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Synthesis of Axially Chiral Biaryls by Atropo‐Diastereoselective Cleavage of Configurationally Unstable Biaryl Lactones with Menthol‐Derived O ‐Nucleophiles
Author(s) -
Bringmann Gerhard,
Breuning Matthias,
Walter Rainer,
Wuzik Andreas,
Peters Karl,
Peters EvaMaria
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199911)1999:11<3047::aid-ejoc3047>3.0.co;2-o
Subject(s) - enantiopure drug , chemistry , atropisomer , diastereomer , nucleophile , racemization , enantiomer , menthol , lactone , chiral auxiliary , enantioselective synthesis , stereochemistry , organic chemistry , combinatorial chemistry , catalysis
Configurationally unstable lactone‐bridged biaryls 4 are cleaved atropo‐diastereoselectively using chiral menthol‐derived alkali metal alkoxides, to give axially chiral biaryl esters of type 5 in high yields and excellent diastereomeric ratios of up to > 99:1. The method permits the optional preparation of each of the two atropisomers from the same lactone precursor (“atropo‐divergence”), simply according to the choice of the appropiate mentholate 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 formed (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: alcoholysis of 4 → in situ reduction → crystallization. The synthetic value of these alcoholysis reactions for asymmetric biaryl synthesis is illustrated by the transformation of 5 into a broad series of enantiopure biaryls of type 6 with various functional groups ortho to the axis.