Stereochemistry of terpene derivatives. Part 4: Fragrant terpenoid derivatives with an unsaturated gem-dimethylbicyclo[3.1.0]hexane system

Starting from (+)-3-carene 1 several chiral fragrant compounds with the bicyclo[3.1.0]hexane system 4–6 and 10–20 were synthesized. These compounds are structural analogues of naturally occurring fragrant compounds, such as ionones and damascones, and possess either an endo- or an exo-cyclic double bond in the bicyclo[3.1.0]hexane moiety. The absolute configuration of selected products was confirmed by X-ray crystallography and circular dichroism analysis.

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(1S)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]but-3-en-1-olC13H20O[α]D25=-56.2 (c 0.76, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′S)

(1R)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]but-3-en-1-olC13H20O[α]D25=-83.1 (c 0.95, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′R)

(1S)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]butan-1-olC13H22O[α]D25=-141.5 (c 0.80, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′S)

(1R)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]butan-1-olC13H22O[α]D25=-98.5 (c 0.90, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′R)

(1S)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]-2-methylpropan-1-olC13H22O[α]D25=-134.2 (c 0.89, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′S)

(1R)-(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]-2-methylpropan-1-olC13H22O[α]D25=-146.0 (c 0.89, CHCl3)Source of chirality: (+)-3-carene and Grignard reactionAbsolute configuration: (1R,5S,1′R)

(1S)-(−)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]but-3-en-1-yl p-nitrobenzoateC20H23NO4[α]D25=-25.4 (c 0.88, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′S)

(1R)-(−)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]but-3-en-1-yl p-nitrobenzoateC20H23NO4[α]D25=-57.9 (c 1.04, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′R)

(1S)-(−)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]but-1-yl p-nitrobenzoateC20H25NO4[α]D25=-28.0 (c 0.60, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′S)

(1R)-(+)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]but-1-yl p-nitrobenzoateC20H25NO4[α]D25=+19.1 (c 0.60, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′R)

(1S)-(−)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]-2-methylprop-1-yl p-nitrobenzoateC20H25NO4[α]D25=-10.1 (c 1.60, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′S)

(1R)-(+)-1-[(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl]-2-methylprop-1-yl p-nitrobenzoateC20H25NO4[α]D25=+100.0 (c 0.20, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S,1′R)

(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]butan-1-oneC13H20O[α]D25=-85.4 (c 0.96, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]-2-methylpropan-1-oneC13H20O[α]D25=-120.0 (c 0.60, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

(−)-1-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]but-2-en-1-oneC13H18O[α]D25=-38.4 (c 0.60, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

(−)-4-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]but-3-en-2-oneC13H18O[α]D25=-52.5 (c 1.77, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

(−)-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]methanolC10H16O[α]D25=-208.4 (c 5.10, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

(−)-[(1R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-2-en-2-yl]methylp-nitrobenzoateC17H19NO4[α]D25=-51.5 (c 5.10, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

Methyl(−)-[(1R,5S)-3,6,6-trimethylbicyclo[3.1.0]hex-2-en-2-yl]acetateC12H18O2[α]D25=-111.6 (c 3.15, CHCl3)Source of chirality: (+)-3-careneAbsolute configuration: (1R,5S)

Ethyl(+)-[(1R,3R,5S)-3,6,6-trimethyl-2-methylenebicyclo[3.1.0]hex-3-yl]acetateC14H22O2[α]D25=+151.2 (c 5.0, CHCl3)Source of chirality: (+)-3-carene and Claisen rearrangementAbsolute configuration: (1R,3R,5S)

(+)-2-[(1R,3R,5S)-3,6,6-Trimethylbicyclo[3.1.0]hex-3-yl]ethanolC12H20O[α]D25=+251.5 (c 2.20, CHCl3)Source of chirality: (+)-3-carene and Claisen rearrangementAbsolute configuration: (1R,3R,5S)

(+)-2-[(1R,3R,5S)-3,6,6-Trimethyl-2-methylenebicyclo[3.1.0]hex-3-yl]acetateC14H22O[α]D25=+243.3 (c 5.0, CHCl3)Source of chirality: (+)-3-carene and Claisen rearrangementAbsolute configuration: (1R,3R,5S)