-Type Regiocontrolled Benzannulation for the Synthesis of Uniquely Substituted α-Arylnaphthalenes: Application to the First Total Synthesis of Chaihunaphthone.

A distinctive method for synthesizing a variety of multisubstituted α-arylnaphthalenes utilizing novel regiocontrolled -type [4 + 2] benzannulation is presented. - and -substituted 1-Ar-1-Ar-2,2-dichlorocyclopropylmethanols (AACM) were transformed to the corresponding -type α-arylnaphthalenes. (i) The reaction of -AACM using TiCl or SnCl (1.0 equiv) proceeded smoothly to afford -type α-arylnaphthalenes (seven examples; 49-69% yield) exclusively, without producing conventional benzannulation isomers. (ii) -AACM also underwent the reaction successfully to afford the desired -type α-arylnaphthalenes (14 examples; 39-98% yield) without producing conventional benzannulation isomers. (iii) In contrast, -AACM underwent the previously reported conventional benzannulation. (iv) The present method exhibited sufficient substrate generality for application to - and -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 -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).