A Unified Route to theWelwitindolinone Alkaloids:Total Syntheses of (−)-N-MethylwelwitindolinoneC Isothiocyanate (−)-N-MethylwelwitindolinoneC Isonitrile and (−)-3-Hydroxy-N-methylwelwitindolinoneC Isothiocyanate

摘要

As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]decane core, we report herein concise asymmetric total syntheses of (−)-N-methylwelwitindolinone C isothiocyanate (>2a), (−)-N-methylwelwitindolinone C isonitrile (>2b), and (−)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate (>3a) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of >2a provided access to >2b and >3a, respectively. Notably, this work provides corrected ¹H and ¹³C NMR spectral data for >3a.