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Approach to Fully Substituted Cyclic Nitrones from N-Hydroxylactam Derivatives: Development and Application to the
Shobu Hiraoka1, Tsutomu Matsumoto1, Koki Matsuzaka1
1Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
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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