Highly enantioselective asymmetric transfer hydrogenation: a practical and scalable method to efficiently access planar chiral [2.2]paracyclophanes.

We report herein a general, practical method based on asymmetric transfer hydrogenation (ATH) to control the planar chirality of a range of substituted [2.2]paracyclophanes (pCps). Our strategy enabled us to perform both the kinetic resolution (KR) of racemic compounds and the desymmetrization of centrosymmetric meso derivatives on synthetically useful scales. High selectivities (up to 99% ee) and good yields (up to 48% for the KRs and 74% for the desymmetrization reactions) could be observed for several poly-substituted paracyclophanes, including a series of bromine-containing molecules. The optimized processes could be run up to the gram scale without any loss in the reaction efficiencies. Because of its broad applicability, the ATH approach appears to be the method of choice to access planar chiral pCps in their enantiopure form.