Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality

The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n≤11) using sec-BuLi-(-)-sparteine at -78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C ₂-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products.