Synthesis of a series of novel N,N-dialkyl-TsDPEN ligands and their application to enantioselective addition of dialkylzinc to benzaldehyde

A series of mono- and dialkylated derivatives of C2-symmetric N-tosyl-1,2-diphenylethylene diamines have been prepared and used as ligands for the enantiomeric control of the addition of diethylzinc to aldehydes. Addition products of up to 79% ee were formed.

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N-(2-Diethylamino-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC25H30N2O2SEe = 100%[α]D20=+11.4 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-(1,2-Diphenyl-2-pyrrolidin-1-yl-ethyl)-4-methyl-benzenesulfonamideC25H28N2O2SEe = 100%[α]D20=-1.6 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-(1,2-Diphenyl-2-piperidin-1-yl-ethyl)-4-methyl-benzenesulfonamideC26H30N2O2SEe = 100%[α]D20=+3.3 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-(2-Azepan-1-yl-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC27H32N2O2SEe = 100%[α]D20=+39 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-[2-(1,3-Dihydro-isoindol-2-yl)-1,2-diphenyl-ethyl]-4-methyl-benzenesulfonamideC29H27N2O2SEe = 100%[α]D23=+16.5 (c 0.2, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

4-Methyl-N-(2-morpholin-4-yl-1,2-diphenyl-ethyl)-benzenesulfonamideC25H28N2O3SEe = 100%[α]D20=+12.7 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

4-Methyl-N-(2-piperidin-1-yl-cyclohexyl)-benzenesulfonamideC18H28N2O2SEe = 100%[α]D20=-92 (c 1, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-N-tosyl-1,2-cyclohexadiamineAbsolute configuration: (1R,2R)

N-[2-(Benzyl-ethyl-amino)-1,2-diphenyl-ethyl]-4-methyl-benzenesulfonamideC30H31N2O2SEe = 100%[α]D20=-33 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-(2-Ethylamino-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC23H26N2O2SEe = 100%[α]D20=-11.5 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-[2-(2,2-Dimethyl-propylamino)-1,2-diphenyl-ethyl]-4-methyl-benzenesulfonamideC26H32N2O2SEe = 100%[α]D20=-37 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-(2-Benzylamino-1,2-diphenyl-ethyl)-4-methyl-benzenesulfonamideC28H28N2O2SEe = 100%[α]D20=-33 (c 0.5, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)

N-Benzyl-N-[1,2-diphenyl-2-(toluene-4-sulfonylamino)-ethyl]-acetamideC30H30N2O3SEe = 100%[α]D25=-46 (c 1.0, CHCl3)Source of chirality: enantiomerically pure starting material, (RR)-TsDPENAbsolute configuration: (1R,2R)

N-[1,2-Diphenyl-2-(toluene-4-sulfonylamino)-ethyl]-acetamideC23H24N2O3SEe = 100%[α]D20=+7 (c 1.0, CHCl3)Source of chirality: enantiomerically pure starting material, (R,R)-TsDPENAbsolute configuration: (1R,2R)