Synthesis of nitrogen-containing heterocycles using exo- and endo-selective radical cyclizations onto enamides

The effect of positional change of the carbonyl group of enamides on BU3SnH-mediated alkyl radical cyclization leading to five-, six-, seven-, and eight-membered nitrogen-containing heterocycles was examined. A 5-exo cyclization is generally preferred over a 6-endo ring closure in systems having an alkyl radical center on the enamide-acyl side chain, whereas enamides having an alkyl radical center opposite to the acyl side chain predominantly gave 6-endo cyclization products. These results suggest that the exo or endo selectivity of radical cyclization onto the alkenic bond of enamides can be controlled by positional change of the carbonyl group. For an understanding of these selectivities, heat of formation for each transition state was calculated. 6-endo-Selective radical cyclization was applied to the radical cascade, enabling a concise synthesis of a cylindricine skeleton. A 7- or 8-endo alkyl radical cyclization, however, predominated over a corresponding 6- or 7-exo ring closure regardless of the positional change of the carbonyt group of enamides. (c) 2008 Elsevier Ltd. All rights reserved.