Copper-catalyzed asymmetric conjugate addition of diethylzinc to substituted chalcones using a chiral phosphine ligand

A series of chiral phosphine PFAM and phosphine oxide POFAM ligands were studied for the copper-catalyzed asymmetric diethylzinc addition to enones. One of these ligands, PFAM2, was an efficient catalyst with a variety of enones to give conjugate addition products in up to 96% yield and 92% ee.

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((R)-1-((R)-1-Hydroxybutan-2-yl)aziridin-2-yl)(ferrocenyl)methanoneC17H21FeNO2Ee = 100%[α]D22=-112.5 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

((S)-1-((R)-1-Hydroxybutan-2-yl)aziridin-2-yl)(ferrocenyl)methanoneC17H21FeNO2Ee = 100%[α]D22=+93.6 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

(R)-2-((R)-2-Ferrocenoylaziridin-1-yl)butyl 4-methylbenzenesulfonateC24H27FeNO4SEe = 100%[α]D22=-138.9 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R)-2-((S)-2-Ferrocenoylaziridin-1-yl)butyl 4-methylbenzenesulfonateC24H27FeNO4SEe = 100%[α]D22=+95.7 (c 0.98, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

Ferrocenyl((R)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNOP[α]D22=+13.0 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNO2P[α]D22=+21.4 (c 0.4, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R)-Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanolC29H32FeNO2P[α]D28=-20.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R,R)

(S)-Ferrocenyl((R)-1-((R)-1-(diphenylphosphinoxy)butan-2-yl)aziridin-2-yl)methanolC29H32FeNO2P[α]D22=+32.8 (c 1.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R,R)

Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNOP[α]D22=+45.9 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanoneC29H30FeNO2P[α]D22=+75.8 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,R)

(S)-Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanolC29H32FeNOP[α]D22=-13.3 (c 0.5, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S,R)

(R)-Ferrocenyl((S)-1-((R)-1-(diphenylphosphino)butan-2-yl)aziridin-2-yl)methanolC29H32FeNOP[α]D22=+12.2 (c 1.0, DCM)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S,R)

(R)-1,3-Diphenylpentan-1-oneC17H18OEe = 90%[α]D25=-1.7 (c 3.2, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(−)-1-Phenyl-3-p-tolylpentan-1-oneC18H20OEe = 85%[α]D25=-3.8 (c 2.2, EtOH)Source of chirality: asymmetric synthesis

(R)-3-(4-Methoxyphenyl)-1-phenylpentan-1-oneC18H20O2Ee = 72%[α]D25=-6.4 (c 3.4, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(+)-3-(4-(Trifluoromethyl)phenyl)-1-phenylpentan-1-oneC18H17 F3OEe = 87%[α]D25=+7.7 (c 3.6, EtOH)Source of chirality: asymmetric synthesis

(+)-3-(4-Chlorophenyl)-1-phenylpentan-1-oneC17H17ClOEe = 88%[α]D25=+0.6 (c 3.6, EtOH)Source of chirality: asymmetric synthesis

(+)-3-(4-Bromophenyl)-1-phenylpentan-1-oneC17H17BrOEe = 91%[α]D25=+3.3 (c 1.9, EtOH)Source of chirality: asymmetric synthesis

(+)-3-(3-Methoxyphenyl)-1-phenylpentan-1-oneC18H20O2Ee = 89%[α]D25=+0.8 (c 2.3, EtOH)Source of chirality: asymmetric synthesis

(+)-3-Ferrocenyl-1-phenylpentan-1-oneC21H22FeOEe = 92%[α]D25=+67.0 (c 4.5, EtOH)Source of chirality: asymmetric synthesis

(+)-3-(Naphthalen-2-yl)-1-phenylpentan-1-oneC21H20OEe = 90%[α]D25=+9.1 (c 2.1, EtOH)Source of chirality: asymmetric synthesis

(+)-3-(Naphthalen-1-yl)-1-phenylpentan-1-oneC21H20OEe = 76%[α]D25=+47.0 (c 2.8, EtOH)Source of chirality: asymmetric synthesis

(R)-1-(4-Methoxyphenyl)-3-phenylpentan-1-oneC18H20O2Ee = 84%[α]D25=+5.3 (c 3.1, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(+)-1-(4-Chlorophenyl)-3-phenylpentan-1-oneC17H17ClOEe = 71%[α]D25=+5.3 (c 3.7, EtOH)Source of chirality: asymmetric synthesis

(+)-1-(4-Bromophenyl)-1-phenylpentan-1-oneC17H17BrOEe = 70%[α]D25=+4.6 (c 3.9, EtOH)Source of chirality: asymmetric synthesis

(−)-1-(3-Methoxyphenyl)-3-phenylpentan-1-oneC18H20O2Ee = 72%[α]D25=-4.8 (c 2.2, EtOH)Source of chirality: asymmetric synthesis