Synthesis and olfactory evaluation of all stereoisomers of the fragrance Nectaryl®

The fragrance Nectaryl®1 was prepared by the radical addition of cyclopentanone to (+)-limonene. All the four stereoisomers of this fragrance were prepared by the enzymatic acetylation of the corresponding alcohols in good de. The absolute configurations have been unambiguously assigned by the chemical correlation and X-ray crystal structure of a dinitrobenzoate derivate. The olfactory evaluation is also reported. The odour perception is mainly related to the configuration at the stereocentre α to the carbonyl group. Chiral protonations of the lithium enolate or the enolester of 1 to give a diastereomeric enriched mixture of 1 are reported.

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(1S,2S)-2-[(R)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanolC15H26O[α]D20=+82.8 (c 0.9, CHCl3)De = 84%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (1S,2S,2′R,1″R)

(1R,2R)-2-[(S)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanolC15H26O[α]D20=+42.2 (c 1.1, CHCl3)De = 92%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (1R,2R,2′S,1″R)

(1S,2S)-2-[(S)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanolC15H26O[α]D20=+62.9 (c 1.1, CHCl3)De = 82%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (1S,2S,2′S,1″R)

(1R,2R)-2-[(R)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanolC15H26O[α]D20=+69.8 (c 1.1, CHCl3)De = 88%Source of chirality: enzymatic resolutionAbsolute configuration: (1R,2R,2′R,1″R)

(1R,2R)-2-[(S)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentyl acetateC17H28O2[α]D20=+43.2 (c 1.1, CHCl3)De = 92%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (1R,2R,2′S,1″R)

(1R,2R)-2-[(R)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanolC17H28O2[α]D20=+52.1 (c 1.3, CHCl3)De = 88%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: 1R,2R,2′R,1″R

(S)-2-[(R)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanoneC15H24O[α]D20=-31.4 (c 1.3, CHCl3)De = 80%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (2S,2′R,1″R)

(R)-2-[(R)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanoneC15H24O[α]D20=+238.2 (c 1.1, CHCl3)De = 86%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (2R,2′R,1″R)

(S)-2-[(S)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanoneC15H24O[α]D20=-71.7 (c 1.4, CHCl3)De = 80%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (2S,2′S,1″R)

(R)-2-[(S)-2-[(R)-4-Methylcyclohex-3-enyl]propyl]cyclopentanoneC15H24O[α]D20=+197.4 (c 0.8, CHCl3)De = 89%Source of chirality: enzymatic resolution and prepared from (+)-limoneneAbsolute configuration: (2R,2′S,1″R)

(R)-4-[(R)-1-Iodopropan-2-yl]-1-methylcyclohex-1-eneC10H17I[α]D20=+37.5 (c 2.0, CHCl3)De = 93%Source of chirality: beaker yeast reductionAbsolute configuration: (2R,4′R)

(1S,2S)-2-[(R)-2-[(R)-4-Methylcyclohex-3- enyl]propyl]cyclopentyl 3,5-dinitrobenzoateC22H28N2O6[α]D20=-53.0 (c 1.0, CHCl3)De ⩾ 99%Source of chirality: enzymatic resolutionAbsolute configuration: (2S,2S,2′R,1′R)