Tetrabromoepifenchone: a convenient precursor for the synthesis of chiral bicyclo[2.2.1]heptane and bicyclo[2.1.1]hexane derivatives

The regiospecific reduction and Favorskii rearrangement of enantiopure tetrabromoepifenchone, which could be easily obtained by bromination of camphor, have been investigated. The selective formation of new functionalized chiral bicyclo[2.2.1]heptane and bicyclo[2.1.1]hexane derivatives in good yield has been demonstrated. Our approach provides a simple pathway for the large-scale synthesis of a wide range of novel functionalized bicyclic terpenoids starting from easily available camphor.

Figure optionsDownload as PowerPoint slide

(1S,4S,7R)-1,7-Dibromo-4-(bromomethyl)-3,3-dimethylbicyclo[2.2.1]heptan-2-oneС10Н13ОBr3Ee = 100%[α]D20 = −41.0 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1S,4R,7R,1′S,4′R,7′R)-4,4′-(E)-Ethene-1,2-diylbis(1,7-dibromo-3,3-dimethylbicyclo[2.2.1]heptan-2-one)С20Н24О2Br4Ee = 100%[α]D20 = +68.3 (c 0.95, DMSO)Source of chirality: (R)-(+)-camphor

(1R,4R,1′R,4′R)-4,4′-(E)-Ethene-1,2-diylbis(1-bromo-3,3-dimethylbicyclo[2.2.1]heptan-2-one)С20Н26О2Br2Ee = 100%[α]D20 = +33.6 (c 0.654, DMSO)Source of chirality: (R)-(+)-camphor

(1R,4R,6S)-6-Bromo-4-(dibromomethyl)-5,5-dimethylbicyclo[2.1.1]hexane-1-carboxylic acidС10Н13О2Br3Ee = 100%[α]D20 = −1.2 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1R,4S,6S)-6-Bromo-4-(bromomethyl)-5,5-dimethylbicyclo[2.1.1]hexane-1-carboxylic acidС10Н14О2Br2Ee = 100%[α]D20 = +33.2 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1R,4S,6R)-6-Bromo-4,5,5-trimethylbicyclo[2.1.1]hexane-1-carboxylic acidС10Н15О2BrEe = 100%[α]D20 = −99.8 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1R,4R)-4,5,5-Trimethylbicyclo[2.1.1]hexane-1-carboxylic acidС10Н16О2Ee = 100%[α]D20 = −7.2 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1R,4R,6R,1′R,4′R,6′R)-4,4′-(E)-Ethene-1,2-diylbis(6-bromo-5,5-dimethylbicyclo[2.1.1]hexane-1-carboxylic acid)С20Н26О4Br2Ee = 100%[α]D20 = −21.6 (c 0.95, EtOH)Source of chirality: (R)-(+)-camphor

(1R,4R,1′R,4′R)-4,4′-(E)-Ethene-1,2-diylbis(5,5-dimethylbicyclo[2.1.1]hexane-1-carboxylic acid)С20Н28О4Ee = 100%[α]D20 = +15.0 (c 0.945, EtOH)Source of chirality: (R)-(+)-camphor

(1S,4S,7R)-4,7-Dibromo-2,2-dimethyl-3-oxobicyclo[2.2.1]heptane-1-carboxylic acidС10Н12О3Br2Ee = 100%[α]D20 = −11.2 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor

(1S,4R)-4-Bromo-2,2-dimethyl-3-oxobicyclo[2.2.1]heptane-1-carboxylic acidС10Н12О3BrEe = 100%[α]D20 = −0.4 (c 0.5, MeOH)Source of chirality: (R)-(+)-camphor