Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (-)-ephedrine or a proline-derived diamine.
Atropisomeric biaryl aldehydes undergo diastereoselective condensation with (-)-ephedrine and with a proline-derived diamine, with selectivity highly dependent on solvent, temperature and reaction conditions. Levels of thermodynamic control up to 5:1 may be obtained by heating the diamine with the aldehyde in a sealed tube. Alternatively, crystallisation-induced dynamic transformation allows isolation of a single diastereoisomer in up to 85% yield. Hydrolysis and reduction of the major diastereoisomeric product of the reaction yields atropisomeric biaryls in >99:1 enantiomeric ratios.
Bracegirdle
Ann
A
School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, UK.
Clayden
Jonathan
J
Lai
Lai Wah
LW