The role of conformational flexibility on the catalytic activity of norbornane-derived β-, γ- and δ-amino alcohols

Enantiopure norbornane-based γ-amino alcohols 1–4 have been obtained from (+)-camphor and their catalytic behaviour as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde compared to these described for homologous β- and δ-amino alcohols. This has allowed the first study on the influence of the size of the catalytic zinc-chelate ring on the catalytic activity, which results in the unexpected observance of a non-linear correlation between enantioselectivity and chelate ring size (conformational flexibility). An empirical rationalisation of the observed phenomenon was realised on the basis of consideration of the energetically-favoured Noyori-type transition states.

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1-[(Ethylamino)methyl]-3,3-dimethylnorbornan-2-olC12H23NO[α]D20=-4.5 (c 0.62, MeOH)Source of chirality: natural (1R)-(+)-camphorAbsolute configuration: (1S,2R)

1-[(Dimethylamino)methyl]-3,3-dimethylnorbornan-2-olC12H23NO[α]D20=-9.3 (c 0.50, MeOH)Source of chirality: natural (1R)-(+)-camphorAbsolute configuration: (1S,2R)

1-[(Diethylamino)methyl]-3,3-dimethylnorbornan-2-olC14H27NO[α]D20(hydrochloride)=-14.5 (c 1.17, MeOH)Source of chirality: natural (1R)-(+)-camphorAbsolute configuration: (1S,2R)

1-[(Dipropylamino)methyl]-3,3-dimethylnorbornan-2-olC16H31NO[α]D20(hydrochloride)=-2.7 (c 0.70, MeOH)Source of chirality: natural (1R)-(+)-camphorAbsolute configuration: (1S,2R)