Novel concepts in directed biaryl synthesis, 80 - Synthesis of axially chiral biaryls by atropo-diastereoselective cleavage of configurationally unstable biaryl lactones with menthol-derived O-nucleophiles

Configurationally unstable lactone-bridged biaryls 4 are cleaved atropo-dia stereoselectively using chiral menthol-derived alkali metal alkoxides, to g ive axially chiral biaryl esters of type 5 in high yields and excellent dia stereomeric ratios of up to > 99:1. The method permits the optional prepara tion of each of the two atropisomers from the same lactone precursor ("atro po-divergence"), simply according to the choice of the appropiate mentholat e or its enantiomer as the O-nucleophile - or by the use of the mentholate in solution or in suspension. Undesired minor atropisomers of 5 possibly fo rmed (if at all) can be recycled ("axially chiral economy") by cyclization back to the lactone 4. For the preparation of larger amounts of enantiopure biaryl alcohols 9, an efficient reaction sequence was developed: alcoholys is of 4 --> in situ reduction --> crystallization. The synthetic value of t hese alcoholysis reactions for asymmetric biaryl synthesis is illustrated b y the transformation of 5 into a broad series of enantiopure biaryls of typ e 6 with various functional groups ortho to the axis.