Palladium-catalyzed ring-opening thiocarbonylation of vinylcyclopropanes with thiols and carbon monoxide

Article abstract of DOI:10.1021/jo801725j

Palladium-catalyzed ring-opening thiocarbonylation of vi- nylcyclopropanes (VCPs) with thiols and carbon monoxide affords the corresponding unsaturated thioesters in moderate to excellent yields. This reaction provides a general method for the ring-openin

Full text of DOI:10.1021/jo801725j

chemistry.10 Containing an olefinic moiety and a cyclopropane
ring, these species demonstrate high reactivity. The ring opening
of VCPs can be catalyzed by complexes of transition metal
catalysts such as those containing palladium, rhodium, zirco-
nium, chromium, nickel, and gold.11 However, there are no
reports of the ring-opening thiocarbonylation of VCPs. We
previously demonstrated that palladium complexes can catalyze
thiocarbonylation reactions of unsaturated species for the
synthesis of unsaturated thioesters.12 We now report a novel
palladium-catalyzed ring-opening thiocarbonylation reaction of
VCPs with thiols and carbon monoxide to give a new class of
unsaturated thioesters.
Palladium-Catalyzed Ring-Opening
Thiocarbonylation of Vinylcyclopropanes with
Thiols and Carbon Monoxide
Chang-Feng Li,†,‡ Wen-Jing Xiao,*,‡ and Howard Alper*,†
Centre for Catalysis Research and InnoVation, Department
of Chemistry, UniVersity of Ottawa, 10 Marie Curie, Ottawa,
Ontario K1N 6N5, Canada, and The Key Laboratory of
Pesticide & Chemical Biology, Ministry of Education,
College of Chemistry, Central China Normal UniVersity,
152 Luoyu Road, Wuhan, Hubei 430079, China
The palladium-catalyzed reaction of 1,1-dimethoxycarbonyl
2-vinylcyclopropane (1a) with thiophenol (2a) and carbon
monoxide was chosen as a model reaction to determine the
howard.alper@uottawa.ca; wxiao@mail.ccnu.edu.cn
ReceiVed August 10, 2008
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Tetrahedron 2003, 59, 3521.
Palladium-catalyzed ring-opening thiocarbonylation of vi-
nylcyclopropanes (VCPs) with thiols and carbon monoxide
affords the corresponding unsaturated thioesters in moderate
to excellent yields. This reaction provides a general method
for the ring-opening thiocarbonylation of VCPs. It further
demonstrates the utility of transition metal catalysts for the
synthesis of organosulfur compounds.
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Transition-metal-catalyzed carbonylation is widely recognized
as one of the most important carbonyl-forming reactions in
organic synthesis.1 Formation of a thiocarbonyl unit and
employing organosulfur compounds, especially thiols and
thiophenols, as a direct substrate represents a challenging subject
in transition-metal-catalyzed reactions. We and others have
investigated some interesting transformations employing orga-
nosulfur compounds as substrates.2 Those results and others
such as thioboration,3 thiosilylation,4 thiophosphorylation,5
thioesterification,6thiopropargylation,7 and carbothiolation8 of
unsaturated compounds developed in the past few years have
corrected the widely accepted concept that “sulfur compounds
are poisons to transition metal catalysts”.9 The chemistry of
vinylcyclopropanes (VCPs) has attracted interest in synthetic
† University of Ottawa.
‡ Central China Normal University.
(1) (a) Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbonylation:
Direct Synthesis of Carbonyl Compounds; Plenum Press: New York, 1991. (b)
Tsuji, J. Palladium Reagents and Catalysts; Wiley: New York, 1995. (c)
Khumtaveeporn, K.; Alper, H. Acc. Chem. Res. 1995, 28, 414. (d) Zeni, G.;
Larock, R. C. Chem. ReV. 2006, 106, 4644.
888 J. Org. Chem. 2009, 74, 888–890
10.1021/jo801725j CCC: $40.75 2009 American Chemical Society
Published on Web 12/02/2008

TABLE 1. Ring-Opening Thiocarbonylation of
1,1-Dimethoxycarbonyl 2-Vinylcyclopropane (1a) with Thiophenol
(2a) under Various Conditionsa
TABLE 2. Scope of the Thiocarbonylation of Vinylcyclopropanesa
yield (%)b
entry
catalyst
solvent
time (h)
3a
22
4a
53
12
25
31
0
6
9
16
trace
9
1
2
3
4
5
6
7
8
Pd(OAc)2/dppb
Pd(OAc)2/dppp
Pd(OAc)2/Cy3P
Pd(OAc)2/Bu3P
Pd(OAc)2/PPh3
Pd(PPh3)4/PPh3
Pd2(dba)·CHCl3/PPh3
RhCl(PPh3)3/PPh3
Pd(OAc)2
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
48
72
48
48
48
72
48
48
48
48
48
48
48
48
0
trace
trace
77
70
46
trace
0
16
9
10
11
12
13
14c
toluene
CH3CN
Et2O
56
0
16
2
trace
trace
41
CH2Cl2
15
a Reaction conditions: 1,1-dimethoxycarbonyl 2-vinylcyclopropane
(1a, 2 mmol), thiophenol (2a, 1 mmol), catalyst (0.05 mmol), PPh3
(22.5 mol %, if used), 400 psi of CO, solvent (5 mL). b Isolated yield.
c 1.0 equiv of 1a was used.
viability of the process and the optimum reaction conditions
(Table 1). A series of reactions between 1a and 2a were carried
out under various conditions. It was shown that Pd(OAc)2 with
PPh3 was the best catalyst system among those examined, and
the reaction proceeded efficiently in dichloromethane (Table 1,
entry 5). Using Pd(OAc)2 without any ligand gave only a trace
amount of the nucleophilic addition product (Table 1, entry 9).
This product arises by using 1 equiv of 1a, while the thiocar-
bonylated product was also formed in lower yield (Table 1,
entries 5 vs 14). In accord with our observation,12b,e,f,i the sulfide
4a can be suppressed by employing excess VCPs (e.g., 2 equiv
relative to thiols). Pd(PPh3)4 with PPh3 is also a good catalytic
system for this reaction (Table 1, entry 6). However, other
catalyst systems, such as Pd2(dba)3 ·CHCl3 and RhCl(PPh3)3 with
PPh3, were ineffective for this transformation (Table 1, entries
7 and 8). The nature of the solvent greatly affected the yield of
ꢀ,γ-unsaturated thioester 3a in this reaction. With the Pd(OAc)2/
PPh3 catalyst system, the reaction works well at 100 °C in
CH2Cl2 and was completed in 48 h to form the pure ꢀ,γ-
unsaturated thioester.
The thiocarbonylation reactions of a series of diastereomeric
mixtures of VCPs (1a-h) with thiols (2a-h) were performed
by using 5 mol % of Pd(OAc)2 and 22.5 mol % of PPh3 in
CH2Cl2 (5 mL per 1 mmol of thiol) at 400 or 600 psi of carbon
monoxide for 48-120 h at 100 °C, and the results are
summarized in Table 2. In most cases, the thiocarbonylation
was accompanied with the isomerization process to the conju-
gated thioester in some extent (Table 2, entries 2-5 and 7-13).
The thiophenols were found to work more effectively than
alkylthiols. For examples, 1a reacted with thiophenol (2a),
a Reaction conditions: 1,1-dimethoxycarbonyl 2-vinylcyclopropane
(1, 2 mmol), thiol (2, 1 mmol), Pd(OAc)2 (5 mol %)/PPh3 (22.5 mol %),
400 psi of CO, CH2Cl2 (5 mL). b isolated yield. c The ratio of 3 and 3′
was determined by 1H NMR. d 9% of the corresponding thioether 4d
was also isolated. e 7% of the corresponding thioether 4e was also
isolated. f 5 equiv of 1 was used. g 600 psi of CO. h 34% of the
corresponding thioether 4m was also isolated. i 150 °C.
p-bromobenzenethiol (2b), and p-chlorobenzenethiol (2c), af-
fording the ring-opening carbonylated products in good to
excellent yields (Table 2, entries 1-3), while the corresponding
reaction with alkane thiols gave the carbonylated products in
moderate yields (Table 2, entries 6 and 7). Reactions involving
alkylthiols took longer to complete than those with arylthiols.
The reactivity of the reaction was rather sensitive to both the
acidity (electronic factor) and the bulkiness (steric fators) of
the thiols. For example, 2d (p-methylbenzenethiol), an arylthiol
with an electron-donating p-methyl group, and 2b (p-bromoben-
zenethiol), an arylthiol with an electron-withdrawing group,
show some different behavior in this reaction. Using 2d as the
substrate gives a mixture of 3d and 3′d (3d/3′d ) 8:1, 77%
yield) and 4d (9% yield) (Table 2, entry 4), whereas 2b gives
only the carbonylative product in 88% yield (3b/3′b ) 11:1)
(12) (a) Xiao, W.-J.; Alper, H. J. Org. Chem. 1997, 62, 3422. (b) Xiao, W.-
J.; Vasapollo, G.; Alper, H. J. Org. Chem. 1998, 63, 2609. (c) Xiao, W.-J.;
Alper, H. J. Org. Chem. 1998, 63, 7939. (d) Xiao, W.-J.; Vasapollo, G.; Alper,
H. J. Org. Chem. 1999, 64, 2080. (e) Xiao, W.-J.; Alper, H. J. Org. Chem.
1999, 64, 9646. (f) Xiao, W.-J.; Vasapollo, G.; Alper, H. J. Org. Chem. 2000,
65, 4138. (g) Xiao, W.-J.; Alper, H. J. Org. Chem. 2001, 66, 6229. (h) Xiao,
W.-J.; Alper, H. J. Org. Chem. 2005, 70, 1802. (i) Cao, H.; Xiao, W.-J.; Alper,
H. AdV. Synth. Catal. 2006, 348, 1807. (j) Cao, H.; Xiao, W.-J.; Alper, H. J.
Org. Chem. 2007, 72, 8562.
J. Org. Chem. Vol. 74, No. 2, 2009 889

SCHEME 1. Proposed Reaction Pathway
regeneration of the palladium catalyst. Further isomerization of
the ꢀ,γ-unsaturated thioester 3 would give the R,ꢀ-unsaturated
isomer 3′.17
In summary, an effective catalytic system [Pd(OAc)2/PPh3]
was developed for the ring-opening thiocarbonylation of VCPs,
thiols, and carbon monoxide to form the corresponding unsatur-
ated thioesters in moderate to excellent yields. This reaction
provides a general method for the ring-opening thiocarbonylation
of VCPs. It further demonstrates the utility of transition metal
catalysts for the synthesis of sulfur compounds. Further
investigation on the mechanism of the reaction as well as a
catalytic asymmetric variant is ongoing.
Experimental Section
General Procedure for the Palladium-Catalyzed Thiocar-
bonylation of VCPs with Thiols and Carbon Monoxide. An
autoclave, its glass liner, and a magnetic stirring bar were dried in
an oven and cooled in a drybox. The liner was charged with
Pd(OAc)2 (0.05 mmol) and PPh3 (0.225 mmol). The vinylcyclo-
propanes (2 mmol), thiol (1 mmol), and 5 mL of CH2Cl2 were then
added to the liner. The gauge and gauge block assembly were
attached. The CO line was flushed three times with CO, and the
system was also pressurized and flushed three times with CO,
gradually increasing the pressure to 400 psi. The autoclave was
then placed in the center of an oil bath on a heater stirrer preset to
100 °C for 48-120 h. The autoclave was removed from the oil
bath and allowed to cool to room temperature. The excess gas was
discharged and the system disassembled. The reaction mixture was
filtered through Celite and washed with diethyl ether. The solvent
was removed by rotary evaporation under reduced pressure. The
residue was separated by flash chromatography on silica gel.
Dimethyl 2-(5-oxo-5-(phenylthio)pent-2-enyl)malonate (3a)
(Table 2, entry 1): Colorless oil; yield 77%; MW ) 322.38; IR
(cm-1, CdO) 1701, 1732; 1H (300 MHz, CDCl3) δ (ppm) 7.42 (s,
5H), 5.59-5.78 (m, 2H), 3.76 (s, 6H), 3.50 (t, J ) 7.5 Hz, 1.4H),
3.34 (d, J ) 2.9 Hz, 1.6H), 2.70 (t, J ) 6.5 Hz, 2H); 13C NMR (75
MHz, CDCl3) δ (ppm) 195.8, 168.7, 134.9, 131.9, 130.0, 129.8,
129.6, 128.0, 125.0, 124.0, 53.1, 53.0, 51.8, 51.6, 47.4, 42.4, 32.2,
27.4; MS (EI, 70 eV) m/z 322.1 (M+); HRMS (EI,70 eV) calcd for
C16H18O5S, 322.0875; found 322.0867.
(Table 2, entry 2). Reactions with arylthiols, such as 2-naph-
thalenethiol (2e), afford a mixture of the ring-opening carbo-
nylated products 3e and 3′e (71% yield, 3e/3′e ) 20:1) and
ring-opening product 4e (7% yield) (Table 2, entry 5). When
1-octanethiol was employed as the substrate, no products were
obtained at all.
Several VCPs were thiocarbonylated by Pd(OAc)2/PPh3 to
give the corresponding unsaturated thioesters in moderate to
excellent yields (Table 2, entries 1 and 8-14). The reactivity
of the VCPs was sensitive to the nature of the substituted
functional group. An electron-withdrawing group of the VCPs
such as methoxycarbonyl and acetyl activate the VCPs for this
reaction. High CO pressure is necessary for improving the yield
when bulky VCPs are used for the reaction (Table 2, entries
9-11). The presence of the acetyl group could decrease the
selectivity between the ꢀ,γ-unsaturated thioester 3 and the R,ꢀ-
unsaturated isomer 3′ (Table 2, entries 8 and 12). 1,1-
Dibenzenesulfonyl 2-vinylcyclopropane only gave the thiocar-
bonylated product in 36% yield, with the corresponding thioether
formed in 34% yield under the optimized conditions (Table 2,
entry 13). 1,1-Diphenyl-2-vinylcyclopropane only gave quite
low conversions due to low activity even at 150 °C under 400
psi of CO.
While a precise reaction mechanism awaits further study, a
possible catalytic cycle for the palladium-catalyzed thiocarbo-
nylation of 1 with thiol 2 is outlined in Scheme 1. Pd(0) is
readily formed in situ by the reduction of Pd(OAc)2 in the
presence of a phosphine ligand.13 Oxidative addition of Pd(0)
to 2 can give the thiopalladium complex 5,14 which can
coordinate with the VCPs, affording the η3-allylpalladium
complex 6 by intramolecular hydropalladation and ring open-
ing.15 Reductive elimination of 6 would afford the thioester 4,
with regeneration of the palladium catalyst. Insertion of CO into
the Pd-C bond of the σ-allyl analogue of 6, followed by
intramolecular transfer, would afford the acylpalladium complex
7.16 Reductive elimination of 7 can form the thioester 3, with
Acknowledgment. We are grateful to the Natural Sciences
and Engineering Research Council of Canada, the National
Natural Science Foundation of China (20672040 and 20872043),
the program for new century excellent talents in university
(NCET-05-0672), and the National Basic Research Program of
China (2004CCA00100) for support of this research.
Supporting Information Available: Full experimental de-
tails, characterization for all new compounds, copies of NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO801725J
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890 J. Org. Chem. Vol. 74, No. 2, 2009