Bicyclic diols and related derivatives as catalysts for the asymmetric diethylzinc addition to benzaldehyde

Chiral bicyclic diols based on bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane have been synthesized and their catalytic capacity in the asymmetric diethylzinc addition to benzaldehyde compared with those described for previously synthesized 2,6-bicyclo[2.2.2]octane-diols (BODOLs). The influence of the number of coordinating sites and the distance between them were studied.

Figure optionsDownload as PowerPoint slide

(−)-(1S,2S,4S,5R)-2-Phenyl-bicyclo[2.2.1]heptane-2,5-diolC13H16O2Ee = 94%[α]D20=-20 (c 1.1, EtOH)Absolute configuration: (1S,2S,4S,5R)

(−)-(1S,2S,4S,5R)-2-(1-Naphthyl)-bicyclo[2.2.1]heptane-2,5-diolC17H18O2Ee = 94%[α]D20=-91 (c 2.4, EtOH)Absolute configuration: (1S,2S,4S,5R)

(−)-(1S,2S,4S,5R)-2-(2-Methoxy-phenyl)-bicyclo[2.2.1]heptane-2,5-diolC14H18O3Ee = 94%[α]D20=-15 (c 1.1, CHCl3)Absolute configuration: (1S,2S,4S,5R)

(+)-(1R,2R,4S,6S)-2-(2-Trifluoromethoxy-phenyl)-bicyclo[2.2.2]octane-2,6-diolC15H17O3F3Ee >99%[α]D20=+60 (c 0.9, CHCl3)Absolute configuration: (1R,2R,4S,6S)

(+)-(1R,2R,4S,6S)-2-(2-Hydroxy-phenyl)-bicyclo[2.2.2]octane-2,6-diolC14H18O3Ee >99%[α]D20=+38 (c 0.56, CHCl3)Absolute configuration: (1R,2R,4S,6S)

(−)-(1S,4S,5S)-5-Hydroxy-5-phenyl-bicyclo[2.2.1]heptan-2-oneC13H14O2Ee >99%[α]D20=-56 (c 1.1, CHCl3)Absolute configuration: (1S,4S,5S)

(−)-(1S,4S,5S)-5- Hydroxy-5-(1-naphthyl)-bicyclo[2.2.1]heptan-2-oneC17H16O2Ee >99%[α]D20=-119 (c 1.15, t-BuOMe)Absolute configuration: (1S,4S,5S)

(−)-(1S,4S,5S)-5-Hydroxy-5-(2-methoxy-phenyl)-bicyclo[2.2.1]heptan-2-oneC14H16O3Ee = 99%[α]D20=-64 (c 1, CHCl3)Absolute configuration: (1S,4S,5S)

(−)-(1S,2S,4S,5S)-2-Phenyl-bicyclo[2.2.1]heptane-2,5-diolC13H16O2Ee >99%[α]D20=-23 (c 0.6, EtOH)Absolute configuration: (1S,2S,4S,5S)

(−)-(1S,2S,4S,5S)-2-(2-Methoxy-phenyl)-bicyclo[2.2.1]heptane-2,5-diolC14H18O3Ee >99%[α]D20=-28 (c 0.55, EtOH)Absolute configuration: (1S,2S,4S,5S)

(−)-(1S,2S,4S,5S)-2-(1-Naphthyl)-bicyclo[2.2.1]heptane-2,5-diolC17H18O2Ee >99%[α]D20=-68 (c 1.1, EtOH)Absolute configuration: (1S,2S,4S,5S)

(+)-(1R,2R,4S,6S)-6-Methoxy-2-(2-methoxy-phenyl)-bicyclo[2.2.2]octan-2-olC16H22O3Ee >99%[α]D20=+67 (c 1.5, CHCl3)Absolute configuration: (1R,2R,4S,6S)

(+)-(1R,2R,4S,6S)-6-Methoxy-2-phenyl-bicyclo[2.2.2]octan-2-olC15H20O2Ee >99%[α]D20=+60 (c 1.1, CHCl3)Absolute configuration: (1R,2R,4S,6S)