Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: A concise total synthesis of ningalin B

Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha, beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3, 4-diaryl pyrroles. The ease of preparation of alpha, beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin 0, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.