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) - Hiraoka, Shobu
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.