Approach to Fully Substituted Cyclic Nitrones from N‐Hydroxylactam Derivatives: Development and Application to the Total Synthesis of Cylindricine C

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.

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.

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