Enantiospecific synthesis of angular triquinanes

The enantiospecific synthesis of angular triquinanes has been developed starting from the readily available (S)-campholenaldehyde. Two alternate strategies have been used, one employing a Johnson’s orthoester Claisen rearrangement followed by an intramolecular cyclopropanation and regioselective cyclopropane ring cleavage, and a second one based on a RCM reaction.

Figure optionsDownload as PowerPoint slide

(3S,5R)-3-(Methoxymethoxy)-6,6,7-trimethylbicyclo[3.3.0]octa-1,7-diene-2-methanolC14H22O3[α]D22=-40.0 (c 0.6, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (3S,5R)

Ethyl 2-[(1R,5S,7S)-7-(methoxymethoxy)-3,4,4-trimethyl-8-methylenebicyclo[3.3.0]oct-2-en-1-yl]acetateC18H28O4[α]D23=-17.6 (c 7.0, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1R,5S,7S)

(1S,2S,4S,8R,11S)-2-(Methoxymethoxy)-5,5,6-trimethyltetracyclo[6.4.0.01,11.04,8]dodec-6-en-10-oneC17H24O3[α]D22=+80.0 (c 1.4, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1S,2S,4S,8R,11S)

(1S,4R,5S,6R,8S,10S)-10-(Methoxymethoxy)-6,7,7-trimethyl-11-methylenetetracyclo [6.3.0.01,5.04,6]undecan-3-oneC17H24O3[α]D22=-8.6 (c 0.7, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1S,4R,5S,6R,8S,10S)

(1R,5S,6S,8S)-6-(Methoxymethoxy)-5,9,9,10-tetramethyltricyclo[6.3.0.01,5]undec-10-en-3-oneC17H26O3[α]D22=-5.0 (c 1.2, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1R,5S,6S,8S)

Methyl (1R,2R,5S)-2-allyl-6,6,7-trimethyl-3-oxo-1-vinylbicyclo[3.3.0]oct-7-ene-2-carboxylateC18H24O3[α]D22=-28.5 (c 3.5, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1R,2R,5S)

Methyl (1R,2S,5S)-2-allyl-6,6,7-trimethyl-3-oxo-1-vinylbicyclo[3.3.0]oct-7-ene-2-carboxylateC18H24O3[α]D23=-13.8 (c 2.1, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1R,2S,5S)

Methyl (1R,5R,8S)-9,9,10-trimethyl-6-oxotricyclo[6.3.0.01,5]undeca-2,10-diene-5-carboxylateC16H20O3[α]D24=+21.9 (c 1.6, CHCl3).Source of chirality: campholenaldehydeAbsolute configuration: (1R,5R,8S)