Au-catalyzed reaction of propargylic sulfides and dithioacetals

Article abstract of DOI:10.1021/jo0618674

(Chemical Equation Presented) Propargylic sulfides and dithioacetals are found to undergo similar transformations as propargylic carboxylates when catalyzed by AuCl or AuCl₃, affording indene derivatives through pentannulation of aromatic rings

Full text of DOI:10.1021/jo0618674

Au-Catalyzed Reaction of Propargylic Sulfides and Dithioacetals
Lingling Peng, Xiu Zhang, Shiwei Zhang, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Green Chemistry Center (GCC),
and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking UniVersity, Beijing 100871, China
wangjb@pku.edu.cn
ReceiVed September 9, 2006
Propargylic sulfides and dithioacetals are found to undergo similar transformations as propargylic
carboxylates when catalyzed by AuCl or AuCl3, affording indene derivatives through pentannulation of
aromatic rings. The reaction presumably involves Au carbene as the reactive intermediate.
Introduction
coordination ability toward transition metals, recent reports
demonstrate that the reaction of allenyl compounds bearing
sulfur groups can also be catalyzed with transition-metal
complexes. Gevorgyan and co-workers have reported 1,2-thio
migration in Cu-catalyzed reactions of allenyl sulfides.4 A recent
The chemistry of transition-metal-complex-activated alkynes
has witnessed increasing development in recent years.1 Among
the various catalytic systems, Au(I) and Pt(II) complexes have
attracted particular attention due to their high affinity to the π
system of the alkyne substrates. A number of novel transforma-
tions have emerged based on the Au(I)- or Pt(II)-catalyzed
reactions of alkynes.2 One of the general processes that is
involved in those transformations is the transition-metal-
catalyzed reaction of propargyl esters that generates a metal
carbene intermediate, as shown by eq 1.1e,3 The activation of
the triple bond by a transition metal triggers an intramolecular
nucleophilic attack by the ester carbonyl oxygen, generating a
cyclic five-centered ionic species. Subsequent 1,2-acyl group
migration leads to the formation of a metal carbene.
Given the high affinity of gold to alkynes as well as the high
reactivity of metal-activated alkynes toward nucleophiles, we
have envisioned that other nucleophiles, such as a thio group
or a halogen group, may also trigger a similar reaction through
a three-centered ionic intermediate, which is generated by
intramolecular 1,3-nucleophilic attack (eqs 2 and 3). Although
sulfur-containing functional groups are known to have a strong
(2) For the selected, most recent developments, see: (a) Harrak, Y.;
Blaszykowski, C.; Bernard, M.; Cariou, K.; Mainetti, E.; Mourie`s, V.;
Dhimane, A.-L.; Fensterbank, L.; Malacria, M. J. Am. Chem. Soc. 2004,
126, 8656. (b) Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 10858. (c) Fu¨rstner, A.; Hannen, P. Chem. Commun. 2004,
2546. (d) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 11806.
(e) Mamane, V.; Hannen, P.; Fu¨rstner, A. Chem.sEur. J. 2004, 10, 4556.
(f) Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978. (g)
Nieto-Oberhuber, C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.; Ca´rdenas,
D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402. (h) Gorin,
D. J.; Davies, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260. (i)
Kusama, H.; Yamabe, H.; Onizawa, Y.; Hoshino, T.; Iwasawa, N. Angew.
Chem., Int. Ed. 2005, 44, 468. (j) Antoniotti, S.; Genin, E.; Michelet, V.;
Geneˆt, J.-P. J. Am. Chem. Soc. 2005, 127, 9976. (k) Fu¨rstner, A.; Davies,
P. W.; Gress, T. J. Am. Chem. Soc. 2005, 127, 8244. (l) Gagosz, F. Org.
Lett. 2005, 7, 4129. (m) Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 9708. (n) Suhre, M. H.; Reif, M.; Kirsch, S. F. Org.
Lett. 2005, 7, 3925. (o) Nieto-Oberhuber, C.; Lo´pez, S.; Echavarren, A. M.
J. Am. Chem. Soc. 2005, 127, 6178. (p) Fu¨rstner, A.; Davies, P. W. J. Am.
Chem. Soc. 2005, 127, 15024. (q) Nakamura, I.; Mizushima, Y.; Yamamoto,
Y. J. Am. Chem. Soc. 2005, 127, 15022. (r) Kusama, H.; Miyashita, Y.;
Takaya, J.; Iwasawa, N. Org. Lett. 2006, 8, 289. (s) Genin, E.; Toullec,
P. Y.; Antoniotti, S.; Brancour, C.; Geneˆt, J.-P.; Michelet, V. J. Am. Chem.
Soc. 2006, 128, 3112. (t) Barluenga, J.; Die´guez, A.; Ferna´ndez, A.;
Rodr´ıguez, F.; Fan˜ana´s, F. J. Angew. Chem., Int. Ed. 2006, 45, 2091. (u)
Sun, J.; Conley, M. P.; Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2006,
128, 9705. (v) Marion, N.; D´ıez-Gonza´lez, S.; de Fre´mont, P.; Noble,
A. R.; Nolan, S. P. Angew. Chem., Int. Ed. 2006, 45, 3647. (w) Sherry,
B. D.; Maus, L.; Laforteza, B. N.; Toste, F. D. J. Am. Chem. Soc. 2006,
128, 8132. (x) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int.
Ed. 2006, 45, 4473.
(1) For recent reviews, see: (a) Aubert, C.; Buisine, O.; Malacria, M.
Chem. ReV. 2002, 102, 813. (b) Me´ndez, M.; Echavarren, A. M. Eur. J.
Org. Chem. 2002, 15. (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51. (d)
Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215. (e) Miki, K.; Uemura,
S.; Ohe, K. Chem. Lett. 2005, 34, 1068. (f) Echavarren, A. M.; Nevado, C.
Chem. Soc. ReV. 2004, 33, 431. (g) Bruneau, C. Angew. Chem., Int. Ed.
2005, 44, 2328. (h) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2005, 44,
6990. (i) Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol. Chem. 2005, 3,
387. (j) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200.
10.1021/jo0618674 CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/19/2007
1192
J. Org. Chem. 2007, 72, 1192-1197

Reaction of Propargylic Sulfides and Dithioacetals
TABLE 1. Reaction of Propargyl Sulfide 1a under Various
Conditions
report by Morita and Krause demonstrates that even allenyl
compounds bearing a thiol group can undergo efficient reaction
with AuCl as the catalyst.5 Encouraged by those reports, we
describe here the investigation of a Au-catalyzed reaction of
propargylic sulfides and dithioacetals.
temp time yieldb
ratioc
(2a:3a)
entry
catalysta
solvent (°C)
(h)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
AuCl
AuCl
AuCl + AgSbF6
AuCl + AgOTf
AuCl + PPh3
AuCl3
AuCl3
PtCl2
PtCl2
[RuCl2(p-cymene)]2 PhCH3
Rh2(OCOCF3)4
AuCl
AuCl
AuCl3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
25
80
80
80
80
25
80
25
80
80
80
70
60
70
60
70
5
1
1
1
26
3
1
30
1
19
8
1
63
75
d
5:1
10:1
d
30
78
85
80
97
30
trace
76
40
82
50
80
1:1
3:1
5:1
1:1
1:1
2:1
PhCH3
DCE
MeCN
DCE
MeCN
DCE
6:1
1:1
5:1
1:1
1:1
1
1
1
6
AuCl3
PtCl2
a All reactions were carried out with 5 mol % of catalyst. b Isolated yield
after silica gel column chromatography. c Ratio determined by 1H NMR of
the crude product. d The reaction gave a complex mixture.
Results and Discussion
Rh2(OCOCF3)4 gave only a trace amount of indene products
(entries 10 and 11).
The propargylic sulfide 1a was subjected to the reaction with
transition-metal catalysts (Table 1). The reaction of 1a with 5
mol % of AuCl in toluene at room temperature for 5 h afforded
a 5:1 mixture of isomeric products in 63% yield (Table 1, entry
1). The structures of the products are characterized as indene
derivatives 2a and 3a by spectral data. The reaction time could
be significantly shortened when the reaction was conducted at
80 °C, with some improvements in both yield and the selectivity
for 2a (Table 1, entry 2). The addition of AgSbF6 or AgOTf to
the gold catalyst led to a complex mixture, and addition of PPh3
to AuCl markedly slowed down the reaction (entries 3-5). The
reaction of 1a with 5 mol % of AuCl3 gave similar yields of
the indene products under the same conditions.
PtCl2 was next examined. It was found that this catalyst had
higher reactivity toward sulfide 1a, as compared with the gold
catalysts. The reaction of 1a with 5 mol % of PtCl2 gave a better
yield but with essentially no selectivity for 2a and 3a (Table 1,
entries 8 and 9). Other metal catalysts were also examined.
RuCl2(p-cymene) dimer was found to be less effective, while
Finally, the effect of solvent was investigated. Switching the
solvent to 1,2-dichloroethane (DCE) afforded comparable results
(entries 12, 14, and 16). However, employing MeCN as the
solvent resulted in diminished yields (entries 13 and 15).
Indene formations have been previously reported in the
transition-metal-catalyzed reaction of propargylic esters.3c,g
Metal carbene has been suggested to be the likely intermediate.
Here, we propose a reaction pathway for the formation of 2a
and 3a (Scheme 1).6 As expected, the lone pair of sulfur attacks
the adjacent metal-activated triple bond, resulting in the forma-
tion of a three-centered thiirenium intermediate B. Subsequent
1,2-migration of the thio group through B generates the metal
carbene species C or D, which are considered to be in resonance
with E. E might be viewed as a metal-stabilized allylic cation.
As a result, C and D are in rapid equilibrium. From C, aromatic
substitution by the metal carbene leads to the formal C-H
insertion product 2a.7 The formation of 3a suggests that a
different pathway for the formal C-H insertion may also
operate.8 One possibility might be a Friedel-Crafts-type reaction
of a phenyl ring with the metal-stabilized cation-like species,
which leads to intermediate F, from which the release of the
metal and the proton transfer to the a or b position generate 2a
and 3a, respectively. Another possible pathway for the formation
of 2a and 3a is intramolecular nucleophilic attack of the phenyl
group on the vinyl metal moiety to generate intermediate F
directly. Intramolecular nucleophilic attack of the CdC bond
(3) (a) Rautenstrauch, V. J. Org. Chem. 1984, 49, 950. (b) Mainetti, E.;
Mourie, V.; Fensterbank, L.; Malacria, M.; Marco-Contelles, J. Angew.
Chem., Int. Ed. 2002, 41, 2132. (c) Miki, K.; Ohe, K.; Uemura, S. J. Org.
Chem. 2003, 68, 8505. (d) Fu¨rstner, A.; Hannen, P. Chem. Commun. 2004,
2546. (e) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 18002. (f) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 5802. (g) Prasad, B. A. B.; Yoshimoto, F. K.;
Sarpong, R. J. Am. Chem. Soc. 2005, 127, 12468. (h) Zhang, L. J. Am.
Chem. Soc. 2005, 127, 16804. (i) Zhang, L.; Wang, S. J. Am. Chem. Soc.
2006, 128, 1442. (j) Ohe, K.; Fujita, M.; Matsumoto, H.; Tai, Y.; Miki, K.
J. Am. Chem. Soc. 2006, 128, 9270. (k) Pujanauski, B. G.; Prasad,
B. A. B.; Sarpong, R. J. Am. Chem. Soc. 2006, 128, 6786. (l) Wang, S.;
Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414.
(6) For recent mechanistic discussions on Au- and Pt-catalyzed reactions
of propargylic esters, see: (a) Fu¨rstner, A.; Hannen, P. Chem.sEur. J. 2006,
12, 3006. (b) Fehr, C.; Galindo, J. Angew. Chem., Int. Ed. 2006, 45, 2901.
(7) For a discussion on formal insertion into the aromatic C-H by a
metal carbene, see: Padwa, A.; Austin, D. J.; Price, A. T.; Semones,
M. A.; Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A.
J. Am. Chem. Soc. 1993, 115, 8669.
(4) (a) For 1,2-thio migration in the Cu-catalyzed reaction of thioallenyl
ketones, see: Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int.
Ed. 2003, 42, 98. (b) For 1,2-halogen migration in Au-catalyzed bromoal-
lenyl ketones, see: Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem.
Soc. 2005, 127, 10500.
(8) Control experiments suggested that isomerization of 2a and 3a did
not occur under the reaction conditions.
(5) Morita, N.; Krause, N. Angew. Chem., Int. Ed. 2006, 45, 1897.
J. Org. Chem, Vol. 72, No. 4, 2007 1193

Peng et al.
SCHEME 1. Mechanistic Hypothesis
SCHEME 3. Kinetic Isotopic Effects
effect has been reported in the range of 1.2-3.3.9 However,
the formal aromatic C-H insertion by a metal carbene has been
known to proceed by initial cyclopropanation, followed by the
hydride shift and the opening of the cyclopropyl ring.7 This is
obviously different from the direct metal carbene insertion into
the aliphatic C-H bond, which has been suggested as a
concerted process in most cases.7,9,10 Consequently, the small
kinetic isotope effect seen in the present work does not provide
evidence to differentiate the possible pathways hypothesized
in Scheme 2. More rigorous studies will be necessary to
assuredly clarify this complicated mechanistic issue.
The scope of this catalytic reaction is demonstrated by a series
of propargylic sulfides 1b-j, as shown in Table 2. Both AuCl
and AuCl3 were tested for all of the sulfide substrates. The
substituent on the sulfur seems to have only a marginal effect
on the reaction (entries 1-5). The slow conversion in the case
of the naphthyl-substituted substrate 1c should be due to steric
effects. The substrate with the alkyl substituent on the sulfur
gave similar results (entry 4). On the other hand, the substituent
in the alkyne moiety seems to have a significant effect on the
outcome of the reaction (entries 6 and 8). In the case of 1g, the
reaction with AuCl or AuCl3 proceeded slowly. In this case,
the corresponding Au carbene intermediate has a methyl
substitute attached to carbene carbon. The reactivity of the Au
carbene is thus diminished due to the stabilizing effect of the
methyl group. In the case of 1i, the reaction with both AuCl
and AuCl3 gave only one product, 2i. This may be due to the
attachment of an electron-withdrawing ester group to the metal
carbene, which may lead to a more carbene-like intermediate
(rather than a cation-like intermediate). Formal C-H insertion
should be more likely to occur from a carbene-like intermediate.
The secondary sulfide was found to be less reactive under the
same reaction conditions (entry 9). This is similar to the catalytic
reaction of propargylic acetate.3c
SCHEME 2. Experiment on Reaction Mechanism
on the vinyl metal moiety in the metal-catalyzed reaction of
propargylic acetates has been proposed.3g,f
To gain some insight into the reaction mechanism, we studied
the catalytic reaction of propargyl sulfide 4, in which the phenyl
substituent of 2a is replaced with the n-butyl group (Scheme
2). Unfortunately, the Au-catalyzed reaction of 4 in the presence
of styrene resulted in the recovery of the starting materials. This
is attributed to the low reactivity of the Au catalyst in the
reaction with secondary propargyl sulfides. However, the PtCl2-
catalyzed reaction of 4 in the presence of styrene under identical
conditions afforded a diastereomeric mixture of cyclopropane
derivative 6 as a major isolated product. The formation of the
cyclopropanation products is a strong evidence to indicate the
generation of metal carbene 7 in such systems.3e
This catalytic reaction can be extended to the sulfide with a
vinyl substituent 11 (Scheme 4). In this case, the reaction
(9) (a) Demonceau, A.; Noels, A. F.; Costa, J.-L.; Hubert, A. J. J. Mol.
Catal. 1990, 58, 21. (b) Wang, P.; Adams, J. J. Am. Chem. Soc. 1994, 116,
3296. (c) Sulikowski, G. A.; Lee, S. Tetrahedron Lett. 1999, 40, 8035.
(d) Ishii, S.; Zhao, S.; Helquist, P. J. Am. Chem. Soc. 2000, 122, 5897.
(10) For mechanistic investigations on Rh(II) carbene C-H insertions,
see: (a) Taber, D. F.; Ruckle, R. E., Jr. J. Am. Chem. Soc. 1986, 108,
7686. (b) Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.; See, M. M.;
Boone, W. P.; Bagheri, V.; Pearson, M. M. J. Am. Chem. Soc. 1993, 115,
958. (c) Pirrung, M. C.; Morehead, A. T., Jr. J. Am. Chem. Soc. 1994, 116,
8991. (d) Wang, J.; Chen, B.; Bao, J. J. Org. Chem. 1998, 63, 1853. (e)
Pirrung, M. C.; Liu, H.; Morehead, A. T., Jr. J. Am. Chem. Soc. 2002, 124,
1014. (f) Nakamura, E.; Yoshikai, N.; Yamanaka, M. J. Am. Chem. Soc.
2002, 124, 7181. (g) Davies, H. M. L.; Jin, Q.; Ren, P.; Kovalevsky, A. Y.
J. Org. Chem. 2002, 67, 4165. (h) Taber, D. F.; Pramod, V.; Joshi, P. V.
J. Org. Chem. 2004, 69, 4276.
Since deuterium kinetic isotope effects have been used to
probe the C-H insertion reaction of metal carbenes, we next
prepared deuterium-labeled substrate 8 as a preliminary probe
of primary kinetic isotope effects (Scheme 3). The AuCl-
catalyzed reaction of 8 afforded a mixture of indene products 9
and 10 in a ratio of approximately 1:1.45. For metal carbene
insertion into an aliphatic C-H bond, the typical kinetic isotope
1194 J. Org. Chem., Vol. 72, No. 4, 2007

Reaction of Propargylic Sulfides and Dithioacetals
TABLE 2. AuCl- or AuCl3-Catalyzed Reaction of 1b-j
TABLE 3. Reaction of Dithioacetal 13a under Various Conditions
temp
(°C)
time
(h)
yieldb
(%)
ratioc
(14:15)
entry
catalysta
1
2
3
4
5
6
7
PtCl2
AuCl
AuPPh3Cl
AuCl3
AuCl
80
80
80
80
25
80
80
23
1
10
1
6
22
22
78d
95
89
92
94
e
1:8
1:0
1:0
1:0
1:0
time
(h)
yielda
(%)
ratiob
(2:3)
entry
1
sulfide
1b, X ) R′ ) H; R ) CH3 AuCl
R′′ ) o-ClC6H4 AuCl3
1c, X ) R′ ) H; R ) CH3 AuCl
R′′ ) â-naphthyl AuCl3
1d, X ) R′ ) H; R ) CH3 AuCl
R′′ ) benzyl AuCl3
1e, X ) R′ ) H; R ) CH3 AuCl
R′′ ) hexyl AuCl3
1f, X ) R′ ) H; R ) CH3 AuCl
R′′ ) CH2C6H4Cl-o AuCl3
catalyst
[RuCl2(p-cymene)]2
Rh2(OCOCF3)4
1
1
34
34
1
1
1
1
1
56
63
15:1
10:1
e
2
3
4
5
6
7
8
9
24 (60) 10:1
30 (51) 5:1
60
75
68
65
70
70
a All reactions were carried out with 5 mol % of catalyst. b Isolated yield
after silica gel column chromatography. c Ratio determined by 1H NMR of
the crude product. d The product contains a small amount of an unknown
impurity. e Starting material was recovered.
8:1
4:1
4:1
3:1
7:1
5:1
c
SCHEME 5. AuCl-Catalyzed Reaction of Propargyl
Dithioacetals
1
1g, X ) H; R′ ) R ) CH3 AuCl
25
25
4
32 (63)
13 (81)
53
R′′ ) C6H5
AuCl3
AuCl
AuCl3
AuCl
AuCl3
AuCl
AuCl3
1h, X ) Br; R′ ) H
R ) CH3; R′′ ) C6H5
1i, X ) H; R′ ) CO2Et
R ) CH3; R′′ ) C6H5
1j, X ) R′ ) R ) H
R′′ ) C6H5
15:1
10:1
2
68
16
16
24
24
57 (25) >20:1d
67 (11) >20:1
9 (32)
10 (30)
c
a Isolated yields after silica gel column chromatography. Numbers in
parentheses refer to the starting material recovered. b Determined by 1H
NMR of the crude product. c The reaction can only give one isomer when
1
R ) R′. d No 3i could be identified by crude H NMR.
SCHEME 4. Catalytic Reaction with 11
afforded a cyclopentadiene derivative 12,3f which was formed
through vinylic C-H insertion of the metal carbene.
After establishing that the metal carbene could be generated
through the metal-catalyzed reaction of propargyl sulfide, we
proceeded to investigate the reaction with propargyl dithio-
acetals. As shown by eq 3, it can be anticipated that propargylic
dithioacetals may work in the same way as propargyl sulfide
upon catalyzation with transition metals. In this case, the five-
membered dithioacetal ring is expanded to a six-membered ring
with the generation of vinylcarbenoids.
in Scheme 5. Indene derivatives were isolated in good to
excellent yields, except in the case of 2-furyl substrate 16, in
which case the reaction proceeded slowly to afford 17.
Compared to the reaction with propargyl sulfide, the Au-
catalyzed reaction with propargyl dithioacetals is generally more
efficient, presumably due to the rigidity of the substrate in the
latter case. Moreover, since dithioacetals are easily available
from the corresponding ketones,11 this catalytic reaction provides
an unique and efficient entry to the indene derivatives.
The investigation started with dithioacetal 13a, as summarized
in Table 3. The PtCl2-catalyzed reaction gave a complicated
1
mixture. From the crude H NMR spectra, 15a was identified
as the major product (entry 1). To our delight, the reaction with
both AuCl and AuCl3 afforded 14a as the only isomer with
high isolated yields (entries 2-5). Ru(II) and Rh(II) catalysts
were also tested. In both cases, most of the starting material
13a was recovered after prolonged reaction time (entries 6
and 7).
(11) (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) Tseng, J.-C.; Chen,
J.-H.; Luh, T.-Y. Synlett 2006, 1209.
The generality of the AuCl-catalyzed reaction of propargyl
dithioacetals is demonstrated by a variety of substrates, as shown
J. Org. Chem, Vol. 72, No. 4, 2007 1195

Peng et al.
Typical Procedure for PtCl2-, AuCl3-, or AuCl-Catalyzed
Rearrangement Reactions of 1a-j and 11. Under a nitrogen
atmosphere, metal catalyst (AuCl, AuCl3) (0.01mmol) and prop-
argylic sulfide (0.2 mmol) were mixed in dry toluene, and the
system was heated at 80 °C. Upon completion of the reaction as
judged by TLC, solvent was removed in vacuo to give a crude
residue which was purified by a silica gel column eluted with
petroleum ether. Isomeric products 2 and 3 were found to be
inseparable on a silica gel column.
In conclusion, we have demonstrated that a neighboring sulfur
group can participate the transition-metal-catalyzed reactions
of alkynes to generate a vinylcarbenoid as the reactive inter-
mediate through 1,2-sulfur migration.12 This result provides a
new entry to these important intermediates and thus significantly
expands the scope of the chemistry of alkyne-generated metal
carbenes. Further studies on the detailed reaction mechanism
and the application of this process in organic synthesis are
underway in our laboratory.
3-Methyl-2-phenylthioindene 2a: oil; IR (film) 3067, 1476,
1461, 1439, 1024, 757, 739, 691 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.27 (t, J ) 2.1 Hz, 3H), 3.44 (d, J ) 2.1 Hz, 2H), 7.16-7.37
(m, 9H); 13C NMR (CDCl3, 75 MHz) δ 11.7, 42.1, 119.1, 123.3,
125.3, 126.2, 126.5, 129.0, 129.3, 132.0, 136.4, 143.2, 144.0, 145.5;
EI-MS (m/z, relative intensity) 238 (M+, 44), 129 (100). Anal.
Calcd for C16H14S: C, 80.63; H, 5.92. Found: C, 80.55; H, 5.95.
Experimental Section
The Synthesis of Propargylic Sulfides 1a-f,h-j. The pro-
pargylic sulfides were synthesized through a catalyzed propargylic
substitution reaction of propargylic alcohols with thiols. We mainly
used two methods, catalysis with ZnI2 (Method A)13 or catalysis
with PTS (p-toluenesulfonic acid monohydrate) (Method B).14 The
sulfides can also be synthesized by catalysis with a thiolate-bridged
diruthenium complex15 or NaAuCl4‚2H2O.16 Recently, some other
methods for preparing propargylic sulfides have appeared in
literature.17
2-Methyl-4-phenyl-1-phenylthiocyclopenta-1,3-diene 12: white
solid; mp 62-63 °C; IR (film) 3053, 1476, 1440, 1373, 752, 739,
1
690 cm-1; H NMR (CDCl3, 300 MHz) δ 2.12 (t, J ) 2.1 Hz,
3H), 3.51-3.52 (m, 2H), 6.83 (s, 1H), 7.10-7.32 (m, 8H), 7.40-
7.46 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 14.2, 45.5, 124.9,
125.5, 127.2, 127.7, 128.6, 128.9, 130.6, 135.3, 138.3, 147.9, 149.7;
EI-MS (m/z, relative intensity) 264 (M+, 43), 249 (9), 171 (13),
155 (100). Anal. Calcd for C18H16S: C, 81.77; H, 6.10. Found: C,
81.53; H, 5.91.
Phenyl-1-methyl-1-phenyl-2-propynyl Sulfide 1a. Yield 49%.
Method A: white solid; mp 45-46 °C; IR (film) 3292, 1439, 1067,
1
750, 692 cm-1; H NMR (CDCl3, 300 MHz) δ 1.94 (s, 3Η), 2.70
(s, 1Η), 7.20-7.36 (m, 8Η), 7.57-7.61 (m, 2Η); 13C NMR (CDCl3,
75 MHz) δ 29.9, 49.2, 74.7, 86.1, 126.7, 127.4, 128.0, 128.2, 129.1,
132.3, 136.4, 141.8; EI-MS (m/z, relative intensity) 238 (M+, 8),
223 (26), 129 (100). Anal. Calcd for C16H14S: C, 80.63; H, 5.92.
Found: C, 80.62; H, 5.95.
The Synthesis of Propargylic Dithioacetals 13a-h and 16.
The propargylic dithioacetals were prepared from the corresponding
propargylic ketones and 1,2-ethanedithiol in the presence of BF3‚
Et2O.11a There are two ways to prepare the propargylic ketones,
Method A by a direct coupling reaction (for the synthesis of 13a,f,h)
and18 Method B by two-step reaction that involves first a nucleo-
philic addition and then oxidation (for the synthesis of 13b-e,g,
and 16).
Phenyl-1,3-dimethyl-1-phenyl-2-propynyl Sulfide 1g. For this
sulfide, the following procedure is followed. Under a nitrogen
atmosphere, BuLi was added dropwise to a solution of phenyl-1-
methyl-1-phenyl-2-propynyl sulfide 1a (238 mg, 1 mmol) in
anhydrous THF (10 mL) at -78 °C. After 1 h, CH3I (0.13 mL, 2
mmol) was added, and the temperature was allowed to increase up
to room temperature. Five hours later, saturated NH4Cl was added,
and the mixture was extracted with CH2Cl2. The combined organic
layers were dried over Na2SO4 and evaporated, and the residue was
purified by a silica gel column eluted with petroleum ether to afford
Method B. A flame-dried, three-necked flask was charged with
dry THF (20 mL) and phenylacetylene (12.0 mmol). The solution
was cooled to -78 °C, and n-BuLi (12.0 mmol, 2.0 M in hexane)
was added slowly. The solution was allowed to stir for 1 h at
-78 °C; then, aldehyde (10.0 mmol) in 20 mL of THF was added
slowly over 20 min. The mixture was stirred for an additional 1 h
at -78 °C; then, the dry ice/acetone bath was removed, and the
mixture was allowed to warm to room temperature. After about 5
h, saturated NH4Cl was added, and most of the organic solvent
was then removed in vacuum. The mixture was extracted with
CH2Cl2. The combined organic layers were dried over Na2SO4 and
evaporated, and the residue was purified by a silica gel column
eluted with petroleum ether/EtOAc (20:1) to afford the correspond-
ing propargylic alcohol.
1
1g (91%): oil; IR (film) 2917, 1438, 1027, 749, 692 cm-1; H
NMR (CDCl3, 300 MHz) δ 1.89 (s, 3Η), 1.91 (s, 3Η), 7.19-7.34
(m, 8Η), 7.56-7.59 (m, 2Η); 13C NMR (CDCl3, 75 MHz) δ 3.8,
30.1, 49.9, 81.5, 82.9, 126.7, 127.2, 127.9, 128.1, 128.8, 132.8,
136.5, 142.9; EI-MS (m/z, relative intensity) 252 (M+, 4), 237
(7), 143 (100), 128 (27). Anal. Calcd for C17H16S: C, 80.90; H,
6.39. Found: C, 80.91; H, 6.42.
Phenyl-1-methyl-1-styryl-2-propynyl Sulfide 11. Yield 63%.
Method B: oil; IR (film) 3288, 1583, 1480, 1438, 744, 693 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.81 (d, J ) 1.5 Hz, 3H), 3.11 (d,
J ) 0.3 Hz, 1H), 5.41 (d, J ) 10.5 Hz, 1H), 5.99-6.03 (m, 1H),
7.21-7.34 (m, 7H), 7.36-7.41 (m, 3H); 13C NMR (CDCl3, 75
MHz) δ 22.7, 53.0, 82.0, 82.2, 118.6, 127.2, 127.4, 127.7, 128.6,
128.6, 132.7, 137.9; EI-MS (m/z, relative intensity) 264 (M+, 4),
249 (5), 155 (100), 129 (13). Anal. Calcd for C18H16S: C, 81.77;
H, 6.10. Found: C, 81.64; H, 6.10.
A solution of propargylic alcohol (10.0 mmol) in CH2Cl2 (50
mL) was cooled to 0 °C, and MnO2 (50.0 mmol) was added by
portion. This was kept in the ice bath for another 2 h. Then, the
solid was removed by filtration. The filtrate was evaporated, and
the crude residue was purified by a silica gel column eluted with
petroleum ether/EtOAc (100:1) to afford the propargylic ketone.
2-Phenyl-2-(2-phenylethynyl)-1,3-dithiolane 13a:11a yield 72%;
IR (film) 1597, 1489, 1446, 756, 718, 690 cm-1; 1H NMR (CDCl3,
300 MHz) δ 3.67-3.81 (m, 4Η), 7.30-7.42 (m, 6Η), 7.50-7.54
(m, 2Η), 8.03-8.06 (m, 2Η); 13C NMR (CDCl3, 75 MHz) δ 41.3,
62.2, 86.8, 91.0, 122.7, 127.6, 128.2, 128.3, 128.4, 131.6, 138.7;
EI-MS (m/z, relative intensity) 282 (M+, 72), 254 (65), 221 (100),
189 (54), 145 (57), 77 (20).
(12) For a review on sulfanyl migration, see: Fox, D. J.; House, D.;
Warren, S. Angew. Chem., Int. Ed. 2002, 41, 2462.
(13) Guindon, Y.; Frenette, R.; Fortin, R.; Rokach, J. J. Org. Chem. 1983,
48, 1357.
(14) Sanz, R.; Martinez, A.; AÄ lvarez-Gutie´rrez, J. M.; Rodr´ıguez, F. Eur.
J. Org. Chem. 2006, 1383.
(15) Inada, Y.; Nishibayashi, Y.; Hidai, M.; Uemura, S. J. Am. Chem.
Soc. 2002, 124, 15172.
Typical Procedure for AuCl-Catalyzed Rearrangement Reac-
(16) Georgy, M.; Boucard, V.; Campagne, J. J. Am. Chem. Soc. 2005,
127, 14180.
tions of 13a-h and 16. Under a nitrogen atmosphere, AuCl (0.01
(17) (a) Kondo, T.; Kanda, Y.; Baba, A.; Fukuda, K.; Nakamura, A.;
Wada, K.; Morisaki, Y.; Mitsudo, T.-a. J. Am. Chem. Soc. 2002, 124, 12960.
(b) Tsutsumi, K.; Fujimoto, K.; Yabukami, T.; Kawase, T.; Morimoto, T.;
Kakiuchi, K. Eur. J. Org. Chem. 2004, 504.
(18) Cox, R. J.; Ritson, D. J.; Dane, T. A.; Berge, J.; Charmant,
J. P. H.; Kantacha, A. Chem. Commun. 2005, 1037.
(19) Oshino, H.; Kwazoe, Y.; Taguchi, T. Synthesis 1974, 713.
1196 J. Org. Chem., Vol. 72, No. 4, 2007

Reaction of Propargylic Sulfides and Dithioacetals
mmol) and propargylic dithioacetal (0.2 mmol) were mixed in dry
toluene, and the system was heated at 80 °C by a boil bath. The
temperature was kept until the reaction was completed as judged
by TLC. Removal of the solvent in vacuo gave a crude residue,
which was purified by a silica gel column eluted with petroleum
ether.
Acknowledgment. The project is generously supported by
the Natural Science Foundation of China (Grant Nos. 20572002,
20521202, 20225205, 20390050) and the Ministry of Education
of China.
9-Phenyl-2,3-dihydro-1,4-dithiofluorene 14a:19 white solid; mp
122-123 °C; IR (film) 1600, 1536, 1493, 1463, 1265, 754, 734,
701 cm-1; 1H NMR (CDCl3, 300 MHz) δ 3.20-3.25 (m, 4H), 4.53
(s, 1H), 7.04-7.31 (m, 9H); 13C NMR (CDCl3, 75 MHz) δ 26.1,
27.3, 59.3, 116.7, 123.0, 123.7, 124.8, 127.0, 127.2, 128.2, 128.7,
132.5, 138.9, 143.0, 145.0; EI-MS (m/z, relative intensity) 282
(M+, 100), 254 (53), 221 (64), 189 (6), 177 (18), 165 (8), 111 (15).
Supporting Information Available: Synthesis of propargylic
sulfides and dithioacetals, spectra data for all new compounds, X-ray
structure of sulfone, cyclopropanation and kinetic isotope effect
experiments, and copies of spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO0618674
J. Org. Chem, Vol. 72, No. 4, 2007 1197