Synthesis of alkyl (α-phenylthioalkenyl) ketones containing a (Z)-trisubstituted olefinic fragment

Article abstract of DOI:10.1023/B:RUCB.0000035654.60768.fb

Warren's method, which has been proposed for the synthesis of α-phenylthiodialkyl ketones, appeared to be inefficient for the preparation of their alkenyl alkyl analogs. The latter were prepared in good yields by alkenylation of alkyl phenylthiomethyl ketones with alkenyl bromides.

Full text of DOI:10.1023/B:RUCB.0000035654.60768.fb

Russian Chemical Bulletin, International Edition, Vol. 53, No. 3, pp. 665—670, March, 2004
665
Synthesis of alkyl (αꢀphenylthioalkenyl) ketones
containing a (Z )ꢀtrisubstituted olefinic fragment
N. Ya. Grigorievaꢀ and P. G. Tsiklauri
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: ves@ioc.ac.ru
Warren's method, which has been proposed for the synthesis of αꢀphenylthiodialkyl keꢀ
tones, appeared to be inefficient for the preparation of their alkenyl alkyl analogs. The latter
were prepared in good yields by alkenylation of alkyl phenylthiomethyl ketones with alkenyl
bromides.
Key words: alkyl (αꢀphenylthioalkenyl) ketones, (Z)ꢀ8ꢀmethylꢀ5ꢀphenylthioundecꢀ7ꢀenꢀ
4ꢀone, (Z)ꢀ8,12ꢀdimethylꢀ5ꢀphenylthiotridecaꢀ7,11ꢀdienꢀ4ꢀone; 1ꢀphenylthiopentanꢀ2ꢀone,
thioacetals, sulfides.
Earlier,1,2 we have demonstrated that condensation of
anions of alkyl trialkylsilylacetates with methyl αꢀphenylꢀ
thioalkyl or ꢀalkenyl ketones proceeds with (Z)ꢀstereoꢀ
selectivity of ~90%. This fact was used, in particular, in
the total synthesis of the sex pheromone of bean beetle.3
The stereochemistry of this reaction with ketones conꢀ
taining the alkyl substituent other than methyl remained
unknown. Elucidation of this question requires the develꢀ
opment of convenient and reliable procedures for the synꢀ
thesis of such ketones.
The present study was aimed at solving this problem
with the use of ketones containing the PhS group in the
Scheme 1
Reagents and conditions: a. BuLi; b.
(2); c. BuLi/TMEDA; d. PrCHO; e. TsOH/PhH, 80 °C;
f. NaH/THF; g.
(9).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 635—639, March, 2004.
1066ꢀ5285/04/5303ꢀ0665 © 2004 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
Grigorieva and Tsiklauri
homoallylic position with respect to the (Z)ꢀdouble bond.
The method,4 which works well with simplest ketones,4,5
appeared to be inefficient for the preparation of the deꢀ
sired compounds. For example, alkenylation of di(phenylꢀ
thio)methane (1) with neryl bromide (2) (Scheme 1) afꢀ
fords dithioacetal 3 in good yield. The latter is smoothly
transformed into alcohol 4 by condensation with butanal.
However, thermolysis of 4 in the presence of TsOH3,4 is
accompanied by strong resinification, and the yield of the
target ketone 5 is no higher than 10%.
A more successful synthesis of ketone 5 was accomꢀ
plished using a reverse sequence of alkenylation steps.
The first step of the synthesis involves condensation
of dithioacetal 1 with butanal to form alcohol 6 (see
Scheme 1), whose thermolysis according to Warren's
method gives rise to ketone 7.* Alkenylation of ketone 7
with neryl bromide (2) affords the target ketone 5 in 70%
yield. Analogously, alkenylation of ketone 7 with broꢀ
mide 9 gives ketone 10. The preparation of ketones 5
and 10 by this method is accompanied by bisꢀalkenylation
giving rise to dienic derivatives 11 and 12, respectively, in
5—7% yields. These byꢀproducts are easily separated from
the target reaction products by chromatography.
Scheme 2 demonstrates that condensation of pentanal
Nꢀtertꢀbutylimine with benzyl ether of glycolaldehyde (13)
afforded (E)ꢀacrolein 14 in 80% yield with stereoselectivity
of >98%. The stereochemistry of compound 14 was conꢀ
1
cluded from its H NMR spectrum based on the integral
intensity ratio of the signals for the protons of the CHO
group in the (E) and (Z ) isomers (δ 9.4 and 10.0, respecꢀ
tively).7 The stereospecific transformation of acrolein 14
into bromide 9 was carried out using standard procedures
through alcohol 15, benzyl ether 16, and alcohol 17. The
structures of previously unknown compounds 9 and
14—17 were confirmed by spectroscopic data, which agree
well with the earlier results.6,8
Experimental
The IR spectra were measured on a Perkin—Elmer 577 specꢀ
trometer in a thin film or (for alcohols) in solutions in CCl4. The
1H and 13C NMR spectra were recorded on a Bruker ACꢀ200
spectrometer in CDCl3 relative to Me4Si as the internal stanꢀ
dard. The electronꢀimpact mass spectra were obtained on Varian
MAT CHꢀ6 or Varian MAT 311A spectrometers at 70 eV;
m/z values of peaks with relative intensities higher than 10% are
given; the exceptions are the molecular ion peaks. Preparative
flash chromatography was carried out on silica gel 60 (Merck);
TLC was performed on Silufol plates (Kavalier, Czech Repubꢀ
lic) in benzene (A) or a diethyl ether—hexane system (1 : 1) (B).
The solvents were purified as follows. Diethyl ether and
THF were kept over KOH, successively distilled from Na and
LiAlH4, refluxed under Ar with sodium benzophenone ketyl
until the solution developed a steady blue color, and then disꢀ
tilled directly into a reaction vessel. Hexane and benzene were
distilled from Na.
The structures of previously unknown compounds 5—8
and 10—12 were confirmed by elemental analysis and
spectroscopic data, which are in good agreement with the
earlier results.1—3
Bromide 9 required for the synthesis of ketone 10, was
prepared by the method, which we have developed earlier6
for the construction of the (Z)ꢀtrisubstituted C=C bond.
Scheme 2
Solutions of LDA were prepared directly in a reaction vessel
from equivalent amounts of diisopropylamine and a 1.3—1.5 M
BuLi solution in hexane, which was prepared according to a
standard procedure.
Experiments with the use of metallic lithium, BuLi, NaH,
and LDA were carried out under argon using glassware which
has been dried at 160 °C for 12 h followed by cooling under a
stream of argon.
The standard workup of organic extracts implies their washꢀ
ing to pH ≈7, drying with MgSO4, and vacuum evaporation of
the solvent.
(Z)ꢀ4,8ꢀDimethylnonaꢀ3,7ꢀdienal (homoꢀneral) diphenyl
dithioacetal (3). A 1.25 M BuLi solution in hexane (11.2 mL,
14 mmol) was added to a solution of di(phenylthio)methane
(3.25 g, 14 mmol) in THF (50 mL) at a temperature from 0
to –3 °C for 15 min. The reaction mixture was stirred at 0 °C for
30 min and cooled to –10 °C. Then a solution of neryl bromide
(2) (Fluka) (3.79 g, 17.5 mmol) in THF (10 mL) was added to
the reaction mixture for 20 min. The mixture was stirred at
–10 °C for 15 min, warmed to ~20 °C over 20 min, stirred for
2 h, and treated with a mixture of ice water and tertꢀbutyl methyl
ether (TBME) (1 : 1, v/v; 50 mL). The aqueous solution was
extracted with TBME (3×20 mL). After standard workup of the
organic extracts, the residue was dried in vacuo (1 Torr) for 8 h
to give acetal 3 (~100% yield) as a paleꢀyellow oil, which was
Reagents and conditions: a. LDA/THF/HMPA;
b. BnOCH2CHO (13); c. H3O+; d. NaBH4;
e. 1) Py•SO3, 2) LiAlH4/THF; f. Li/NH3; g. PBr3/Et2O.
* Thermolysis of alcohol 6 was accompanied by the rearrangeꢀ
ment giving rise to aldehyde 8 in ~8% yield. Under conditions of
chromatography on SiO2, alcohol 6 was partially decomposed to
give ketone 7 in ~7% yield.
1
used without additional purification. H NMR, δ: 1.60 (s, 3 H,

Alkyl (αꢀphenylthioalkenyl) ketones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
667
cisꢀMeC(8)); 1.70 (s, 3 H, transꢀMeC(8)); 1.76 (s, 3 H, MeC(4));
1095, 1075, 1033, 1010, 935, 920, 910, 860, 730, 700, 688, 500.
1H NMR, δ: 0.92 (t, 3 H, Me, J = 7.2 Hz); 1.45 (m, 2 H,
C(4)H2); 1.75 (m, 2 H, C(3)H2); 2.73 (d, 1 H, OH, J = 4.7 Hz);
3.84 (m, 1 H, C(2)H); 4.50 (d, 1 H, C(1)H, J = 3.9 Hz); 7.40
(m, 10 H, Ph). 13C NMR, δ: 13.9 (Me); 19.1 (C(4)); 35.6
(C(3)); 66.8 (C(1)); 72.2 (C(2)). MS, m/z (Irel (%)): 304 [M]+
(2), 195 (61), 135 (13), 123 (29), 121 (18), 111 (14.5), 110 (22),
109 (26.5), 85 (74), 79 (11), 78 (14), 77 (33.5), 71 (26), 67
(31.5), 66 (12), 65 (28), 58 (12), 57 (67), 55 (14), 51 (19), 45
(52), 43 (100), 41 (39).
1ꢀPhenylthiopentanꢀ2ꢀone (7) and 2ꢀphenylthiopentanal (8).
Tolueneꢀpꢀsulfonic acid monohydrate (3.23 g) was added in one
portion to a stirred solution of alcohol 6 (5.2 g, 17.1 mmol) in
benzene (400 mL) at 80 °C. The reaction mixture was stirred for
15 min, cooled to ~20 °C for 3 min, and poured into a saturated
aqueous Na2CO3 solution (150 mL). The mixture was stirred for
15 min. Then the layers were separated. After standard workup
of the benzene layer, a mixture of the reaction products was
obtained in a yield of 4.62 g as a paleꢀyellow oil. Chromatoꢀ
graphy on SiO2 (100 g) using gradient elution (hexane→benzene)
afforded ketone 7 in a yield of 1.83 g (55%), aldehyde 8 in a yield
of 0.26 g (~8%), and the starting alcohol 6 in a yield of
0.68 g (~12%).
2.05 (m, 4 H, CH2C=C); 2.60 (dd, 2 H, C(2)H2, J1 = J2
=
6.5 Hz); 4.40 (t, 1 H, C(1)H, J = 6.5 Hz); 5.06 (poorly reꢀ
solved t, 1 H, C(7)H); 5.40 (t, 1 H, C(3)H, J = 6.5 Hz); 7.40 (m,
10 H, Ph).
(Z)ꢀ8,12ꢀDimethylꢀ5,5ꢀdi(phenylthio)tridecaꢀ7,11ꢀdienꢀ4ꢀol
(4). A 1.3 M BuLi solution in hexane (15 mL, 20 mmol) was
added dropwise to a stirred solution of dithioacetal 3 (4.75 g,
12.9 mmol) and TMEDA (2.45 mL, 15.6 mmol) in THF
(120 mL) at –5 °C for 20 min. The solution was warmed to 0 °C
and stirred for 30 min. Then a solution of butanal (1.1 g,
14 mmol) in THF (3 mL) was added dropwise. The reaction
mixture was stirred at 0 °C for 10 min, warmed to ~20 °C over
10 min, stirred for 1 h, and poured into ice water (100 mL).
After 15 min, the aqueous layer was separated and extracted
with TBME (5×50 mL). After standard workup of the organic
extracts, the residue (5.15 g) was chromatographed on SiO2
(100 g). Gradient elution (hexane→benzene, 2 : 3) afforded
alcohol 4 in a yield of 3.32 g (60%) as a colorless oil, Rf 0.50 (A).
1H NMR, δ: 0.95 (t, 3 H, Me, J = 7.1 Hz); 1.35 (m, 2 H, C(2)H2);
1.55 (s, 3 H, cisꢀMeC(12)); 1.65 (s, 3 H, transꢀMeC(12)); 1.73
(s, 3 H, MeC(8)); 1.90 (m, 6 H, C(3)H2, C(9)H2, C(10)H2);
2.20—2.60 (2 H, C(6)H2, AB portion of ABX system, δ 2.29,
A
δ
2.49, JAB = 9.9 Hz, JAX = JBX = 6.0 Hz); 2.65 (d, 1 H, OH,
Ketone 7, paleꢀyellow crystals, m.p. 25—27 °C, b.p.
108—110 °C (1 Torr). Found (%): C, 68.41; H, 7.27; S, 16.35.
C11H14OS. Calculated (%): C, 68.00; H, 7.26; S, 16.50. IR,
ν/cm–1: 3080, 3060, 3020, 2965, 2940, 2905, 2880, 1710, 1585,
1485, 1465, 1440, 1405, 1380, 1370, 1305, 1275, 1190, 1160,
1130, 1090, 1075, 1055, 1045, 1030, 1005, 915, 750, 495, 480.
1H NMR, δ: 0.89 (t, 3 H, Me, J = 7.4 Hz); 1.60 (tq, 2 H,
C(4)H2, J1 = J2 = 7.4 Hz); 2.57 (t, 2 H, C(3)H2, J = 7.4 Hz);
3.67 (s, 2 H, C(1)H2); 7.40 (m, 5 H, Ph). 13C NMR, δ: 13.5
(Me); 17.1 (C(4)); 42.4 (C(3)); 43.8 (C(1)); 205.6 (C(2)). MS,
m/z (Irel (%)): 195 (18), 194 [M]+ (66), 125 (17), 124 (79), 123
(90), 109 (14), 108 (31.5), 78 (11), 77 (28), 72 (10), 71 (100), 69
(12), 65 (19).
Aldehyde 8, b.p. 111—113 °C (1 Torr). Found (%): C, 67.93;
H, 7.51; S, 15.89. C11H14OS. Calculated (%): C, 68.00; H, 7.26;
S, 16.50. IR, ν/cm–1: 3060, 2960, 2940, 2880, 2820, 2720, 1720,
1585, 1480, 1470, 1460, 1440, 1380, 1310, 1185, 1160, 1125,
1095, 1075, 1030, 1005, 985, 850, 750, 700, 500, 380. 1H NMR,
δ: 0.97 (t, 3 H, Me, J = 7.15 Hz); 1.65 (m, 4 H, CH2); 3.55 (dt,
1 H, C(2)H2, J1 = 4.25 Hz, J2 = 7.2 Hz); 7.40 (m, 5 H, Ph); 9.38
(d, 1 H, CHO, J = 4.25 Hz). 13C NMR, δ: 13.65 (Me);
20.1 (C(4)); 29.7 (C(3)); 56.4 (C(2)); 195.2 (C(1)). MS,
m/z (Irel (%)): 196 (4.5), 195 (11), 194 [M]+ (63), 167 (14), 166
(30), 165 (77.5), 135 (12), 125 (23), 124 (41), 123 (100), 111
(16), 110 (45), 109 (61), 91 (16), 87 (21), 77 (29), 69 (17), 66
(20), 65 (45), 55 (80), 51 (24).
(Z)ꢀ8,12ꢀDimethylꢀ5ꢀphenylthiotridecaꢀ7,11ꢀdienꢀ4ꢀone (5)
and (7Z,2´Z)ꢀ8,12ꢀdimethylꢀ5ꢀ(3,7ꢀdimethyloctaꢀ2,6ꢀdienyl)ꢀ5ꢀ
phenylthiotridecaꢀ7,11ꢀdienꢀ4ꢀone (11). A solution of ketone 7
(2.32 g, ~12 mmol) in THF (3 mL) was added to a stirred
suspension of NaH (0.56 g of a 50% emulsion in mineral oil was
washed three times with hexane) in THF (75 mL) at ~20 °C
for 7 min. After completion of the vigorous reaction, the mixture
was stirred at ~20 °C for 1 h and cooled to 10 °C. Then a
solution of neryl bromide (Fluka) (2.6 g, 11.8 mmol) in THF
(5 mL) was added over 20 min. The reaction mixture was stirred
at ~20 °C for 2 h, kept for 16 h, transferred to a mixture of a
saturated aqueous NH4Cl solution and TBME (1 : 1, v/v;
B
J = 5.5 Hz); 3.73 (m, 1 H, CHOH); 4.97 (dt, 1 H, C(11)H, J1 =
1.14 Hz, J2 = 5.6 Hz); 5.55 (t, 1 H, C(7)H, X portion of
ABX system, JAX = JBX = 6.0 Hz); 7.50 (m, 10 H, Ph). 13C NMR,
δ: 13.9 (Me); 17.4 (cisꢀMeC(12)); 19.9 (C(2)); 23.5 (MeC(8)),;
25.5 (transꢀMeC(12)); 25.9, 32.2, 34.3 (C(3), C(6), C(9), C(10));
74.0 (C(5)); 75.6 (C(4)); 119.6 (C(7)); 123.8 (C(11)); 131.4
(C(12)); 137.3 (C(8)).*
Thermolysis of compound 4. Tolueneꢀpꢀsulfonic acid monoꢀ
hydrate (0.53 g) was added in one portion with stirring under
argon to a boiling solution of alcohol 4 (3.18 g, ~7 mmol) in
anhydrous benzene (160 mL). The reaction mixture was stirred
for 15 min, cooled to ~5 °C, and poured into a stirred saturated
aqueous Na2CO3 solution at ~20 °C. The benzene layer was
separated. After standard workup of this layer, a brown viscous
1
oil was obtained in a yield of 2.31 g. According to the H NMR
spectroscopic data, the oil contained no more than 10% of
ketone 5.
1,1ꢀDi(phenylthio)pentanꢀ2ꢀol (6). A 1.3 M BuLi solution in
hexane (57 mL, 74 mmol) was added to a stirred solution of 1
(14.46 g, 63.33 mmol) in THF (250 mL) at 0 °C for 30 min.
After 15 min, a solution of butanal (4.49 g, 62.33 mmol) in THF
(10 mL) was added at the same temperature. The reaction mixꢀ
ture was stirred at 0 °C for 10 min and then at ~20 °C for 40 min,
after which the mixture was transferred into a cooled mixture of
water and TBME (1 : 1, v/v; 200 mL). The mixture was stirred
for 15 min. The aqueous layer was separated and extracted with
TBME (3×100 mL). After standard workup of the combined
organic extracts, the reaction product (17.05 g) was divided into
three equal portions. Each portion was chromatographed on
SiO2 (100 g). Gradient elution (hexane→benzene) afforded alꢀ
cohol 6 in a yield of 11.08 g (58.5%) and ketone 7 in a yield of
1.35 g (~7%) (see below). Alcohol 6, Rf 0.26 (A). IR, ν/cm–1
3540, 3080, 3060, 3040, 3020, 3010, 2965, 2940, 2880, 1585,
1485, 1470, 1445, 1385, 1340, 1310, 1290, 1210, 1160, 1125,
:
* The 13C NMR spectra of compounds 4—8 and 10—16 have
also signals of the Ph group.

668
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
Grigorieva and Tsiklauri
100 mL), and stirred for 10 min. The layers were separated. The
aqueous layer was extracted with TBME (3×20 mL). After stanꢀ
dard workup of the organic extracts, the residue (5.47 g)
was chromatographed on SiO2 (100 g). Gradient elution
(hexane→benzene, 7 : 3) afforded ketone 5 in a yield of 2.78 g
(70%), ketone 11 in a yield of 0.34 g (7.3%), and the starting
ketone 7 in a yield of 0.12 g (~5%).
Ketone 5, b.p. 160 °C (0.1 Torr), Rf 0.23 (A). Found (%):
C, 76.49; H, 9.23; S, 9.45. C21H30OS. Calculated (%): C, 76.30;
H, 9.15; S, 9.70. IR, ν/cm–1: 3080, 3060, 3040 3020, 2970,
2940, 2880, 1710, 1585, 1480, 1455, 1440, 1410, 1380, 1360,
1270, 1160, 1130, 1090, 1070, 1030, 1005, 840, 750, 700, 685,
500. 1H NMR, δ: 0.91 (t, 3 H, Me, J = 7.4 Hz); 1.60 (m,
2 H, C(2)H2); 1.62 (s, 3 H, cisꢀMeC(12)); 1.76 (s, 6 H,
transꢀMeC(12)); MeC(8)); 2.06 (m, 4 H, C(9)H2, C(10)H2);
(s, 3 H, MeC(8)); 1.99 (m, 2 H, C(9)H2); 2.50 (m, 2 H, C(6)H2);
2.53 (t, 2 H, C(3)H2, J = 7.3 Hz); 3.63 (dd, 1 H, C(5)H, J1 =
J2 = 7.5 Hz); 5.14 (t, 1 H, C(7)H, J = 6.4 Hz); 7.4 (m, 5 H, Ph).
13C NMR, δ: 13.7, 14.0 (Me); 17.3, 21.1 (C(2), C(10)); 23.4
(MeC(8)); 29.2 (C(6)); 34.0 (C(9)); 42.0 (C(3)); 57.2 (C(5));
120.5 (C(7)); 138.8 (C(8)); 207.0 (C(4)). MS, m/z (Irel (%)):
291 (0.8), 290 [M]+ (7), 219 (31), 196 (12), 195 (30), 194 (76),
182 (39.5), 181 (81), 165 (13), 149 (18), 137 (38), 135 (24), 125
(15), 124 (16), 123 (47.5), 122 (10), 115 (10), 110 (25), 109 (59),
108 (100), 106 (15), 99 (14), 97(29), 95 (27.5), 91 (22), 81 (39),
79 (35), 77 (29.5), 72 (10), 71 (58), 69 (37.5), 68 (18), 67 (52.5),
66 (31), 65 (32), 59 (10), 58 (45), 56 (10), 55 (71), 53 (26), 51
(24.5), 46 (32), 45 (48), 44 (91), 43 (27), 41 (52), 40 (70), 39 (42).
Ketone 12, Rf 0.61 (A). Found (%): C, 77.67; H, 9.89; S, 8.14.
C
25H39OS. Calculated (%): C, 77.46; H, 10.14; S, 8.27. IR,
2.52 (m, 4 H, C(3)H2, C(6)H2); 3.65 (dd, 1 H, C(5)H, J1
=
ν/cm–1: 3064, 3032, 2960, 2944, 2936, 2888, 2872, 2760, 2728,
2344, 1700, 1676, 1664, 1604, 1584, 1552, 1440, 1392, 1376,
1320, 1304, 1208, 1128, 1104, 1088, 1040, 1024, 1016, 1000,
928, 896, 856, 784, 768, 748, 716, 700. 1H NMR, δ: 0.89 (t, 6 H,
C(11)H3, C(6´)H3, J = 7.4 Hz); 0.97 (t, 3 H, C(1)H3, J =
7.5 Hz); 1.37 (m, 4 H, C(10)H2, C(5´)H2); 1.65 (m, 2 H,
C(2)H2); 1.69 (s, 6 H, MeC(8), MeC(3´)); 1.93 (t, 4 H, C(9)H2,
7.07 Hz, J2 = 7.2 Hz); 5.15 (m, 2 H, C(7)H, C(11)H); 7.35
(m, 5 H, Ph). 13C NMR, δ: 13.6 (Me); 17.2 (C(2)); 17.5
(cisꢀMeC(12)); 23.3 (MeC(8)); 25.6 (transꢀMeC(12)); 26.3, 29.0
(C(6), C(10)); 32.0 (C(9)); 41.8 (C(3)); 57.0 (C(5)); 120.6
(C(7)); 123.9 (C(11)); 131.6 (C(12)); 138.4 (C(8)); 206.8 (C(4)).
MS, m/z (Irel (%)): 331 (5.5), 330 [M]+ (18), 221 (48), 194 (69),
163 (17), 150 (26), 148 (41), 137 (24), 135 (31), 123 (100), 121
(21), 109 (34), 108 (41), 106 (30), 104 (15), 95 (30.5), 93 (63),
91 (16), 82 (15), 81 (84), 80 (16), 79 (23), 77 (18), 71 (87.5), 70
(20), 69 (98.5), 67 (32).
C(4´)H2), J = 7.7 Hz); 2.43 (dd, 4 H, C(6)H2, C(1´)H2, J1
=
J2 = 6.4 Hz); 2.74 (t, 2 H, C(3)H2, J = 7.5 Hz); 5.14 (t, 2 H,
C(7)H, C(2´)H), J = 6.4 Hz); 7.35 (m, 5 H, Ph). 13C NMR, δ:
14.1 (Me); 17.7, 21.0 (C(2), C(10), C(5´)); 23.7 (MeC(8),
MeC(3´)); 30.4 (C(6)); C(1´)); 34.4 (C(9), C(4´)); 39.0 (C(3));
64.1 (C(5)); 119.0 (C(7), C(2´)); 138.7 (C(8), C(3´)); 208.0
(C(4)). MS, m/z (Irel (%)): 387 (1), 386 [M]+ (1), 316 (20), 315
(42), 291 (17), 290 (18), 289 (14), 278 (26), 277 (51.5), 233 (30),
221 (15), 220 (37), 219 (57), 207 (11), 206 (24), 205 (45), 194
(16), 193 (18), 191 (20), 181 (30.5), 179 (27), 165 (29), 163 (25),
151 (17), 149 (33), 147 (14.5), 137 (27), 135 (47), 134 (10), 124
(12), 123 (54), 121 (36.5), 119 (11), 110 (20), 109 (48), 108
(66.5), 107 (13), 106 (28), 104 (24), 99 (11), 98 (33), 97(79), 95
(30), 94 (11), 93 (32), 92 (12), 91 (34), 84 (11), 83 (27), 81 (35),
80 (16), 79 (37.5), 78 (20.5), 77 (33.5), 72 (29), 71 (82), 69 (56),
68 (15), 67 (42), 66 (28), 65 (31), 63 (13), 58 (37), 57 (41), 56
(28), 55 (100), 53 (34), 52 (12), 51 (28), 50 (15), 46 (26), 45
(54), 44 (95), 42 (32), 41 (53), 40 (38), 39 (35), 37 (13).
2(E)ꢀ(2ꢀBenzyloxyethylidene)pentanal (14). A solution of
pentanal tertꢀbutylimine9 (8.3 g, 39 mmol) in THF (30 mL) was
added dropwise to a stirred solution of LDA (45 mmol) in a
THF—hexane mixture (9 : 1, v/v; 280 mL) at –10 °C for 15 min.
The reaction mixture was stirred at 0 °C for 40 min and cooled
to –15 °C. Then HMPA (50 mL) was added. The reaction
mixture was stirred for 15 min and cooled to –70 °C. Then a
solution of benzyl ether of glycolaldehyde (13) (4.8 g, 32 mmol),
which has been prepared as described earlier,10 in THF (10 mL)
was added dropwise. The reaction mixture was stirred at –70 °C
for 2.5 h, warmed to 0 °C over 4 h, transferred into a stirred
mixture TBME and 3% HCl at 0 °C, and stirred at ~20 °C for
3.5 h. The layers were separated. The aqueous layer was exꢀ
tracted with TBME. After standard workup of the combined
organic extracts, the residue (5.2 g) was chromatographed on
SiO2 (100 g). Gradient elution (hexane→ethylacetate, 3 : 1)
afforded enal 14 in a yield of 4.26 g (61%) as a colorless oil, b.p.
110 °C (1 Torr). Found (%): C, 77.16; H, 8.48. C14H18O2.
Calculated (%): C, 77.03; H, 8.31. IR, ν/cm´–1: 3060—2860,
2740, 1690, 1640, 1500, 1470, 1450, 1380, 1340, 1320, 1230,
Ketone 11, Rf 0.40 (A). IR, ν/cm–1: 3080, 3060, 3040, 2970,
2940, 2880, 2860, 2730, 1710, 1585, 1480, 1450, 1440, 1410,
1380, 1360, 1270, 1160, 1125, 1090, 1070, 1030, 1010, 835, 755,
1
700, 685, 500. H NMR, δ: 0.98 (t, 3 H, Me, J = 7.4 Hz); 1.61
(s, 6 H, cisꢀMeC(12), cisꢀMeC(7´)); 1.62 (m, 2 H, C(2)H2);
1.69 (s, 6 H, transꢀMeC(12), transꢀMeC(7´)); 1.72 (s, 6 H,
MeC(8), MeC(3´)); 1.99 (m, 8 H, C(9)H2, C(10)H2, C(4´)H2,
C(5´)H2); 2.45 (m, 4 H, C(6)H2, C(1´)H2); 2.76 (dd, 2 H,
C(3)H2, J1 = 7.3 Hz, J2 = 7.6 Hz); 5.13 (m, 4 H, C(7)H,
C(11)H, C(2´)H, C(6´)H); 7.35 (m, 5 H, Ph). 13C NMR, δ: 13.8
(Me); 17.5 (C(2), cisꢀMeC(12), cisꢀMeC(7´)); 23.5 (MeC(8),
MeC(3´)); 25.5 (transꢀMeC(12), transꢀMeC(7´)); 26.2, 30.3
(C(6), C(10), C(1´), C(5´)); 32.3 (C(9), C(4´)); 38.7 (C(3));
63.7 (C(5)); 119.0 (C(7), C(2´)); 124.0 (C(11), C(6´));
131.4 (C(12), C(7´)); 138.2 (C(8), C(3´)); 207.5 (C(4)). MS,
m/z (Irel (%)): 467 (1.6), 466 [M]+ (4), 395 (23), 357 (53), 273
(23), 259 (19.5), 189 (16), 177 (19), 163 (28), 161 (19.5), 150
(23), 148 (55), 146 (26), 137 (66), 135 (59), 123 (59), 122 (16),
121 (26.5), 119 (19.5), 110 (16), 109 (65), 108 (75), 106 (53),
104 (23), 95 (59), 93 (58), 91 (20), 83 (26), 82 (29), 81 (76), 79
(46), 77 (24), 72 (16), 71 (87.5), 70 (30), 69 (100), 67 (43), 66
(32), 65 (16), 56 (48).
(Z)ꢀ8ꢀMethylꢀ5ꢀphenylthioundecꢀ7ꢀenꢀ4ꢀone (10) and
(7Z,2´Z)ꢀ8ꢀmethylꢀ5ꢀ(3ꢀmethylhexꢀ2ꢀenyl)ꢀ5ꢀphenylthioundecꢀ
7ꢀenꢀ4ꢀone (12). Analogously to the aboveꢀdescribed synthesis
of ketones 5 and 11, ketone 10 (60% yield) and ketone 12 (5.4%
yield) were prepared from ketone 7 and bromide 9 (see below).
Ketone 10, b.p. 135—137 °C (0.09 Torr), Rf 0.52 (A).
Found (%): C, 74.23; H, 9.03; S, 10.86. C18H26OS. Calcuꢀ
lated (%): C, 74.43; H, 9.02; S, 11.04. IR, ν/cm–1: 3065, 2960,
2944, 2936, 2888, 2872, 1708, 1604, 1585, 1544, 1460, 1448,
1440, 1392, 1376, 1240, 1120, 1104, 1088, 1036, 1024, 1016,
1000, 976, 916, 856, 744, 716, 692. 1H NMR, δ: 0.89 (t, 6 H,
Me, J = 7.4 Hz); 1.40 and 1.58 (both m, 2 H each, CH2); 1.69

Alkyl (αꢀphenylthioalkenyl) ketones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
669
1180, 1090, 1080, 1030, 950, 910, 860, 700. 1H NMR, δ: 0.90 (t,
3 H, Me, J = 7.0 Hz); 1.35 (m, 2 H, C(4)H2); 2.20 (t, 2 H,
C(3)H2, J = 7.0 Hz); 4.37 (d, 2 H, C(2´)H2, J = 6.0 Hz); 4.60 (s,
2 H, H2CPh); 6.58 (t, 1 H, C(1´)H, J = 6.0 Hz); 7.35 (m, 5 H,
Ph); 9.40 (s, 1 H, CHO). 13C NMR, δ: 13.9 (Me); 21.7 (C(4));
26.25 C(3)); 66.5 (C(2´)); 73.0 (CH2Ph); 143.8 (C(2)); 149.9
(C(1´)); 194.5 (C(1)). MS, m/z (Irel (%)): 218 [M]+ (0.25), 108
(10), 107 (13.85), 105 (21), 92 (22), 91 (64), 78 (16), 77
(23), 71 (27).
(100 g). Gradient elution (hexane→benzene, 3 : 1) afforded a
fraction containing alcohol 17, which was noticeably volatile
with diethyl ether and hexane. An aliquot of this fraction was
concentrated to dryness to give alcohol 17 with 98% purity
(1H NMR spectroscopic data) as a colorless oil, Rf 0.10 (A),
0.40 (B). IR, ν/cm–1: 3616, 3560, 3432, 3072, 3008, 2960, 2936,
2872, 1664, 1452, 1380, 1212, 1200, 1164, 1120, 1104, 1064,
984, 948, 900, 860, 820, 700, 664, 624. 1H NMR, δ: 0.82 (t, 3 H,
Me, J = 7.45 Hz); 1.28 (br.s, 1 H OH); 1.43 (m, 2 H, C(5)H2);
1.75 (s, 3 H, Me(C(3)); 2.06 (t, 2 H, C(4)H2, J = 7.6 Hz); 4.12
(d, 2 H, C(1)H2, J = 7.1 Hz); 5.43 (t, 1 H, C(2)H, J = 7.1 Hz).
13C NMR, δ: 14.3 (Me); 21.75 (C(5)); 23.8 (MeC(3));
34.3 (C(4)); 59.35 (C(1)); 124.7 (C(2)); 140.2 (C(3)). MS,
m/z (Irel (%)): 115 (2), 114 [M]+ (7), 113 (23.5), 108 (23), 107
(30), 99 (37), 97 (36.5), 96 (16), 95 (12), 91 (27), 87 (16.5), 86
(12), 83 (24.5), 81 (52), 79 (31), 77 (23), 73 (26), 71 (100), 70
(19), 69 (25), 67 (19.5), 65 (14), 60 (24), 57 (63), 56 (28), 55
(88), 54 (16), 53 (35), 51 (13).
The major portion of the fraction containing alcohol 17 was
concentrated to ~7 mL under atmospheric pressure. According
to the 1H NMR spectroscopic data, the solution contained only
trace amounts of benzene. A comparison of the integral intensiꢀ
ties of the signals of MeC(3) (δ 1.75) with the signals of the Me
group of hexane and diethyl ether (δ 0.82) demonstrated that the
solution contained ~30% (~2 g, 17—18 mmol) of alcohol 17.
Diethyl ether (25 mL) was added to the resulting solution of
alcohol 17. The mixture was dried with 4 A molecular sieves and
used without additional purification.
(Z)ꢀ3ꢀMethylhexꢀ2ꢀenyl bromide (9). Pyridine (0.5 mL) was
added with stirring to the solution of alcohol 17 (see above). The
mixture was cooled to –15 °C and then a solution of freshly
distilled PBr3 (0.9 mL) in diethyl ether (7 mL) was added for
20 min. The reaction mixture, which was protected from light
with an Al foil, was stirred at a temperature from –15 to –10 °C
for 4 h and poured into ice water (20 mL). The mixture was
stirred for 15 min and the layers were separated. The organic
layer was washed with saturated NaHCO3 and NaCl solutions,
dried with Na2SO4, filtered, and dried with 4 A molecular sieves
for 12 h. An aliquot of the resulting solution was concentrated to
dryness to give bromide 9 with 95—97% purity (according to the
1H NMR spectroscopic data). Bromide 9, Rf 0.72 (B). 1H NMR,
δ: 0.92 (t, 3 H, Me, J = 7.5 Hz); 1.48 (m, 2 H, C(5)H2); 1.78 (s,
3 H, Me(C(3)); 2.13 (t, 2 H, C(4)H2, J = 7.6 Hz); 4.02 (d, 2 H,
C(1)H2, J = 7.1 Hz); 5.56 (t, 1 H, C(2)H, J = 7.1 Hz). The
major portion of the solution of bromide 9 was used without
additional purification for the preparation of ketone 10 (see
above).
2(E)ꢀ(2ꢀBenzyloxyethylidene)pentanꢀ1ꢀol (15) was prepared
by reduction of enal 14 with NaBH4 according to a standard
procedure and purified by flash chromatography on SiO2. The
yield was 94%, b.p. 151 °C (1 Torr). Found (%): C, 76.17; H,
9.22. C14H20O2. Calculated (%): C, 76.33; H, 9.15. IR, ν/cm–1
:
3600, 3550—3150, 3000—2860, 1670, 1600, 1490, 1470, 1450,
1380, 1360, 1320, 1230, 1120, 1070, 1030, 1000, 940, 850, 700.
1H NMR, δ: 0.90 (t, 3 H, Me, J = 7.2 Hz); 1.40 (m, 2 H,
C(4)H2); 2.05 (m, 3 H, C(3)H2, OH); 4.03 (s, 2 H, C(1)H2);
4.08 (d, 2 H, C(2´)H2, J = 6.3 Hz); 4.50 (s, 2 H, H2CPh); 5.65
(t, 1 H, C(1´)H, J = 6.3 Hz); 7.30 (m, 5 H, Ph). 13C NMR, δ:
14.2 (Me); 21.9 (C(4)); 30.4 C(3)); 66.0, 66.1 (C(1), C(2´));
72.3 (CH2Ph); 121.9 (C(1´)); 143.3 (C(2)).
(Z)ꢀ1ꢀBenzyloxyꢀ3ꢀmethylhexꢀ2ꢀene (16). Pyridineꢀsulfur
trioxide (Fluka) (11.13 g, 70 mmol) was added portionwise to a
stirred solution of alcohol 15 (10.22 g, 46.455 mmol) in THF
(160 mL) at 0 °C. The resulting suspension was stirred at 0 °C
for 3 h (TLC control) and cooled to –10 °C. A 0.57 M LiAlH4
solution in THF (480 mL, 273.6 mmol) was added dropwise
over 2 h. The reaction mixture was stirred for 25 h and cooled to
–10 °C. Then water (10.5 mL), a 15% NaOH solution (10.5 mL),
and water (31.5 mL) were successively added with caution. The
precipitate that formed was filtered off and thoroughly washed
with TBME. After standard workup of the filtrate, the residue
(10.48 g) was chromatographed on SiO2 (150 g). Elution with
hexane afforded benzyl ether 16 in a yield of 6.36 g (67%) as a
colorless oil, b.p. 110—112 °C (2.5 Torr). Found (%): C, 81.99;
H, 10.08. C14H20O. Calculated (%): C, 82.30; H, 9.86. IR,
ν/cm–1: 3090, 3070, 3040, 2970, 2940, 2880, 2860, 1670, 1500,
1470, 1460, 1380, 1370, 1355, 1210, 1140, 1100, 1080, 1035,
1020, 950, 910, 745, 705. 1H NMR, δ: 0.94 (t, 3 H, Me, J =
7.3 Hz); 1.47 (m, 2 H, C(5)H2); 1.80 (s, 3 H, MeC(3)); 2.09 (t,
2 H, C(4)H2, J = 7.6 Hz); 4.08 (d, 2 H, C(1)H2, J = 6.9 Hz);
4.56 (s, 2 H, H2CPh); 5.50 (t, 1 H, C(2)H, J = 6.9 Hz); 7.40 (m,
5 H, Ph). 13C NMR, δ: 13.9 (Me); 21.2 (C(5)); 23.5 (MeC(3));
34.0 (C(4)); 66.3 (C(1)); 72.0 (CH2Ph); 121.6 (C(2)); 140.8
(C(3)). MS, m/z (Irel (%)): 204 [M]+ (0.1), 161 (9.4), 113 (28),
112 (9.8), 107 (12), 105 (13), 98 (25), 97 (24), 96 (30), 95 (30),
92 (70), 91 (98), 81 (40), 79 (11), 77(17), 71 (22), 70 (22),
69 (100), 67 (14), 65 (27), 57 (16), 56 (14), 55 (72), 43
(58), 41 (44).
This study was financially supported by the President
of the Russian Federation (the Federal Program for the
Support of Leading Scientific Schools of the Russian
Foundation, Grant NShꢀ1802.2003.3).
(Z)ꢀ3ꢀMethylhexꢀ2ꢀenꢀ1ꢀol (17). Metallic lithium (0.7 g,
100 mmol) was added portionwise to a stirred solution of comꢀ
pound 16 (5.17 g, 25.34 mmol) in liquid NH3 (300 mL) at
–50 °C. The reaction mixture was stirred at –40 °C for 3 h,
NH4Cl was added up to discoloration of the solution, and NH3
was evaporated. The residue was treated with an H2O—Et2O
mixture (1 : 1, v/v; 60 mL) and stirred for 15 min. The layers
were separated. The aqueous layer was extracted with diethyl
ether. After standard workup, the combined extracts were conꢀ
centrated to ~5 mL, hexane (50 mL) was added, and the resultꢀ
ing solution was chromatographed on a column with SiO2
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Received December 17, 2003;
in revised form January 21, 2004