Substituted 2,2a2-bipyrroles and pyrrolylfurans via intermediate isoxazolylpyrroles

We describe a new synthesis of the 3-chloro-(4a2-methoxy)-2,2a2-pyrrolylfuran segment (3) of (+)-roseophilin. The route exploits a isoxazoylpyrrole intermediate, wherein the isoxazole ring serves as a [beta]-diketone equivalent and a directing group for palladium catalyzed chlorination of the attached pyrrole. Subsequent reduction of the NaO 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-(4a2-alkoxy)-2,2a2-pyrrolylfurans (16aac) and 4-alkoxy-2,2a2-bipyrroles (20aac), which are building blocks to synthesize bioactive prodiginine natural products and their congeners.