Lithium-sulfoxide-lithium exchange for the asymmetric synthesis of atropisomers under thermodynamic control.
Ortholithiation and reaction with (-)-menthyl p-toluenesulfinate introduces a sulfoxide substituent ortho to the stereogenic Ar-CO axis of an aromatic amide. The sulfoxide exerts a powerful conformational bias on the axis, such that after rapid equilibration at ambient temperature essentially only one of two diastereoisomeric Ar-CO atropisomers is populated. Sulfoxide-lithium exchange by treatment with t-BuLi regenerates the ortholithiated amide in an enantiomerically pure and conformationally stable form. Rapid electrophilic trapping of the organolithium therefore generates highly enantiomerically enriched atropisomeric tertiary aromatic amides. The overall process, involving temporary substitution of lithium to sulfoxide to lithium, amounts to a dynamic resolution under thermodynamic control.
Clayden
Jonathan
J
Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK. j.p.clayden@man.ac.uk
Mitjans
David
D
Youssef
Latifa H
LH
D000577:Amides / Q000138:chemical synthesis*; D008094:Lithium / Q000737:chemistry*; D013237:Stereoisomerism; D013454:Sulfoxides / Q000138:chemical synthesis* / Q000737:chemistry*; D013816:Thermodynamics
D000577:Amides; D013454:Sulfoxides; D008094:Lithium