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

Abstract

The synthesis of N-protected (E)-3-alkylidenepyrrolidines is reported. Nitroalkanes react with unsaturated 1,4-diesters and 1,4-keto esters, giving a tandem Michael addition/elimination of nitrous acid. The obtained 1,4-dicarbonyl compounds are reduced to the corresponding diols and then converted into their mesylates. Reaction of mesylates with benzylamine or 4-methylbenzenesulfonylamide affords the unsaturated pyrrolidines. Use of the sulfonylamide for the cyclization step has advantages over that of benzylamine, since it gives better yields of pyrrolidines, and furthermore, the benzenesulfonyl group can be efficiently removed in the presence of unsaturated bonds.