Novel concepts in directed biaryl synthesis, part 101. The lactone concept-a novel approach to the metal-assisted atroposelective construction of axially chiral biaryl systems

The atroposelective synthesis of axially chiral biaryls via configurationally unstable, lactone-bridged biaryls is reviewed. These key molecules are easily accessible by regioselective intramolecular cross-coupling of ester-linked, even sterically hindered aromatic portions and can be cleaved highly atropo-enantio- or -diastereoselectively by three principal options, either (a) by using a wide range of chiral metalated nucleophiles (usually with external asymmetric induction), (b) after Lewis acid activation of the lactone C=O function using uncharged chiral or achiral nucleophiles, or (c) with internal asymmetric induction, using the stereoelement of planar chirality originating from eta(6)-coordination (typically involving Cr or Ru complexes). The resulting ring-opened configurationally stable biaryls are obtained in mostly excellent chemical and optical yields. By the choice of the respective enantiomer of the nucleophile, the method allows the atropo-divergent synthesis of both atropisomers from the same immediate biaryl precursor and, if required, a recycling of the undesired minor atropisomer is possible, too. Such advantages are otherwise well-known for the stereoselective preparation of centrochiral compounds. (C) 2002 Elsevier Science B.V. All rights reserved.