Access to Multisubstituted Furan-3-carbothioates via Cascade Annulation of α‑Oxo Ketene Dithioacetals with Isoindoline-1,3-dione-Derived Propargyl Alcohols

• Published in: Journal of organic chemistry Vol. 83; no. 15; pp. 7648 - 7658
• Main Authors: Bai, Li-Gang, Chen, Ming-Tao, Xiao, Dong-Rong, Zhao, Liu-Bin, Luo, Qun-Li
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.08.2018; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ORGANIC-SYNTHESIS; FACILE SYNTHESIS; ACID; GOLD CARBENES; BOND-FORMING REACTIONS; ISOCYANIDES; REGIOSELECTIVE SYNTHESIS; OXOKETENE DITHIOACETALS; ALKYNES; 3+2 CYCLOADDITION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b00401

A Brønsted acid-promoted, unprecedented formal (3 + 2) annulation strategy for the synthesis of multisubstituted furan-3-carbothioates is reported. This transformation represents the first regioselective annulation of α-oxo ketene dithio-acetals as 1,3-bis-nucleophiles in a cascade manner. The choice of isoindoline-1,3-dione-derived propargyl alcohols is crucial to the uncommon annulation mode between an alkyne-type bis-electrophile and a 1,3-bis-nucleophile under metal-free conditions. The scale-up of the synthesis and several interesting transformations of an as-synthesized product were further investigated. A Nazarov-like cyclization is proposed for the ring-closure process according to the experimental observations.