Enantioselective aldol reactions of α,β-unsaturated ketones with trifluoroacetophenone catalyzed by a chiral primary amine

Chiral primary amine catalyzed direct asymmetric aldol reactions of ketones with trifluoroacetophenone, afforded trifluoromethylated β-hydroxycarbonyl aldol products bearing a quaternary carbon stereogenic center in high yields (up to 93% yield) and with high to excellent enantioselectivities of up to 99% ee.

Figure optionsDownload as PowerPoint slide

(R,E)-6,6,6-Trifluoro-5-hydroxy-1,5-diphenylhex-1-en-3-one82% ee[α]D25 = −228.2 (c 0.11, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-1-(4-fluorophenyl)-5-hydroxy-5-phenylhex-1-en-3-one87% ee[α]D25 = −256.3 (c 0.16, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one86% ee[α]D25 = −217.2 (c 0.18, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(4-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one87% ee[α]D25 = −233.2 (c 0.22, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-5-hydroxy-5-phenyl-1-(p-tolyl)hex-1-en-3-one91% ee[α]D25 = −283.0 (c 0.10, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-5-hydroxy-1-(4-methoxyphenyl)-5-phenylhex-1-en-3-one87% ee[α]D25 = −251.9 (c 0.16, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(2-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one83% ee[α]D25 = −131.6 (c 0.19, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(2-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one83% ee[α]D25 = −142.3 (c 0.26, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(3-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one85% ee[α]D25 = −162.6 (c 0.19, CH2Cl2).Absolute configuration: (R)

(R,E)-1-(3-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-5-phenylhex-1-en-3-one83% ee[α]D25 = −170.0 (c 0.30, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-5-hydroxy-5-phenyl-1-(m-tolyl)hex-1-en-3-one87% ee[α]D25 = −250.0 (c 0.16, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-trifluoro-5-hydroxy-1-(3-methoxyphenyl)-5-phenylhex-1-en-3-one87% ee[α]D25 = −146.0 (c 0.10, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-1-(furan-2-yl)-5-hydroxy-5-phenylhex-1-en-3-one85% ee[α]D25 = −138.0 (c 0.05, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-5-hydroxy-5-phenyl-1-(thiophen-2-yl)hex-1-en-3-one87% ee[α]D25 = −153.8 (c 0.03, CH2Cl2).Absolute configuration: (R)

(R,E)-5-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-1-phenylhex-1-en-3-one92% ee[α]D25 = −290.0 (c 0.13, CH2Cl2).Absolute configuration: (R)

(R,E)-5-(4-Chlorophenyl)-6,6,6-trifluoro-5-hydroxy-1-(p-tolyl)hex-1-en-3-one93% ee[α]D25 = −227.2 (c 0.18, CH2Cl2).Absolute configuration: (R)

(R,E)-5-(4-Bromophenyl)-6,6,6-trifluoro-5-hydroxy-1-phenylhex-1-en-3-one99% ee[α]D25 = −263.6 (c 0.20, CH2Cl2).Absolute configuration: (R)

(R,E)-6,6,6-Trifluoro-5-hydroxy-1-phenyl-5-(p-tolyl)hex-1-en-3-oneyield: 68%, 86% ee[α]D25 = −170.0 (c 0.21, CH2Cl2).Absolute configuration: (R)

(S,E)-6,6,6-Trifluoro-5-hydroxy-1-phenyl-5-(thiophen-2-yl)hex-1-en-3-one81% ee[α]D25 = −156.2 (c 0.20, CH2Cl2).Absolute configuration: (S)

(R,E)-1,1,1-Trifluoro-2-hydroxy-2-phenylnon-5-en-4-oneyield: 64%, 93% ee[α]D25 = −71.8 (c 0.28, CH2Cl2).Absolute configuration: (R)

(R,E)-1,1,1-Trifluoro-2-hydroxy-2-phenyldodec-5-en-4-one92% ee[α]D25 = −90.8 (c 0.21, CH2Cl2).

(R,E)-1,1,1-Trifluoro-2-hydroxy-7-methyl-2-phenyloct-5-en-4-one92% ee[α]D25 = −103.0 (c 0.16, CH2Cl2).Absolute configuration: (R)