Synthesis of (Z)-1-organylthiobut-1-en-3-ynes: Hydrothiolation of symmetrical and unsymmetrical buta-1,3-diynes

Article abstract of DOI:10.1055/s-0028-1088196

Hcny BRAdrothiolation of l-organcny BRAlbuta-l,3-dicny BRAnes and 1,4-diorgancny BRAlbuta-l,3-dicny BRAnes with the sodium organcny BRAlthiolate anions, which were generated in situ bcny BRA reacting diphencny BRAl and dibutcny BRAl disulfide with NaBH

Full text of DOI:10.1055/s-0028-1088196

986
LETTER
Synthesis of (Z)-1-Organylthiobut-1-en-3-ynes: Hydrothiolation of
Symmetrical and Unsymmetrical Buta-1,3-diynes
Synthesis of
(
Z
)
-1-Org
i
anylthi
g
u
Palimécio G. Guerrero, Jr., d Carlos E. D. Nazário,e Luiz H. Viana,e Amanda S. Santana,f Adriano C. M. Baroni*f
a
LASCO-Laboratório de Síntese de Compostos Organocalcogênios – Departamento de Química, FFCLRP, Universidade de São Paulo,
Av. Bandeirantes, 3900 Ribeirão Preto, SP, Brazil
E-mail: migjodab@usp.br
LASOL-Lab, Síntese Orgânica Limpa, Universidade Federal de Pelotas, P.O. Box 354, 96010-900 Pelotas, RS, Brazil
Departamento de Farmácia-Bioquímica, Universidade Federal do Vale do Jequitinhonha e Mucuri, Diamantina, MG, Brazil
Departamento de Química e Biologia, Universidade Tecnológica Federal do Parana, UTFPR, Curitiba, PR, Brazil
b
c
d
e
Departamento de Química, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil
Departamento de Farmácia-Bioquímica, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil
f
Fax +55(67)33457365; E-mail: adriano@nin.ufms.br
Received 21 August 2008
to perform the synthesis of several di-13b and polyfunc-
Abstract: Hydrothiolation of 1-organylbuta-1,3-diynes and 1,4-di-
tionalized olefins.13a,c
organylbuta-1,3-diynes with the sodium organylthiolate anions,
which were generated in situ by reacting diphenyl and dibutyl di-
sulfide with NaBH4 in ethanol, results in the regio-, stereo-, and
chemoselective formation of (Z)-1-organylthio-4-organylbut-1-en-
3-ynes and (Z)-1-organylthio-1,4-diorganylbut-1-en-3-ynes, re-
spectively.
One of the more widely used methods for the synthesis of
vinyl heteroatomic derivatives is the nucleophilic addition
of heteroatomic anions to acetylenes. Except for some few
charged acetylene derivatives, or in radical conditions,
this type of reaction occurs in a trans addition process,
and furnishes selectively the Z-vinylic isomer. Almost all
of the methods described in the literature for the prepara-
tion of vinyl sulfides employ the addition of thiolate an-
ions to terminal alkynes. The nucleophilic species are
generated by the reaction of volatile, bad-smelling, highly
toxic, and air-sensitive alkylthiols with an alkaline base
(KOH, NaOH, NaOR, or KOR)13 and in liquid ammo-
nia.14 Although the Z-isomer is the main product, forma-
tion of the E-isomer (4–5%) has also been described. 15
Key words: hydrothiolation, organylthiolate anion, vinyl sulfides,
1,3-diacetylenes, (Z)-1-organylthiobut-1-en-3-ynes
Vinyl sulfides are present in naturally occurring com-
pounds with important biological activity.1 Griseoviridin,
for example, is a type A streptogramin antibiotic, first iso-
lated from Streptomyces graminofaciens,1a,b and benzyl-
thiocrellidone is a yellow pigment isolated from the
bright-red sponge Crella spinulata.1c
Despite the large number of papers describing the synthe-
sis of vinyl sulfides, the preparation of (Z)-1-organylthio-
but-1-en-3-ynes by the hydrothiolation of mono- and
disubstituted 1,3-diacetylenes has been little studied.16
These compounds are versatile and useful intermediates
in organic synthesis.2–13 They can be converted into the
corresponding aldehyde, ketone,2 carboxylic acid, or
ester3 by acid hydrolysis or through the thio-Claisen rear-
rangement.4 The carbon–sulfur bond can be reductively
cleaved by reactions with lithium5 or samarium reagents,6
affording the corresponding vinyl lithium or vinyl samari-
um species, which are trapped with electrophiles.5,6 Vinyl
sulfides are acceptors in Michael addition, Peterson olefi-
nation,7 and have shown good reactivity in Diels–Alder
cycloadditions reactions.9
We describe here a new, general, and highly stereoselec-
tive method for the preparation of (Z)-1-organylthiobut-1-
en-3-ynes 2 and 3, employing the addition of the orga-
nylthiolate anions, generated in situ by the reaction of
commercially available PhSSPh and BuSSBu with
NaBH4, to buta-1,3-diynes17,18 (Scheme 1, Table 1).
To the best of our knowledge, the method described here-
in is the first employment of the YSSY/NaBH4 system
(Scheme 1) for the selective reduction of conjugated triple
bonds. Moreover, to furnish exclusively the Z-isomer 2
and/or 3, the in situ generation of the organylthiolate an-
Another factor that increases the range of synthetic possi-
bilities of vinyl sulfides is the stabilizing influence of a
sulfur atom toward neighboring cations or anions,10 as
well as their use as synthetic equivalents of enolonium
ions.11 Indeed, vinyl sulfides can be desulfurized by
Raney nickel12 or stereospecifically reduced through a
cross-coupling reaction with Grignard reagents using
nickel(II) salts as catalysts.13 This last reaction was used
R1
R2
YSSY
a
R1
R2
and/or
1a–j
YS
YS
1a,b,j: R1 = R2
1c–i: R1 ≠ R2
Y = Ph, Bu
2a–l
3f–h
R2
R1
SYNLETT 2009, No. 6, pp 0986–0990
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088196; Art ID: S07508ST
Scheme 1 Reagents and conditions: (a) EtOH, NaBH4, N2, reflux.
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of (Z)-1-Organylthiobut-1-en-3-ynes
987
ions avoids the use of the bad-smelling, volatile, toxic gives exclusively (Z)-1-phenylthio-1,4-diphenylbut-1-en-
PhSH or BuSH.
3-yne (2a)19 and (Z)-butylthio-1,4-diphenylbut-1-en-3-
yne (2i) with 72% and 76% yields, respectively (entries 1
and 9, Table 1).
The reaction described in Scheme 1 was studied with sev-
eral 1,3-diacetylenes. In all cases, only the Z-isomer was
obtained, with no formation of the E-isomer. Thus, sym-
metrical 1,4-diphenylbuta-1,3-diyne (1a, R1 = R2 = Ph)
Table 1 (Z)-1-Organylthiobut-1-en-3-ynes Obtained
Entry
Buta-1,3-diyne 1a
Products 2 and 3
Ratio 2/3b
Time (h)
3
Yield (%)c,d
Ph
Ph
Ph
1
–
72
PhS
1a
2a
HO
PhS
2b
Ph
HO
OH
2
–
2.5
93
1b
OH
H
H
Ph
75e
78f
PhS
2c
3
4
100:0
100:0
2
1c
Ph
PhS
2d
C6H13
2.5
1d
C6H13
HO
HO
Ph
5
6
100:0
97:3
3
6
54
35
PhS
1e
2e
Ph
Ph
C6H13
+
Ph
C6H13
PhS
PhS
1f
2f
3f
Ph
C6H13
HO
C6H13
+
HO
C6H13
7
69:31
3
62
PhS
PhS
1g
2g
3g
HO
C6H13
HO
C6H13
HO
Ph
+
8
9
91:9
3
8
68
71
C6H13
PhS
2h
PhS
3h
1h
HO
C6H13
Ph
Ph
–
BuS
1a
2i
Ph
Synlett 2009, No. 6, 986–990 © Thieme Stuttgart · New York

988
M. J. Dabdoub et al.
LETTER
Table 1 (Z)-1-Organylthiobut-1-en-3-ynes Obtained (continued)
Entry
10
Buta-1,3-diyne 1a
Products 2 and 3
Ratio 2/3b
Time (h)
5
Yield (%)c,d
BuS
100:0
50g
H
2j
1i
C6H13
C6H13
C6H13
11
12
–
9
4
65
BuS
1j
2k
C6H13
BuS
2l
100:0
70e
H
C6H13
1d
C6H13
a Terminal butadiynes 1c and 1d were prepared and used in situ.
b Determined by GC and 1H NMR.
c Isolated yields.
d Products purified by column chromatography.
e Overall yield (two steps from the alcohol 1e).
f Overall yield (two steps from the alcohol 1g).
g Overall yield (two steps from the 6-cyclohexenyl-2-methylhexa-3,5-diyn-2-ol 1k).
The 2,7-dimethyl-3,5-octadiyne-2,7-diol 1b, R1 = R2 = In the cases of compounds 1e,g,h, the propargylic triple
i-PrOH) gives the (Z)-2,7-dimethyl-3-phenylthiooct-3- bonds underwent addition of the phenylthiolate anion
en-5-yne-2,7-diol (2b) with 93% yield after refluxing for more easily than did triple bonds bearing a phenyl (entry
2.5 hours (entry 2, Table 1).
5, Table 1) or alkyl substituent (entries 7 and 8, Table 1).
This occurred because of the formation of cyclic five-
membered transition states 4g–i (Figure 1), which is re-
sponsible for the intramolecular protonation of the incipi-
ent carbanion formed in C-2. For the reaction of 1c,d,f,
ethanol acts as the proton donor, as depicted in 4f and 5f
(Figure 1). With the propargylic derivatives 1e,g,h the
role of the steric and electronic factors is more easily seen.
Thus, the (Z)-2-methyl-3-phenylthio-6-phenylhex-3-en-
5-yn-2-ol (2e) was the only product obtained when 2-me-
thyl-6-phenylhexa-3,5-diyn-2-ol 1e was submitted to the
hydrothiolation reaction for three hours (54% yield, entry
5, Table 1). This result indicates a preference for addition
at the propargylic triple bond. Formation of the intermedi-
ate 4g (Figure 1) is favored by both the cyclic intermedi-
ate and the phenyl acetylenic moiety. However, the
hydrothiolation of compound 1g (entry 7, Table 1) occurs
with lower chemoselectivity, due the weak stabilization of
the transition state 4h (Figure 1).
When the unsymmetrical buta-1,3-diynes 1c–i (R1 π R2,
entries 3–8, 10, 12) were used, the (Z)-1-phenylthiobut-1-
en-3-ynes20 and (Z)-1-butylthiobut-1-en-3-yne21 type 2
were obtained with high chemoselectivity. Thus, (Z)-1-
phenylthio-4-phenylbut-1-en-3-yne (2c, 75%) and (Z)-1-
butylthiodec-1-en-3-yne (2l, 70%) obtained exclusively
by reacting the terminal 4-phenylbuta-1,3-diyne 1c and
deca-1,3-diyne 1d with the phenyl and butylthiolate an-
ions, respectively, as described in Scheme 1 (entries 3 and
12, Table 1).
We observed that the terminal triple bond is more reactive
than the substituted triple bond, because of the steric hin-
drance caused by the phenyl 1c or n-hexyl group 1d. Re-
placing the terminal hydrogen in 1c with the larger n-
hexyl group results in a slower reaction rate and loss of se-
lectivity in 1f, showing that steric factors are acting. Thus,
a mixture of 2f and 3f was obtained in a 97:3 ratio and
modest yield (35%) after refluxing 1f and phenylthiolate
anion for six hours (entry 5, Table 1). This last result
shows that electronic factors are also important. During
the attack of the phenylthiolate anion on the diacetylene
1f, a negative charge is developed at the adjacent carbon
(C-2), and two possible transition states 4f and 5f could be
proposed (Figure 1). Transition state 4f is more stable
than 5f, because of stabilization of the incipient carbanion
by the phenyl acetylenic moiety, which removes electrons
The difference in yields and chemoselectivities between
the hydrothiolation of 1h (68%, 2h/3h = 91:9) and 1g
(62%, 2g/3g = 69:31) is due to steric factors, when the
carbinolic hydrogens in 1h are replaced by two methyl
groups in 1g (compare structures 4i and 4h, Figure 1).
However, the intramolecular protonation via the forma-
tion of the cyclic structure 4h or 4i is more important.
Thus, 2g remains the main product formed.
more effectively than the octynyl group in 5f (electronic Consequently, it is noteworthy that the hydrothiolation of
factor). However, 3% of 3f was obtained, because the buta-1,3-diynes 1a–e and 1i,j was regio-, stereo-, and
bulky group n-hexyl impedes the PhS– attack (steric fac- chemoselective, affording only one of the possible iso-
tor).
Synlett 2009, No. 6, 986–990 © Thieme Stuttgart · New York

LETTER
Synthesis of (Z)-1-Organylthiobut-1-en-3-ynes
989
Takemoto, Y. J. Chem. Soc., Chem. Commun. 1992, 269.
(i) Guerrero, P. G. Jr.; Dabdoub, M. J.; Marques, F. A.;
Wosch, C.; Baroni, A. C. M.; Ferreira, A. G. Synth.
Commun. 2008, 38, 4379.
Ph
C6H13
δ–
δ–
PhS
PhS
δ–
δ–
C6H13
(3) Fortes, C. C.; Fortes, H. C.; Gonçalves, D. R. G. J. Chem.
Soc., Chem. Commun. 1982, 857.
(4) Oshima, K.; Takahashi, H.; Yamamoto, H.; Nozaki, H.
J. Am. Chem. Soc. 1973, 95, 2693.
H
OEt
Ph
H
OEt
5f
4f
C6H13
Ph (C6H13
)
(5) (a) Cohen, T.; Weisenfeld, R. B. J. Org. Chem. 1979, 44,
3601. (b) Screttas, C. G.; Micha-Screttas, M. J. Org. Chem.
1978, 43, 1064. (c) Screttas, C. G.; Micha-Screttas, M.
J. Org. Chem. 1979, 44, 713. (d) Foubelo, F.; Gutierrez, A.;
Yus, M. Tetrahedron Lett. 1999, 40, 8173.
δ–
δ–
PhS
PhS
δ–
H
δ–
H
O
O
(6) Hojo, M.; Harada, H.; Yoshizawa, J.; Hosomi, A. J. Org.
Chem. 1993, 58, 6541.
(7) Kanemasa, S.; Kobayashi, H.; Tanaka, J.; Tsuge, O. Bull.
4g (4h)
4i
Figure 1 Possible transition states in the hydrothiolation reaction
Chem. Soc. Jpn. 1988, 61, 3957.
(8) (a) For a review, see: De Lucchi, O.; Pasquato, L.
Tetrahedron 1988, 44, 6755. (b) Dittami, J. P.; Nie, X. Y.;
Nie, H.; Ramanathan, H.; Buntel, C.; Rigatti, S.; Bordner, J.;
Decosta, D. L.; Williard, P. J. Org. Chem. 1992, 57, 1151.
(9) Harmata, M.; Jones, D. Tetrahedron Lett. 1996, 37, 783.
(10) (a) See, for instance: Corey, E. J.; Seebach, D. J. Org. Chem.
1966, 31, 4097. (b) For a review, see: Kolb, M. Synthesis
1990, 171.
(11) (a) Trost, B. M.; Lavoie, A. C. J. Am. Chem. Soc. 1983, 105,
5075. (b) Trost, B. M.; Tanigawa, Y. J. Am. Chem. Soc.
1979, 101, 4413.
(12) Barton, D. H. R.; Boar, R. B. J. Chem. Soc., Perkin Trans. 1
1973, 654.
(13) (a) Okamura, H.; Miura, M.; Takei, H. Tetrahedron Lett.
1979, 20, 43. (b) Trost, B. M.; Ornstein, P. L. Tetrahedron
Lett. 1981, 22, 3463. (c) Wenkert, E.; Ferreira, T. W.
J. Chem. Soc., Chem. Commun. 1982, 840. (d) Truce, W.
E.; Goldhamer, D. L.; Kruse, R. B. J. Am. Chem. Soc. 1959,
81, 4931. (e) Truce, W. E.; Heine, R. F. J. Am. Chem. Soc.
1957, 79, 5311. (f) Freeman, F.; Lu, H.; Zeng, Q.;
Rodriguez, E. J. Org. Chem. 1994, 59, 4350. (g) Zschunke,
A.; Muegge, C.; Hintzsche, E.; Schroth, W. J. Prakt. Chem.
1992, 334, 141.
mers, whereas in the other cases only two isomers were
observed.
On the basis of the results obtained, we believe that the
mechanism of the hydrothiolation of alkynes is similar to
the hydroselenation and hydrotelluration.22,23
In conclusion, we developed a new method for the re-
gio-, stereo-, and chemoselective hydrothiolation of buta-
1,3-diynes employing the sodium phenyl and butylthi-
olate generated in situ by reaction of PhSSPh and BuSSBu
with NaBH4 in ethanol, respectively. The method is gen-
eral and can be used for preparation of conjugated (Z)-
thioenynes in good yields, avoiding the use of highly toxic
and bad-smelling thiols as starting material. Studies re-
garding the use of these thioenynes in the preparation of
enediynes and iodo thiophenes are now in progress in our
laboratory.
Acknowledgment
This work was supported by grants from FAPESP, FUNDECT-MS,
FAPERGS, PROPP-UFMS and CNPq. Thanks are due to Dr. Janet
W. Reid (JWR Associates) for assistance in English corrections.
(14) Levanova, E. P.; Volkov, A. N.; Volknova, K. A. Zh. Org.
Khim. 1983, 19, 62.
(15) (a) Truce, W. E.; Goldhamer, D. L.; Kruse, R. B. J. Am.
Chem. Soc. 1959, 81, 4931. (b) Truce, W. E.; Heine, R. F.
J. Am. Chem. Soc. 1957, 79, 5311.
(16) (a) Peach, M. E. In The Chemistry of the Thiol Group, Vol.
2; Patai, S., Ed.; Wiley: London, 1974. (b) Ichinose, Y.;
Wakamatsu, K.; Nozaki, K.; Birbaum, J.-L.; Oshima, K.;
Utimoto, K. Chem. Lett. 1987, 1647. (c) Benati, L.; Capella,
L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin
Trans. 1 1995, 1035. (d) Griesbaum, K. Angew. Chem., Int.
Ed. Engl. 1970, 9, 273; and references therein.
(17) (a) Shostakovskii, M. F.; Bogdanova, A. V. The Chemistry
of Diacetylenes; Halsted Press: Jerusalem, 1974.
(b) Bohlmann, F.; Bornowski, H.; Kramer, D. Chem. Ber.
1963, 96, 584.
References and Notes
(1) For the synthesis of griseoviridin, see: (a) Marcantoni, E.;
Massaccesi, M.; Petrini, M. J. Org. Chem. 2000, 65, 4553.
(b) Kuligowski, C.; Bezzenine-Lafollée, S.; Chaume, G.;
Mahuteau, J.; Barrière, J.-C.; Bacqué, E.; Pancrazi, A.;
Ardisson, J. J. Org. Chem. 2002, 67, 4565. (c) For the
synthesis of benzylthicrellidone, see, for example: Lan,
H. W.; Cooke, P. A.; Pattenden, G.; Bandaranayake, W. M.;
Wickramasinghe, W. A. J. Chem Soc., Perkin Trans. 1 1999,
847.
(2) (a) Corey, E. J.; Shulman, J. I. J. Am. Chem. Soc. 1970, 92,
5522. (b) Oshima, K.; Shimoji, K.; Takahashi, H.;
Yamamoto, H.; Nozaki, H. J. Am. Chem. Soc. 1973, 95,
2694. (c) Mura, A. J. Jr.; Bennet, D. A.; Cohen, T.
Tetrahedron Lett. 1975, 16, 4433. (d) Mura, A. J. Jr.;
Majetich, G.; Grieco, P. A.; Cohen, T. Tetrahedron Lett.
1975, 16, 4437. (e) Mukayama, T.; Fukuyama, S.;
Kumamoto, T. Tetrahedron Lett. 1968, 3787. (f) Waters,
M. S.; Cowen, J. A.; McWilliams, J. C.; Maligres, P. E.;
Askin, D. Tetrahedron Lett. 2000, 41, 141. (g) Sato, T.;
Taguchi, D.; Suzuki, C.; Fujisawa, S. Tetrahedron 2001, 57,
493. (h) Imanishi, T.; Ohara, T.; Sugiyama, K.; Ueda, Y.;
(18) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier:
New York, 1971.
(19) Typical Procedure for the Synthesis of (Z)-1-Phenylthio-
1,4-diorganylbut-1-en-3-ynes
To a solution of 1,4-diphenylbuta-1,3-diyne 1a17 (1.797 g, 5
mmol) and PhSSPh (1.845 g, 2.5 mmol) in 95% EtOH (20
mL) under a nitrogen atmosphere, NaBH4 (0.57 g, 15 mmol)
was added at r.t. and under vigorous stirring. Gas evolution
was observed during addition. The reaction mixture was
stirred under reflux for 3 h, allowed to reach r.t., diluted with
EtOAc (3 × 20 mL), and washed with brine (3 × 30 mL) and
Synlett 2009, No. 6, 986–990 © Thieme Stuttgart · New York

990
M. J. Dabdoub et al.
LETTER
reduced pressure, and the residue purified by flash
H2O (3 × 30 mL). After drying the organic phase over anhyd
MgSO4, the solvent was removed under reduced pressure
and the residue purified by flash chromatography on SiO2
using hexane as mobile phase, to give pure (Z)-1-phenylthio-
1,4-diphenylbut-1-en-3-yne (2a) as a white solid; mp 92–
95 °C; yield 72%. GC-MS: m/z (%) = 312 [M+], 202, 149,
105, 77, 28 (100). IR (KBr): 3072 (m), 2195 (m), 1680 (m),
1580 (s), 1481 (vs), 1440 (vs), 1071 (m), 1024 (m), 750 (vs),
740 (s), 687 (s) cm–1. 1H NMR (400 MHz, CDCl3): d = 6.32
(s, 1 H), 7.03–7.7 (m, 15 H). 13C NMR (100 MHz, CDCl3):
d = 87.60, 98.36, 112.27, 123.34, 126.39, 127.49, 127.88,
127.93, 128.27, 128.35, 128.64, 128.75, 129.25, 129.51,
131.60, 138.38, 147.20.
chromatography on SiO2 using hexane as mobile phase, to
give the pure phenylthio enyne 2c as a yellow oil; yield 75%.
GC-MS: m/z = 236 [M+], 202, 149, 126, 115, 77, 51, 28
(100). IR (neat): 689 (vs), 742 (s), 756 (s), 816 (m), 1480
(m), 1488 (m), 1553 (w), 1585 (w), 2205 (w), 3055 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 5.83 (d, J = 10 Hz, 1 H),
6.75 (d, J = 10 Hz, 1 H), 7.22–7.54 (m, 10 H). 13C NMR (100
MHz, CDCl3): d = 85.62, 97.95, 106.36, 123.26, 127.45,
128.30, 129.18, 129.19, 129.23, 130.31, 130,33, 130.36,
130.39, 130.41, 131.45, 131.49, 134.73, 138.91.
(21) 1-Butylthio-4-cyclohexenylbut-1-en-3-yne (2j)
The same procedure for obtaining 2c was performed,20
however, 6-cyclohexenyl-2-methylhexa-3,5-diyn-2-ol (1k)
and BuSSBu were used as starting materials, affording the
pure compound 2j as a yellow oil; yield 50%. 1H NMR (300
MHz, CDCl3): d = 0.74–1.72 (m, 11 H), 2.07 (m, 2 H), 2.15
(m, 2 H), 2.74 (t, J = 7.2 Hz, 2 H)), 5.56 (d, J = 9.6 Hz, 1 H),
6.11 (s, 1 H), 6.39 (d, J = 9.6 Hz, 1 H). 13C NMR (75 MHz,
CDCl3): d = 13.4, 21.4, 21.5, 22.2, 25.6, 29.1, 32.4, 33.3,
83.4, 99.1, 104.8, 120.8, 134.2, 138.7.
(20) Typical Procedure for the Synthesis of (Z)-1-Phenylthio-
4-organylbut-1-en-3-ynes
A solution of 1-phenylbuta-1,3-diyne (1c, 10 mmol) was
obtained in situ by reaction of 2-hydroxy-2-methyl-6-
phenylhexa-3,5-diyne (1e, 1.84 g, 10 mmol) with powered
NaOH (25 mg) in dry xylene (11 mL) under reflux for 15
min.22 The temperature was then allowed to reach r.t., and
95% EtOH (70 mL) and PhSSPh (1.845 g, 5.0 mmol) were
added. The reaction was run under an atmosphere of N2 and
NaBH4 (0.57 g, 15 mmol) was added. The resulting reaction
mixture was refluxed for 3 h, diluted with EtOAc (70 mL),
and washed with brine (4 × 30 mL). After drying the organic
phase over anhyd MgSO4, the solvent was removed under
(22) Dabdoub, M. J.; Baroni, A. C. M.; Lenardão, E. J.; Gianeti,
T. R.; Hurtado, G. R. Tetrahedron 2001, 57, 4271.
(23) Dabdoub, M. J.; Dabdoub, V. B. Tetrahedron 1995, 36,
9839.
Synlett 2009, No. 6, 986–990 © Thieme Stuttgart · New York