Chemoenzymatic cascade reaction as a sustainable and scalable access to para-quinols

Abstract

A novel protocol for the synthesis of para-quinols from inexpensive phenols based on a chemoenzymatic cascade reaction is reported. The protocol combines an enzymatic oxidation of hydroquinones to benzoquinones and their transformation in situ to p-quinols via a catalytic process. Mild ambient conditions and a thoroughly optimized catalytic system provide target products with excellent yields. In an advancement of previous classical approaches, the scope of products available has been extended. It should be noted that the enzyme not only participates in the oxidation reaction of hydroquinones, which is the first step of the chemoenzymatic cascade, but also modulates the activity of the metal catalyst in a highly effective manner, significantly increasing the efficiency of the carbon–carbon bond formation in the second step. This specific interaction of the protein with the metal is also manifested in the stereochemical course of the addition reaction of vinyl aryl boronic acid, resulting in the enhancement of the Z/E ratio. The developed cascade approach allowed for the elimination of side-products, thus increasing the atom economy of the process and simplifying the purification step. Moreover, the versatility of the method was demonstrated on 19 examples in isolated product yields up to 99%. In addition, the possibility of reuse of both the catalytic system and the reaction medium reduces the amount of waste and the cost of the process.