Efficient preparation of [1-15N]-3-Cyano-4-methyl-1H-pyrrole by a Wittig-based strategy

3-Cyano-4-methyl-1H-pyrrole (1) was prepared by a new Wittig procedure from simple, commercially available starting materials in four steps with an overall yield of 39%. Similarly, [1-N-15]-3-cyano-4-methyl-1H-pyrrole (1a) was prepared starting from [N-15]-phthalimide. In this synthesis, Wittig coupling was used to form the central C-C bond of intermediate 6, which has nitrile and methyl substituents. Upon deprotection and cyclization pyrrole 1 is obtained directly in one pot. This scheme also allows stable isotope incorporation at any position or a combination of positions. 3-Cyano-4methyl-1H-pyrrole was converted into the novel 1-benzyl-3cyano-4-methylpyrrole and the novel 4-methyl-1H-pyrrole-3-aldehyde. It is clear that this novel Wittig procedure has a wide scope that will allow the easy preparation of many new pyrrole systems. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).