Regioselective Synthesis of Polyfunctional Arenes by a 4-Component Catellani Reaction

Abstract

Summary Polyfunctional arenes are an important part of the chemical value chain. To improve the efficiency of their synthesis, we have investigated a multicomponent approach built upon the Catellani platform. Here, we describe a 4-component coupling of aryl iodides lacking an ortho substituent that installs 3 discrete functional groups on the arene in a single step. The process is regio- and chemoselective and uncovers remote substituent effects that have a pronounced influence over intermediate Pd-(II) complexes. These intermediates have been a long-standing focus of the Catellani-reaction development, but persistent challenges have given rise to the well-known “ortho effect.” We now show that the ortho effect can be a positive element of reaction design, and that previously problematic iodides can now be used in complexity-generating transformations. In expanding the scope of the Catellani platform, we hope to provide mechanistic considerations to guide future reaction design, while also improving the environmental footprint of synthesizing polyfunctional arenes.