General Synthesis of the Nitropyrrolin Family of Natural Products via Regioselective CO2-Mediated Alkyne Hydration.

The total synthesis of the 2-nitropyrrole natural products nitropyrrolins A and B and the formal synthesis of nitropyrrolin D are reported. The key 2-nitro-4-alkylpyrrole core was efficiently assembled by Sonogashira cross-coupling, with complete control of regioselectivity. An unusual carboxylative cyclization, sulfonylcarbamate formation, and base-promoted cleavage sequence enabled access to the key hydroxy ketone without affecting the protected 2-nitropyrrole unit. The total synthesis provides a general approach for preparation of the bioactive nitropyrrolin family of natural products.