Approach to Fully Substituted Cyclic Nitrones from N‐Hydroxylactam Derivatives: Development and Application to the Total Synthesis of Cylindricine C. Issue 13 (18th February 2019)

• Record Type: Journal Article
• Authors: Hiraoka, Shobu; Matsumoto, Tsutomu; Matsuzaka, Koki; Sato, Takaaki; Chida, Noritaka
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 13(2019)
• Page Start: 4381
• Page End: 4385
• Publication Date: 2019-02-18
• Subjects: amides -- nitrones -- nucleophilic addition -- synthetic methods -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201901049
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: An approach to cyclic nitrones from N ‐hydroxylactam derivatives is documented. The nucleophilic addition of an organolithium reagent to an N ‐OSEM [SEM=2‐(trimethylsilyl)ethoxymethyl] lactam forms a five‐membered chelated intermediate, which undergoes both elimination and deprotection to give a fully substituted nitrone in a one‐pot process. When combined with the N ‐oxidation of easily available chiral lactams, this method becomes especially useful for the quick synthesis of chiral nitrones in enantio‐pure form, enabling the concise total synthesis of cylindricine C. Abstract : Fully substituted cyclic nitrones are accessed from N ‐hydroxylactam derivatives. The reaction proceeds through nucleophilic addition of an organolithium reagent and subsequent elimination in a one‐pot process. When combined with N ‐oxidation of a chiral lactam, the method allows utilization of an easily available lactam as a chiral nitrone equivalent, enabling the enantioselective total synthesis of cylindricine C.