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.