Recent Advances in Stereoselective [2+2+2] Cycloadditions

The [2+2+2] cycloaddition reaction is considered one of the most efficient methods for the rapid and straightforward preparation of complex polycyclic (and heterocyclic) compounds in a highly selective and atom-economical fashion. Over the last half-century, remarkable advances in terms of chemo-and regioselectivities have been realized, endowing this reaction with attractive features as a key step in the synthesis of various biologically active molecules and materials. The development of stereoselective methodologies is more recent. In this field, asymmetric transition-metal catalysis has emerged as the most convenient tool with which to perform these [2+2+2] cycloadditions in their enantio-and diastereo-selective variants. All the catalytic systems that have been developed so far are based on very close association of a transition metal (Co, Ni, Ir, Rh,...) with a chiral ligand. The success of these reactions is then related to the reaction pattern involved (inter-and intramolecular), implying an efficient substrate/active species interaction. Thus, judicious design both of chiral ligands and of unsaturated substrates is necessary. In light of these aspects, numerous stereoselective cycloadditions have been reported; these allow the construction in one-step fashion of central, axial, planar, and helical chiralities. This review details the recent advances in this area, with specific attention to catalysts and reaction scope.