Enantioselective Claisen Rearrangements with a Hydrogen-Bond Donor Catalyst

摘要

Chorismate mutases catalyze the [3,3]-sigmatropic rearrangement of chorismate to prephenate. Structural, site-directed mutagenesis, and computational studies have established the importance of several key hydrogen-bond donating residues in the active site of the enzyme. Through a combination of transition-state stabilization and restriction of the substrate in a reactive conformation, chorismate mutase is capable of achieving rate accelerations on the order of 10~6 relative to the thermal reaction. Acceleration of the Claisen rearrangement has also been observed in hydrogen-bonding solvents; using quantum mechanical computational methods, Jorgensen has advanced a model for the aqueous acceleration of the Claisen rearrangement involving H-bond interactions between two water molecules and the core heteroatom of the allyl vinyl ether in the optimized transition state structure. Consistent with this hypothesis, compounds capable of dual hydrogen-bonding such as ureas and thioureas have been studied in the context of Claisen rearrangement reactions and have been demonstrated to induce modest rate accelerations when used in stoichiometric or superstoichiometric amounts.