Hexachlorocyclohexa-2,5-dien-1-one

Introduction

Hexachlorocyclohexa-2,5-dien-1-one is informally called hexachlorophenol (HCP). It is an efficient reagent for the chlorination of a wide variety of compounds and was used in several chiral organocatalytic reactions. HCP is a yellow to brown crystalline solid, which is usually prepared via electrophilic chlorination of phenol by chlorine gas in the presence of a metal chloride catalyst, such as iron(III) chloride.[1]

Scheme 1

Abstracts

(A) The application of HCP in the halogenation of aromatic heterocyclic compounds has been investigated.[2] For example, equimolar amounts of HCP convert N-methylindole into the corresponding 3-chloro-N-methylindole in 81% yield.[3]
(B) Lectka and co-workers have established a tandem catalytic asymmetric chlorination–esterification process using cinchona alkaloid derivatives as catalysts and polychlorinated quinones as the halogenating agents.[4] For instance, they reported the reaction of phenyl acetyl chloride in the presence of benzoyl quinine (BQ; chiral organocatalyst), sodium hydride, and HCP to form α-chloro ester 1 and ester 2 in 37% and 52% yield, respectively.[5]
(D) Diastereo- and enantioselective synthesis of β,γ-dichloroaldehydes 6 derived from cyclopropylcarbaldehyde 3 was achieved using HCP, amine 4 (chiral organocatalyst), and 2,4,6-collidine 5.[6] The aldehyde is activated via imine formation with 4. Ring opening occurs by the attack of Cl–. In the last step, the enamine functionality attacks Cl+, which is followed by hydrolysis to give the product. MacMillan had previously reported the use of HCP for the synthesis of other α-chloroaldehydes.[7]
(E) Huang et al. developed an innovative strategy for the preparation of a series of asymmetric α-halo-β-aryl aldehydes from α,β-unsaturated aldehydes 8.[8] In this enantioselective organocatalytic cascade reaction, amine 7 was employed as catalyst for the functionalization of enals in the presence of HCP as the chlorination agent. Activated heterocycles behave as nucleophiles in this reaction.
(F) The chiral N-heterocyclic carbene (NHC) percusor 10 efficiently promotes the organocatalytic chlorination and esterification of disubstituted ketenes 9.[9] The corresponding tertiary α-halo esters 11 are isolated from ketenes 9 in the presence of HCP catalyzed by the NHC derived from 10 in good yield and promising levels of asymmetric induction (up to 61% ee).

• References

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