreductase enzyme to give (+)- 1 and the (+)-form of the endo -alcohol, and (3) reoxidation of the (+)- endo -alcohol with another ketoreductase to give (–)- 1 . With a selectivity factor of 310, the enantiomeric ratios of the resolved (+)- endo -alcohol and (+)-ketone are both >99:1. Both enzymatic oxidations could be performed with a at least 300:1 substrate/catalyst ratio (w/w).