Synthesis of enantiopure 2-aminoalkylphenols by stereoselective addition of Grignard reagents to chiral 2-imidoylphenols

The stereoselective addition of Grignard reagents to chiral 2-imidoylphenols affords enantiopure 2-aminoalkylphenols, a class of ligands useful in stereoselective synthesis. Unusually benzyl- and allyl-magnesium chlorides add to ketimines derived from enolizable o-acylphenols with high yields and stereoselectivities. In this way a stereogenic quaternary C-1 carbon atom is introduced, which could not be obtained by other methods available till now. The mechanism and the asymmetric induction have been explained in agreement with previously obtained results.

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2-((1S)-1-Methyl-2-phenyl-1-{[(1′R)-1′-phenylethyl]amino}ethyl)phenolC23H25NOE.e.=98%[α]D20=+95.0 (c 1.6, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: 1S,1′R

2-((1S)-1-Ethyl-1-{[(1′R)-1′-phenylethyl]amino}but-3-enyl)phenolC20H25NOE.e.=98%[α]D20=−28.0 (c 3.0, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: 1S,1′R

2-((1S)-1-Ethyl-2-phenyl-1-{[(1′R)-1′-phenylethyl]amino}ethyl)phenolC24H27NOE.e.=98%[α]D20=+83.5 (c 1.2, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: 1S,1′R

2-((1S)-1-Ethyl-2-phenyl-1-{[(1′R)-1′-phenylethyl]amino}ethyl)phenolC24H25NOE.e.=98%[α]D20=+52.9 (c 1.6, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: R,R

2-((1R)-1,2-Diphenyl-1-{[(1′R)-1′-phenylethyl]amino}ethyl)phenolC28H27NOE.e.=98%[α]D20=+61.8 (c 2.0, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: R,R