Substituted 2,2′-bipyrroles and pyrrolylfurans via intermediate isoxazolylpyrroles

We describe a new synthesis of the 3-chloro-(4′-methoxy)-2,2′-pyrrolylfuran segment (3) of (+)-roseophilin. The route exploits a isoxazoylpyrrole intermediate, wherein the isoxazole ring serves as a β-diketone equivalent and a directing group for palladium catalyzed chlorination of the attached pyrrole. Subsequent reduction of the N–O bond and acid promoted cyclization afford roseophilin segment 3b in five steps and 19% overall yield. This strategy was extended to the synthesis of 3-chloro-(4′-alkoxy)-2,2′-pyrrolylfurans (16a–c) and 4-alkoxy-2,2′-bipyrroles (20a–c), which are building blocks to synthesize bioactive prodiginine natural products and their congeners.