Radical cyclizations involving the evolution of nitrogen

The rsuiical cyclizations of N-aziridinyl imines and alkyl azides provided reliable methods for the formation of fiveand six-membered carbon-centered and nitrogen-centered radicals from acyclic precursors. NAziridinyl imino and azido groups were utilized as radical precursors as well as radical acceptors in radical cyclization. Furthermore, intramolecular addition of aminyl radicals to carbonyl groups proceeded cleanly, yielding 1,5-acyl group transfer from carbon to nitrogen. Despite the synthetic usefulness of radical cyclization reactions, the cyclization pathway is mainly limited to 5-ex0 closure alonp with somewhat less efficient 6-ex0 and 6-endo closure due to stereoelectronic and geometric reasons. Fundamentally new approaches for the formation of fiveand six-membered ring radicals from acyclic precursors were sought, and the radical cyclizations of 2-phenyl-N-aziridinyl imines and alkyl azides provided general solutions to these problem. Radical cyclization of N-aziridinyl imines. Our approach is outlined in Scheme 1 and is based on three factors along with the original Eschenmoser reaction.' First, alkyl radicals are known to add to oxime ethem3 Second, &fragmentation of three-membered rings is a facile process due to the relief of ring strain. Third, consecutive p-fragmentations via ejection of styrene and nitrogen are expected to be fast processes. Scheme I Our initial study focused on the use of the N-aziridinyl imines as radical acceptors! Treatment of the bromide l a (Table 1) with Bu$nH (2.0 equiv) and AIBN (0.1 equiv) in benzene at 80 "C for 4 h afforded 30% of 2a along with 33% of the N-aziridinylpiperidine resulting from intramolecular N-alkylation. Under the same condibons, the use of the phenylselenide l b solved the problem of intramolecular N-alkylation and gave 2a in 75% yield. l c was cleanly cyclized to 2c, and there was no evidence of the N-alkylated product. As shown in Table 1, radical cyclization of 3, 5a, and 7a using structurally different radical precursors proceeded smoothly, yielding the cyclized products in high yields. Similarly, the keto hydrazones 5b and 7b were cyclized without significant difference in their reactivity. Table 1. Radical Cyclization of 2-PhenylN-aZiridiny1 Imines substratea time$ product (yield, %) I substrate" time,h product (yield, %)