Enantioselective aza-Michael reactions catalyzed by samarium iodobinaphtholate

Samarium iodobinaphtholate is an efficient enantioselective catalyst for the Michael addition of aromatic amines to fumaryl oxazolidinone affording aspartic acid derivatives in good yields. Influence of temperature on the addition of p-anisidine revealed an isoinversion effect with the maximum enantiomeric excess of 88% at −40 °C.

Figure optionsDownload as PowerPoint slide

(S)-Ethyl 2-(4-methoxyphenylamino)-4-oxo-4-(2-oxooxazolidin-3-yl)-butanoateC16H20N2O6Ee = 88% by HPLC on Chiralpak® AD column[α]D25=-3.9 (c 3.00, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-Ethyl 4-oxo-4-(2-oxooxazolidin-3-yl)-2-phenylaminobutanoateC15H18N2O5Ee = 65% by HPLC on WHELK O1 column[α]D25=+1.5 (c 1.08, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-Ethyl 2-(2-methoxyphenylamino)-4-oxo-4-(2-oxooxazolidin-3-yl)-butanoateC16H20N2O6Ee = 21% by HPLC on WHELK O1 column[α]D25=+3.5 (c 4.53, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-Ethyl 2-(4-bromophenylamino)-4-oxo-4-(2-oxooxazolidin-3-yl)-butanoateC15H17N2O5BrEe = 46% by HPLC on Chiralpak® AD column[α]D25=+6.2 (c 1.12, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S

(S)-Ethyl 2-(4-chlorophenylamino)-4-oxo-4-(2-oxooxazolidin-3-yl)-butanoateC15H17N2O5ClEe = 26% by HPLC on Chiralpak® AD column[α]D25=+3.0 (c 1.04, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: S