Asymmetric Michael reactions of α,α-disubstituted aldehydes with maleimides using a primary amine thiourea organocatalyst

Primary amine thiourea organocatalyst 8 was used to promote Michael additions of bulky α,α-disubstituted aldehydes, such as isobutyraldehyde with maleimides to afford the corresponding adducts in high to excellent yields and with up to 91% ee.

Figure optionsDownload as PowerPoint slide

(S)-1-(1-Amino-3-phenylpropan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)thioureaC18H17F6N3SEe = 100%[α]D20=-57.6 (c 1.00, CHCl3)Source of chirality: l-phenylalanineAbsolute configuration: (S)

(S)-1-(1-Azido-3-phenylpropan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)thioureaC18H15F6N5SEe = 100%[α]D22=+4.8 (c 1.00, CHCl3)Source of chirality: l-phenylalanineAbsolute configuration: (S)