Synthesis of chiral norbornane derivatives as γ-amino alcohol catalysts: the effect of the functional group positions on the chirality transfer

Starting from (1S,4R) chiral ketone (+)-6, we developed a synthetic route to the synthesis of new chiral γ-amino alcohols (+)- and (−)-syn-2-amino-7-hydroxy norbornane derivatives with excellent yields and enantiomeric excesses (up to 99%). These compounds were tested as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde presenting moderate results. The results obtained, compared with others previously reported, showed that the relative disposition of the amino and hydroxyl groups on C(2) and C(7) positions, play an important role in the catalytic activity.

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(−)-7,7-Dimethoxy-2-oximo-norbornaneC9H15NO3Ee >99%[α]D20=-35.5 (c 1.1, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,4R)

(−)-7,7-Dimethoxy-2-exo-amino-norbornaneC9H17NO2Ee >99%[α]D20=-18.0 (c 1.0, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R)

(−)-7,7-Dimethoxy-2-exo-trifluoroacetamide-norbornaneC11H16NO3F3Ee >99%[α]D20=-7.4 (c 1.2, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R)

(−)-2-exo-Piperidine-7-syn-hydroxy-norbornaneC12H21NOEe >99%[α]D20=-30.0 (c 1.0, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(+)-2-exo-Acetamido-7-syn-hydroxy-norbornaneC9H15NO2Ee >99%[α]D20=+5.4 (c 1.1, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(−)-2-exo-Ethylamino-7-syn-hydroxy-norbornaneC9H17NOEe >99%[α]D20=-20.0 (c1.0, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(+)-2-exo-Acetylethylamino-7-syn-acetate-norbornaneC13H21NO3Ee >99%[α]D20=+2.0 (c 1.1, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(−)-2-exo-N,N-Diethylamino-7-syn-hydroxy-norbornaneC11H21NOEe >99%[α]D20=-41.0 (c 1.1, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(−)-2-exo-N,N-Dimethylamino-7-syn-hydroxy-norbornaneC9H17NOEe >99%[α]D20=-25.0 (c 1.2, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(+)-2-exo-Trifluoroacetamide-7-one-norbornaneC9H10NO2F3Ee >99%[α]D20=+8.5 (c 2.0, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R)

(−)-2-exo-Trifluoroacetamide-7-syn-hydroxy-norbornaneC9H12NO2F3Ee >99%[α]D20=-3.6 (c 1.1, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(−)-2-exo-Amino-7-syn-hydroxy-norbornaneC7H13NOEe >99%[α]D20=-5.0 (c 1.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)

(+)-2-exo-Acetamido-7-syn-acetate-norbornaneC11H17NO3Ee >99%[α]D20=+22.3 (c 1.2, EtOAc)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,7S)