Highly efficient synthesis of chiral aminoalcohols and aminodiols with camphane skeleton

Methylidene substituted camphor was easily epoxidized to give bridgehead oxirane-substituted camphor in the form of two diastereoisomers, isolated in pure form. These were used in aminolysis reactions with different secondary amines leading to series of chiral aminoalcohols bearing a ketone functionality. The latter could be reduced by using LAH or DIBAL to a series of aminodiols. For the determination of the configuration of the newly formed stereogenic centre, advanced NMR experiments and X-ray crystallography were used. The new aminoalcohols and aminodiols were tested as pre-catalysts for the enantioselective addition of Et2Zn to benzaldehyde showing moderate enantioselectivity.

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(1R,4R)-7,7-Dimethyl-1-((R)-oxiran-2-yl)bicyclo[2.2.1]heptan-2-oneC11H16O2[α]D20=+12.0 (c 1.25, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10R)

(1R,4R)-7,7-Dimethyl-1-((S)-oxiran-2-yl)bicyclo[2.2.1]heptan-2-oneC11H16O2[α]D20=+28.2 (c 1.25, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10S)

(1R,4R)-1-((R)-2-(Diisopropylamino)-1-hydroxyethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC17H31NO2[α]D20=-24.6 (c 1.26, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10R)

(1R,4R)-1-((R)-1-Hydroxy-2-(pyrrolidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC15H25NO2[α]D20=-10.95 (c 1.24, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10R)

(1R,4R)-1-((R)-1-Hydroxy-2-(piperidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC16H27NO2[α]D20=-15.6 (c 1.01, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10R)

(1R,4R)-1-((R)-1-Hydroxy-2-(4-methylpiperidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC17H29NO2[α]D20=-21 (c 1.30, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10R)

(1R,4R)-1-((S)-2-(Diisopropylamino)-1-hydroxyethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC17H31NO2[α]D20=+48.91 (c 1.26, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10S)

(1R,4R)-1-((S)-1-Hydroxy-2-(pyrrolidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC15H25NO2[α]D20=+1.41 (c 1.30, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10S)

(1R,4R)-1-((S)-1-Hydroxy-2-(piperidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC16H27NO2[α]D20=+34.6 (c 1.00, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10S)

(1R,4R)-1-((S)-1-Hydroxy-2-(4-methylpiperidin-1-yl)ethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-oneC17H29NO2[α]D20=+32.5 (c 1.30, CHCl3)Source of chirality: (+)-Camphor-10-sulfonyl chlorideAbsolute configuration: (1R,4R,10S)