Synthesis of (E)-3-alkylidenepyrrolidines by nucleophilic ring closure of (E)-2-alkylidene-1,4-diol derivatives

The synthesis of N-protected (E)-3-alkylidenepyrrolidines is reported. Nitr oalkanes react with unsaturated 1,4-diesters and 1,4-keto esters, giving a tandem Michael addition/elimination of nitrous acid. The obtained 1,4-dicar bonyl compounds are reduced to the corresponding diols and then converted i nto their mesylates. Reaction of mesylates with benzylamine or 4-methylbenz enesulfonylamide affords the unsaturated pyrrolidines. Use of the sulfonyla mide for the cyclization step has advantages over that of benzylamine, sinc e it gives better yields of pyrrolidines, and furthermore, the benzenesulfo nyl group can be efficiently removed in the presence of unsaturated bonds.