Synthesis of Axially Chiral Biaryls by Atropo-Diastereoselective Cleavage of Configurationally Unstable Biaryl Lactones with Menthol-Derived O-Nucleophiles

✍ Scribed by Gerhard Bringmann; Matthias Breuning; Rainer Walter; Andreas Wuzik; Karl Peters; Eva-Maria Peters

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 480 KB
• Volume: 1999
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/(sici)1099-0690(199911)1999:11<3047::aid-ejoc3047>3.0.co;2-o

✦ Synopsis

Configurationally unstable lactone-bridged biaryls 4 are 5 possibly formed (if at all) can be recycled ("axially chiral economy") by cyclization back to the lactone 4. For the cleaved atropo-diastereoselectively using chiral mentholderived alkali metal alkoxides, to give axially chiral biaryl preparation of larger amounts of enantiopure biaryl alcohols 9, an efficient reaction sequence was developed: alcoholysis esters of type 5 in high yields and excellent diastereomeric ratios of up to Ͼ 99:1. The method permits the optional of 4 Ǟ in situ reduction Ǟ crystallization. The synthetic value of these alcoholysis reactions for asymmetric biaryl synthesis preparation of each of the two atropisomers from the same lactone precursor ("atropo-divergence"), simply according to is illustrated by the transformation of 5 into a broad series of enantiopure biaryls of type 6 with various functional groups the choice of the appropiate mentholate or its enantiomer as the O-nucleophile -or by the use of the mentholate in ortho to the axis.