Thiylation of (R)-4-menthen-3-one and its derivatives

Article abstract of DOI:10.1007/s10600-013-0766-y

Thiylation of (R)-4-menthen-3-one and its derivatives was studied. New sulfides and sulfoxides of the menthane series were synthesized.

Full text of DOI:10.1007/s10600-013-0766-y

Chemistry of Natural Compounds, Vol. 49, No. 5, November, 2013 [Russian original No. 5, September–October, 2013]
THIYLATION OF (R)-4-MENTHEN-3-ONE AND ITS DERIVATIVES
1,2*
2
1
G. Yu. Ishmuratov,
V. S. Tukhvatshin, R. R. Muslukhov,
UDC 547.596+547.596.4
1
2
2
M. P. Yakovleva, A. V. Allagulova, E. R. Latypova,
2
and R. F. Talipov
Thiylation of (R)-4-menthen-3-one and its derivatives was studied. New sulfides and sulfoxides of the menthane
series were synthesized.
Keywords: (R)-4-menthen-3-one and its derivatives, thiylation and oxidation, sulfides and sulfoxides of the menthane
series.
We have previously reported pathways for transforming the available optically pure (R)-4-menthen-3-one (1) via
ozonolysis [1] and showed that enone 1 was significantly less reactive than ordinary cyclic ꢀ,ꢁ-unsaturated ketones in 1,2- and
1,4-addition reactions of organometallic reagents [2] and inert to Michael reactions and pyrazoline formation [3].
a
O
O
d
R
2 (86%)
OH
O
b
c
5 (100%), 6 (100%)
5: R = Me; 6: R = Et
1
OH
CH CO Et
2
2
3 (89%)
4 (65%)
a. H O , NaOH; b. i-Bu AlH, CH Cl , –78ꢂC; c. MeC(OEt) , AcOH, 130ꢂC; d. MeLi or EtLi, Et O, –78ꢂC
2
2
2
2
2
3
2
a
HS
S
2
+
SH
O
S
b
S
1
8
a
76%
98%
O
S
HS
SH
H S
2
+
7
9
S
a. TsOH, PhH, 80ꢂC; b. HSCH CH SH, BF 4Et O, AcOH
2
2
3
2
In continuation of research on the reactivity, we studied thiylation of 1 itself and its derivatives such as the epoxide 2
[4], (1R,3R)-menthen-3-ol (3) [5], the product of Claisen orthoester rearrangement 4 [6], and enols 5 and 6, which were
products of 1,2-addition of MeLi or EtLi to cycloenone 1 [2]. The results acquired a special significance because it is known
[7–9] that S-containing derivatives of mono- and bicyclic monoterpenoids exhibit various types of biological activity.
1) Institute of Organic Chemistry, Ufa Scientific Center, RussianAcademy of Sciences, 450054, Ufa, Prosp. Oktyabrya,
71, e-mail: insect@anrb.ru; 2) Bashkir State University Continuing Education Center, 450074, Ufa, Ul. Zaki Validi, 32,
e-mail: vadimtukhvatshin@yandex.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 5, September–October, 2013,
pp. 743–749. Original article submitted June 27, 2013.
©
864
0009-3130/13/4905-0864 2013 Springer Science+Business Media New York

We performed a series of experiments on electrophilic (with catalysis by ZnCl or BF 4OEt ) and nucleophilic (in the
2
3
2
presence of K CO or AcONa) addition of thiols [PhSH, n-C H SH, HS(CH ) SH] to (R)-4-menthen-3-one (1) in various
2
3
12 25
2 2
solvents at 20 or 55°C. As a result, enone 1 seemed to be less reactive toward catalyzed thiylation involving thiols (PhSH or
n-C H SH) than (–)-carvone [10–12]. This was probably due to the steric influence of the i-Pr group.
12 25
The inertness of menthenone 1 to electrophilic addition of HS(CH ) SH under ZnCl or BF 4OEt catalysis conditions
2 2
2
3
2
provided a basis for the method developed by us for purifying (R)-4-menthen-3-one from a (–)-menthone impurity [13].
However, saturated dithiolane 7 could be prepared under more forcing conditions (TsOH, 80°C, 24 h) through the action of
HS(CH ) SH on 1 whereas PhSH was inert under these conditions. Apparently, the initially formed allyl dithiolane 8 was
2 2
reduced further to its saturated analog 7 through the action of H S [14], which was released by thermal decomposition of
2
HS(CH ) SH as before [15]. This was confirmed by the presence in the reaction mixture of HS(CH ) S(CH ) SH and
2 2
2 2
2 2
–
–
elemental S. The mass spectrum of the reaction mixture showed molecular ions for 153.0 [M – H] , 171.0 ([M – H] + H O),
and 120.0 ([M – H] – SH) . The C NMR spectrum had resonances at 34.78 and 26.62 ppm [16] that were indicative of the
2
–
+
13
formation of HS(CH ) S(CH ) SH. The stereochemistry of S-containing product 7 was confirmed by NMR spectroscopy and
2 2
2 2
convergent synthesis from (–)-menthone (9) by the literature method [17].
It was found during the study of the thiylation of epoxyketone 2 by n-C H SH [or HS(CH ) SH or HSCH CO H]
12 25
2 2
2
2
that it occurred analogously to transformations of carvone 1,2-oxide [18] and was accompanied by regeneration of starting
(R)-4-menthen-3-one probably through dehydration of intermediate ketoalcohol 10 and not formation of hydroxysulfides 11–
13. In turn, the production of 1 and not (R)-pulegone (14) was confirmed by GC and spectral data, i.e., the presence in the
PMR spectrum of a resonance for olefinic proton HC=C–C=O at 5.6 ppm and the opposite phases of the resonances for the
13
C atoms of the multiple bond of the ꢀ,ꢁ-unsaturated ketone 1 in the C NMR spectrum in JMOD mode.
1
(89%)
a
a
-H O
2
RS
HO
O
O
O
O
HO
O
11 - 13
2
10
(11), CH CO H (12), (CH ) SH (13)
14
R = n-C
H
12 25
2
2
2 2
a. RSH, EtONa
Thiylation of (1R,3R)-menthen-3-ol (3), in contrast with 1, occurred smoothly under ZnCl catalysis conditions even
2
at room temperature with substitution of the hydroxyl group by sulfide function. Formation of sulfides 15–20 was accompanied
(according to PMR and capillary GC data) by complete configuration inversion of the O-containing asymmetric center, as was
noted earlier for cis-verbenol [19].
a
OH
SR
3
15 - 20
R = Ph (15), n-C H (16), n-C
H
(17), n-C
H
(18),
6
13
12 25
16 33
(CH ) SH (19), CH CO H (20)
2 2
2
2
a. RSH, ZnCl , CH Cl
2
2
2
The stereochemistry of the reaction products, terpene sulfides 15–20, was established by PMR data. Thus, the SSCC
3
of the C-1 proton in the spectrum of 3 ( J = 8.4 and 5.3 Hz) implied the equatorial orientation of the hydroxyl function whereas
3
the small SSCC (H–H) ( J = 5.4 and 6.3 Hz) of the C-6 protons in sulfides 16–18 and C-1 protons in sulfides 15, 19, and 20
were indicative of the axial orientation of the S-containing substituent. Therefore, thiylation of 3 was accompanied by complete
configuration inversion of the OH-containing asymmetric center.
The reaction of orthoester Claisen rearrangement product of (1R,3R)-menthen-3-ol, i.e., acetate 4, with PhSH with
ZnCl catalysis went without configuration inversion of the asymmetric center on C-1 and formed sulfide 15, which was
2
prepared earlier from 3. The reaction occurred through an S i mechanism according to the following proposed scheme.
N
Acetate 4 was transformed initially into intermediate 21 that then dissociated to form contact ion pair 22. The components of
–
this pair were situated very close to each other. Therefore, attack of the nucleophile (PhS ) was forced to occur from the same
865

–
–
side where the leaving group ( CH CO Et) was previously located. The contact ion pair decomposed so rapidly that PhS
2
2
attacked frontally at the carbonium ion before it managed to convert into the planar state. As a result, sulfide 15 was formed
[20, 21].
H C
2
a
O
C
O
95%
CH CO Et
SP h
CH C
2
2
2
PhS
SP h
4
21
22
a. PhSH, ZnCl , CH Cl
2
15
2
2
Thiylation of tertiary allyl alcohols 5 and 6 in the presence of catalytic amounts of ZnCl also occurred with OH
2
substitution. In contrast with 3, the reaction was accompanied by allyl rearrangement to form secondary terpene sulfides 23–
25, the PMR spectra of which lacked a resonance for the olefinic proton and retained other resonances of the starting enols 5
3
and 6. The small SSCC for the C-1 proton ( J = 1.4 and 4.3 Hz) in 23–25 indicated that the thioalkyl groups had the axial
orientation.
a
5
or 6
R S
1
R
23 - 25
23: R = Me, R = n-C
H
12 25
1
24: R = Me, R = (CH ) SH
1
2 2
25: R = Et, R = Ph
1
a. PhSH, ZnCl , CH Cl
2
2
2
Sulfides 15, 16, and 18 gave a series of menthene sulfoxides 26–28 upon oxidation by H O (30%) in AcOH and
2
2
m-CPBA in CH Cl .
2
2
a
b
SR
SR
O
SP h
O
26
15, 16, 18
15, 26: R = Ph
16, 27: R = n-C H
26, 27, 28
6
13
18, 28: n-C
H
16 33
a. m-CPBA, CH Cl ; b. H O , AcOH
2
2
2 2
Thus, we studied the reactivity of available monoterpenoid (R)-4-menthenone and its derivatives in electrophilic and
nucleophilic thiylation reactions and demonstrated their potential in the synthesis of new potentially biologically active sulfides
and sulfoxides of the menthane series.
EXPERIMENTAL
IR spectra were recorded in a thin layer on an IR Prestige-21 instrument (Shimadzu). NMR spectra were taken in
CDCl with TMS internal standard on a Bruker Avance III 500 spectrometer (operating frequency 500.13 MHz for PMR and
3
13
13
125.20 MHz for C NMR). PMR and C NMR spectra were analyzed and resonances were assigned using two-dimensional
COSY (H–H), HSQC, and HMBC correlation spectroscopy. Chromatographic analysis was performed on Chrom-5 instruments
using columns (1.2 m long) with stationary phase silicone SE-30 (5%) + OV-225 (3%) on a Chromaton N-AW-DMCS
(0.16–0.20 mm, operating temperature 50–300°C) and on a GC-9A instrument (Shimadzu) (quartz capillary column, 25 m
long with stationary phase OV-101, operating temperature 80–280°C) with He carrier gas. Optical rotation was measured on
a PerkinElmer 241-MC polarimeter. Melting points were determined on a Kofler apparatus, modification S 30A/G. Column
chromatography was carried out over silica gel L (60–200 ꢃm) (Sorbfil, Russia). Sorbfil plates (Russia) were used for TLC.
866

Mass spectra were measured on a LC MS 2010 EV instrument (Shimadzu) (syringe injection, sample solution in MeCN at
flow rate 60 ꢃL/min) using electrospray ionization (ESI) with simultaneous recording of positive and negative ions at capillary
potentials 4.5 and 3.5 kV, respectively; capillary interface temperature 230°C; and nebulizer gas (dry N ) flow rate 1.5 L/min;
2
and on a MAT95XPhigh-resolution spectrometer (Thermo Finnigan) with the Xcalibur data processing system (chromatographic
sample injection, HP-5MS column, 25 m long) by electron impact (ionizing electron energy 70 eV, ionizing chamber temperature
250°C). Chromatography used petroleum ether (PE) with bp 40–70°C. Solvents were dried by standard methods. Elemental
analyses of newly synthesized compounds agreed with those calculated.
Procedure for Reaction of (R)-4-Menthen-3-one (1) with HS(CH ) SH. A mixture of 1 (1.00 g, 6.6 mmol),
2 2
HS(CH ) SH (1.20 g, 12.8 mmol), p-TsOH (0.05 g), and PhH (60 mL) was refluxed with a Dean-Stark trap for 24 h [additional
2 2
p-TsOH (0.10 g) was added 12 h of refluxing]; cooled to room temperature; diluted with hexane (80 mL); washed sequentially
with NaOH solution (5%, 3 ꢄ 10 mL), H O (3 ꢄ 10 mL), and saturated NaCl solution (2 ꢄ 10 mL); dried over Na SO , and
2
2
4
evaporated. The residue (1.20 g) was purified by column chromatography (SiO , PE) to afford (6S,9R)-6-(1-methylethyl)-9-
2
20
21
methyl-1,4-dithiaspiro[4,5]decane (7, 1.12 g, 76%), R 0.77 (PE–EtOAc 2:1). [ꢀ] –13.0ꢂ (ñ 1.01; ÅtOH), lit. [ꢀ] –13.4ꢂ
(ñ 0.97; EtOH) [17]. IR spectrum (KBr, ꢅ, cm ): 758 (C–S–C). PMR spectra were identical to those described before [17].
Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 18.35 (q, Ñ-3ꢆꢆ), 21.79 (q, ÑÍ -9), 24.21 (q, Ñ-2ꢆꢆ), 27.73 (d, Ñ-9, Ñ-1ꢆꢆ),
f
D
D
–1
13
3
3
32.22 (d, Ñ-7), 38.57 (t, Ñ-8), 39.11 (t, Ñ-2, Ñ-3), 51.92 (d, Ñ-6), 55.77 (t, Ñ-10), 74.92 (s, Ñ-5).
Procedure forThiylation of (1R,4R,6R)-4-Methyl-1-(1-methylethyl)-7-oxabicyclo[4.1.0]heptan-2-one (2). Sodium
thiolate prepared from Na (0.18 g, 7.8 mg-at) and the appropriate thiol (7.8 mmol) [n-C H SH or HS(CH ) SH or
12 25
2 2
HSCH CO H] was treated with 2 (1.00 g, 6.0 mmol) in anhydrous EtOH (40 mL), stirred and refluxed for 5 h, cooled to 20°C,
2
2
diluted with H O (25 mL), and extracted with Et O (3 ꢄ 30 mL). Then, the combined organic extract was washed with
2
2
saturated NH Cl solution (3 ꢄ 20 mL), dried over Na SO , and evaporated. The residue (1.20 g) was purified by column
4
2
4
20
chromatography (SiO , PE:EtOAc, 20:1) to afford 1 (0.75 g, 89%), bp 86–88ꢂÑ (12 mm Hg), [ꢀ] –67.1ꢂ (ñ 4.95; CHCl ),
lit. [ꢀ] –67.5ꢂ (ñ 5.3; CHCl ) [22]. IR spectrum (KBr, ꢅ, cm ): 1672 (Ñ=Ñ–C=O). PMR and C NMR spectral data were
2
D
3
20
–1
13
D
3
identical to those described before [22].
Procedure for Thiylation of (1R,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-ol (3). A solution of 3
(2.0 mmol) in anhydrous CH Cl (10 mL) was stirred at room temperature, treated sequentially with the appropriate thiol
2
2
(2.5 mmol) [PhSH or n-C H SH or n-C H SH or n-C H SH or HSCH CO H or HS(CH ) SH] in anhydrous CH Cl
6
13
12 25
16 33
2
2
2 2
2
2
(10 mL) and ZnCl (0.03 g, 0.2 mmol), stirred for 8 h, diluted with H O (20 mL), and extracted with CH Cl (3 ꢄ 30 mL). The
2
2
2
2
extract was dried over MgSO and evaporated. Then, the products were isolated by column chromatography (SiO , PE).
4
2
{[(1S,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]thio}benzene (15). Yield 0.29 g (62%) of 15. R 0.74
f
20
–1
(PE–EtOAc 2:1), [ꢀ] +1.8ꢂ (ñ 0.35; ÑH Cl ). IR spectrum (KBr, ꢅ, cm ): 736 (C–S–C), 810 (C–S), 1583 (Ar), 1653 (Ñ=Ñ).
D
2
2
+
+
+
1
Mass spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan) : 247.0 ([Ì + H] , 2.6), 137.0 ([M – SPh] , 100). H NMR
rel.
2
spectrum (500.13 MHz, CDCl , , ppm, J/Hz): 0.88 (3Í, d, J = 6.8, Í-3ꢆꢆ), 0.98 (3Í, d, J = 6.7, ÑÍ -5ꢆ), 1.03 (3Í, d, J = 6.8,
3
3
2
3
3
2
3
3
Í-2ꢆꢆ), 1,38 (1Í, ddd, J = 13.1, J = 6.3, J = 11.4, H -6ꢆ), 1.84 (1Í, ddd, J = 10.4, J = 2.7, J = 2.0, H -4ꢆ), 2.00–2.18 (1Í,
m, Í -4ꢆ, H-5ꢆ), 2.10–2.14 (1Í, m, H -6ꢆ), 2.51 (1Í, sept, J = 6.8, Í-1ꢆꢆ), 3.73 (1H, dd, J = 5.6, J = 6.3, H -1ꢆ), 5.56 (1Í, dd,
J = 2.7, J = 4.8, Í-3ꢆ), 7.13 (1Í, t, J = 7.8, Í-4), 7.22 (2Í, d, J = 7.3, Í-2, Í-6), 7.32 (2Í, t, J = 7.1, Í-3, Í-5). Ñ NMR spectrum
à
à
2
3
e
å
å
2
3
13
(125.20 MHz, CDCl , , ppm): 21.63 (q, Ñ-3ꢆꢆ), 21.75 (q, Ñ-2ꢆꢆ), 23.53 (q, ÑH -5ꢆ), 29.69 (d, Ñ-5ꢆ), 31.79 (d, Ñ-1ꢆꢆ), 34.03 (t, Ñ-6ꢆ),
3
3
37.69 (t, Ñ-4ꢆ), 48.75 (d, Ñ-1ꢆ), 122.94 (d, Ñ-3ꢆ), 126.25 (d, Ñ-4), 128.87 (d, Ñ-3, Ñ-5), 130.61 (d, Ñ-2, Ñ-6), 137.56 (s, Ñ-1),
142.29 (s, Ñ-2ꢆ).
(4R,6S)-6-(Hexylthio)-4-methyl-1-(1-methylethyl)cyclohexene (16). Yield 0.39 g (80%) of 16. R 0.77
f
20
–1
(PE–EtOAc 2:1), [ꢀ] +2.3ꢂ (ñ 1.01; ÑH Cl ). IR spectrum (KBr, ꢅ, cm ): 725 (C–S–C), 810 (C–S), 1635 (Ñ=Ñ).
D
2
2
+
+
+
Mass spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 255.0 ([Ì + H] , 25.8), 169.0 ([Ì – C H ] , 3.1), 137.0
([M – SC H ] , 100). H NMR spectrum (500.13 MHz, CDCl , , ppm, J/Hz): 0.82 (3Í, d, J = 6.8, Í-3ꢆꢆ), 0.91 (3Í, d,
rel.
2
6 13
+
1
6
13
3
J = 6.8, Í-2ꢆꢆ), 0.96 (3Í, t, J = 6.7, Í-6ꢆ), 0.98 (3Í, d, J = 6.7, ÑÍ -4), 1.25–1.35 (2Í, m, Í-4ꢆ), 1.35–1.48 (1Í, m, H -3),
3
à
2
3
3
1.52–1.73 (6Í, m, H-2ꢆ, H-3ꢆ, H-5ꢆ), 1.90–2.05 (1Í, m, H-4), 1.91 (1Í, ddd, J = 12.8, J = 1.4, J = 1.4, Í -5), 2.30–2.45 (1Í,
m, Í-1ꢆꢆ), 2.30–2.50 (1Í, m, H -3), 2.40–2.62 (1Í, m, H -5), 2.42–2.63 (2Í, m, H-1ꢆ), 3.26 (1H, dd, J = 7.9, J = 4.2, H -6),
5.50 (1Í, d, J = 2.6, Í-2). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 13.92 (q, Ñ-6ꢆ), 20.74 (q, Ñ-2ꢆꢆ), 21.77 (t, Ñ-5ꢆ),
à
2
3
å
å
å
13
3
22.95 (q, ÑH -4), 23.51 (q, Ñ-3ꢆꢆ), 28.79 (t, Ñ-3ꢆ), 29.49 (d, Ñ-1ꢆ), 29.60 (t, Ñ-4ꢆ), 29.71 (d, Ñ-4), 29.94 (t, Ñ-2ꢆ), 32.60 (t, Ñ-1ꢆ),
3
34.06 (t, Ñ-5), 41.12 (t, Ñ-3), 45.08 (d, Ñ-6), 121.92 (d, Ñ-2), 143.12 (s, Ñ-1).
867

(4R,6S)-6-(Dodecylthio)-4-methyl-1-(1-methylethyl)cyclohexene (17). Yield 0.85 g (64%) of 17. R 0.65 (hexane–
f
20
–1
EtOAc 2:1), [ꢀ] +1.1ꢂ (ñ 0.56; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 721 (C–S–C), 810 (C–S), 1658 (Ñ=Ñ). Mass spectrum
D
3
+
+
+
1
(ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 339.0 ([Ì + H] , 1.5), 137.0 ([Ì – SC H ] , 100]. H NMR spectrum
rel.
2
12 25
(500.13 MHz, CDCl , , ppm, J/Hz): 0.88 (3Í, t, J = 6.4, Í-12ꢆ), 0.97 (3Í, d, J = 6.7, ÑÍ -4), 1.00 (3Í, d, J = 6.8, Í-3ꢆꢆ), 1.07
3
3
(3Í, d, J = 6.8, Í-2ꢆꢆ), 1.22–1.30 (12Í, m, H-4ꢆ, H-5ꢆ, H-6ꢆ, H-7ꢆ, H-8ꢆ, H-9ꢆ), 1.32–1.65 (10Í, m, H-1ꢆ, H-2ꢆ, H-3ꢆ, H-10ꢆ,
2
3
H-11ꢆ), 1.88 (1Í, dd, J = 12.1, J = 3.4, Í -3), 1.98–2.10 (1Í, m, H -3), 2.12–2.18 (2Í, m, H -5, H-4), 2.30–2.43 (1Í, m,
à
å
à
2
3
2
3
13
H -5), 2.48 (1Í, sept, J = 6.6, Í-1ꢆꢆ), 3.29 (1H, dd, J = 6.4, J = 5.2, H -6), 5.50 (1Í, dd, J = 4.9, J = 2.2, Í-2). Ñ NMR
å
å
spectrum (125.20 MHz, CDCl , , ppm): 14.12 (q, Ñ-12ꢆ), 21.51 (q, Ñ-3ꢆꢆ), 21.85 (q, Ñ-2ꢆꢆ), 22.69 (t, Ñ-11ꢆ), 23.62 (q, ÑH -4),
3
3
28.77 (t, Ñ-3ꢆ), 29.01 (t, Ñ-9ꢆ), 29.54 (t, Ñ-4ꢆ, Ñ-5ꢆ, Ñ-6ꢆ, Ñ-7ꢆ, Ñ-8ꢆ), 29.82 (d, Ñ-4), 30.06 (t, Ñ-2ꢆ), 31.50 (d, Ñ-1ꢆꢆ), 31.92 (t,
Ñ-10ꢆ), 32.70 (t, Ñ-1ꢆ), 34.13 (t, Ñ-5), 38.27 (t, Ñ-3), 45.12 (d, Ñ-6), 121.43 (d, Ñ-2), 143.23 (s, Ñ-1).
(4R,6S)-6-(Hexadecylthio)-4-methyl-1-(1-methylethyl)cyclohexene (18). Yield 0.58 g (76%) of 18. R 0.85 (PE–
f
20
–1
EtOAc 2:1), [ꢀ] +1.0ꢂ (ñ 1.12; ÑH Cl ). IR spectrum (KBr, ꢅ, cm ): 719 (C–S–C), 810 (C–S), 1664 (Ñ=Ñ). Mass spectrum
(ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 395.0 ([Ì + H] , 1.6), 137.0 ([M – SC H ] , 100). H NMR spectrum
D
2
2
+
+
+
1
rel.
2
16 33
(500.13 MHz, CDCl , , ppm, J/Hz): 0.88 (3Í, t, J = 6.7, Í-16ꢆ), 0.97 (3Í, d, J = 6.7, ÑÍ -4), 1.01 (3Í, d, J = 6.8, Í-3ꢆꢆ), 1.06
3
3
(3Í, d, J = 6.8, Í-2ꢆꢆ), 1.24–1.33 (16Í, m, H-5ꢆ, H-6ꢆ, H-7ꢆ, H-8ꢆ, H-9ꢆ, H-10ꢆ, H-11ꢆ, H-12ꢆ), 1.26–1.35 (2Í, m, H-15ꢆ), 1.35–1.42
2
3
3
(6Í, m, Í-4ꢆ, Í-13ꢆ, Í-14ꢆ), 1.45–1.68 (6Í, m, Í-1ꢆ, Í-2ꢆ, Í-3ꢆ), 1.90 (1Í, ddd, J = 11.0, J = 3.2, J = 2.1, Í -3), 2.12–2.18
à
2
3
(1Í, m, H -5), 2.18–2.20 (3Í, m, H-4, H -5, H -3), 2.47–2.58 (1Í, m, Í-1ꢆꢆ), 3.28 (1H, dd, J = 6.8, J = 5.4, H -6), 5.52 (1Í,
dd, J = 2.7, J = 5.6, Í-2). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 14.09 (q, Ñ-16ꢆ), 21.49 (q, Ñ-3ꢆꢆ), 21.84 (q,
à
å
å
å
2
3
13
3
Ñ-2ꢆꢆ), 22.67 (t, Ñ-15ꢆ), 23.59 (q, ÑH -4), 28.71 (t, Ñ-13ꢆ), 28.81 (t, Ñ-3ꢆ), 29.20 (t, Ñ-11ꢆ), 29.36 (t, Ñ-12ꢆ), 29.68 (t, Ñ-4ꢆ,
3
Ñ-5ꢆ, Ñ-6ꢆ, Ñ-7ꢆ, Ñ-8ꢆ, Ñ-9, Ñ-10ꢆ), 29.91 (d, Ñ-4), 30.04 (t, Ñ-2ꢆ), 31.46 (t, Ñ-14ꢆ), 31.46 (d, Ñ-1ꢆꢆ), 32.67 (t, Ñ-1ꢆ), 33.97 (t,
Ñ-5), 38.21 (t, Ñ-3), 45.12 (d, Ñ-6), 121.37 (d, Ñ-2), 143.18 (s, Ñ-1).
2-{[(1S,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]thio}ethanethiol (19). Yield 0.90 g (76%) of 19.
20
–1
R 0.45 (PE–EtOAc 2:1), [ꢀ] –1.2ꢂ (ñ 5.4; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 810 (C–S), 1615 (Ñ=Ñ), 2528 (S–H). Mass
f
D
3
+
+
1
spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 137.0 ([M – S(CÍ ) SH] , 100). H NMR spectrum (500.13 MHz,
rel.
2
2 2
CDCl , , ppm, J/Hz): 0.89 (3Í, d, J = 6.7, ÑÍ -5ꢆ), 1.04 (3Í, d, J = 6.9, Í-3ꢆꢆ), 1.13 (3Í, d, J = 6.9, Í-2ꢆꢆ), 1.48 (1Í, dd,
3
3
2
3
2
3
3
2
3
J = 12.9, J = 2.0, Í -6ꢆ), 1.55 (1Í, s, SH), 1.59 (1Í, ddd, J = 17.7, J = 11.0, J = 3.1, Í -4ꢆ), 1.89 (1Í, dd, J = 12.9, J = 4.2,
Í -6ꢆ), 2.13 (1Í, dd, J = 17.7, J = 4.9, Í -4ꢆ), 2.43 (1Í, sept, J = 6.9, Í-1ꢆꢆ), 2.67–2.82 (4Í, m, Í-1, Í-2), 3.31 (1Í, dd,
J = 4.2, J = 2.0, Í -1ꢆ), 5.50 (1H, dd, J = 4.9, J = 3.1, H-3ꢆ). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 21.41 (q,
à
a
2
3
e
e
2
3
2
3
13
å
3
Ñ-3ꢆꢆ), 21.91 (q, Ñ-2ꢆꢆ), 23.49 (d, Ñ-5ꢆ), 23.58 (q, ÑH -5ꢆ), 25.20 (q, Ñ-1), 31.59 (d, Ñ-1ꢆꢆ), 34.04 (t, Ñ-6ꢆ), 38.55 (t, Ñ-4ꢆ),
3
38.64 (t, Ñ-2), 45.49 (d, Ñ-1ꢆ), 121.87 (d, Ñ-3ꢆ), 142.98 (s, Ñ-2ꢆ).
{[(1S,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]thio}acetic Acid (20). Yield 0.38 g (43%) of 20. R 0.54
f
20
–1
(PE–EtOAc 2:1), [ꢀ] –1.3ꢂ (ñ 2.73; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 810 (C–S), 1618 (Ñ=Ñ), 3750–3320 (ÑO H). Mass
spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 227.0 ([Ì – H] , 100); (Scan ):137.0 ([M – SCÍ ÑO H] , 100).
H NMR spectrum (500.13 MHz, CDCl , , ppm, J/Hz): 0.93 (3Í, d, J = 6.7, ÑÍ -5ꢆ), 0.98 (3Í, d, J = 6.7, Í-3ꢆꢆ), 1.12 (3Í,
d, J = 6.7, Í-2ꢆꢆ), 1.47 (1Í, ddd, J = 13.3, J = 13.2, J = 3.5, Í -6ꢆ), 1.58 (1Í, dd, J = 17.7, J = 10.5, Í -4ꢆ), 1.89 (1Í, dd,
J = 13.3, J = 1.4, Í -6ꢆ), 1.98–2.08 (1Í, m, Í-5ꢆ), 2.12 (1Í, dd, J = 17.7, J = 5.4, Í -4ꢆ), 2.42 (1Í, sept, J = 6.7, Í-1ꢆꢆ), 3.19
(1Í, d, J = 14.7, Í-2), 3.32 (1Í, d, J = 14.7, Í-2), 3.54 (1Í, dd, J = 3.5, J = 1.4, Í -1ꢆ), 5.89 (1H, dd, J = 5.4, J = 3.5, H-3ꢆ),
11.2 (1Í, br. s, Í-1). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 21.34 (q, Ñ-2ꢆꢆ), 21.67 (q, Ñ-3ꢆꢆ), 23.35 (d, Ñ-5ꢆ), 23.51 (q,
D
3
2
–
–
+
+
rel.
2
2
2
1
3
3
2
3
3
2
3
à
a
2
3
2
3
e
e
2
3
2
3
å
13
3
ÑH -5ꢆ), 31.36 (d, Ñ-1ꢆꢆ), 33.91 (t, Ñ-2, Ñ-6ꢆ), 37.22 (t, Ñ-4ꢆ), 45.12 (d, Ñ-1ꢆ), 122.97 (d, Ñ-3ꢆ), 141.98 (s, Ñ-2ꢆ), 177.33 (s, Ñ-1).
3
Procedure for Thiylation of Products of 1,2-Addition of Organolithium Reagents to (R)-4-Menthen-3-one (1).
A suspension of MeLi or EtLi prepared from Li (0.31 g, 44.3 mmol) and alkylhalide (44.3 mmol) (MeI or EtBr) in anhydrous
Et O (30 mL) (–78°C, Ar) was treated dropwise with 1 (0.50 g, 3.3 mmol) in anhydrous Et O (20 mL) (–78°C, Ar), stirred for
2
2
6 h (–78°C, Ar), treated with saturated NH Cl solution (10 mL) over 1 h, adjusted to room temperature, and extracted with
4
Et O (3 ꢄ 50 mL). The combined organic extract was washed with saturated NaCl solution (3 ꢄ 5 mL) until the pH was 7, dried
2
over Na SO , and evaporated. The resulting tertiary allyl alcohols (5 and 6) were used without further purification in the next
2
4
step. For this, the residues (0.54 g of 5 or 0.60 g of 6) after evaporation were dissolved in anhydrous CH Cl (10 mL), treated
2
2
sequentially at room temperature with stirring with the appropriate thiol (2.5 mmol) [PhSh or n-C H SH or HS(CH ) SH] in
12 25
2 2
anhydrous CH Cl (10 mL) and ZnCl (0.03 g, 0.2 mmol), stirred for 8 h, diluted with H O (20 mL), and extracted with
2
2
2
2
CH Cl (3 ꢄ 30 mL). The extract was dried over MgSO and evaporated. Then, products were isolated by column
2
2
4
chromatography (SiO , PE).
2
868

(1R,5S)-3,5-Dimethyl-2-(1-methylethyl)cyclohex-2-en-1-yl Dodecyl Sulfide (23). Yield 0.40 g (57%) of 23 per
20
–1
enone 1. R 0.75 (PE–EtOAc 2:1), [ꢀ] +17.6ꢂ (ñ 3.34; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 721 (C–S–C), 806 (C–S), 1631
f
D
3
–
+
+
+
(Ñ=Ñ). Mass spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 351.0 ([Ì – H] , 26.25); (Scan ): 201.0 ([([Ì + H] –
rel.
2
+
1
C H ] , 6.6). H NMR spectrum (500.13 MHz, CDCl , , ppm, J/Hz): 0.93 (3Í, t, J = 6.5, Í-12ꢆ), 1.06 (3Í, d, J = 6.7,
11 20
3
ÑÍ -5), 1.18–1.60 (20Í, m, H-2ꢆ, H-3ꢆ, H-4ꢆ, H-5ꢆ, H-6ꢆ, H-7ꢆ, H-8ꢆ, H-9ꢆ, H-10ꢆ, H-11ꢆ), 1.19 (3Í, d, J = 6.7, Í-3ꢆꢆ), 1.23 (3Í,
3
2
3
d, J = 6.7, Í-2ꢆꢆ), 1.62–1.80 (2Í, m, Í -4, Í -6), 1.72 (3Í, s, ÑÍ -3), 1.89 (1H, dd, J = 13.2, J = 4.7, H -6), 2.10–2.40 (1Í,
m, H-5), 2.16 (1H, dd, J = 17.4, J = 5.6, H -4), 2.57–2.70 (1Í, m, H-3ꢆꢆ), 2.78–2.83 (2Í, m, H-1ꢆ), 3.41 (1H, dd, J = 4.2,
J = 1.6, H -1). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 14.04 (q, Ñ-12ꢆ), 19.33 (q, ÑÍ -3), 20.35 (q, Ñ-3ꢆꢆ), 21.87 (q,
à
à
3
å
2
3
2
å
3
13
å
3
3
Ñ-2ꢆꢆ), 22.64 (q, ÑH -5), 22.64 (t, Ñ-11ꢆ), 23.62 (d, Ñ-5), 28.49 (t, Ñ-2ꢆ), 29.06–29.76 (t, Ñ-3ꢆ, Ñ-4ꢆ, Ñ-5ꢆ, Ñ-6ꢆ, Ñ-7ꢆ, Ñ-8ꢆ,
3
Ñ-9ꢆ), 30.68 (d, Ñ-1ꢆꢆ), 31.88 (t, Ñ-10ꢆ), 32.51 (t, Ñ-1ꢆ), 37.66 (t, Ñ-6), 39.09 (t, Ñ-4), 44.36 (d, Ñ-1), 130.17 (s, Ñ-3), 134.00
(s, Ñ-2).
2-{[(1R,5S)-3,5-Dimethyl-2-(1-methylethyl)cyclohex-2-en-1-yl]thio}ethanethiol (24). Yield 0.60 g (56%) of 24
20
–1
per enone 1. R 0.63 (PE–EtOAc 2:1), [ꢀ] +6.0ꢂ (ñ 0.63; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 739 (C–S–C), 1634 (Ñ=Ñ),
f
D
3
1
2566 (S–Í). H NMR spectrum (500.13 MHz, CDCl , , ppm, J/Hz): 0.88 (3Í, d, J = 6.6, ÑÍ -5ꢆ), 1.01 (3Í, d, J = 6.4, Í-2ꢆꢆ),
1.03 (3Í, d, J = 6.4, Í-3ꢆꢆ), 1.60–1.78 (2Í, m, Í -6ꢆ, Í -4ꢆ), 1.70 (1Í, dd, J = 12.7, J = 4.0, Í -6ꢆ), 1.60 (3Í, s, ÑÍ -3ꢆ), 1.82
(1Í, s, SH), 1.95 (1Í, dd, J = 15.4, J = 5.3, Í -4ꢆ), 2.09–2.20 (1Í, m, H-3ꢆꢆ, H-5ꢆ), 2.54–2.78 (4Í, m, Í-1, Í-2), 3.29 (1Í,
dd, J = 4.1, J = 1.2, Í -1ꢆ). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 19.60 (q, ÑH -3ꢆ), 20.55 (q, Ñ-3ꢆꢆ), 21.90 (q,
3
3
2
3
à
a
e
3
2
3
e
2
3
13
å
3
3
ÑH -5ꢆ), 22.64 (q, Ñ-2ꢆꢆ), 23.64 (d, Ñ-1ꢆꢆ), 24.99 (t, Ñ-1), 30.79 (d, Ñ-5ꢆ), 36.71 (t, Ñ-2), 37.93 (t, Ñ-6ꢆ), 41.55 (t, Ñ-4ꢆ), 44.75
3
(d, Ñ-1ꢆ), 131.14 (s, Ñ-3ꢆ), 133.54 (s, Ñ-2ꢆ).
{[(1R,5S)-3-Ethyl-5-methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]thio}benzene (25). Yield 0.60 g (51%) of 25
20
–1
per enone 1. R 0.73 (PE–EtOAc 2:1), [ꢀ] –1.7ꢂ (ñ 4.0; ÑHCl ). IR spectrum (KBr, ꢅ, cm ): 741 (C–S–C), 1582 (Ar), 1654
f
D
3
+
+
+
1
(Ñ=Ñ). Mass spectrum (ESI), m/z (I , %), MeCN–H O 95:5, (Scan ): 166.0 ([M + Í] – SPh] , 15.11). H NMR spectrum
rel.
2
(500.13 MHz, CDCl , , ppm, J/Hz): 0.96 (3Í, d, J = 6.6, ÑÍ -5ꢆ), 1.04 (3Í, t, J = 6.8, ÑÍ ÑÍ -3ꢆ), 1.14 (3Í, d, J = 6.8,
3
3
3
2
3
2
3
2
Í-2ꢆꢆ), 1.27 (3Í, d, J = 6.8, Í-3ꢆꢆ), 1.53 (1Í, dd, J = 13.2, J = 4.2, Í -4ꢆ), 1.63 (1Í, dd, J = 17.6, J = 10.4, H -6ꢆ), 1.82 (1Í,
dd, J = 13.2, J = 1.4, H -4ꢆ), 2.12 (2Í, q, J = 6.8, ÑÍ ÑÍ -3ꢆ), 2.18 (1Í, dd, J = 17.6, J = 6.0, H -6ꢆ), 2.20–2.36 (1Í, m,
H-5ꢆ), 2.83 (1Í, sept, J = 6.8, H-1ꢆꢆ), 3.88 (1H, dd, J = 4.2, J = 1.5, H -1ꢆ), 7.21 (1Í, t, J = 7.7, Í-4), 7.30 (2Í, t, J = 7.6,
Í-3, Í-5), 7.51 (2Í, d, J = 7.6, Í-2, Í-6). Ñ NMR spectrum (125.20 MHz, CDCl , , ppm): 13.28 (q, ÑÍ ÑÍ -3), 21.25 (q,
à
à
2
3
2
3
å
3
2
å
2
3
å
13
3
3
2
Ñ-3ꢆꢆ), 22.03 (q, Ñ-2ꢆꢆ), 23.41 (q, ÑH -5ꢆ), 23.77 (d, Ñ-5ꢆ), 26.43 (t, ÑÍ ÑÍ -3), 30.51 (d, Ñ-1ꢆꢆ), 37.55 (t, Ñ-4ꢆ), 38.47 (t,
3
3
2
Ñ-6ꢆ), 47.43 (d, Ñ-3ꢆ), 126.09 (d, Ñ-4), 127.53 (d, Ñ-3, Ñ-5), 129.12 (d, Ñ-2, Ñ-6), 132.74 (s, Ñ-1ꢆ), 137.08 (s, Ñ-1), 137.80 (s,
Ñ-2ꢆ).
Procedure forThiylation of Ethyl [(1R,5R)-5-methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]acetate (4). Asolution
of 4 (0.40 g, 1.8 mmol) in anhydrous CH Cl (5 mL) was stirred at room temperature, treated sequentially with PhSH (0.20 g,
2
2
1.8 mmol) in anhydrous CH Cl (10 mL) and ZnCl (0.03 g, 0.2 mmol), stirred for 10 h, diluted with H O (25 mL), and
2
2
2
2
extracted with CH Cl (3 ꢄ 40 mL). The extract was dried over Na SO and evaporated to afford 15 (0.42 g, 95%). R 0.74
2
2
2
4
f
20
13
(PE:EtOAc, 2:1), [ꢀ] +1.7° (c 2.2, CH Cl ). PMR and C NMR spectra were identical to those for 15 prepared from
D
2
2
(1R,3R)-menthen-3-ol (3).
Procedure for Oxidation of Sulfides 15, 16, and 18. a. Sulfides (0.50 mmol) (15 or 16 or 18) dissolved in glacial
AcOH (3 mL) were treated dropwise at 0°C with H O solution (0.12 mL, 30%, 1.00 mmol), heated to room temperature,
2
2
stirred for 4 h, diluted with H O (25 mL), and extracted with EtOAc (3 ꢄ 15 mL). The combined organic extract was washed
2
sequentially with saturated solutions of NaHCO (2 ꢄ 3 mL) and NaCl (2 ꢄ 3 mL), dried over Na SO , and evaporated.
3
2
4
b. Sulfide 16 (0.12 g, 0.46 mmol) was dissolved in CH Cl (3 mL), treated dropwise at 0°C with m-CPBA (0.21 g,
2
2
0.92 mmol, 75% solution) in CH Cl (2 mL), heated to room temperature, stirred for 8 h, diluted with H O (30 mL), and
2
2
2
extracted with CH Cl (3 ꢄ 20 mL). The combined organic extract was washed sequentially with saturated solutions of
2
2
NaHCO (3 ꢄ 5 mL) and NaCl (2 ꢄ 3 mL), dried over Na SO , and evaporated.
3
2
4
{[(1S,5R)-5-Methyl-2-(1-methylethyl)cyclohex-2-en-1-yl]sulfanyl}benzene (26). Yield 0.19 g (88%) of 26 (by
method a) and 0.10 g (87%) (by method b). R 0.47 (PE–EtOAc 2:1), [ꢀ] +31.0ꢂ (ñ 0.28; ÑH Cl ). IR spectrum (KBr, ꢅ,
cm ): 1076 (SO), 1584 (Ar), 1635 (Ñ=Ñ). Mass spectrum (EI, 70 eV), m/z (I , %): 77.0 ([M – C H SO] , 39.3), 125.0
20
f
D
2
2
–1
+
+
rel.
10 17
+
+
+
+
+
+
1
([M – C H ] , 11.4), 137.1 ([M – SOPh] , 100.0), 186.0 ([M + H] – Ph] , 1.4). H NMR spectrum (500.13 MHz, CDCl ,
10 17
3
, ppm, J/Hz): 0.83 (3Í, d, J = 6.7, ÑÍ -5ꢆ), 0.97 (3Í, d, J = 6.8, Í-2ꢆꢆ), 1.10 (3Í, d, J = 6.8, Í-3ꢆꢆ), 1.18 (1Í, ddd,
3
2
3
3
2
3
2
3
3
J = 14.4, J = 5.6, J = 14.2, H -6ꢆ), 1.55 (1Í, d, J = 18.4, J = 3.1, Í -4ꢆ), 1.98 (1Í, ddd, J = 14.4, J = 1.6, J = 3.2, H -6ꢆ),
à
à
å
2
3
3
2.05–2.11 (1Í, m, H-5ꢆ), 2.23 (1Í, ddd, J = 18.4, J = 4.7, J = 2.0, H -4ꢆ), 2.64 (1Í, sept, J = 6.8, Í-1ꢆꢆ), 3.84 (1H, dd,
å
869

2
3
2
3
J = 5.5, J = 1.6, Í -1ꢆ), 5.88 (1Í, dd, J = 4.7, J = 3.1, Í-3ꢆ), 7.41 (1Í, t, J = 7.4, Í-4), 7.56 (2Í, t, J = 7.4, Í-3, Í-5), 7.86
å
13
(2Í, d, J = 7.3, Í-2, Í-6). C NMR spectrum (125.20 MHz, CDCl , , ppm): 20.86 (q, Ñ-3ꢆꢆ), 21.87 (q, Ñ-2ꢆꢆ, ÑH -5ꢆ), 22.48
(d, Ñ-5ꢆ), 32.15 (d, Ñ-1ꢆꢆ), 32.71 (t, Ñ-6ꢆ), 33.53 (t, Ñ-4ꢆ), 64.66 (d, Ñ-1ꢆ), 128.43 (d, Ñ-2, Ñ-6), 128.59 (d, Ñ-3ꢆ), 129.33 (d, Ñ-3,
Ñ-5), 131.35 (d, Ñ-4), 133.34 (s, Ñ-1), 135.41 (s, Ñ-2ꢆ).
3
3
(4R,6S)-6-(Hexylsulfanyl)-4-methyl-1-(1-methylethyl)cyclohexene (27). Yield 0.11 g (97%) of 27 by method a.
20
–1
R 0.57 (PE–EtOAc 2:1), [ꢀ] –1.0ꢂ (ñ 0.47; ÑH Cl ). IR spectrum (KBr, ꢅ, cm ): 1119 (SO), 1655 (Ñ=Ñ). Mass spectrum
f
D
2
2
+
+
–
1
(EI, 70 eV), m/z (I , %): 137.1 ([M – SOC H ] , 100.0), 269.1 ([M – H] , 3.1). H NMR spectrum (500.13 MHz, CDCl ,
rel.
6
13
3
, ppm, J/Hz): 0.88 (3Í, t, J = 6.9, Í-6ꢆ), 0.97 (3Í, d, J = 6.5, ÑÍ -4), 1.01 (3Í, d, J = 6.7, Í-3ꢆꢆ), 1.12 (3Í, d, J = 6.7, Í-2ꢆꢆ),
3
2
3
1.27–1.36 (4Í, m, H-4ꢆ, H-5ꢆ), 1.36–1.47 (2Í, m, H-3ꢆ), 1.38–1.46 (1Í, m, Í -5), 1.66 (1Í, dd, J = 10.9, J = 7.8, H -3), 1.82–
à
à
1.90 (2Í, m, Í-2ꢆ), 2.03–2.13 (1Í, m, H-4), 2.31 (1Í, d, J = 10.9, H -3), 2.34 (1Í, d, J = 11.9, H -5), 2.67 (1Í, sept, J = 6.7,
å
å
2
3
2
3
Í-1ꢆꢆ), 2.88 (1Í, dd, J = 13.5, J = 7.5, H-1ꢆ), 2.93 (1Í, dd, J = 13.5, J = 8.8, H-1ꢆ), 3.72 (1H, d, J = 5.1, H -6), 5.88 (1Í, dd,
å
2
3
13
J = 3.7, J = 3.8, Í-2). C NMR spectrum (125.20 MHz, CDCl , , ppm): 13.92 (q, Ñ-6ꢆ), 20.86 (q, Ñ-3ꢆꢆ), 21.26 (t, Ñ-2ꢆ),
21.92 (t, Ñ-5ꢆ), 21.93 (q, Ñ-2ꢆꢆ), 23.18 (d, Ñ-4), 23.45 (q, ÑH -4), 28.36 (t, Ñ-3ꢆ), 31.29 (t, Ñ-4ꢆ), 31.98 (d, Ñ-1ꢆꢆ), 32.80 (t,
Ñ-5), 33.60 (t, Ñ-3), 52.46 (t, Ñ-1ꢆ), 63.35 (d, Ñ-6), 127.39 (d, Ñ-2), 135.91 (s, Ñ-1).
3
3
(4R,6S)-6-(Hexadecylsulfanyl)-4-methyl-1-(1-methylethyl)cyclohexene (28). Yield 0.17 g (85%) of 28 by method a.
20
–1
R 0.77 (PE–EtOAc 2:1), mp 60–62ꢂ (from hexane), [ꢀ] –2.5ꢂ (ñ 0.89; ÑH Cl ). IR spectrum (KBr, ꢅ, cm ): 1118 (SO),
f
D
2
2
+
+
1
1652 (Ñ=Ñ). Mass spectrum (EI, 70 eV, m/z (I , %): 137.1 ([M – SOC H ] , 100.0). H NMR spectrum (500.13 MHz,
rel.
16 33
CDCl , , ppm, J/Hz): 0.80 (3Í, m, J = 6.1, Í-16ꢆ), 0.95 (3Í, d, J = 6.8, Í-3ꢆꢆ), 0.97 (3Í, d, J = 6.7, ÑÍ -4), 1.07 (3Í, d,
3
3
J = 6.8, Í-2ꢆꢆ), 1.12–1.30 (24Í, m, H-3ꢆ, H-4ꢆ, H-5ꢆ, H-6ꢆ, H-7ꢆ, H-8ꢆ, H-9ꢆ, H-10ꢆ, H-11ꢆ, H-12ꢆ, H-13ꢆ, H-14ꢆ), 1.33–1.45 (4Í,
2
3
3
m, Í-2ꢆ, Í-15ꢆ), 1.68 (1Í, ddd, J = 16.4, J = 10.2, J = 2.6, Í -3), 1.91–2.08 (1Í, m, H-4), 2.20–2.32 (1Í, m, H -5), 2.21–
à
a
2.32 (1Í, m, H -3), 2.61 (1Í, sept, J = 6.8, Í-1ꢆꢆ), 2.71–2.92 (3Í, m, H -5, H-1ꢆ), 3.63 (1H, d, J = 5.0, H -6), 5.81 (1Í, dd,
å
e
å
2
3
13
J = 5.3, J = 2.6, Í-2). C NMR spectrum (125.20 MHz, CDCl , , ppm): 14.10 (q, Ñ-16ꢆ), 20.86 (q, Ñ-3ꢆꢆ), 21.91 (q, Ñ-2ꢆꢆ),
3
22.66 (t, Ñ-15ꢆ), 23.44 (q, ÑH -4), 28.66 (t, Ñ-3ꢆ), 28.94 (d, Ñ-4), 29.12 (t, Ñ-2ꢆ), 29.25 (t, Ñ-12ꢆ), 29.34 (t, Ñ-13ꢆ), 29.66 (t,
3
Ñ-4ꢆ, Ñ-5ꢆ, Ñ-6ꢆ, Ñ-7ꢆ, Ñ-8ꢆ, Ñ-9ꢆ, Ñ-10ꢆ, Ñ-11ꢆ), 31.90 (t, Ñ-14ꢆ), 31.97 (d, Ñ-1ꢆꢆ), 32.79 (t, Ñ-5), 33.42 (t, Ñ-3), 52.47 (t, Ñ-1),
63.34 (d, Ñ-6), 127.35 (d, Ñ-2), 135.92 (s, Ñ-1).
REFERENCES
1.
G. Yu. Ishmuratov, A. V. Bannova, E. R. Latypova, V. S. Tukhvatshin, O. S. Kukovinets, R. R. Muslukhov, and
G. A. Tolstikov, Zh. Org. Khim., 49, 52 (2013).
2.
3.
A. V. Bannova, Dissertation, Inst. Org. Chem., USC RAS, Ufa, 2012, 23 pp.
G. Yu. Ishmuratov, E. R. Latypova, R. Ya. Kharisov, R. R. Muslukhov, A. V. Bannova, R. F. Talipov, and G. A. Tolstikov,
Zh. Org. Khim., 44, 663 (2008).
4.
5.
J. Katsuhara, H. Yamasaki, and N. Yamamoto, Bull. Chem. Soc. Jpn., 43, 1584 (1970).
G. Yu. Ishmuratov, E. R. Latypova, V. S. Tukhvatshin, A. A. Smolꢆnikov, R. R. Muslukhov, N. M. Ishmuratova, and
R. F. Talipov, Khim. Prir. Soedin., 866 (2012).
6.
7.
E. R. Latypova, V. S. Tukhvatshin, R. R. Muslukhov, M. P. Yakovleva, N. K. Lyapina, R. F. Talipov, and
G. Yu. Ishmuratov, Vestn. Bashkir. Univ., 2, 358 (2009).
L. E. Nikitina, V. A. Startseva, L. Yu. Dorofeeva, N. P. Artemova, I. V. Kuznetsov, S. A. Lisovskaya, and N. P. Glushko,
Chem. Nat. Compd., 46, 28 (2010).
8.
L. E. Nikitina, V. A. Startseva, I. V. Vakulenko, I. M. Khismatulina, S. A. Lisovskaya, N. P. Glushko, and
N. S. Fassakhov, Khim.-farm. Zh., 43 (5), 20 (2009).
9.
L. Yu. Dorofeeva, I. V. Kuznetsov, L. E. Nikitina, V. A. Startseva, N. P. Artemova, A. V. Bodrov, S. A. Lisovskaya, and
N. I. Glushko, V Mire Nauchn. Otkryt., No. 4(10), Part 15, 23–25 (2010).
10.
E. V. Sirazieva, V. A. Startseva, L. E. Nikitina, V. V. Plemenkov, V. V. Klochkov, and B. I. Khairutdinov, Chem. Nat.
Compd., 40, 478 (2004).
11.
12.
13.
B. Ngo Bakopki, R. V. Palei, and V. V. Plemenkov, Zh. Obshch. Khim., 73 (4), 667 (2003).
E. V. Sirazieva, V. A. Startseva, L. E. Nikitina, I. V. Kuznetsov, and V. V. Klochkov, Khim. Prir. Soedin., 564 (2006).
G. Yu. Ishmuratov, V. S. Tukhvatshin, E. R. Latypova, R. R. Muslukhov, and R. F. Talipov, Butlerovskie Soobshch.,
32 (10), 18 (2012).
870

14.
M. G. Voronkov, N. S. Vyazankin, E. N. Deryaginva, A. S. Nakhmanovich, and V. A. Usov, Reactions of Sulfur with
Organic Compounds [in Russian], Nauka, Novosibirsk, 1979, 368 pp.
A. V. Mashkina and V. N. Yakovleva, Khim. Interesakh Ustoich. Razvit., 9, 269 (2001).
Sigma-Aldrich electronic catalog, M 4007.
A. V. Timshina, S. A. Rubtsova, M. I. Kodess, E. G. Matochkina, P. A. Slepukhin, and A. V. Kuchin, Zh. Org. Khim.,
44 (7), 1053 (2008).
15.
16.
17.
18.
19.
E. V. Sirazieva, Dissertation, Kazan State Technol. Univ., Kazan, 2006.
I. A. Vakulenko, V. A. Startseva, L. E. Nikitina, N. P. Artemova, L. L. Frolova, and A. V. Kuchin, Chem. Nat. Compd.,
41, 686 (2005).
20.
21.
22.
C. Ingold, Structure and Mechanism in Organic Chemistry, Cornell Univ. Press, Ithaca, 1969.
P. Sykes, A Guidebook to Mechanism in Organic Chemistry, Wiley, New York, 1970.
W. Treibs and H. Albrecht, J. Prakt. Chem., 13, 291 (1961).
871