Concise Total Syntheses of (+)-Haplocidine and (+)-Haplocine via Late-Stage Oxidation of (+)-Fendleridine Derivatives

摘要: We report the first total syntheses of (+)-haplocidine and its N1-amide congener (+)-haplocine. Our concise synthesis these alkaloids required development a late-stage highly selective C–H oxidation complex aspidosperma alkaloid derivatives. A versatile, amide-directed ortho-acetoxylation indoline amides enabled our implementation unified strategy for diversification hexacyclic C19-hemiaminal ether structures via corresponding pentacyclic C19-iminium ions. An electrophilic amide activation readily available C21-oxygenated lactam, followed by transannular cyclization in situ trapping transiently formed ion, expediently provided access to (+)-fendleridine, (+)-acetylaspidoalbidine, (+)-propionylaspidoalbidine. effective enzymatic resolution non-β-branched primary alcohol (E = 22) allowed rapid preparation both enantiomeric forms precursor sy...