Modular Synthesis of Dipyrroloquinolines: A Combined Synthetic and Mechanistic Study.

Abstract

A straightforward synthesis of [1,2-a][3',2'-c]dipyrroloquinolines has been developed generating up to eight new σ-bonds and five new stereogenic centers in a simple and modular one-pot operation. Generally good to excellent yields and moderate to good stereoselectivities in favor of the all-cis stereoisomer were observed. A detailed investigation combining synthetic studies, analytical measurements, and theoretical calculations has been conducted to elucidate the reaction mechanism using ESI- and liquid-beam IR-laser desorption mass spectrometry as well as DFT calculations. Key steps of this sequential transformation include a Lewis acid-catalyzed vinylogous Mukaiyama-Mannich reaction of bis(silyl) dienediolate 1 and a Brønsted acid-promoted Mannich-Pictet-Spengler reaction cascade reaction to complete the synthesis of the dipyrroloquinoline core of the target compounds.