SmI2-catalysed cyclization cascades by radical relay

Abstract

Radical cyclization cascades are powerful tools used to construct the complex three-dimensional structures of some of society’s most prized molecules. Since its first use 40 years ago, SmI2 has been used extensively for reductive radical cyclizations. Unfortunately, SmI2 must almost always be used in significant excess, thus raising issues of cost and waste. Here, we have developed radical cyclization cascades that are catalysed by SmI2 and exploit a radical relay/electron-catalysis strategy. The approach negates the need for a super-stoichiometric co-reductant and requires no additives. Complex cyclic products, including products of dearomatization, containing up to four contiguous stereocentres are obtained in excellent yield. Mechanistic studies support a single-electron-transfer radical mechanism. Our strategy provides a long-awaited solution to the problem of how to avoid the need for stoichiometric amounts of SmI2 and establishes a conceptual platform on which other catalytic radical processes using the ubiquitous reducing agent can be built. Samarium iodide is a remarkably useful and mild reductant in organic synthesis, but its use can be problematic due to the need for (super)stoichiometric loadings. Now a method that employs samarium iodide as a catalyst—without the need for a stoichiometric co-reductant—is reported. Loadings as low as 5% are shown to catalyse radical cyclization cascades.