Ipso-Type Regiocontrolled Benzannulation for the Synthesis of Uniquely Substituted α-Arylnaphthalenes: Application to the First Total Synthesis of Chaihunaphthone
| Autor: | Daisuke Tanaka, Yoshinobu Kamakura, Kento Moriguchi, Yoo Tanabe, Ryosuke Sasaki, Jun-ichi Morita |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | ACS Omega, Vol 6, Iss 28, Pp 18135-18156 (2021) ACS Omega |
| ISSN: | 2470-1343 |
| DOI: | 10.1021/acsomega.1c02000 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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