Ruthenium(II) and rhodium(III) catalyzed asymmetric transfer hydrogenation (ATH) of acetophenone in isopropanol and in aqueous sodium formate using new chiral substituted aromatic monosulfonamide ligands derived from (1R,2R)-diaminocyclohexane

A series of aromatic monosulfonamide ligands derived from (1R,2R)-diaminocyclohexane were synthesized with electron withdrawing and donating groups. These were complexed with Rh(Cp∗) or Ru(arene) and their catalytic efficiencies were compared in the ATH of acetophenone using sodium formate/water or isopropanol/KOH as the hydrogen source. Results suggest that substituents on the benzene ring of the sulfonamide have very little electronic impact on the enantioselectivity and mechanism of the reaction.

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N-(1R,2R)-(2-Aminocyclohexyl)-2-(trifluoromethyl)benzenesulfonamideC13H17F3N2O2SEe = 100%[α]D25=-25 (c 0.13, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-{(1R,2R)-(2-Aminocyclohexyl)-3-trifluoromethyl}benzenesulfonamideC13H17F3N2O2SEe = 100%[α]D25=-34 (c 0.52, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-(trifluoromethyl)benzenesulfonamideC13H17F3N2O2SEe = 100%[α]D25=-57 (c 0.26, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-2,3,4-(trifluoro)benzenesulfonamideC12H15F3N2O2SEe = 100%[α]D25=-46 (c 0.56, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-2-fluorobenzenesulfonamideC12H17FN2O2SEe = 100%[α]D25=-30 (c 0.66, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-3-fluorobenzenesulfonamideC12H17FN2O2SEe = 100%[α]D25=-64 (c 0.52, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-5-fluoro-2-methyl-benzenesulfonamideC13H19FN2O2SEe = 100%[α]D25=-63 (c 0.41 CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-iodobenzenesulfonamideC12H17IN2O2SEe = 100%[α]D25=-39 (c 0.42 CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-chloro-benzenesulfonamideC12H17ClN2O2SEe = 100%[α]D25=-22 (c 0.31, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-2,5-dichlorobenzenesulfonamideC12H16Cl2N2O2SEe = 100%[α]D25=-29 (c 0.11, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-chloro-2-methoxybenzenesulfonamideC13H19ClN2O3SEe = 100%[α]D25=-33 (c 0.57, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-cyano-benzenesulfonamideC13H17N3O2SEe = 100%[α]D25=-47 (c 0.45, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-3-cyano-benzenesulfonamideC13H17N3O2SEe = 100%[α]D25=-63 (c 0.42 CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

4-Acetyl-N-(1R,2R)-(2-aminocyclohexyl)benzenesulfonamideC14H20N2O3SEe = 100%[α]D25=-28 (c 0.22, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-2-Aminocyclohexyl-4-butoxy-benzenesulfonamideC16H26N2O3SEe = 100%[α]D25=-33 (c 0.44, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-2,5-dimethoxy-benzenesulfonamideC14H22N2O4SEe = 100%[α]D25=-15 (c 0.81, CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-4-methoxy-benzenesulfonamideC13H20N2O3SEe = 100%[α]D25=-57 (c 0.26 CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)

N-(1R,2R)-(2-Aminocyclohexyl)-3-methoxy-benzenesulfonamideC13H20N2O3SEe = 100%[α]D25=-85 (c 1.0 CH2Cl2)Source of chirality: chiral starting materialAbsolute configuration: (R,R)