New Dienone-Type Musk Odorants
H3), 1.54–1.62 (m, 1 H, 5-H), 1.69–1.84 (m, 2 H, 3-, 4-Ha), 1.82
(br. s, 2 H, OH), 1.85–1.94 (m, 1 H, 1ЈЈ-H), 4.59/4.60 (2q, J =
a pad of Celite®, and washed with Et2O (50 mL). The combined
filtrates were evaporated on a rotary evaporator, and the resulting
6.5 Hz, 1 H, 3Ј-H) ppm. 13C NMR (CDCl3): δ = 21.6/21.7 (2q, 1ЈЈ- residue was purified by silica gel FC (pentane/Et2O, 98:2, Rf = 0.12)
Me2), 22.2/22.4 (2q, 2-Me2), 24.3/24.5 (2q, C-4Ј), 25.4/26.8 (2t, C-
to provide the odoriferous title compound 18 (1.12 g, 89%) as col-
4), 30.1/32.3 (2d, C-1ЈЈ), 35.4/35.7 (2t, C-3), 46.1/48.3 (2s, C-2), orless liquid. IR (neat): ν = 1688 (s, νC=O, conj.), 1458 [m,
˜
54.0/54.1 (2d, C-5), 58.3/58.4 (2d, C-3Ј), 80.1/82.0 (2s, C-1), 84.3/
δas(CH3)], 1360 [m, δs(CH3)], 1252 (s, νC=C–C=O), 973 (m,
86.4 (s, C-1Ј), 87.8/89.6 (2s, C-2Ј) ppm. MS (EI): m/z (%) = 224 (2) δC=C–H) cm–1. 1H NMR (CDCl3): δ = 1.04 (d, J = 7.0 Hz, 6 H, 1ЈЈ-
[M]+, 209 (3) [M – CH3]+, 206 (10) [M – H2O]+, 191 (61) [M – Me2), 1.18 (s, 6 H, 5Ј-Me2), 1.67 (t, J = 7.5 Hz, 2 H, 4Ј-H2), 2.29
C2H5O]+, 45 (12) [C2H5O]+.
(s, 3 H, 1-H3), 2.34 (d, J = 7.5 Hz, 2 H, 3Ј-H2), 2.99 (sept, J =
7.0 Hz, 1 H, 1ЈЈ-H), 6.28 (d, J = 16.5 Hz, 1 H, 3-H), 7.37 (d, J =
16.5 Hz, 1 H, 4-H) ppm. 13C NMR (CDCl3): δ = 21.2 (q, 1ЈЈ-Me2),
26.9 (q, 5Ј-Me2), 27.3 (d, C-1ЈЈ), 27.6 (q, C-1), 28.7 (t, C-3Ј), 40.2
(t, C-4Ј), 46.3 (s, C-5Ј), 125.7 (d, C-3), 136.4 (d, C-4), 138.3 (s, C-
1Ј), 159.0 (s, C-2Ј), 199.0 (s, C-2) ppm. MS (EI): m/z (%) = 206 (6)
[M]+, 191 (5) [M – CH3]+, 163 (100) [M – C2H3O]+, 43 (38)
[C3H7]+. C14H22O (206.3): calcd. C 81.50, H 10.75; found C 81.43,
H 10.70. Odor: Powerful musk note with a special fruity-floral
character recalling pumpkins, dried apples, violets and orris, in
front of an elegant woody background. Odor threshold:
5.7 ng/L air.
4-(2Ј-Isopropyl-5Ј,5Ј-dimethylcyclopent-1Ј-enyl)but-3-yn-2-ol (16):
At 0 °C, a solution of 15 (4.82 g, 21.5 mmol) in THF (20 mL) was
added within 5 min to a mixture of 20% aq. H2SO4 (150 mL) and
THF (150 mL). After stirring for 2 h at 0 °C, the reaction mixture
was extracted with Et2O (3ϫ200 mL), and the combined organic
extracts were washed with satd. aq. NaHCO3 solution (2ϫ200 mL)
and brine (2ϫ100 mL). After drying (Na2SO4), the solvent was
evaporated on a rotary evaporator, and the resulting residue was
purified by silica gel FC (pentane/Et2O, 95:5, Rf = 0.14) to provide
the title compound 16 (2.27 g, 51%) as colorless oil. IR (neat): ν =
˜
3331 (m, νO–H), 2150 (w, δCϵC–C), 1455 [m, δas(CH3)], 1360 [m,
1
δs(CH3)], 1093 (s, νC–O) cm–1. H NMR (CDCl3): δ = 1.00 (d, J =
5-tert-Butyl-2,2-dimethylcyclopentanone (19): At –70 °C, a solution
of 2,2-dimethylcyclopentanone (10.1 g, 90.0 mmol) in THF
(200 mL) was added within 30 min. to a stirred solution of lithium
diisopropylamide (2 in THF, 45.0 mL, 90.0 mmol). After 15 min
of stirring at –70 °C, chlorotrimethylsilane (19.6 g, 180 mmol) was
added dropwise over a period of 10 min, and the reaction mixture
was warmed to 0 °C, stirred for 1 h at this temp., and then 2 h at
room temp. The formed precipitate was filtered off by suction with
the aid of a sintered funnel, and the filter cake was washed with
Et2O (100 mL). The combined filtrates were concentrated under
reduced pressure to furnish the crude silyl enol ether (16.8 g,
88.9 mmol), which was taken up in CH2Cl2 (200 mL). At –60 °C,
2-chloro-2-methylpropane (8.80 g, 95.0 mmol) was added, followed
by slow injection of a solution of TiCl4 (17.1 g, 90 mmol) in
CH2Cl2 (30 mL) within 10 min. Stirring was continued at –60 °C
for further 30 min, before the reaction mixture was warmed to 0 °C.
After quenching by slow addition of water (500 mL), the product
was extracted with Et2O (3ϫ400 mL), and the combined organic
extracts were washed with 10% aq. NaHCO3 (2ϫ150 mL) and
brine (2ϫ100 mL). After drying (Na2SO4), and evaporation of the
solvent on a rotary evaporator, the resulting residue was purified
by silica gel FC (pentane/Et2O, 98:2, Rf = 0.27) to provide the title
7.0 Hz, 6 H, 1ЈЈ-Me2), 1.06 (s, 6 H, 5Ј-Me2), 1.50 (d, J = 6.5 Hz, 3
H, 1-H3), 1.66 (t, J = 7.0 Hz, 2 H, 4Ј-H2), 1.95 (br. s, 1 H, OH),
2.30 (d, J = 7.0 Hz, 2 H, 3Ј-H2), 2.87 (sept, J = 7.0 Hz, 1 H, 1ЈЈ-
H), 4.71 (q, J = 6.5 Hz, 1 H, 2-H) ppm. 13C NMR (CDCl3): δ =
20.8 (q, 1ЈЈ-Me2), 24.8 (q, C-1), 27.0/27.1 (2q 5Ј-Me2), 28.7 (t, C-
3Ј), 29.1 (d, C-1ЈЈ), 38.3 (t, C-4Ј), 46.6 (s, C-5Ј), 59.1 (d, C-2), 79.5
(s, C-3), 95.9 (s, C-4), 125.2 (s, C-1Ј), 155.2 (s, C-2Ј) ppm. MS (EI):
m/z (%) = 206 (63) [M]+, 191 (88) [M – CH3]+, 173 (23) [M –
CH4O]+, 163 (46) [M – C3H7]+, 45 (10) [C2H5O]+, 43 (100)
[C3H7]+.
(E)-4-(2Ј-Isopropyl-5Ј,5Ј-dimethylcyclopent-1Ј-enyl)but-3-en-2-ol (17):
At room temp., a solution of 16 (1.91 g, 9.25 mmol) in THF
(20 mL) was added dropwise to a stirred suspension of LiAlH4
(351 mg, 9.25 mmol) in THF (5.0 mL). The resulting reaction mix-
ture was stirred for 4 h at room temp., prior to quenching with
cooling in an ice bath by dropwise addition of water (0.35 mL),
followed by 15% aq. NaOH (0.35 mL) and again water (1.05 mL).
After stirring for further 30 min at room temp., the formed precipi-
tate was filtered off by suction with the aid of a sintered funnel,
and the filter cake washed with Et2O (30 mL). The combined fil-
trates were evaporated under reduced pressure, and the resulting
residue was purified by silica gel FC (pentane/Et2O, 9:1, Rf = 0.21)
to provide the title compound 17 (1.66 g, 86%) as colorless oil. IR
compound 19 (13.8 g, 91%) as colorless liquid. IR (neat): ν = 1722
˜
(s, νC=O), 1463 [m, δas(CH3)], 1361 [m, δs(CH3)] cm–1. 1H NMR
(CDCl3): δ = 0.92/1.05 (2s, 6 H, 2-Me2), 0.99 (s, 9 H, 1Ј-Me3), 1.51–
1.59 (m, 1 H, 5-H), 1.64–1.80 (m, 2 H, 3-, 4-Hb), 1.92–2.15 (m, 2
H, 3-, 4-Ha) ppm. 13C NMR (CDCl3): δ = 22.3 (t, C-4), 23.0/24.8
(2q, 2-Me2), 27.8 (q, 1Ј-Me3), 32.3 (s, C-1Ј), 35.8 (t, C-3), 45.7 (s,
C-2), 223.5 (s, C-1) ppm. MS (EI): m/z (%) = 168 (24) [M]+, 153
(11) [M – CH3]+, 112 (100) [M – C4H8]+, 111 (52) [M – C4H9]+, 57
(45) [C4H9]+.
(neat): ν = 3318 (m, νO–H), 1455 [m, δas(CH3)], 1361 [m, δs(CH3)],
˜
1
1029 (s, νC–O), 964 (s, δC=C–H) cm–1. H NMR (CDCl3): δ = 0.99
(d, J = 7.0 Hz, 6 H, 1ЈЈ-Me2), 1.10/1.11 (2s, 6 H, 5Ј-Me2), 1.31 (d,
J = 6.5 Hz, 3-H, 1-H3), 1.60 (t, J = 7.5 Hz, 2 H, 4Ј-H2), 2.24 (t, J
= 7.5 Hz, 2 H, 3Ј-H2), 2.84 (sept, J = 7.0 Hz, 1 H, 1ЈЈ-H), 4.34
(quint, J = 6.5 Hz, 1 H, 2-H), 5.73 (dd, J = 16.0, 6.5 Hz, 1 H, 3-
H), 6.18 (d, J = 16.0 Hz, 1 H, 4-H) ppm. 13C NMR (CDCl3): δ =
21.3 (q, 1ЈЈ-Me2), 24.5 (q, C-1), 27.0 (d, C-1ЈЈ), 27.1/27.2 (2q, 5Ј-
Me2), 27.8 (t, C-3Ј), 40.1 (t, C-4Ј), 46.5 (s, C-5Ј), 70.0 (d, C-2),
123.1 (d, C-3), 133.0 (d, C-4), 138.3 (s, C-1Ј), 146.8 (s, C-2Ј) ppm.
MS (EI): m/z (%) = 208 (10) [M]+, 193 (14) [M – CH3]+, 175 (40)
[M – CH4O]+, 135 (100) [C10H15]+, 45 (11) [C2H5O]+, 43 (49)
[C3H7]+.
5-tert-Butyl-1-(3Ј-hydroxybut-1Ј-ynyl)-2,2-dimethylcyclopentanol (20):
As described for the preparation of 15, from 19 (12.3 g, 73.0 mmol),
3-butyn-2-ol (5.61 g, 80 mmol) and cerium(III) chloride (18.0 g,
73.0 mmol) in THF (250 mL). The title compound 20 was obtained
after standard workup and purification by silica gel FC (pentane/
Et2O, 6:4, Rf = 0.26) as slightly yellowish oil. Yield 61% (10.6 g).
IR (neat): ν = 3301 (m, νO–H), 1465 [m, δas(CH3)], 1366 [m,
˜
(E)-4-(2Ј-Isopropyl-5Ј,5Ј-dimethylcyclopent-1Ј-enyl)but-3-en-2-one (18):
δs(CH3)], 1078 (s, νC–O) cm–1. 1H NMR (CDCl3): δ = 1.01/1.03 (2s,
At room temp., pyridinium chlorochromate (1.97 g, 9.15 mmol) 6 H, 2-Me2), 1.07 (s, 9 H, 1ЈЈ-Me3), 1.44 (d, J = 6.5 Hz, 3 H, 4Ј-
was added portionwise to a stirred suspension of 17 (1.27 g,
6.10 mmol) and Celite® (5.00 g) in CH2Cl2 (40 mL). After stirring
for 5 h at room temp., the insoluble materials were filtered off over
H3), 1.65–1.70 (m, 2 H, 3-, 4-Hb), 1.72–1.78 (m, 2 H, 3-, 4-Ha),
2.10–2.14 (m, 1 H, 5-H), 2.16 (br. s, 2 H, OH), 4.56 (q, J = 6.5 Hz,
1 H, 3Ј-H), ppm. 13C NMR (CDCl3): δ = 21.5/26.9 (2q, 2-Me2),
Eur. J. Org. Chem. 2008, 4806–4814
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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