Stereoselective synthesis of 3,4-diaryl β-lactams

Novel 3,4-diaryl β-lactams were prepared with high stereoselectivity in an efficient manner by a palladium-catalyzed [2+2] carbonylative cycloaddition of benzyl halides with heteroarylidene amines. The type of alkyl group linked to the nitrogen atom influences the reaction’s stereoselectivity. Moreover, using chiral imines, separable diastereomeric mixtures of chiral 3,4-diaryl-β-lactams were isolated with good yields and high trans diastereoselections.

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(−)-(3R,4S,1′R)-(trans)-3-Phenyl-1-(1-phenylethyl)-4-pyridin-2-ylazetidin-2-oneC22H20N2OEe = 100%[α]D30.6=-99.25 (c 0.008, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)-3-Phenyl-1-(1-phenylethyl)-4-pyridin-2-ylazetidin-2-oneC22H20N2OEe = 100%[α]D31.4=+113.9 (c 0.015, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)

(−)-(3R,4S,1′R)-(trans)-3-Phenyl-1-(1-phenylethyl)-4-pyridin-4-ylazetidin-2-oneC22H20N2OEe = 100%[α]D28.2=-93.3 (c 0.01, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)-3-Phenyl-1-(1-phenylethyl)-4-pyridin-4-ylazetidin-2-oneC22H20N2OEe = 100%[α]D29.4=+103.3 (c 0.012, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)

(−)-(3R,4S,1′R)-(trans)-3-Phenyl-1-(1-phenylethyl)-4-pyridin-3-ylazetidin-2-oneC22H20N2OEe = 100%[α]D27.2=-79.9 (c 0.012, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)- 3-Phenyl-1-(1-phenylethyl)-4-pyridin-3-ylazetidin-2-oneC22H20N2OEe = 100%[α]D28.2=+51.5 (c 0.010, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)

(−)-(3R,4S,1′R)-(trans)-4-(4-Methylthiazol-2-yl)-3-phenyl-1-(1-phenylethyl)azetidin-2-oneC21H20N2OSEe = 100%[α]D23.0=-88.1 (c 0.010, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)-4-(4-Methylthiazol-2-yl)-3-phenyl-1-(1-phenylethyl)azetidin-2-oneC21H20N2OSEe = 100%[α]D23.0=+100.6 (c 0.012, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)

(−)-(3R,4S,1′R)-(trans)-4-Benzothiazol-2-yl-3-phenyl-1-(1-phenylethyl)azetidin-2-oneC24H20N2OSEe = 100%[α]D28.0=-72.5 (c 0.015, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)-4-Benzothiazol-2-yl-3-phenyl-1-(1-phenylethyl)azetidin-2-oneC24H20N2OSEe = 100%[α]D31.0=+86.1 (c 0.013, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)

(−)-(3R,4S,1′R)-(trans)- 3-(4-Methoxyphenyl)-1-(1-phenylethyl)-4-pyridin-2-ylazetidin-2-oneC23H22N2O2Ee = 100%[α]D24.9=-205.0 (c 0.012, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3R,4S,1′R)

(+)-(3S,4R,1′R)-(trans)- 3-(4-Methoxyphenyl)-1-(1-phenylethyl)-4-pyridin-2-ylazetidin-2-oneC23H22N2O2Ee = 100%[α]D25.7=+110.0 (c 0.012, CHCl3)Source of chirality: asymmetric inductionAbsolute configuration: (3S,4R,1′R)