Brønsted acid catalyzed enantio- and diastereoselective one-pot three component Mannich reaction

A chiral derivative of 1,2-benzenedisulfonimide, (−)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Mannich protocol. Reaction conditions are mild and green, while the enantio- and diastereoselectivity are excellent.

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(R)-1,3-Diphenyl-3-(N-phenylamino)propan-1-oneC21H19NOEe = 90.2% determined by GC connected to a chiral stationary phase column[α]D21 = −14.4 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-Phenyl-3-(N-phenylamino)-3-(4-tolyl)propan-1-oneC22H21NOEe = 92.8% determined by GC connected to a chiral stationary phase column[α]D21 = −18.4 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-Phenyl-3-(N-phenylamino)-3-(2-tolyl)propan-1-oneC22H21NOEe = 92.2% determined by GC connected to a chiral stationary phase column[α]D21 = −12.8 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-Phenyl-3-(N-phenylamino)-3-(3-tolyl)propan-1-oneC22H21NOEe = 93.6% determined by GC connected to a chiral stationary phase column[α]D21 = −14.7 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-(4-Nitrophenyl)-1-phenyl-3-(N-phenylamino)propan-1-oneC21H18N2O3Ee = 96.4% determined by GC connected to a chiral stationary phase column[α]D21 = −19.5 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-(2-Nitrophenyl)-1-phenyl-3-(N-phenylamino)propan-1-oneC21H18N2O3Ee = 96.4% determined by GC connected to a chiral stationary phase column[α]D21 = −19.9 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-(3-Nitrophenyl)-1-phenyl-3-(N-phenylamino)propan-1-oneC21H18N2O3Ee = 97.8% determined by GC connected to a chiral stationary phase column[α]D21 = −13.7 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-(4-Chlorophenyl)-1-phenyl-3-(N-phenylamino)propan-1-oneC21H18ClNOEe = 97.8% determined by GC connected to a chiral stationary phase column[α]D21 = −15.2 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1,3-Diphenyl-3-[N-(4-tolyl)amino]propan-1-oneC22H21NOEe = 90.3% determined by GC connected to a chiral stationary phase column[α]D21 = −11.7 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1,3-Diphenyl-3-[N-(3-tolyl)amino]propan-1-oneC22H21NOEe = 96.2% determined by GC connected to a chiral stationary phase column[α]D21 = −5.4 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1,3-Diphenyl-3-[N-(4-nitrophenyl)amino]propan-1-oneC21H18N2O3Ee = 96.3% determined by GC connected to a chiral stationary phase column[α]D21 = −13.8 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1,3-Diphenyl-3-[N-(3-nitrophenyl)amino]propan-1-oneC21H18N2O3Ee = 92.0% determined by GC connected to a chiral stationary phase column[α]D21 = −12.2 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1,3-Diphenyl-3-[N-(4-chlorophenyl)amino]propan-1-oneC21H18ClNOEe = 95.0% determined by GC connected to a chiral stationary phase column[α]D21 = −14.1 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-Phenyl-3-(N-phenylamino)-1-(4-tolyl)propan-1-oneC22H21NOEe = 92.2% determined by GC connected to a chiral stationary phase column[α]D21 = −15.8 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-Phenyl-3-(N-phenylamino)-1-(4-chlorophenyl)propan-1-oneC21H18ClNOEe = 95.4% determined by GC connected to a chiral stationary phase column[α]D21 = −13.2 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-3-Phenyl-3-(N-phenylamino)-1-(4-tolyl)propan-1-oneC22H21NOEe = 95.0% determined by GC connected to a chiral stationary phase column[α]D21 = +13.2 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-Phenyl-3-(N-phenylamino)-3-(2-thienyl)propan-1-oneC19H17NOSEe = 90.6% determined by GC connected to a chiral stationary phase column[α]D21 = −10.4 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-Phenyl-1-(N-phenylamino)hexan-3-oneC18H21NOEe = 94.2% determined by GC connected to a chiral stationary phase column[α]D21 = −9.4 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R)

(R)-1-(N-Phenylamino)-1-(4-tolyl)hexan-3-oneC19H23NOEe = 92.4% determined by GC connected to a chiral stationary phase column[α]D21 = −10.7 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R)

(R)-1-[N-(4-Nitrophenyl)amino]-1-phenylhexan-3-oneC18H20N2O3Ee = 90.1% determined by GC connected to a chiral stationary phase column[α]D21 = −10.0 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R)

(R)-1-(4-Chlorophenyl)-3-(4-nitrophenyl)-3-[N-(4-tolyl)amino]propan-1-oneC22H19ClN2O3Ee = 91.8% determined by GC connected to a chiral stationary phase column[α]D21 = −18.3 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-1-(4-Chlorophenyl)-3-(4-nitrophenyl)-3-[N-(4-tolyl)amino]propan-1-oneC22H19ClN2O3Ee = 91.2% determined by GC connected to a chiral stationary phase column[α]D21 = −16.9 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R)

(R)-2-[(R)-Phenyl(N-phenylamino)methyl]cyclohexanoneC19H21NOEe = 92.0% determined by GC connected to a chiral stationary phase column[α]D21 = +35.9 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)

(R)-2-[(R)-4-Tolyl(N-phenylamino)methyl]cyclohexanoneC20H23NOEe = 94.1% determined by GC connected to a chiral stationary phase column[α]D21 = +24.2 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)

(R)-2-[(R)-4-Nitrophenyl(N-phenylamino)methyl]cyclohexanoneC19H20N2O3Ee = 93.8% determined by GC connected to a chiral stationary phase column[α]D21 = +27.7 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)

(R)-2-[(R)-4-Chlorophenyl(N-phenylamino)methyl]cyclohexanoneC19H20ClNOEe = 92.6% determined by GC connected to a chiral stationary phase column[α]D21 = +29.8 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)

(R)-2-{(R)-Phenyl[N-(4-nitrophenylamino)]methyl}cyclohexanoneC19H20N2O3Ee = 90.0% determined by GC connected to a chiral stationary phase column[α]D21 = +25.1 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)

(R)-2-{(R) Phenyl[N-(4-chlorophenylamino)]methyl}cyclohexanoneC19H20ClNOEe = 91.4% determined by GC connected to a chiral stationary phase column[α]D21 = +32.3 (c 0.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (2R)