Development of a merged conjugate addition/oxidative coupling sequence. Application to the enantioselective total synthesis of metacycloprodigiosin and prodigiosin R1.

A merged conjugate addition/oxidative coupling sequence that represents an efficient strategy for preparing structurally diverse pyrroles has been developed. Success of the method hinged upon the controlled oxidative coupling of unsymmetrical silyl bis-enol ether intermediates, formed by the 1,4-addition of a Grignard reagent with subsequent enolate trapping by a (chloro)silylenol ether. The process was applied to the first enantioselective syntheses of the biologically active pyrrolophane natural products, metacycloprodigiosin and prodigiosin R1.