A practical method for the synthesis of pyrrolizidine, indolizidine and pyrroloazepinolizidine nucleus

The alkylation of α,ω-dibromoalkanes, with the sodium salt of succinimide, followed by the reduction with sodium borohydride gives the respective N-ω-bromoalkyl-5-hydroxy-2-pyrrolidinones. These substrates are precursors of N-acyliminium ions under acidic conditions. The condensation of these intermediates with ethyl malonate in the presence of TiCl4 and diisopropylethylamine following the intramolecular cyclization provides a convenient route to substituted pyrrolizidinone, indolizidinone and pyrroloazepinolizidinone nucleus in a good yield.