A structural examination of the impact of oxygenated side chains in Ephedra compounds in the catalytic asymmetric addition of diethylzinc to aldehydes

An investigation of the impact of oxygenated side chains in Ephedra compounds on the catalytic asymmetric addition of diethylzinc to aldehydes has been conducted. (1R,2S)-Ephedrine and (1S,2S)-pseudoephedrine were alkylated with either alkyl halides or β-alkoxyalkyl halides to afford a series of ligands 9a–h and 10a–h. These compounds were employed in the enantioselective addition of diethylzinc to a variety of aldehydes. It was determined that the presence of oxygen could have a negative effect in terms of obtaining high levels of enantiomeric discrimination, but the effect is diminished with higher levels of substitution near the oxygen.

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(1R,2S)-2-Butyl(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-184 (c 0.71, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-Butyl(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-84 (c 0.85, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((2-Methoxyethyl)(methyl)amino)-1-phenylpropan-1-olC13H22NO2[α]D25=-196 (c 0.71, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-((2-Methoxyethyl)(methyl)amino)-1-phenylpropan-1-olC13H22NO2[α]D25=-553 (c 0.107, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-(Isobutyl(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-165 (c 0.83, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-(Isobutyl(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-136 (c 0.61, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((2-Ethylbutyl)(methyl)amino)-1-phenylpropan-1-olC16H28NO[α]D25=-225 (c 0.61, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-((2-Ethylbutyl)(methyl)amino)-1-phenylpropan-1-olC16H28NO[α]D25=-166 (c 0.55, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((2,2-Dimethoxyethyl)(methyl)amino)-1-phenylpropan-1-olC14H24NO3[α]D25=-337 (c 0.40, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-((2,2-Dimethoxyethyl)(methyl)amino)-1-phenylpropan-1-olC14H24NO3[α]D25=-45.6 (c 1.13, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((2,2-Diethoxyethyl)(methyl)amino)-1-phenylpropan-1-olC16H28NO3[α]D25=-170 (c 0.81, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-((2,2-Diethoxyethyl)(methyl)amino)-1-phenylpropan-1-olC16H28NO3[α]D25=-138 (c 0.65, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-((Cyclopentylmethyl)(methyl)amino)-1-phenylpropan-1-olC16H26NO[α]D25=-211 (c 0.65, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-((Cyclopentylmethyl)(methyl)amino)-1-phenylpropan-1-olC16H26NO[α]D25=-173 (c 0.52, CHCl3)Source of chirality: (1S,2S)-pseudoephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-(((1,3-Dioxolan-2-yl)methyl)(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-126 (c 1.15, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)

(1R,2S)-2-(((1,3-Dioxolan-2-yl)methyl)(methyl)amino)-1-phenylpropan-1-olC14H24NO[α]D25=-51 (c 1.08, CHCl3)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (1R,2S)