Regioselective, metal‐free, CH chlorination of phenols is challenging. These reactions generally proceed via electrophilic aromatic substitution, resulting in pure 2‐ or 4‐chlorinated products or a mixture of 2‐ and 4‐substituted isomers. However, 3‐substitution is electronically forbidden in these cases. Electrophilic aromatic chlorination involves toxic reagents, low tolerance for functional groups, and the generation of waste products from the chlorinating agent. Improvizations involving classical preformed chlorinating agents, oxidative chlorination, and transition metal catalysis, among others, require harsh conditions, high temperatures, directing groups, and low atom economy, despite achieving high selectivity. Few reports have also utilized the activation of arenes to facilitate regioselective nucleophilic chlorination. In a unique progression in phenol chemistry, we report a regioselective, indirect, catalyst‐ and metal‐free synthesis of 2‐chlorophenols via the chlorination of quinone monoacetals (QMA), derived from the oxidative dearomatization of phenol, using dimethyl chlorohydrosilane as a chloride source. Further, Brønsted acid‐catalyzed chlorination of QMA–MBH adducts afforded regioselective, metal‐free, solvent‐switchable 3‐ or 2‐chlorophenols via a one‐pot cascade reaction. C‐2‐chlorination proceeds via Michael addition of Cl − ion to the intermediate phenoxonium ion, while C‐3 chlorination occurs via Cl − addition to a silane‐activated quinone intermediate. This approach is well‐suited for late‐stage functionalization in pharmaceuticals, natural products, and complex molecules.
Sharma et al. (Sun,) studied this question.