Synthesis of planar chiral [2.2]paracyclophane-based amino thioureas and their application in asymmetric aldol reactions of ketones with isatins

Several novel [2.2]paracyclophane-based amino thioureas have been designed and synthesized. The [2.2]paracyclophane-based amino thioureas were used as bifunctional catalysts for organocatalytic enantioselective aldol reactions between ketones and isatins, affording the desired adducts containing a chiral tertiary alcohol in high yields (up to 92% yield) and with good enantioselectivity (up to 88% ee). This is a successful example of employing planar chiral [2.2]paracyclophane-based amino thioureas in asymmetric aldol reactions.

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(RP,RP)-Bis(12-(3,5-bis(trifluoromethyl)phenyl thiocarboxamino)[2.2]paracyclophan-4-yl methylene)amineC52H43F12N5S2[α]D20=-79 (c 0.07, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP,RP)

(RP,S)-4-(3,5-Bis(trifluoromethyl)phenyl thiocarboxamino)-12-prolinamido[2.2]paracyclophaneC30H28F6N4OS[α]D20=-146 (c 0.08, CH2Cl2)Source of chirality: (S)-proline; (RP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,RP)

(SP,S)-4-(3,5-Bis(trifluoromethyl)phenyl thiocarboxamino)-12-prolinamido[2.2]paracyclophaneC30H28F6N4OS[α]D20=+86 (c 0.1, CH2Cl2)Source of chirality: (S)-proline; (SP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,Sp)

(RP)-4-Aminomethyl-12-bromo[2.2]paracyclophaneC17H19BrN[α]D20=-165 (c 0.1, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)

(RP,RP)-Bis(12-bromo[2.2]paracyclophan-4-yl methylene)amineC34H34Br2N[α]D20=-91 (c 0.05, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)

(RP,RP)-Bis(12-amino[2.2]paracyclophan-4-yl methylene)amineC34H38N3[α]D20=-102 (c 0.1, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)

(RP,S)-4-Amino-12-(N-Boc-prolinamido)[2.2]paracyclophaneC26H34N3O3[α]D20=-248 (c 0.09, CH2Cl2)Source of chirality: (S)-proline; (RP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,RP)