Novel protection of 1,2-diol for trans-dihydroxycyclopentene ring construction by the CH insertion of alkylidene carbene: Formal total synthesis of (+)-trehazolin

• Published in: Tetrahedron letters Vol. 60; no. 39
• Main Authors: Ohira, Susumu, Kuboki, Atsuhito, Takimoto, Yoshimi, Matsuda, Kyosuke, Itasaki, Saori, Urushibata, Yuki, Takano, Yoshiyuki, Nakamura, Yuuki
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 26.09.2019
• Subjects: Alkylidene carbene; C[sbnd]H insertion; Glycosidase inhibitor; Protecting group; CH insertion; Glycosidase inhibitor; Protecting group; Alkylidene carbene
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.151085

[Display omitted] •Vicinal diol was protected as 6-methylene-1,4-dioxepane.•The protected trans-dihydroxycyclopentene ring was constructed by the CH insertion of alkylidene carbene.•Diol was regenerated from the 6-methylene-1,4-dioxepane derivative by two routes.•The known intermediate for (+)-trehazolin was synthesized from d-diethyl tartrate using these reactions.•The reaction route was considerably improved using the d-mannitol derivative as the starting material. The chiral vicinal diol was protected as 6-methylene-1,4-dioxepane to construct a cyclopentene ring by the CH insertion of alkylidene carbene. The removal of the protecting group was achieved in a few steps, affording the corresponding diol in a reasonable yield. Using these reactions, the known synthetic intermediate for (+)-trehazolin was synthesized from d-diethyl tartrate. In addition, a short route to the intermediate from a d-mannitol derivative was described.