N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines

N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.

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(1S,2S)-2-(Benzylamino)-1-phenylpropan-1-olC16H19NO[α]D24=+128.9 (c 1, CH2Cl2)Source of chirality: (1S,2S)-pseudonorephedrineAbsolute configuration: (1S,2S)

(1S,2S)-1-Phenyl-2-(pyridin-2-ylmethylamino)propan-1-olC15H18N2O[α]D25=+92.1 (c 1, CH2Cl2)Source of chirality: (1S,2S)-pseudonorephedrineAbsolute configuration: (1S,2S)

(1S,2S)-2-((6-Methylpyridin-2-yl)methylamino)-1-phenyl-1-propanolC16H21N2Owhite solid[α]D25=+112.5 (c 1, CH2Cl2)Source of chirality: (1S,2S)-pseudonorephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((6-Methylpyridin-2-yl)methylamino)-1-phenyl-1-propanolC16H20N2O[α]D25=+12.8 (c 1, CH2Cl2)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

(1S,2S)-1-Phenyl-2-(quinolin-2-ylmethylamino)-1-propanolC19H20N2O[α]D25=+132.5 (c 1, CH2Cl2)Source of chirality: (1S,2S)-pseudonorephedrineAbsolute configuration: (1S,2S)

(1R,2S)-1-Phenyl-2-(quinolin-2-ylmethylamino)-1-propanolC19H20N2O[α]D25=+34.9 (c 1, CH2Cl2)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-(Benzyl(methyl)amino)-1-phenyl-1-propanolC17H21NO[α]D23=+110.7 (c 1, CH2Cl2)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)-ephedrine

(1S,2S)-2-(Methyl(pyridin-2-ylmethyl)amino)-1-phenyl-1-propanolC16H20NO2[α]D23.2=+98.2 (c 1.0, CH2Cl2)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-(Dibenzylamino)-1-phenylpropan-1-olC23H25NO[α]D24.4=-40.4 (c 1.38, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(R)-1-(Naphthalen-2-yl)propan-1-olC13H14O[α]D24.4=-40.4 (c 1.38, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (R)

(1R,2S)-2-(Methyl(pyridin-3-ylmethyl)amino)-1-phenylpropan-1-olC16H20NO2[α]D23.2=+98.2 (c 1.0, CH2Cl2)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(R,E)-1-Phenylpent-1-en-3-olC11H14O[α]D25=+4.8 (c 1.0, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (R)

(R)-P,P-Diphenyl-N-(1-phenylpropyl)phosphinic amideC21H22NOP[α]D24=+20.4 (c 0.6, CHCl3)Source of chirality: (1R,2S)-N-benzylephedrineAbsolute configuration: (1R,2S)-ephedrine

(R)-1-(Benzyloxy)butan-2-olC11H16O2[α]D25=+0.3 (c 1.7, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1R,2S)-2-(Benzyl(methyl)amino)-1-phenylpropan-1-olC17H21NO[α]D23=-22.2 (c 1.03, CH2Cl2)Source of chirality: (1R,2S)-N-benzylephedrineAbsolute configuration: (1R,2S)-ephedrine

(R)-N-(1-(4-Chlorophenyl)propyl)-P,P-diphenylphosphinic amideC21H21ClNOP[α]D23=+45.3 (c 0.4, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(R)-N-(1-(4-Fluorophenyl)propyl)-P,P-diphenylphosphinic amideC21H21FNOP[α]D24.0=+19.0 (c 1.0, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(R)-N-(1-(4-Methoxyphenyl)propyl)-P,P-diphenylphosphinic amideC22H24NO2P[α]D25=+35.6 (c 0.9, CHCl3)Source of chirality: (1R,2S)-N-benzylephedrineAbsolute configuration: (1R,2S)