Synthesis of novel norephedrine-based chiral ligands with multiple stereogenic centers and their application in enantioselective addition of diethylzinc to aldehyde and chalcone

Novel norephedrine-based chiral ligands with multiple stereogenic centers were conveniently prepared from norephedrine and N-substituted pyrrole. These novel chiral ligands were used to catalyze the enantioselective addition of diethylzinc to aldehydes and to chalcone in high yields and with good to high enantioselectivities. The absolute configuration of products was found to be affected by the stereogenic centers on the norephedrine part of the novel chiral ligands.

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2-Methyl-1-((1S)-1-phenylethyl)-1H-pyrrole-3-carbaldehydeC14H15NO[α]D25=-21.9 (c 0.8, CHCl3)Source of chirality: (S)-1-phenylethylamine

(1S,2R)-2-((2-Methyl-1-((1S)-1-phenylethyl)-1H-pyrrol-3-yl)methylamino)-1-phenylpropan-1-olC23H28N2O[α]D25=+3.7 (c 11, CHCl3)Source of chirality: (1S,2R)-norephedrine, (S)-2-methyl-1-(1-phenylethyl)-1H-pyrrole

(1S,2R)-2-((2-Methy-1-((1R)-1-phenylethyl)-1H-pyrrol-3-yl)methylamino)-1-phenylpropan-1-olC23H28N2O[α]D25=+5.6 (c 7.3, CHCl3)Source of chirality: (1S,2R)-norephedrine, (R)-2-methyl-1-(1-phenylethyl)-1H-pyrrole

5-Methyl-1-((1S)-1-phenylethyl)-1H-pyrrole-2-carbaldehydeC14H15NO[α]D25=-118.9 (c 11, CHCl3)Source of chirality: (R)-1-phenylethylamine

(1S,2R)-2-((5-Methyl-1-((1S)-1-phenylethyl)-1H-pyrrol-2-yl)methylamino)-1-phenylpropan-1-olC23H28N2O[α]D27=+28.2 (c 11, CHCl3)Source of chirality: (1S,2R)-norephedrine, (S)-2-methyl-1-(1-phenylethyl)-1H-pyrrole

(1S,2R)-2-((5-Methyl-1-((1R)-1-phenylethyl)-1H-pyrrol-2-yl)methylamino)-1-phenylpropan-1-olC23H28N2O[α]D27=+20.6 (c 15.7, CHCl3)Source of chirality: (1S,2R)-norephedrine, (R)-2-methyl-1-(1-phenylethyl)-1H-pyrrole