Axial chirality in xanthene-4,5-dicarboxamides: 1,9-stereocontrol mediated by remote interactions between conformationally constrained amide groups

Tertiary 9,9-dimethylxanthene-4,5-dicarboxamides have a C2-symmetric, axially chiral ground state due to remote interactions between the conformationally constrained tertiary amide substituents. Double ortholithiation–alkylation blocks amide rotation, and the 3,6-dialkylated products are chiral, existing as a pair of enantiomeric C2-symmetric atropisomers. Double lateral lithiation–electrophilic quench introduces a pair of 1,9-related stereogenic centres—each under the control of one of the conformationally constrained amides—with complete diastereoselectivity.