Lithium−Sulfoxide−Lithium Exchange for the Asymmetric Synthesis of Atropisomers under Thermodynamic Control
- 17 April 2002
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 124 (19) , 5266-5267
- https://doi.org/10.1021/ja017702o
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Lithiation and Stereoselective Transformations of 3-Aroyl-2,2,4,4-tetramethyloxazolidines (TMO Amides), a New Class of Acid-labile Atropisomeric AmidesSynlett, 2002
- Atropisomeric Amides as Chiral Ligands: Using (−)-Sparteine-Directed Enantioselective Silylation to Control the Conformation of a Stereogenic AxisThe Journal of Organic Chemistry, 2000
- Axial chirality in xanthene-4,5-dicarboxamides: 1,9-stereocontrol mediated by remote interactions between conformationally constrained amide groupsTetrahedron Letters, 2000
- Synthesis and first application of a new family of monophosphine ferrocene ligands (MOPF)Chemical Communications, 1999
- A Straightforward Asymmetric Synthesis of Enantiopure 1,2-Disubstituted FerrocenesThe Journal of Organic Chemistry, 1998
- Atroposelectivity in the reactions of ortholithiated aromatic tertiary amides with aldehydesJournal of the Chemical Society, Perkin Transactions 1, 1997
- Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromaticsChemical Reviews, 1990
- Stereoselective reactions. VII. Synthesis of racemic and optically pure stegane, isostegane, picrostegane, and isopicrostegane via highly selective isomerization.CHEMICAL & PHARMACEUTICAL BULLETIN, 1985
- Carbon-Sulfur Bond Cleavage in the Reaction of Alkyllithiums with SulfoxidesCanadian Journal of Chemistry, 1974
- Racemization and cleavage of sulfoxides by methyllithiumJournal of the American Chemical Society, 1967