Conformational preference and remote (1,10) stereocontrol in biphenyl-2,2′-dicarboxamides

(Matrix Presented) The double ortholithiation and electrophilic quench of N,N,N′N′-tetraisopropylbiphenyl-2,2′-dicarboxamide 1 is diastereoselective, giving the chiral C₂-symmetric atropisomers of the 3,3′-disubstituted products 3. These chiral atropisomers can be converted with moderate to good stereoselectivity to their achiral, centrosymmetric epimers by heating. The stereoselectivity of the double lithiation-quench reaction is determined by the stereochemistry of the intermediate doubly lithiated species 2, either diastereoisomer of which may be formed stereospecfically from the corresponding atropisomeric dibromo compounds.