New bicyclic γ- and δ-aminoalcohols as catalysts for the asymmetric diethylzinc addition to benzaldehyde

A new class of chiral non-racemic γ- and δ-amino alcohols based on bicyclo[2.2.1]heptane and bicyclo[2.2.2]octane have been synthesized and used as catalysts in the asymmetric diethylzinc addition to benzaldehyde.

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(1S,2R,4S,5R)-2-Benzyl-bicyclo[2.2.1]heptan-2,5-diolC14H18O2[α]D20=-18 (c 1.0, CHCl3), 96% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4S,5R)

(1R,2S,4S,6S)-2-Benzyl-bicyclo[2.2.2]octane-2,6-diolC15H20O2[α]D20=+61 (c 1.05, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2S,4S,6S)

(1S,4S,5R)-5-Benzyl-5-hydroxy-bicyclo[2.2.1]heptan-2-oneC14H16O2[α]D20=-45 (c 1.1, CHCl3), 96% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,4S,5R)

(1S,4R,6S)-6-Benzyl-6-hydroxy-bicyclo[2.2.2]octane-2-oneC15H18O2[α]D20=+46 (c 0.95, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,4S,6S)

(1S,4R,6R)-6-Hydroxy-6-phenyl-bicyclo[2.2.2]octan-2-oneC14H16O2[α]D20=+13 (c 1.0, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,4R,6R)

(1S,4R,6R)-6-Hydroxy-6-(1-naphthyl)-bicyclo[2.2.2]octan-2-oneC18H18O2[α]D20=+14 (c 0.65, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,4R,6R)

(1S,4R,6R)-6-Hydroxy-6-(2-methoxy-phenyl)-bicyclo[2.2.2]octan-2-oneC15H18O3[α]D20=-33 (c 1.3, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,4R,6R)

(1R,2R,4R,5R)-5-Benzylamino-2-phenyl-bicyclo[2.2.1]heptane-2-olC20H23ON[α]D20=+40 (c 0.7, CHCl3), >99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4R,5R)

(1S,2S,4S,5S)-5-Benzylamino-2-(2-methoxy-phenyl)-bicyclo[2.2.1]heptane-2-olC21H25O2N[α]D20=-5 (c 0.5, CHCl3), 99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2S,4S,5S)

(1S,2R,4S,5S)-2-Benzyl-5-benzylamino-bicyclo[2.2.1]heptan-2-olC21H25ON[α]D20=-41 (c 1.2, CHCl3), 98% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4S,5S)

(1S,2S,4S,5S)-5-Benzylamino-2-(1-naphthyl)-bicyclo[2.2.1]heptan-2-olC24H25ON[α]D20=-45 (c 0.55, CHCl3), >99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2S,4S,5S)

(1R,2R,4R,5R)-5-(N-Benzyl-N-ethyl-amino)-2-phenyl-bicyclo[2.2.1]heptan-2-olC22H27ON[α]D20=+20 (c 3.0, CHCl3), >99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1R,2R,4R,5R)

(1S,2R,4S,5S)-2-Benzyl-5-(N-benzyl-N-ethyl-amino)-bicyclo[2.2.1]heptan-2-olC23H29ON[α]D20=-21 (c 1.3, CHCl3), 98% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2R,4S,5S)

(1S,2S,4S,5S)-5-(N-Benzyl-N-ethyl-amino)-2-(2-methoxy-phenyl)-bicyclo[2.2.1]heptan-2-olC23H29O2N[α]D20=+21 (c 2.5, CHCl3), 99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2S,4S,5S)

(1S,2S,4S,5S)-5-(N-Benzyl-N-ethyl-amino)-2-(1-naphthyl)-bicyclo[2.2.1]heptan-2-olC26H29ON[α]D20=-1.5 (c 1.4, CHCl3), >99% eeSource of chirality: enzymatic resolutionAbsolute configuration: (1S,2S,4S,5S)

(1R,2R,4S,6S)-6-(N-Benzyl-N-ethyl-amino)-2-phenyl-bicyclo[2.2.2]octan-2-olC23H29ON[α]D20=+165 (c 0.6, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2R,4S,6S)

(1S,2R,4R)-2-Acetoxy-6-oxo-2-phenyl-bicyclo[2.2.2]octaneC16H18O3[α]D20=-48 (c 0.4, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,2R,4R)

(1S,2R,4R)-2-Acetoxy-6-oxo-2-(1-naphthyl)-bicyclo[2.2.2]octaneC20H20O3[α]D20=-28 (c 0.6, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,2R,4R)

(1S,2R,4R)-2-Acetoxy-6-oxo-2-(2-methoxy-phenyl)-bicyclo[2.2.2]octaneC17H20O4[α]D20=+24 (c 0.25, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,2R,4R)

(1R,2S,4S,6S)-6-Benzylamino-2-benzyl-bicyclo[2.2.2]octan-2-olC22H27ON[α]D20=+88 (c 0.65, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2S,4S,6S)

(1R,2S,4S,6S)-6-(N-Benzyl-N-ethyl-amino)-2-benzyl-bicyclo[2.2.2]octan-2-olC24H31ON[α]D20=+170 (c 0.5, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2S,4S,5S)

(1S,2R,3S)-3,6-Dibenzyl-5-methyl-4-oxa-6-aza-tricyclo[5.3.1.03,8]undecaneC24H29ON[α]D20=+4 (c 0.5, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,2R,3S)

(1S,2S,4R)-2-Acetoxy-6-oxo-2-benzyl-bicyclo[2.2.2]octaneC17H20O3[α]D20=+51 (c 0.8, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1S,2S,4R)

(1R,2R,4S,6S)-6-Benzylamino-2-phenyl-bicyclo[2.2.2]octan-2-olC21H25ON[α]D20=+129 (c 1.2, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2R,4S,6S)

(1R,2R,4S,6S)-6-Benzylamino-2-(1-naphthyl)-bicyclo[2.2.2]octan-2-olC25H27ON[α]D20=+13 (c 0.45, CHCl3), 99% eeSource of chirality: Baker’s yeast reductionAbsolute configuration: (1R,2R,4S,6S)