Asymmetric Enzymatic Hydration of Hydroxystyrene Derivatives

摘要

The stereoselective addition of water across C=C bonds transforms prochiral alkenes to nonracemic alcohols and represents a major challenge in synthetic organic chemistry. In general, alkene hydration is an equilibrium reaction slightly favoring the alcohol side in 1,4-additions and somewhat disfavored on isolated C=C bonds. Acid-catalyzed alkene hydration, which follows the rule of Markovnikov, usually proceeds with low regioselectivity and is often accompanied by rearrangement yielding regioisomeric product mixtures; with a few exceptions, no generally applicable protocol has been developed so far. Likewise, base-catalyzed 1,4-addition of water to α,β-unsaturated (Michael) acceptors is impeded by the poor nucleophilicity of water. Overall, an astonishingly limited number of asymmetric alkene-hydration protocols are reported: 1) The stereoselective hydration of α,β-unsaturated carboxylic acids by using a heterobimetallic chiral biopolymer (wool-Pd~(II)-Co~(II)) catalyst furnished β-hydroxy carboxylic acids in high optical purities, and 2) the asymmetric syn-hydration of α,β-unsaturated acyl imidazoles while applying a DNA-based Cu~(II) catalyst yielded P-hydroxy carbonyl compounds with moderate ee values. To compensate for the insufficient nucleophilicity of water, indirect methods using strong nucleophiles (alkoxides, N-silyloxycarbamates, oximes, silicon and boron reagents) have been employed, which require cumbersome reductive or oxidative follow-up chemistry to yield the desired P-hydroxy carbonyl compounds.