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Updated: Oct 26, 2025

Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of α,β-Unsaturated Compounds and Alkynes
Published on: December 16, 2019
-Type Regiocontrolled Benzannulation for the Synthesis of Uniquely Substituted α-Arylnaphthalenes: Application to
Kento Moriguchi1, Ryosuke Sasaki1, Jun-Ichi Morita1
1Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
Abstract:
A distinctive method for synthesizing a variety of multisubstituted α-arylnaphthalenes utilizing novel regiocontrolled ipso-type [4 + 2] benzannulation is presented. Ortho- and para-substituted 1-Ar1-1-Ar2-2,2-dichlorocyclopropylmethanols (AACM) were transformed to the corresponding ipso-type α-arylnaphthalenes. (i) The reaction of ortho-AACM using TiCl4 or SnCl4 (1.0 equiv) proceeded smoothly to afford ipso-type α-arylnaphthalenes (seven examples; 49-69% yield) exclusively, without producing conventional benzannulation isomers. (ii) Para-AACM also underwent the reaction successfully to afford the desired ipso-type α-arylnaphthalenes (14 examples; 39-98% yield) without producing conventional benzannulation isomers. (iii) In contrast, meta-AACM underwent the previously reported conventional benzannulation. (iv) The present method exhibited sufficient substrate generality for application to ortho- and para-substituted AACM substrates bearing Me-, Cl-, and MeO- groups. (v) The six key structures were unambiguously confirmed by X-ray structure analyses. (vi) A plausible reaction mechanism for the present ipso-type reaction is proposed and supported by three careful cross-over and comparable experiments. To demonstrate the utility of the present reaction, we achieved the first total synthesis of chaihunaphthone, a uniquely (highly congested) substituted and less accessible natural lignan lactone with three contiguous trimethoxy substituents (total eight steps, overall 6.4% yield).
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