Ag-catalyzed diastereo- and enantioselective vinylogous Mannich reactions of alpha-ketoimine esters. Development of a method and investigation of its mechanism.
An efficient diastereo- and enantioselective Ag-catalyzed method for additions of a commercially available siloxyfuran to alpha-ketoimine esters is disclosed. Catalytic transformations require an inexpensive metal salt (AgOAc) and an air stable chiral ligand that is prepared in three steps from commercially available materials in 42% overall yield. Aryl- as well as heterocyclic substituted ketoimines can be used effectively in the Ag-catalyzed process. Additionally, two examples regarding reactions of alkyl-substituted ketoimines are presented. An electronically modified N-aryl group is introduced that is responsible for high reaction efficiency (>98% conversion, 72-95% yields after purification) as well as diastereo- (up to >98:2 dr) and enantioselectivity (up to 97:3 er or 94% ee). The new N-aryl unit is crucial for conversion of the asymmetric vinylogous Mannich (AVM) products to the unprotected amines in high yields. Spectroscopic and X-ray data are among the physical evidence provided that shed light on the identity of the Ag-based chiral catalysts and some of the mechanistic subtleties of this class of enantioselective C-C bond forming processes.
Wieland
Laura C
LC
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Vieira
Erika M
EM
Snapper
Marc L
ML
Hoveyda
Amir H
AH
D000588:Amines / Q000138:chemical synthesis*; D001555:Benzene Derivatives / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012834:Silver / Q000737:chemistry; D013237:Stereoisomerism
D000588:Amines; D001555:Benzene Derivatives; D004952:Esters; D005663:Furans; D007097:Imines; D007659:Ketones; D012834:Silver