Geometric distortion as an enabling tool for organic synthesis

Abstract

π-bonds are typically associated with well-defined arrangements of atoms. However, when the arrangement of atoms associated with these bonds becomes geometrically distorted, heightened reactivity is seen, enabling a wide range of transformations that can proceed under mild reaction conditions. As a result, molecules bearing complex structures can be rapidly assembled from simple building blocks. Here we describe the strategic use of synthetic building blocks containing π-bonds that feature geometric distortion, with a focus on recent applications to organic synthesis. The specific building blocks discussed are arynes, cyclic allenes, cyclic 1,2,3-trienes and anti-Bredt olefins. Developments in transition metal-mediated chemistry that enable previously unknown transformations are discussed, as well as new strategies for complex molecule and natural product synthesis that take advantage of geometrically distorted intermediates. We hope this Review will inspire future advances in the strategic use of geometric distortion in chemical synthesis. Although π-bonds are typically associated with having well-defined arrangements of atoms, ring constraints can lead to geometric distortion, resulting in heightened reactivity. These effects can be leveraged to enable synthetic transformations. This Review features processes wherein geometric distortion is leveraged to provide rapid access to structurally complex products.