Tandem Enyne Allene−Radical Cyclization: Low-Temperature Approaches to Benz[e]indene and Indene Compounds

Abstract

In an effort to lower the temperatures required to prepare multicyclic compounds using the tandem enediyne−radical cyclization, we have developed the tandem enyne allene−radical cyclization which proceeds at temperatures as low as 37 °C. The reactions were carried out using three different methods for the preparation of the enyne allenes. The first method involved the [3,3] sigmatropic rearrangement of an enediyne followed by a tandem enyne allene−radical cyclization. This reaction could be effected either by thermolysis (150 °C) or by AgBF₄ rearrangement followed by heating at 75 °C. A second technique utilized a [2,3] sigmatropic shift of an enediyne at −78 °C followed by tandem cyclization at 37 or 75 °C depending on the substrate. The final method involved the base-catalyzed isomerization of propargyl sulfones which yielded enyne allenes that underwent cyclization at 37 °C. These three sequences provide a method for the synthesis of ring systems using conditions that may be compatible with the sensitive functionality needed during the synthesis of complex natural products.