Elimination of β-thioalkoxy alcohols under Mitsunobu conditions. A new synthesis of conjugated enynes from propargylic dithioacetals

Article abstract of DOI:10.1021/jo8013885

(Chemical Equation Presented) Treatment of propargylic dithiolanes 1 with ⁿBuLi followed by a carbonyl electrophile yields the corresponding homopropargylic alcohol 3. Upon treatment with 2 equiv of PPh₃ and DIAD, elimination of SR and OH moieties from 3 affords the corresponding olefins 4 in moderate to good yield. The reaction can be considered an alternative of McMurry coupling of two different carbonyl equivalents.

Full text of DOI:10.1021/jo8013885

Elimination of ꢀ-Thioalkoxy Alcohols under Mitsunobu Conditions.
A New Synthesis of Conjugated Enynes from Propargylic
Dithioacetals
Chih-Wei Chen and Tien-Yau Luh*
Department of Chemistry, National Taiwan UniVersity, Taipei, Taiwan 106, Republic of China
tyluh@ntu.edu.tw
ReceiVed July 3, 2008
n
Treatment of propargylic dithiolanes 1 with BuLi followed by a carbonyl electrophile yields the
corresponding homopropargylic alcohol 3. Upon treatment with 2 equiv of PPh3 and DIAD, elimination
of SR and OH moieties from 3 affords the corresponding olefins 4 in moderate to good yield. The reaction
can be considered an alternative of McMurry coupling of two different carbonyl equivalents.
Introduction
the corresponding ꢀ-heteroatom-substituted alcohols. In addition,
the sulfur moiety of an episulfonium ion can be extruded in the
presence of a nucleophile (e.g., Bu3P or Et3N) to give alkenes
(eq 2).12 It is envisaged that the hydroxyl group in 3 may be
converted into a suitable leaving group so that intramolecular
displacement may occur to generate in situ an episulfonium ion
5. A similar extrusion process may lead to the corresponding
alkenes. In this paper, we report an unprecedented protocol for
the elimination of ꢀ-hydroxythioethers under Mitsunobu condi-
Carbon-carbon double bond formation by means of elimina-
tion of ꢀ-heteroatom substituted alcohols is well-documented.1-6
The starting material can be easily accessible from a heteroatom-
stabilized carbanion and a carbonyl electrophile. We recently
reported that aryl- or alkynyl-substituted ꢀ-hydroxythioethers
3, obtained from the reaction of dithioacetals 1 with BuLi and
then with an aldehyde 2, can readily undergo low-valent iron-
promoted elimination reaction leading to the stereoselective
synthesis of olefins 4 (eq 1).7,8 The net reaction can be
considered as an alternative of McMurry coupling of two
different carbonyl equivalents. It is known that oxiranes,9
aziridines,10 as well as thiiranes11 are obtained selectively from
(9) (a) Ferrier, R. J.; Schmidt, P.; Tyler, P. C. J. Chem. Soc., Perkin Trans.
1 1985, 2, 301. (b) Callam, C. S.; Gadikota, R. R.; Lowary, T. D. J. Org. Chem.
2001, 66, 4549. (c) Dave, R.; Sasaki, N. A. Org. Lett. 2004, 6, 15. (d) Koyama,
Y.; Lear, M. J.; Yoshimura, F.; Ohashi, I.; Mashimo, T.; Hirama, M. Org. Lett.
2005, 7, 267. (e) Thoret, S.; Gueritte, F.; Guenard, D.; Dubois, J. Org. Lett.
2006, 8, 2301. (f) Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9672. (g)
Garcia-Delgado, N.; Riera, A.; Verdaguer, X. Org. Lett. 2007, 9, 635.
(10) (a) Bose, A. K.; Sahu, D. P.; Manhas, M. S. J. Org. Chem. 1981, 46,
1229. (b) Ibuka, T.; Mimura, N.; Aoyama, H.; Akaji, M.; Ohno, H.; Miwa, Y.;
Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. J. Org. Chem.
1997, 62, 999. (c) Hillier, M. C.; Davidson, J. P.; Martin, S. F. J. Org. Chem.
2001, 66, 1657. (d) Ohno, H.; Miyamura, K.; Tanaka, T.; Oishi, S.; Toda, A.;
Takemoto, Y.; Fujii, N.; Ibuka, T. J. Org. Chem. 2002, 67, 1359. (e) Galonic,
D. P.; Ide, N. D.; van der Donk, W. A.; Gin, D. Y. J. Am. Chem. Soc. 2005,
127, 7359. (f) Gandhi, S.; Bisai, A.; Prasad, B. A. B.; Singh, V. K. J. Org.
Chem. 2007, 72, 2133. (g) Caldwell, J. J.; Craig, D. Angew. Chem., Int. Ed.
2007, 46, 2631.
(1) (a) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry:
Reactions, Mechanisms and Structure, 6th ed.; Wiley: Hoboken, NJ, 2007; pp
1534-1546. (b) Bruckner, R. AdVanced Organic Chemistry: Reaction Mecha-
nisms; Harcourt: San Diego, CA, 2002; pp 160-167. (c) Concello´n, J. M.;
Rodr´ıguez-Solla, H. Chem. Soc. ReV. 2004, 33, 599. (d) Shinokubo, H.; Oshima,
K. Synlett 2000, 322.
(2) Corey, E. J.; Winter, A. E. J. Am. Chem. Soc. 1963, 85, 2677.
(3) For a review, see: Wong, H. N. C.; Fok, C. C. M.; Wong, T. Heterocycles
1987, 26, 1345.
(4) For reviews, see: (a) Maercker, A. Org. React. 1965, 14, 270. (b)
Wadsworth, W. S. Org. React. 1977, 25, 73. (c) Maryanoff, B. E.; Reitz, A. B.
Chem. ReV. 1989, 89, 863. (d) Shen, Y.-C. Acta Chim. Sin. 2000, 58, 253.
(5) For reviews, see: (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780. (b)
Ager, D. J. Org. React. 1990, 38, 1. (c) Barrett, A. G. M.; Hill, J. M.; Wallace,
E. M.; Flygare, J. A. Synlett 1991, 764. (d) van Staden, L. F.; Gravestock, D.;
Ager, D. J. Chem. Soc. ReV. 2002, 31, 195.
(6) (a) Kocienski, P. J. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, UK, 1991; Vol. 6 (Winterfeldt, E., Ed.),
pp 975-1039. (b) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563.
(7) Huang, L.-F.; Chen, C. -W.; Luh, T. Y. Org. Lett. 2007, 9, 3663.
(8) A related coupling of a propargylic dithioacetal with a carbonyl compound
in the presence of Cp2Ti[P(OEt)3]2 has recently been disclosed. See: Takeda,
T.; Ozaki, M.; Kuroi, S.; Tsubouchi, A. J. Org. Chem. 2005, 70, 4233.
(11) Camp, D.; Jenkins, I. D. Aust. J. Chem. 1990, 43, 161.
(12) (a) Gybin, A. S.; Smit, A. S. Tetrahedron 1980, 36, 1361. (b) Denis,
J. N.; Dumont, W.; Krief, A. Tetrahedron Lett. 1979, 42, 4111. (c) Helmkamp,
G. K.; Pettitt, D. J. J. Org. Chem. 1960, 25, 1754. (d) Mukaiyama, T.; Shiono,
M.; Sato, T. Chem. Lett. 1974, 1, 37. (e) Mukaiyama, T.; Shiono, M.; Watanabe,
K.; Onaka, M. Chem. Lett. 1975, 7, 871. (f) Mukaiyama, T.; Imaoka, M. Chem.
Lett. 1978, 4, 413.
(13) For reviews on Mitsunobu reaction, see: (a) Mitsunobu, O. Synthesis
1981, 1. (b) Hughes, D. L. OrgReact. (N.Y.) 1992, 42, 335. (c) But, T. Y. S.;
Toy, P. H. Chem. Asian J. 2007, 2, 1340.
10.1021/jo8013885 CCC: $40.75
Published on Web 10/01/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8357–8363 8357

Chen and Luh
TABLE 1. Elimination of ꢀ-Thioalkoxy Alcohols under Mitsunobu Conditions
entry
substrate 1
R1
R2
R3
R4
PR3
yield of 3 (dr)a
yield of 4 (E/Z)
1
2
3
4
5
6
7
8
1a
iPr
Bu
Ph
Bu
H
H
PPh3
PPh3
PBu3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PBu3
PPh3
PBu3
PPh3
PBu3
PPh3
PBu3
PPh3
PPh3
PBu3
PBu3
a 74 (2.3/1)
b 54c
a 81 (2.9/1)b
b 43 (10/1)
b 61 (24/1)
c 65 (1/20)
d 72 (1/3.9)
e 91 (5.0/1)
f 68 (1.7/1)
g 78 (3.2/1)
h 72 (14/1)d
h 72 (6.5/1)
i 48 (1/1.2)
i 69 (1/1.5)
j 48 (3.3/1)
j 81 (3.3/1)
k 39 (1.4/1)
k 89 (2.0/1)
l 76 (2.1/1)
m 62 (1.6/1)
n 17
Mes
H
H
H
H
H
H
c 72 (1.1/1)
d 87 (6.0/1)
e 56 (6.4/1)
f 51 (5.4/1)
g 72 (4.6/1)
h 78 (5.3/1)
1-Naphthyl
p-C6H4OMe
p-C6H4Br
Ph
1b
1c
iPr
Bu
TMS
TMS
9
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
Bu
H
H
H
i 35 (1.3/1)
j 80 (3.6/1)
k 83 (1.6/1)
p-C6H4CF3
p-C6H4CN
o-tol
H
H
Me
Ph
l 67 (1.7/1)
m 37 (1.7/1)
n 53
1d
Bu
Bu
p-C6H4CO2But
Me
Ph
o 78
o 28
o 44e
o 45f
a Diastereomeric ratio (major isomer/minor isomer) was determined by 1H NMR integrals. b When 1 equiv of Mitsunobu reagent was used, the yield
c
was 63%. dr cannot be resolved by H NMR. d Identical results were obtained when the reaction was carried out from -78 to -30 °C. e Reaction time
1
) 48 h. f 4 equiv each of DIAD and Bu3P were used.
tions for the olefination of propargylic dithioacetals with a
carbonyl compound.
was obtained in moderated to good yield. Representative
examples are summarized in Table 1. The stereochemical
assignments for 4 were based on NOE experiments. Mitsunobu
reaction of 3p obtained from 1e [(1). BuLi, (2) PhCHO, (3)
TBSCl, imidizole] under the same conditions gave the corre-
sponding enyne 4p (E/Z ) 1.6/1) in 38% yield (eq 3).
Interestingly, the yield of 4 was significantly improved when
Ph3P was replaced by Bu3P (entries 3, 12, 14, and 16). Tertiary
alcohols are normally quite unreactive under typical Mitsunobu
conditions.15 Indeed, when 3n was allowed to react with DIAD
and Ph3P at rt, no reaction was observed. However, alkenes 4n
and 4o were isolated in low yield from the corresponding 3n
and 3o when Bu3P was employed (entries 19-22), starting
materials being recovered in 40-80% yield. It is noteworthy
that longer reaction time (entry 21) or excess of Mitsunobu
reagent (entry 22) gave better yield of the reaction.
The reaction can also be carried out in one pot from 1. Thus,
reaction of 1a with BuLi and then with benzaldehyde gave the
corresponding alkoxide, which was directly treated with 2 equiv
each of DIAD and Ph3P to give 4a (E/Z ) 4.5/1) in 34% yield.
Results and Discussion
The starting 3 were obtained from the reaction of 1 with nBuLi
followed by treatment with 2 according to literature procedures.7
In the beginning of this study, several Lewis acids (BF3 ·OEt2,
BBr3, and TiCl4) were employed to react with 3c, only starting
material being recovered in 63-85% yields. Interestingly, when
3 was allowed to react with 2 equiv each of DIAD and Ph3P in
THF at rt for 18 h under Mitsunobu conditions,13,14 alkene 4
(14) R-Hydroxyalkyldithiolanes have been known to be converted into
2-azido-1,4-dithianes under Mitsunobu conditions in the presence of sodium
azide. 1,2-Sulfur migration has been suggested. The corresponding 2,3-dihydro-
1,4- dithiins are isolated as side products. See: Afonso, C. A. M.; Barros, M. T.;
Maycock, C. D. Tetrahedron 1999, 55, 801.
(15) (a) Takahashi, M.; Ogasawara, K. Tetrahedron: Asymetry 1997, 8, 3125.
(b) Lochead, A.; Galli, F.; Jegham, S.; Nedelec, P.; George, P. Synth. Commun.
1999, 29, 799. (c) Yus, M.; Soler, T.; Foubelo, F. Tetrahedron: Asymmetry 2001,
12, 801. (d) Shi, Y.-J.; Hughes, D. L.; McNamara, J. M. Tetrahedron Lett. 2003,
44, 3609. (e) La Clair, J. J. Angew. Chem., Int. Ed. 2006, 45, 2769.
8358 J. Org. Chem. Vol. 73, No. 21, 2008

New Synthesis of Conjugated Enynes
SCHEME 1. Possible Mechanism for the Formation of 4
SCHEME 2. Evidence for Thio Migration
It is worthy to mention that the stereoselectivities of the
elimination reaction under Mitsunobu conditions were very
different from those of the low-valent iron-promoted reactions.7
Apparently, the two processes may proceed via very different
mechanisms. In addition, the stereoselectivity appeared to be
temperature independent (entry 9). It seems plausible that the
hydroxyl group in 3 would be activated by R3P to generate
intermediate 6. The phosphine oxide may serve as a leaving
group with the concomitant participation of the neighboring
sulfur moiety leading to the formation of episulfonium ion 5
(Scheme 1). Stereoselective extrusion of the sulfur moiety16 may
lead to the corresponding olefin stereospecifically. The fate of
the sulfur moiety was assigned to be 7 as detected by the high-
resolution mass spectrometry.16 Presumably, the episulfonium
ion may be attached by the amidic anion leading to 4 and 7.
These results support the earlier mechanism proposed by Smit
et al.12a
The stereospecificity has been tested by studying the elimina-
tion reaction of diasteromerically pure ꢀ-thioalkoxyalcohol.
Thus, treatment of 3ka with 2 equiv each of Bu3P and DIAD
afforded stereospecifically Z-4k in 71% yield (eq 2). On the
other hand, the reaction of the other diastereomer 3kb (94%
de) under the same conditions afforded 4k (E/Z ) 34/1) in 71%
yield (eq 5). If the conversion of 6 to 5 would occur via an
SN2-type mechanism, the stereochemistry for 3ka and 3kb
would thus be assigned.
To establish the sulfur migration shown in Scheme 1, 8,
prepared from the carbanion derived from the corresponding
dithioacetal 9 and aldehyde 10, was treated with 2 equiv each
of DIAD and Bu3P under the usual conditions to give 11 (E/Z
) 1/2) in 69% yield. Apparently, the sulfur migration may take
place leading to 11 via the episulfonium ion intermediate 12
(Scheme 2).17 It is noteworthy that 1,2-thio migration in cyclic
dithioacetals is well documented.18
When terephthaldehyde was employed, bis-enyne 13 was
obtained from in 27% overall yield from 1a (eq 6). Treatment
of 1c with BuLi followed by aldehyde 14 having a dithiolane
functionality afforded alcohol 15 in 45% yield. Reaction of 15
under Mitsunobu conditions for 18 h gave the corresponding
endiyne 16 in 68% yield (eq 7). It is worthy to note that the
silyl substituent in 16 can be further modified by functional
group transformation. This strategy could be used for the
convergent synthesis of higher homologues of conjugated
enynes. A similar approach has been employed toward the
synthesis of monodispersed polymers without repetitive units.19
It is interesting to note that a bulky aryl substituent in 3 would
lead the elimination process to form Z isomer predominantly
(entries 4 and 5). Isomerization may take place to give
thermodynamically more stable products.
(16) Calcd for C14H29O4N2S2 (M + 1) 353.1569, found 353.1572.
J. Org. Chem. Vol. 73, No. 21, 2008 8359

Chen and Luh
characteristic 1H NMR signals for the minor isomer: δ 2.16 (sept,
Conclusions
J ) 6.7 Hz), 2.88 (d, J ) 4.8 Hz, 1 H); IR (KBr) ν 3446 cm-1
;
HRMS (FAB) (M + H)+ calcd for C19H29OS2 337.1660, found
337.1666.
In summary, we have demonstrated a new enyne preparation
by coupling of a carbonyl compound with a propargylic
dithioacetal. A range of substituted enynes can be readily
obtained by this protocol. The present reaction can compliment
our earlier work7 on low-valent iron-promoted elimiation of
ꢀ-thioalkoxy alcohols. An episulfonium ion intermediate has
been suggested. Both reactions can be considered as an
alternative of McMurry-type coupling of two different carbonyl
equivalents to give the corresponding olefins.
7-(1-Hydroxypentyl)-7-isopropyl-8,11-dithiapentadec-5-yne (3b):
1
72%; H NMR (CDCl3, 400 MHz) δ 0.92 (t, J ) 7.4 Hz, 9 H),
1.02-1.12 (m, 6 H), 1.28-1.64 (m, 14 H), 1.68-1.80 (m, 1 H),
1.95-2.14 (m, 1 H), 2.28 (t, J ) 6.8 Hz, 2 H), 2.50 (t, J ) 7.8 Hz,
2 H), 2.62-2.98 (m, 4 H), 3.56-3.64 (m, 1 H); IR (KBr) ν 3482
cm-1; HRMS (FAB) (M + H) calcd for C21H41OS2 373.2599, found
373.2599.
7-(r-Hydroxy-2,4,6-trimethylbenzyl)-7-isopropyl-8,11-dithia-
1
pentadec-5-yne (3c): 51% (dr ratio ) 1.1/1); H NMR (CDCl3,
400 MHz) δ 0.82-0.98 (m, 6 H), 1.02-1.18 (m, 6 H), 1.23-1.48
(m, 6 H), 1.52-1.66 (m, 2 H), 1.70-1.98 (m, 1 H), 2.07-2.17 (m
1 H), 2.23-2.47 (m, 11 H), 2.50-2.62 (m, 2 H), 2.6-2.84 (m, 4
Experimental Section
3-(2-Isopropyl-1,3-dithiolan-2-yl)prop-2-yn-1-ol (1e). Under
N2, to a THF solution (50 mL) of 2-ethynyl-2-isopropyl-1,3-
dithiolane7 (3.35 g, 20 mmol, 1.0 equiv) cooled at -78 °C was
added dropwise BuLi (10 mL, 1.25 equiv, 2.5 M hexane solution).
After stirring 0.5 h, formaldehyde gas was introduced to the mixture
until white participate appeared. The mixture was gradually warmed
to rt and stirred for 8 h, quenched with sat. NH4Cl, washed with
brine, and extracted with EtOAc. The organic layer was dried
(MgSO4) and filtered and the filtrate was evaporated in vacuo to
give the residue, which was chromatographed on silica gel (hexane/
EtOAc ) 3/1) to give 1e as a pale yellow liquid (3.60 g, 89%). 1H
NMR (CDCl3, 400 MHz) δ 1.22 (d, J ) 6.8 Hz, 6 H), 1.78 (t, J )
6.2 Hz, 1 H), 2.27 (sept, J ) 6.7 Hz, 1 H), 3.37-3.60 (m, 4 H),
4.35 (d, J ) 6.4 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 21.1,
39.7, 40.4, 50.9, 66.2, 83.3, 86.4; IR (KBr) •3371 cm-1; HRMS
(FAB) (M) calcd for C9H15OS2 203.0564, found 203.0566.
General Procedure for Prepartion of Homopropargylic Alcohol
3. Under N2 atmosphere, to a THF solution (50 mL) of 1 (5.0 mmol,
1.0 equi.) cooled at -78 °C was added dropwise BuLi (2.2 mL,
1.10 equiv, 2.5 M hexane solution). After the solution was stirred
for 1 h, carbonyl compound (1.0 equiv) in THF (10 mL) was then
added dropwise and the mixture was gradually warmed to rt and
stirred for 2-8 h, quenched with sat. NH4Cl, washed with brine,
and extracted with ether. The organic layer was dried (MgSO4)
and filtered and the filtrate was evaporated in vacuo to give the
residue, which was chromatographed on silica gel (hexane/EtOAc
) 10-30/1) to give 3.
1
H), 5.63-5.68 (m, 1 H), 6.81 (s, 2 H); characteristic H NMR
signals for the major isomer δ 2.09 (d, J ) 3.6 Hz, 1 H), 5.66 (d,
1
J ) 3.6 Hz, 1 H); minor isomer H NMR (CDCl3, 400 MHz) δ
2.15 (d, J ) 3.6 Hz, 1 H), 5.64 (d, J ) 3.6 Hz, 1 H); IR (KBr) ν
3455 cm-1; HRMS (FAB) (M) calcd for C26H42OS2 434.2677,
found 434.2686.
7-[r-Hydroxy-(1-naphthylmethyl)]-7-isopropyl-8,11-dithiapen-
1
tadec-5-yne (3d): 87% (dr ratio ) 6.0/1); major isomer H NMR
(CDCl3, 400 MHz) δ 0.72-1.12 (m, 6 H), 1.17-1.58 (m, 11 H),
1.76-1.90 (m, 2 H), 2.08-2.62 (m, 6 H), 3.22 (d, J ) 8.6 Hz, 1
H), 5.86 (d, J ) 8.6 Hz, 1 H), 7.40-7.52 (m, 3 H), 7.77-7.86 (m,
2 H), 7.93-7.98 (d, J ) 7.6 Hz, 1 H), 8.18-8.24 (m, 1 H);
characteristic 1H NMR signals for the minor isomer δ 2.77 (d, J )
6.0 Hz, 1 H), 8.37 (d, J ) 8.0 Hz, 1 H); IR (KBr) ν 3426 cm-1
;
HRMS (FAB) (M + H) calcd for C27H39OS2 443.2441, found
443.2442.
7-(r-Hydroxy-4-methoxybenzyl)-7-isopropyl-8,11-dithiapenta-
1
dec-5-yne (3e): 80% (dr ratio ) 6.4/1); major isomer H NMR
(CDCl3, 400 MHz) δ 0.92 (t, J ) 7.0 Hz, 3 H), 0.94 (t, J ) 7.0
Hz, 3 H), 1.11 (d, J ) 6.4, Hz, 6 H), 1.34-1.47 (m, 4 H), 1.48-1.58
(m, 4 H), 1.84 (sept, J ) 6.6 Hz, 1 H), 2.29 (t, J ) 7.0 Hz, 2 H),
2.47 (t, J ) 7.4 Hz, 2 H), 2.51-2.72 (m, 4 H), 3.04 (d, J ) 6.0
Hz, 1 H), 3.82 (s, 3 H), 4.74 (d, J ) 6.0 Hz, 1 H), 6.82-6.88 (m,
1
2 H), 7.42-7.47 (m, 2 H); characteristic H NMR signals for the
minor isomer δ 3.90 (s, 3 H), 4.78 (d, J ) 4.8 Hz, 1 H); IR (KBr)
ν 3467 cm-1; HRMS (EI+) (M) calcd for C24H38O2S2 422.2313,
found 422.2309.
7-(r-Hydroxybenzyl)-7-isopropyl-8,11-dithiapentadec-5-yne (3a):
74% (dr ratio ) 2.3/1); major isomer 1H NMR (CDCl3, 400 MHz)
δ 0.92 (t, J ) 6.7 Hz, 3 H), 0.94 (t, J ) 6.7 Hz, 3 H), 1.12 (d, J
) 6.4 Hz, 3 H), 1.34 (d, J ) 6.4 Hz, 3 H), 1.34-1.48 (m, 4 H),
1.48-1.60 (m, 4 H), 1.88 (sept, J ) 6.4 Hz, 1 H), 2.29 (t, J ) 7.0
Hz, 2 H), 2.41-2.68 (m, 6 H), 3.08 (d, J ) 6.8 Hz, 1 H), 4.80 (d,
J ) 6.8 Hz, 1 H), 7.27-7.33 (m, 3 H), 7.49-7.58 (m, 2 H);
7-(r-Hydroxy-4-bromobenzyl)-7-isopropyl-8,11-dithiapentadec-
5-yne (3f): 56% (dr ratio ) 5.4/1); major isomer 1H NMR (CDCl3,
400 MHz) δ 0.92 (t, J ) 7.4 Hz, 3 H), 0.94 (t, J ) 7.2 Hz, 3 H),
1.11 (d, J ) 6.6, Hz, 3 H), 1.13 (d, J ) 6.6 Hz, 3 H), 1.35-1.46
(m, 4 H), 1.47-1.57 (m, 4 H), 1.84 (sept, J ) 6.6 Hz, 1 H), 2.27
(t, J ) 7.0 Hz, 2 H), 2.46 (t, J ) 7.2 Hz, 2 H), 2.49-2.68 (m, 4
H), 3.11 (d, J ) 6.8 Hz, 1 H), 4.76 (d, J ) 6.8 Hz, 1 H), 7.38-7.45
1
(m, 4 H); characteristic H NMR signals for the minor isomer δ
(17) No extrusion of sulfur moiety to give vinyl sulfide 11′ was observed.
The presence of an extra thiolato substituent on olefin in 12 might result in
different behavior.
2.32 (t, J ) 7.0 Hz, 2 H), 3.04 (d, J ) 4.8 Hz, 1 H), 4.78 (d, J )
4.8 Hz, 1 H); IR (KBr) ν 3405 cm-1; HRMS (FAB) (M + H)+
calcd for C23H36OBrS2 471.1391, found 471.1389.
3-(r-Hydroxybenzyl)-3-isopropyl-1-trimethylsilyl-4,7-dithiaun-
1
dec-1-yne (3g): 83% (dr ratio ) 4.6/1); major isomer H NMR
(CDCl3, 400 MHz) δ 0.19 (s, 9 H), 0.90 (t, J ) 6.4 Hz, 3 H),
1.08-1.20 (m, 6 H), 1.36-1.42 (m, 2 H), 1.44-1.58 (m, 2 H),
1.87 (sept, J ) 6.6 Hz, 1 H), 2.40-2.64 (m, 6 H), 2.41-2.68 (m,
6 H), 3.08 (d, J ) 6.8 Hz, 1 H), 4.82 (d, J ) 6.8 Hz, 1 H),
.
(18) For examples see: (a) Maldonado, L. A.; Manjarrez, N. Heterocycles
1985, 23, 1985. (b) Caputo, R.; Ferreri, C.; Palumbo, G. Tetrahedron Lett. 1986,
42, 2369. (c) Tani, H.; Inamasu, T.; Tamura, R.; Suzuki, H. Chem. Lett. 1990,
1323. (d) Jeko¨, J.; Tima´r, T.; Jaszberenyi, J. C. J. Org. Chem. 1991, 56, 6748.
(e) Tani, H.; Kamada, Y.; Azuma, N.; Ono, N. Tetrahedron Lett. 1994, 35, 7051.
(f) Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2003, 42,
98. (g) Peng, L.; Zhang, X.; Zhang, S.; Wang, J. J. Org. Chem. 2007, 72, 1192.
(19) (a) Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J.-C.; Luh,
T.-Y. J. Am. Chem. Soc. 2000, 122, 4992. (b) Lee, C.-F.; Lin, C.-Y.; Song,
H.-C.; Luo, S.-J.; Tseng, J.-C.; Tso, H.-H.; Luh, T.-Y. Chem. Commun. 2002,
2824. (c) Chou, C.-M.; Chen, W.-Q.; Chen, J.-H.; Lin, C.-L.; Tseng, J.-C.; Lee,
C.-F.; Luh, T.-Y. Chem. Asia. J. 2006, 1, 46. (d) For a review, see: Luh, T.-Y.;
Lee, C.-F. Eur. J. Org. Chem. 2005, 3839.
1
7.26-7.34 (m, 3 H), 7.50-7.60 (m, 2 H); characteristic H NMR
signals for the minor isomer δ 0.23 (s, 9 H), 2.96 (d, J ) 4.8 Hz,
1 H).7
3-Butyl-3-(r-hydroxybenzyl)-1-trimethylsilyl-4,7-dithiaundec-1-
1
yne (3h): 78% (dr ratio ) 5.3/1); major isomer H NMR (CDCl3,
400 MHz) δ 0.20 (s, 9 H), 0.84-0.97 (m, 6 H), 1.22-1.70 (m, 8
H), 2.51 (t, J ) 7.2 Hz, 2 H), 2.60-2.93 (m, 4 H), 3.18 (d, J ) 4.8
Hz, 1 H), 4.60 (d, J ) 4.8 Hz, 1 H), 7.28-7.34 (m, 3 H), 7.46-7.52
1
(m, 2 H); characteristic H NMR signals for the minor isomer δ
8360 J. Org. Chem. Vol. 73, No. 21, 2008

New Synthesis of Conjugated Enynes
0.21 (s, 9 H), 2.56 (t, J ) 7.4 Hz, 2 H), 3.20 (d, J ) 2.2 Hz, 1 H),
4.71 (d, J ) 2.2 Hz, 1 H); IR (KBr) ν 3458 cm-1; HRMS (FAB)
(M + H) calcd for C23H39OSiS2 423.2212, found 423.2209.
7-Butyl-7-(2-hydroxy-2-propyl)-8,11-dithiapentadec-5-yne (3n):
53%; 1H NMR (CDCl3, 400 MHz) δ 0.82-0.96 (m, 9 H), 1.2-1.68
(m, 19 H), 1.79 (dt, J ) 4.1, 12 Hz, 1 H), 2.26 (t, J ) 7.0 Hz, 2
H), 2.41 (s, 1 H), 2.52 (t, J ) 7.4 Hz, 2 H), 2.63-2.78 (m, 2 H),
2.83-2.96 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 13.6, 13.7,
14.2, 18.6, 22.0, 22.1, 22.9, 25.5, 28.8, 31.0, 31.8, 31.9, 32.9, 33.2,
36.7, 60.6, 76.1, 78.1, 89.4; IR (KBr) ν 3487 cm-1; HRMS (EI+)
(M) calcd for C20H38OS2 358.2364, found 358.2353.
3-Butyl-3-(1-hydroxypentyl)-1-trimethylsilyl-4,7-dithiaundec-1-
1
yne (3i): 35% (dr ratio ) 1.3/1); major isomer H NMR (CDCl3,
400 MHz) δ 0.19 (s, 9 H), 0.90-0.96 (m, 9 H), 1.25-1.87 (m, 14
H), 2.23 (d, J ) 6.2 Hz, 1 H), 2.57 (t, J ) 7.4 Hz, 2 H), 2.68-3.00
1
(m, 4 H), 3.48-3.56 (m, 2 H); characteristic H NMR signals for
the minor isomer δ 0.20 (s, 9 H); IR (KBr) ν 3484 cm-1; HRMS
(FAB) (M + H) calcd for C21H43OS2Si 403.2525, found 403.2517.
7-Butyl-7-(1-hydroxy-1,1-diphenylmethyl)-8,11-dithiapentadec-
1
5-yne (3o): 78%; H NMR (CDCl3, 400 MHz) δ 0.85 (t, J ) 7.2
Hz, 3 H), 0.91 (t, J ) 7.2 Hz, 3 H), 0.93 (t, J ) 7.2 Hz, 3 H),
1.23-1.62 (m, 12 H), 1.95-2.19 (m, 4 H), 2.47-2.58 (m, 4 H),
2.63-2.79 (m, 2 H), 2.98 (s, 1 H), 7.21-7.44 (m, 10 H); 13C NMR
(100 MHz, CDCl3) δ 13.8, 14.0, 14.1, 22.1, 22.4, 22.7, 29.9, 30.6,
30.7, 31.7, 31.8, 31.9, 32.0, 33.8, 81.3, 108.1, 118.0, 127.0, 127.2,
127.7, 145.0, 145.1; IR (KBr) Ρ3488 cm-1; HRMS (FAB) (M +
H) calcd for C30H42OS2 483.2755, found 483.2756.
4-Isopropyl-4-(r-hydroxybenzyl)-5,8-dithia-2-dodecyn-1-yl tert-
Butyldimethylsilyl Ether (3p). Under N2 atmosphere, to a THF
solution (50 mL) of 1e (1.01 g, 5.0 mmol, 1.0 equiv) cooled at-78
°C was added dropwise BuLi (4.4 mL, 2.2 equiv, 2.5 M hexane
solution). After the solution was stirred for 1 h, benzaldehyde (0.51
mL, 5.0 mmol, 1.0 equiv) in THF (10 mL) was added dropwise at
- 78 °C. The mixture was gradually warmed to rt and stirred for
8 h, quenched with sat. NH4Cl, washed with brine, and extracted
with ether. The organic layer was dried (MgSO4) and filtered and
the filtrate was evaporated in vacuo to give the residue, which was
chromatographed on silica gel (hexane/EtOAc ) 9/1) to give the
crude diol (1.47 g, 77%).
3-Butyl-3-(r-hydroxy-4-trifluoromethylbenzyl)-1-trimethylsilyl-
4,7-dithiaundec-1-yne (3j): 80% (dr ratio ) 3.6/1); major isomer
1H NMR (CDCl3, 400 MHz) δ 0.20 (s, 9 H), 0.83-0.96 (m, 6 H),
1.19-1.78 (m, 8 H), 2.51 (t, J ) 7.4 Hz, 2 H), 2.63-3.00 (m, 4
H), 3.33 (d, J ) 4.6 Hz, 1 H), 4.63 (d, J ) 4.6 Hz, 1 H), 7.57 (d,
1
J ) 8.4 Hz, 2 H), 7.62 (d, J ) 8.4 Hz, 2 H); characteristic H
NMR signals for the minor isomer δ 0.21 (s, 9 H), 3.45-3.52 (m,
1 H), 4.76 (br s, 1 H); IR (KBr) ν 3449 cm-1; HRMS (FAB) (M
+ H) calcd for C24H38OF3SiS2:491.2085, found 491.2079.
3-Butyl-3-(r-hydroxy-4-cyanobenzyl)-1-trimethylsilyl-4,7-dithi-
aundec-1-yne (3k): 83% (dr ratio ) 1.6/1). The two isomers were
separated by preparative HPLC (LiChrospher Si 60, eluent:CHCl3/
EtOAc ) 100/1): major isomer (3kb) 1H NMR (CDCl3, 400 MHz)
δ 0.18 (s, 9 H), 0.90 (t, J ) 8.0 Hz, 3 H), 0.91 (t, J ) 7.4 Hz, 3
H), 1.16-1.66 (m, 8 H), 2.52 (t, J ) 7.6 Hz, 2 H), 2.62-3.01 (m,
4 H), 3.37 (d, J ) 4.4 Hz, 1 H), 4.61 (d, J ) 4.4 Hz, 1 H),
1
7.59-7.64 (m, 4 H); minor isomer (3ka) H NMR (CDCl3, 400
MHz) δ 0.20 (s, 9 H), 0.84 (t, J ) 7.2 Hz, 3 H), 0.93 (t, J ) 7.4
Hz, 3 H), 1.18-1.66 (m, 8 H), 2.57 (t, J ) 7.2 Hz, 2 H), 2.62-3.01
(m, 4 H), 3.52 (d, J ) 1.6 Hz, 1 H), 4.73 (d, J ) 1.6 Hz, 1 H),
7.59-7.64 (m, 4 H); IR (KBr) ν 3471 cm-1; HRMS (FAB) (M +
H) calcd for C24H38ONSiS2 448.2164, found 448.2175.
Under N2 atmosphere, to a DCM solution (40 mL) of the crude
diol (1.47 g, 3.85 mmol) and imidazole (0.26 g, 3.85 mmol, 1.0
equiv) cooled at -78 °C was added TBSCl (0.58 g, 3.85 mmol,
1.0 equiv) in DCM (10 mL) dropwise. The mixture was gradually
warmed to rt and stirred for 8 h and then washed with brine. The
organic layer was dried (MgSO4) and filtered and the filtrate was
evaporated in vacuo to give the residue, which was chromato-
graphed on silica gel (hexane/EtOAc ) 30/1) to give 3p as a pale
yellow liquid (1.51 g, 63% in two steps, dr ratio ) 3.5/1). Major
3-Butyl-3-(r-hydroxy-o-methylbenzyl)-1-trimethylsilyl-4,7-dithi-
aundec-1-yne (3l): 67% (dr ratio ) 1.7/1); major isomer 1H NMR
(CDCl3, 400 MHz) δ 0.18 (s, 9 H), 0.85-0.95 (m, 6 H), 1.24-1.66
(m, 8 H), 2.40 (s, 3 H), 2.46-2.88 (m, 8 H), 3.23 (d, J ) 5.2 Hz,
1 H), 4.89 (d, J ) 5.2 Hz, 1 H), 7.09-7.16 (m, 1 H), 7.17-7.22
1
(m, 2 H), 7.77-7.82 (m, 1 H); characteristic H NMR signals for
1
isomer H NMR (CDCl3, 400 MHz) δ 0.12 (s, 6 H), 0.88-0.98
the minor isomer δ 0.18 (s, 9 H), 2.94 (d, J ) 4.0 Hz, 1 H), 5.04
t
(m, 12 H embodied a singlet at 0.93 for Bu group), 1.14 (d, J )
(d, J ) 4.0 Hz, 1 H), 7.60-7.65 (m, 2 H); IR (KBr) Ρ 3455 cm-1
;
6.7 Hz, 6 H), 1.33-1.42 (m, 2 H), 1.47-1.56 (m, 2 H), 1.89 (sept,
J ) 6.7 Hz, 1 H), 2.41-2.70 (m, 6 H), 3.10 (s, 1 H), 4.40 (s, 2 H),
4.84 (s, 1 H), 7.26-7.36 (m, 3 H), 7.50-7.60 (m, 2 H);
HRMS (FAB) (M + H)+ calcd for C24H41OSiS2 437.2368, found
437.2370.
7-Butyl-7-(r-hydroxy-4-(tert-butoxycarbonyl)benzyl)-8,11-dithia-
pentadec-5-yne (3m). Under N2 atmosphere, to a DCM solution
(45 mL) of 4-carboxybenzaldehyde (4.5 g, 30 mmol), imidazole
(4.08 g, 60 mmol), 4-dimethylaminopyridine (0.37 g, 3 mmol), and
tert-butanol (8.6 mL, 90 mmol) cooled at 0 °C was added a DCM
solution (15 mL) of DCC (6.81 g, 33 mmol, 1.1 equiv) dropwise.
The mixture was stirred for 3 h at rt and filtered. The filtrate was
washed with 0.5 N HCl(aq) and NaHCO3(sat.). The organic layer was
dried (MgSO4) and filtered and the filtrate was evaporated in vacuo
to give the residue, which was chromatographed on silica gel
(hexane/CHCl3 ) 1/1) to give tert-butyl 4-formylbenzoate as a
1
characteristic H NMR signals for the minor isomer δ 0.14 (s, 6
H), 2.19 (sept, J ) 6.8 Hz, 1 H), 4.43 (s, 2 H); IR (KBr) Ρ 3459
cm-1; HRMS (FAB) (M + H) calcd for C26H45O2SiS2 481.2630,
found 481.2632.
General Procedure for the Preparation of Enyne 4. Under N2
atmosphere, to a THF solution (5 mL) of 3 (0.5 mmol, 1.0 equiv)
and Ph3P (0.26 g, 1.0 mmol, 2.0 equiv) was added DIAD (0.20
mL 1.0 mmol, 2.0 equiv) at rt. After being stirred for 18 h, the
mixture was evaporated in vacuo to give the residue, which was
chromatographed on silica gel (hexane/CHCl3 ) 1/0 to 10/1) to
give 4.
1
white solid (2.91 g, 49%). Mp 45-46 °C; H NMR (CDCl3, 400
2-Isopropyl-1-phenyloct-1E-en-3-yne (4a): 81% (E/Z ) 3.0/1);
E isomer 1H NMR (CDCl3, 400 MHz) δ 0.97 (t, J ) 7.4 Hz, 3 H),
1.13 (d, J ) 6.4 Hz, 6 H), 1.44-1.66 (m, 4 H), 2.40 (t, J ) 6.8
Hz, 2 H), 3.04 (sept, J ) 6.6 Hz, 1 H), 6.70 (s, 1 H), 7.20-7.36
MHz) δ 1.60 (s, 9 H), 7.90 (d, J ) 8.0 Hz, 2 H), 8.11 (d, J ) 8.0
Hz, 2 H), 10.06 (s, 1 H).20
3m: 37% (dr ratio ) 1.7/1); major isomer H NMR (CDCl3,
1
1
400 MHz) δ 0.82-1.00 (m, 9 H), 1.18-1.68 (m, 17 H), 2.27 (t, J
) 7.0 Hz, 2 H), 2.50 (t, J ) 7.4 Hz, 2 H), 2.63-2.88 (m, 4 H),
3.32 (d, J ) 4.4 Hz, 1 H), 4.60, (d, J ) 4.4 Hz, 1 H), 7.51-7.55
(m, 5 H); characteristic H NMR signals for Z isomer δ 2.48 (t, J
) 7.0 Hz, 2 H), 2.55 (sept, J ) 6.8 Hz, 1 H), 6.49 (s, 1 H), 7.82
(d, J ) 7.6 Hz, 2 H); HRMS (FAB) (M) calcd for C17H22 226.1722,
found 226.1721.
1
(m, 4 H), 7.7.91-7.95 (m, 2 H); characteristic H NMR signals
for the minor isomer δ 3.46 (d, J ) 1.8 Hz, 1 H), 4.73 (d, J ) 1.8
Hz, 1 H); IR (KBr) ν 3471 cm-1; HRMS (FAB) (M + H) calcd
for C29H47O3S2 507.2967, found 507.2959.
6-Isopropyldodec-5E-en-7-yne (4b): 43% (E/Z ) 10/1); E isomer
1H NMR (CDCl3, 400 MHz) δ 0.89 (t, J ) 7.2 Hz, 3 H), 0.93 (t,
J ) 7.2 Hz, 3 H), 1.04 (d, J ) 7.0 Hz, 6 H), 1.28-1.38 (m, 4 H),
1.39-1.57 (m, 4 H), 2.09 (td, J ) 7.4, 6.8 Hz), 2.32 (t, J ) 7.0
Hz, 2 H), 2.73 (sept, J ) 7.0 Hz, 1 H), 5.66 (t, J ) 7.4 Hz, 1 H);
13C NMR (100 MHz, CDCl3) δ 14.1, 14.4, 19.4, 21.9, 22.4, 22.8,
(20) Kangn, S. U.; Choi, W. J.; Oishi, S.; Lee, K.; Karki, R. G.; Worthy,
K. M.; Bindu, L. K.; Nicklaus, M. C.; Fisher, R. J.; Burke, T. R., Jr J. Med.
Chem. 2007, 50, 1978.
1
27.9, 28.4, 31.5, 32.0, 79.9, 88.3, 129.6, 134.2; characteristic H
J. Org. Chem. Vol. 73, No. 21, 2008 8361

Chen and Luh
NMR signals for Z isomer δ 5.58 (t, J ) 7.0 Hz, 1 H); HRMS
(FAB) (M) calcd for C15H26 206.2035, found 206.2040.
[3-Butyl-4-(4-cyanophenyl)but-3E-en-1-yn-1-yl]trimethylsilane
(4k): 39% (E/Z ) 1.4/1). When 0.25 mL of Bu3P was used in place
of Ph3P, 89% yield of 4k was isolated (E/Z ) 2.0/1). Under these
conditions, 3ka was converted into Z-4k in 71% yield and 3kb
2-Isopropyl-1-mesityloct-1Z-en-3-yne (4c): 65% (E/Z ) 1/20);
characteristic 1H NMR signals for E isomer δ 0.85 (t, J ) 7.4 Hz,
1
1
(94% de) into E-4k (containing 3% Z-4k) in 71% yield. E-4k: H
3 H), 6.61 (s, 1 H); Z isomer H NMR (CDCl3, 400 MHz) δ 1.01
NMR (CDCl3, 400 MHz) δ 0.25 (s, 9 H), 0.91 (t, J ) 7.4 Hz, 3
H), 1.30-1.42 (m, 2 H), 1.58-1.66 (m, 2 H), 2.34 (t, J ) 7.6 Hz,
2 H), 6.84 (s, 1 H), 7.31 (d, J ) 8.4 Hz, 2 H), 7.61 (d, J ) 8.4 Hz,
(t, J ) 7.4 Hz, 3 H), 1.07 (d, J ) 6.8 Hz, 6 H), 1.41-1.53 (m, 2
H), 1.61-1.70 (m, 2 H), 2.28 (s, 6 H), 2.31 (s, 3 H), 2.33 (t, J )
7.4 Hz, 2 H), 2.55 (sept, J ) 6.8 Hz, 1 H), 6.46 (s, 1 H), 6.87 (s,
2 H); 13C NMR (100 MHz, CDCl3) δ 14.4, 20.7, 21.4, 21.5, 22.5,
23.3, 31.1, 37.8, 79.0, 99.6, 126.5, 127.3, 132.2, 133.6, 135.3, 135.7;
HRMS (FAB) (M) calcd for C10H28 268.2191, found 268.2188.
2-Isopropyl-1(1-naphthyl)-oct-1-Z-en-3-yne (4d): 72% (E/Z )
1
2 H). Z-4k: H NMR (CDCl3, 400 MHz) δ 0.26 (s, 9 H), 0.95 (t,
J ) 7.2 Hz, 3 H), 1.37-1.42 (m, 2 H), 1.58-1.66 (m, 2 H), 2.33
(t, J ) 7.6 Hz, 2 H), 6.53 (s, 1 H), 7.58 (d, J ) 8.4 Hz, 2 H), 7.92
(d, J ) 8.4 Hz, 2 H); HRMS (FAB) (M) calcd for C18H24NSi
282.1678, found 282.1678.
1
1/3.9); characteristic H NMR signals for E isomer δ 0.89 (t, J )
[3-Butyl-4-(4-tolyl)but-3E-en-1-yn-1-yl]trimethylsilane (4l): 67%
(E/Z ) 2.1/1); E isomer 1H NMR (CDCl3, 400 MHz) δ 0.25 (s, 9
H), 0.86 (t, J ) 7.4 Hz, 3 H), 1.25-1.35 (m, 2 H), 1.52-1.67 (m,
2 H), 2.22 (t, J ) 7.6 Hz, 2 H), 2.27 (s, 3 H), 6.90 (s, 1 H),
7.2 Hz, 3 H), 1.28 (d, J ) 6.8 Hz, 6 H), 2.32 (t, J ) 6.8 Hz, 2 H),
2.70 (sept, J ) 6.8 Hz, 1 H), 7.14 (s, 1 H); Z isomer δ 1.00 (t, J
) 7.2 Hz, 3 H), 1.09 (d, J ) 6.6 Hz, 6 H), 1.50-1.69 (m, 4 H),
2.46 (t, J ) 7.0 Hz, 2 H), 2.79 (sept, J ) 6.6 Hz, 1 H), 7.09 (s, 1
H), 7.30 (d, J ) 7.2 Hz, 1 H), 7.42-7.54 (m, 3 H), 7.78 (d, J )
8.0 Hz, 1 H), 7.81-7.89 (m, 1 H), 7.97-8.07 (m, 1 H); HRMS
(FAB) (M) calcd for C17H22 276.1878, found 276.1875.
2-Isopropyl-1-(4-methoxyphenyl)oct-1E-en-3-yne (4e): 91% (E/Z
) 5.0/1); E isomer 1H NMR (CDCl3, 400 MHz) δ 0.96 (t, J ) 7.2
Hz, 3 H), 1.13 (d, J ) 6.7 Hz, 6 H), 1.40-1.66 (m, 4 H), 2.39 (t,
J ) 6.8 Hz, 2 H), 3.04 (sept, J ) 6.7 Hz, 1 H), 3.82 (s, 3 H), 6.64
(s, 1 H), 6.82-6.89 (m, 2 H), 7.14-7.19 (m, 2 H); characteristic
1H NMR signals for Z isomer δ 3.80 (s, 3 H), 6.43 (s, 1 H),
7.78-7.81 (m, 2 H); HRMS (FAB) (M) calcd for C18H24O
256.1827, found 256.1831.
1
7.09-7.24 (m, 4 H); characteristic H NMR signals for Z isomer
δ 1H NMR (CDCl3, 400 MHz) δ 0.19 (s, 9 H), 0.96 (t, J ) 7.2 Hz,
3 H), 1.19 (d, J ) 6.4 Hz, 6 H), 1.35-1.46 (m, 2 H), 2.30-2.36
(m, 5 H), 6.70 (s, 1 H), 8.09-8.14 (m, 1 H); HRMS (FAB) (M+)
calcd for C18H26Si 270.1804, found 270. 1801.
2-Butyl-1-(4-tert-butoxycarbonylphenyl)oct-1E-en-3-yne (4m):
62% (E/Z ) 1.6/1); E isomer 1H NMR (CDCl3, 400 MHz) δ
0.88-0.99 (m, 6 H), 1.29-1.66 (m, 17 H, embodied a singlet at
1.60 for tert-butyl group), 2.28-2.40 (m, 2 H), 2.45 (t, J ) 7.2
Hz, 2 H), 6.76 (s, 1 H), 7.26 (d, J ) 8.0 Hz, 2 H), 7.93 (d, J ) 8.0
1
1
Hz, 2 H); characteristic H NMR signals for Z isomer δ H NMR
(CDCl3, 400 MHz) δ 6.48 (s, 1 H), 7.83 (d, J ) 8.4 Hz, 2 H), 7.91
(d, J ) 8.4 Hz, 2 H); HRMS (FAB) (M) calcd for C23H32O2
340.2402, found 340.2398.
1-(4-Bromophenyl)-2-isopropyl-oct-1E-en-3-yne (4f): 68% (E/Z
) 1.7/1); E isomer 1H NMR (CDCl3, 400 MHz) δ 0.94 (t, J ) 7.4
Hz, 3 H), 1.10 (d, J ) 6.5 Hz, 6 H), 1.44-1.61 (m, 4 H), 2.38 (t,
J ) 7.0 Hz, 2 H), 2.95 (sept, J ) 6.5 Hz, 1 H), 6.58 (s, 1 H),
7.04-7.08 (m, 2 H), 7.40-7.44 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ 13.8, 19.3, 21.8, 22.1, 28.8, 31.1, 79.9, 92.0, 120.6, 130.1,
3-Butyl-2-methylnon-2-en-4-yne (4n): 17% (Bu3P was used); 1H
NMR (CDCl3, 400 MHz) δ 0.92 (t, J ) 7.2 Hz, 3 H), 0.94 (t, J )
7.2 Hz, 3 H), 1.26-1.38 (m, 4 H), 1.41-1.57 (m, 4 H), 1.73 (s, 3
H), 1.93 (s, 3 H), 2.12 (t, J ) 7.6 Hz, 2 H), 2.36 (t, J ) 6.8 Hz, 2
H); 13C NMR (100 MHz, CDCl3) δ 13.8, 14.2, 19.3, 19.7, 22.1,
22.5, 23.7, 31.0, 31.4, 32.2, 81.3, 91.8, 117.6, 137.3; HRMS (EI+)
(M) calcd for C14H24 192.1878, found 192.1873.
1
131.2, 131.3, 133.5, 135.8; characteristic H NMR signals for Z
isomer δ 2.47 (t, J ) 7.0 Hz, 2 H), 2.53 (sept, J ) 6.8 Hz, 1 H),
6.42 (s, 1 H), 7.67-7.71 (m, 2 H); HRMS (FAB) (M) calcd for
C17H2179Br 304.0827, found 304.0824.
2-Butyl-1,1-diphenyloct-1-en-3-yne (4o): 28% (Bu3P was used);
1H NMR (CDCl3, 400 MHz) δ 0.85 (t, J ) 7.6 Hz, 3 H), 0.88 (t,
J ) 7.4 Hz, 3 H), 1.22-1.38 (m, 4 H), 1.39-1.48 (m, 2 H),
1.55-1.65 (m, 2 H), 2.21 (t, J ) 7.4 Hz, 2 H), 2.28 (t, J ) 6.8 Hz,
2 H), 7.11-7.42 (m, 10 H); 13C NMR (100 MHz, CDCl3) δ 14.1,
14.4, 19.7, 22.2, 22.6, 30.9, 31.5, 34.7, 81.5, 94.0, 122.0, 126.4,
126.5, 127.0, 127.6, 129.2, 129.4, 141.3, 141.9, 145.0; HRMS
(FAB) (M) calcd for C24H28 316.2191, found 316.2193.
2-Isopropyl-1-phenyl-4-trimethylsilylbut-1E-en-3-yne (4g): 78%
(E/Z ) 3.2/1); E isomer 1H NMR (CDCl3, 400 MHz) δ 0.25 (s, 9
H), 1.15 (d, J ) 6.8 Hz, 6 H), 3.04 (sept, J ) 6.8 Hz, 1 H), 6.83
(s, 1 H), 7.20-7.37 (m, 5 H); characteristic 1H NMR signals for Z
isomer δ 0.26 (s, 9 H), 1.19 (d, J ) 6.4 Hz, 6 H), 2.56 (sept, J )
6.1 Hz, 1 H), 6.57 (s, 1 H), 7.86 (d, J ) 7.6 Hz, 2 H).7
(3-Butyl-4-phenylbut-3E-en-1-yn-1-yl)trimethylsilane (4h): 72%
1
(E/Z ) 13.5/1); E isomer H NMR (CDCl3, 400 MHz) δ 0.26 (s,
(5-Phenyl-4-isopropyl-pent-4E-en-2-yn-1-yl tert-butyldimethyl-
9 H), 0.93 (t, J ) 7.4 Hz, 3 H), 1.33-1.44 (m, 2 H), 1.58-1.79
(m, 2 H), 2.39 (t, J ) 7.6 Hz, 2 H), 6.92 (s, 1 H), 7.22-7.30 (m,
3 H), 7.31-7.38 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 0.24,
14.1, 22.5, 30.7, 31.0, 93.7, 107.7, 125.4, 127.0, 128.1, 128.7, 136.5;
1
silyl ether (4p): 38% (E/Z ) 1.6/1); E isomer H NMR (CDCl3,
400 MHz) δ 0.19 (s, 9 H), 0.96 (s, 6 H), 2.14 (d, J ) 6.8 Hz, 6 H),
3.06 (sept, J ) 6.8 Hz, 1 H), 4.53 (s, 2 H), 6.77 (s, 1 H), 7.21-7.39
(m, 5 H); characteristic 1H NMR signals for Z isomer δ 0.17 (s, 9
H), 0.96 (s, 6 H), 2.19 (d, J ) 6.8 Hz, 6 H), 2.58 (sept, J ) 6.7
Hz, 1 H), 4.58 (s, 2 H), 6.56 (s, 1 H), 7.78-7.84 (m, 2 H); HRMS
(EI+) (M) calcd for C20H30OSi 314.2066, found 314.2062.
1
characteristic H NMR signals for Z isomer δ 0.29 (s, 9 H), 2.32
(t, J ) 7.6 Hz, 2 H), 6.56 (s, 1 H), 7.87 (d, J ) 7.6 Hz, 2 H);
HRMS (FAB) (M) calcd for C17H24Si 256.1674, found 256.1654.
(3-Butyloct-3E-en-1-yn-1-yl)trimethylsilane (4i): 69% (E/Z )
1/1.5); characteristic 1H NMR signals for E isomer δ 0.19 (s, 9 H),
1-(Naphthyl)-2-phenyl-2,2-bis(propylthio)ethanol (8). Under N2
atmosphere, to a THF solution (50 mL) of benzaldehyde bispro-
pyldithioacetal (1.20 g, 5 mmol) cooled at -78 °C was added
dropwise LDA (2.5 mL, 1.0 equiv, 2.0 M THF/n-heptane/ethyl-
benzene solution). After the solution was stirred for 2 h, 1-naph-
thaldehyde (0.68 mL, 5.0 mmol) in THF (10 mL) was added. The
mixture was gradually warmed to rt and stirred for 8 h, quenched
with sat. NH4Cl, washed with brine, and extracted with ether. The
organic layer was dried (MgSO4) and filtered and the filtrate was
evaporated in vacuo to give the residue, which was chromato-
graphed on silica gel (hexane/EtOAc ) 10/1) to give 8 as a light
yellow solid (0.89 g, 45%): mp 78-79 °C; 1H NMR (CDCl3, 400
MHz) δ 0.90 (t, J ) 7.2 Hz, 3 H), 1.16 (t, J ) 7.4 Hz, 3 H),
1.45-1.55 (m, 2 H), 1.73-1.87 (m, 2 H), 2.23-2.31 (m, 1 H),
2.47-2.55 (m, 1 H), 2.89-3.07 (m, 2 H), 3.88 (s, 1 H), 5.84 (s, 1
1
5.92 (t, J ) 7.6 Hz, 1 H); Z isomer H NMR (CDCl3, 400 MHz)
δ 0.20 (s, 9 H), 0.87-0.95 (m, 6 H), 1.26-1.42 (m, 6 H), 1.44-1.53
(m, 2 H), 2.05-2.14 (m, 2 H), 2.26 (q, J ) 7.2 Hz, 2 H), 5.69 (t,
J ) 7.2 Hz, 1 H); HRMS (FAB) (M) calcd for C15H28Si 236.1960,
found 236.1961.
[3-Butyl-4-(4-trifluomethylphenyl)but-3E-en-1-yn-1-yl]trimeth-
1
ylsilane (4j): 48% (E/Z ) 3.3/1); E isomer H NMR (CDCl3, 400
MHz) δ 0.26 (s, 9 H), 0.93 (t, J ) 7.2 Hz, 3 H), 1.32-1.46 (m, 2
H), 1.59-1.70 (m, 2 H), 2.37 (t, J ) 7.8 Hz, 2 H), 6.90 (s, 1 H),
7.34 (d, J ) 8.2 Hz, 2 H), 7.59 (d, J ) 8.2 Hz, 2 H); characteristic
1H NMR signals for Z isomer δ 0.28 (s, 9 H), 0.97 (t, J ) 7.4 Hz,
3 H), 6.56 (s, 1 H), 7.95 (d, J ) 8.4 Hz, 2 H); HRMS (FAB) (M)
calcd for C18H23F3Si 324.1521, found 324.1525.
8362 J. Org. Chem. Vol. 73, No. 21, 2008

New Synthesis of Conjugated Enynes
H), 6.68 (d, J ) 7.2 Hz, 1 H), 7.14-7.29 (m, 4 H), 7.40-7.46 (m,
2 H), 7.47-7.53 (m, 2 H), 7.73 (d, J ) 8.0 Hz, 1 H), 7.78-7.84
(m, 1 H), 8.08-8.14 (m, 1 H); 13C NMR (CDCl3, 100 MHz) δ
14.1, 14.3, 22.0, 22.4, 32.0, 33.1, 72.5, 123.7, 124.2, 124.8, 125.1,
127.3, 127.6, 128.3, 128.4, 130.1, 132.1, 132.9, 133.1, 136.7; IR
(KBr) ν 3449 cm-1; HRMS (ESI) (M + Na)+ calcd for
C24H28OS2Na 419.1479, found 419.1489.
g, 10 mmol) and celite (2.16 g) at rt. After being stirred for 12 h,
the mixture was filtered and the filtrate was evaporated in vacuo to
give the residue, which was chromatographed on silica gel (hexane/
CHCl3 ) 3/1) to give 14 as an orange yellow liquid (1.74 g, 87%).
1H NMR (CDCl3, 400 MHz) δ 1.24 (d, J ) 6.7 Hz, 6 H), 2.34
(sept, J ) 6.7 Hz, 1 H), 3.40-3.58 (m, 4 H), 9.28 (s, 1 H); 13C
NMR (100 MHz, CDCl3) δ 21.2, 39.9, 40.0, 65.3, 84.2, 97.2, 176.4;
IR (KBr) ν 1662 cm-1; HRMS (FAB) (M + H) calcd for C9H13OS2
201.0408, found 201.0410.
Alcohol 15. According to general procedure for the preparation
of 3, 1c7 (1.29 g, 5.0 mmol) and 14 (1.00 g, 5.0 mmol) were
converted to 15 as a pale yellow liquid (1.16 g, 45%, dr ratio )
1.3/1). Major diastereomer 1H NMR (CDCl3, 400 MHz) δ 0.20 (s,
9 H), 0.88-0.96 (m, 6 H), 1.24 (d, J ) 6.8 Hz, 6 H), 1.30-1.47
(m, 4 H), 1.49-1.73 (m, 4 H), 2.23-2.32 (m, 1 H), 2.56 (t, J )
6.6 Hz, 2 H), 2.68-3.16 (m, 5 H), 3.35-3.42 (m, 2 H), 3.48-3.57
(m, 2 H), 4.44 (d, J ) 6.4 Hz, 1 H); characteristic 1H NMR signals
for the minor diastereomer δ 0.21 (s, 9 H), 2.57 (t, J ) 6.6 Hz, 2
H), 4.41 (d, J ) 9.6 Hz, 1 H); IR (KBr) ν 3421 cm-1; HRMS
(FAB) (M + H) calcd for C25H45OSiS4 517.2123, found 517.2128.
Endiyne 16. According to teh general procedure for the prepara-
tion of 4, 15 (258 mg, 0.5 mmol) and PPh3 were converted to 16
as a colorless liquid (119 mg, 68%, E/Z ) 1/1.4): characteristic 1H
NMR signals for E isomer δ 0.20 (s, 9 H), 0.93 (t, J ) 7.4 Hz, 3
H), 1.22 (d, J ) 6.8 Hz, 6 H), 2.31 (sept, J ) 6.8 Hz, 1 H), 2.36
(t, J ) 7.4 Hz, 2 H), 5.86 (s, 1 H); Z isomer δ 0.21 (s, 9 H), 0.91
(t, J ) 7.2 Hz, 3 H), 1.28 (d, J ) 6.6 Hz, 6 H), 1.29-1.41 (m,
2H), 1.46-1.58 (m, 2H), 2.15-2.21 (m, 2H), 2.32 (sept, J ) 6.6
Hz, 1 H), 3.36-3.46 (m, 2H), 3.46-3.60 (m, 2H), 5.71 (t, J ) 1.2
Hz, 1 H); HRMS (FAB) (M + H) calcd for C19H31SiS2 351.1636,
found 351.1631.
1-(2-Phenyl-1,2-bis(propylthio)vinyl)naphthalene (11). In a man-
ner similar to that described in the general procedure for the
preparation 4, 8 (99 mg, 0.25 mmol) and PBu3 (0.25 mL, 1 mmol)
were converted to 11 as a colorless liquid (65 mg, 69%, E/Z )
1
1/2): characteristic H NMR signals for E isomer δ 0.64 (t, J )
7.4 Hz, 3 H), 0.68 (t, J ) 7.4 Hz, 3 H), 1.22-1.37 (m, 4 H); Z
1
isomer H NMR (CDCl3, 400 MHz) δ 0.79 (t, J ) 7.4 Hz, 3 H),
0.99 (t, J ) 7.4 Hz, 3 H), 1.37-1.46 (m, 2 H), 1.59-1.66 (m, 2
H), 2.05-2.14 (m, 2 H), 2.45 (t, J ) 7.2 Hz, 2 H), 6.93-6.97 (m,
2 H), 7.07-7.09 (m, 2 H), 7.17 (d, J ) 8.0 Hz, 1 H), 7.24-7.30
(m, 1 H), 7.41-7.60 (m, 1 H), 7.60-7.67 (m, 2 H), 7.78 (d, J )
8.0 Hz, 1 H), 7.89-7.95 (m, 1 H), 8.21-8.25 (m, 1 H); HRMS-
FAB (M+) calcd for C24H26S2 378.1476, found 378.1480.
1,4-Bis(2-butyloct-1E-en-3-yn-1-yl)benzene (13). Under N2 at-
mosphere, to a THF solution (50 mL) of 1d7 (1.21 g, 5.0 mmol,
1.00 equiv) cooled at -78 °C was added dropwise BuLi (2.2 mL,
1.10 equiv, 2.5 M hexane solution). After the solution was stirred
for 1 h, terephthaldehyde (0.34 g, 2.5 mmol, 0.50 equiv) in THF
(20 mL) was added dropwise. The mixture was gradually warmed
to rt and stirred for 8 h, quenched with sat. NH4Cl, washed with
brine, and extracted with ether. The organic layer was dried
(MgSO4) and filtered and the filtrate was evaporated in vacuo to
give the residue, which was chromatographed on silica gel (hexane/
EtOAc ) 10/1) to give corresponding diol (1.26 g, 69%).
A THF solution (5 mL) of the diol (368 mg) and PPh3 (524 mg,
2 mmol, 4.00 equiv) was allowed to react with DIAD (0.40 mL, 2
mmol, 4.00 equiv) and the mixture was stirred at rt for 18 h, then
evaporated in vacuo to give the residue, which was chromato-
graphed on silica gel (hexane) to give 13 (78 mg, 39%, 27% in
Acknowledgement. We thank the National Science Council
and the National Taiwan University of the Republic of China
for financial support.
1
two steps, EE/EZ ) 1/3.2): characteristic H NMR signals for EE
isomer δ 6.74 (s, 2 H), 7.20 (s, 4 H); EZ isomer δ 0.90-0.99 (m,
12 H), 1.32-1.67 (m, 16 H), 2.29 (t, J ) 7.2 Hz, 2 H), 2.39 (t, J
) 6.8 Hz, 4 H), 2.44-2.50 (m, 2 H), 6.43 (s, 1 H), 6.73 (s, 1 H),
7.19 (d, J ) 8.4 Hz, 2 H), 7.78 (d, J ) 8.4 Hz, 2 H); HRMS (FAB)
(M) calcd for C30H42 402.3287, found 402.3292.
Supporting Information Available: 1H NMR spectra of 1e,
3a-f, 3h-p, 3ka, 3kb, 4a-p, Z-4k, E-4k, 8, 11, and 13-16.
This material is available free of charge via the Internet at
http://pubs.acs.org.
2-Isopropyl-2-(2-formylethynyl)-1,3-dithiolane (14). To a DCM
solution (100 mL) of 1e (2.02 g, 10 mmol) was added PCC (2.16
JO8013885
J. Org. Chem. Vol. 73, No. 21, 2008 8363