Palladium(0)-catalyzed, copper(I)-mediated coupling of cyclic thioamides with alkenylboronic acids, organostannanes, and siloxanes

Article abstract of DOI:10.1021/jo900848s

(Chemical Presented) The Pd-catalyzed cross-coupling of cyclic thioamides and thioureas with alkenylboronic acids, vinyl- and (het)arylstannanes, and arylsiloxanes in the presence of stoichiometric amounts of a Cu(I) cofactor is described. The desulfitati

Full text of DOI:10.1021/jo900848s

requirement of stoichiometric amounts of a Cu(I) carboxylate
as metal cofactor.7 Due to the higher thiophilicity of the soft
Cu(I) metal, selective sulfide coupling under base-free Liebeskind-
Srogl conditions can be performed even in the presence of a
Suzuki-active bromide.3 Initially described in 2000 for the
synthesis of ketones from thioesters and boronic acids,1 the
scope of the Liebeskind-Srogl cross-coupling was extended
considerably in the past few years to accommodate a variety of
different thioorganics2,7 and organometallic reagents4-7 as
coupling partners (Figure 1a). The ever-increasing potential of
this mechanistically unique base-free cross-coupling method has
already led to an impressive number of interesting applications
in heterocyclic/medicinal chemistry, peptide and solid-phase
synthesis, and the total synthesis of natural products.7
Palladium(0)-Catalyzed, Copper(I)-Mediated
Coupling of Cyclic Thioamides with
Alkenylboronic Acids, Organostannanes, and
Siloxanes
Nuzhat Arshad, Jamshed Hashim, and C. Oliver Kappe*
Christian Doppler Laboratory for MicrowaVe Chemistry
(CDLMC) and Institute of Chemistry,
Karl-Franzens-UniVersity Graz, Heinrichstrasse 28,
A-8010 Graz, Austria
oliVer.kappe@uni-graz.at
ReceiVed April 24, 2009
The Pd-catalyzed cross-coupling of cyclic thioamides and
thioureas with alkenylboronic acids, vinyl- and (het)aryl-
stannanes, and arylsiloxanes in the presence of stoichiometric
amounts of a Cu(I) cofactor is described. The desulfitative
C-C cross-coupling protocol of the Liebeskind-Srogl type
is performed under neutral conditions and can be applied to
a range of heterocyclic structures with embedded thioamide
fragments. Employing controlled microwave irradiation at
100 °C utilizing either a single-mode reactor or a multimode
parallel reaction platform, cross-couplings can generally be
completed within 1-3 h and proceed in good yields.
FIGURE 1. (a) Classical Liebeskind-Srogl desulfitative C-C cross-
coupling of thioorganics. (b) C-C versus C-S cross-coupling of cyclic
thioamides with boronic acids.
In 2004, we discovered that the Liebeskind-Srogl cross-
coupling protocol can also be applied to cyclic thioureas/
thioamides using arylboronic acids as coupling partners.8,9
A
distinct advantage of using such thioamide substrates containing
a latent free thiol functionality is that by exchanging the anerobic
Pd(0)/Cu(I) catalytic system for an aerobic Cu(II) system, the
reactivity can easily be tuned from C-C toward C-S cross-
coupling (Figure 1b).9 In this paper, we describe the C-C cross-
coupling of substrates containing a thioamide motif with
alkenylboronic acids, organostannanes, and arylsiloxanes as
coupling partners.10
The Liebeskind-Srogl cross-coupling protocol has emerged
as valuable method for the highly selective construction of C-C
bonds from thioorganic building blocks and nucleophilic orga-
nometallic reagents.1-7 A key feature of these Pd-catalyzed
desulfitative C-C couplings under neutral conditions is the
(1) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260.
(2) (a) Liebeskind, L. S.; Srogl, J. Org. Lett. 2002, 4, 979. (b) Kusturin,
C. L.; Liebeskind, L. S.; Neumann, W. L. Org. Lett. 2002, 4, 983. (c) Savarin,
C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3, 91. (d) Yang, H.; Li, H.;
Wittenberg, R.; Egi, M.; Huang, W.; Liebeskind, L. S. J. Am. Chem. Soc. 2007,
129, 1132.
(3) (a) Kusturin, C.; Liebeskind, L. S.; Rahman, H.; Sample, K.; Schweitzer,
B.; Srogl, J.; Neumann, W. L. Org. Lett. 2003, 5, 4349. (b) Aguilar-Aguilar, A.;
Pen˜a-Cabrera, E. Org. Lett. 2007, 9, 4163.
(4) (a) Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 801. (b) Wittenberg,
R.; Srogl, J.; Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 3033. (c) Alphonse,
F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G. Org. Lett. 2003, 5,
803. (d) Leconte, N.; Pellegatti, L.; Tatiboue¨t, A.; Suzenet, F.; Rollin, P.;
Guillaumet, G. Synthesis 2007, 857. (e) Li, H.; Yang, H.; Liebeskind, L. S. Org.
Lett. 2008, 10, 4375.
As a starting point in our investigations, we examined the
C-C cross-coupling of model substrate pyridine-2(1H)-thione
(1a) with (E)-ꢀ-styrylboronic acid (2a).11 Applying our previ-
ously utilized 100 °C coupling conditions optimized for the use
of arylboronic acids,9 we quickly realized that an extension of
the reaction time from 2 to 3 h and an increase of the Pd catalyst
loading from 8 to 10 mol % was required in order to achieve
high product yields. The use of higher reaction temperatures
did not improve the efficiency of this transformation and led to
diminished product purity due to the formation of undesired
(5) Mehta, V. P.; Sharma, A.; Van der Eycken, E. AdV. Synth. Catal. 2008,
350, 2174.
(6) (a) Mehta, V. P.; Sharma, A.; Van der Eycken, E. Org. Lett. 2008, 10,
1147. (b) Shook, B. C.; Charkravarty, D.; Jackson, P. F. Tetrahedron Lett. 2009,
50, 1013.
(8) Lengar, A.; Kappe, C. O. Org. Lett. 2004, 6, 771.
(9) (a) Prokopcova´, H.; Kappe, C. O. AdV. Synth. Catal. 2007, 349, 448. (b)
Prokopcova´, H.; Kappe, C. O. J. Org. Chem. 2007, 72, 4440.
(10) The use of linear substrates in all of our examples (refs 8 and 9) did
not provide any of the desired coupling products.
(7) For a review on the Liebeskind-Srogl reaction, see: Prokopcova´, H.;
Kappe, C. O. Angew. Chem., Int. Ed. 2009, 48, 2276.
(11) For the use of alkenylboronic acids in the Liebeskind-Srogl reaction,
see: Yang, H.; Liebeskind, L. S. Org. Lett. 2007, 9, 2993.
5118 J. Org. Chem. 2009, 74, 5118–5121
10.1021/jo900848s CCC: $40.75  2009 American Chemical Society
Published on Web 05/22/2009

TABLE 1. Carbon-Carbon Cross-Coupling of Cyclic Thioamides
1a-h with (E)-ꢀ-Styrylboronic Acid 2aa
TABLE 2. Carbon-Carbon Cross-Coupling of Pyrimidine-
2-thiones 4a-c with Alkenylboronic Acids 2a-c
yield (%)a
single-mode/
multimode
5
DHPM 4
boronic acid 2
5a 4a (R1 ) R2 ) H, R3) Et)
5b 4a (R1 ) R2 ) H, R3 ) Et)
5c 4a (R1 ) R2 ) H, R3 ) Et)
5d 4b (R1 ) R3 ) Me, R2 ) H)
5e 4b (R1 ) R3 ) Me, R2 ) H)
5f 4b (R1 ) R3 ) Me, R2 ) H)
2a (R4 ) H, R5 ) Ph)
65
66
65
60
65
69
62
63
67
65
2b (R4 ) H, R5 ) tBu) 64
2c (R4 ) R5 ) Me)
55
68
2a (R4 ) H, R5 ) Ph)
2b (R4 ) H, R5 ) tBu) 71
2c (R4 ) R5 ) Me)
61
65
5g 4c (R1 ) H, R2 ) OH, R3 ) Et) 2a (R4 ) H, R5 ) Ph)
5h 4c (R1 ) H, R2 ) OH, R3 ) Et) 2b (R4 ) H, R5 ) tBu) 60
5i 4c (R1 ) H, R2 ) OH, R3 ) Et) 2c (R4 ) R5 ) Me)
63
a Yields of pure product after column chromatography.
strategy for the generation of a small set of nine potentially
biologically active 2-alkenyl-1,4-dihydropyrimidines 5a-i (Table
2). The corresponding 2-aryl-substituted heterocycles have been
found to be highly potent nonnucleosidic inhibitors of hepatits
B virus replication that have in vitro and in vivo antiviral
activity,8,13 whereas the biological activity of the 2-alkenyl
analogues has not been explored yet. The required functionalized
cyclic thioureas of type 4a-c (DHPMs) can be rapidly
synthesized by microwave-assisted three-component condensa-
tion of the appropriate aromatic aldehydes, ꢀ-keto esters, and
thiourea (Biginelli reaction).14 Cross-coupling of a set of three
DHPMs 4a-c with three commercially available alkenylboronic
acids 2a-c applying slightly modified reaction conditions
provided a small collection of nine 2-alkenyl-1,4-dihydropyri-
midines 5a-i.15 The highest isolated yields (55-71%) were
obtained by a single microwave irradiation cycle at 100 °C for
60 min, applying 10 mol % of Pd(PPh3)4 as a catalyst (Table
2). In addition to the traditional automated sequential single-
mode microwave processing technology,14 which here requires
an overall microwave processing time of almost 10 h, we have
also synthesized the small library of nine dihydropyrimidines
5a-i in a single microwave irradiation experiment (60 min)
utilizing a recently developed reactor platform for use in
conjunction with multimode microwave instrumentation.16 In
this high-throughput experimentation platform, parallel micro-
wave chemistry is performed in sealed HPLC/GC vials serving
as reaction vessels. The system consists of a strongly microwave-
absorbing silicon carbide plate with cylindrical wells in which
standard HPLC/GC autosampler vials are fitted.16 Gratifyingly,
the isolated product yields comparing the two methods were
very similar (Table 2), validating the concept of parallel
microwave synthesis in the silicon carbide reactor. In addition,
a For a general procedure, see the Experimental Section. b Yields of
pure product after column chromatography.
byproducts. Ultimately, the reaction proceeded heating 1 equiv
of pyridine-2(1H)-thione (1a), 1.5 equiv of (E)-ꢀ-styryl boronic
acid (2a), 3 equiv of Cu(I)-thiophene-2-carboxylate (CuTC),
and 5 mol % of Pd(PPh3)4 in THF at 100 °C for 90 min applying
a sealed vessel microwave reactor (argon atmosphere).12 In order
to further improve the product yield, an additional quantity of
Pd(PPh3)4 (5 mol %) was added after the first heating cycle.
The reaction mixture was subsequently heated at 100 °C for an
additional 90 min. This two-step procedure consistently led to
a 70% isolated product yield of coupling product 3a after
purification by flash chromatography.
With the optimized conditions in hand, we explored the scope
and limitations of this C-C cross-coupling reaction with a set
of eight cyclic thioamides/thioureas already used in our previous
study involving arylboronic acids.9 We were pleased to find
that successful cross-coupling with (E)-ꢀ-styrylboronic acid (2a)
was observed with aromatic and nonaromatic, six- and five-
membered heterocycles containing thioamide fragments. As
shown in Table 1, moderate to high product yields were achieved
using our standard reaction conditions. The only exception
proved to be 1,3-dihydroimidazole-2(1H)-thione (entry 7) where
only traces of the anticipated coupling product could be isolated.
In general, the reactivity in this coupling observed for styryl-
boronic acid 2a was very similar to that found for phenylboronic
acid.9
Having demonstrated that a variety of different simple cyclic
thioamide scaffolds 1 can be useful substrates for the
Liebeskind-Srogl-type desulfitative C-C coupling with (E)-
ꢀ-styrylboronic acid (2a) (Table 1), we next focused our
attention on the use of a more complex heterocyclic core and
on the scope of the alkenylboronic acid diversity. In this context,
we have employed the thioamide-boronic acid cross-coupling
(13) Deres, K.; Schro¨der, C. H.; Paessens, A.; Goldmann, S.; Hacker, H. J.;
Weber, O.; Kra¨mer, T.; Niewoehner, U.; Pleiss, U.; Stoltefuss, J.; Graef, E.;
Koletzki, D.; Masantschek, R. N. A.; Reimann, A.; Jaeger, R.; Groꢀ, R.;
Beckermann, B.; Schlemmer, K.-H.; Haebich, D.; Ru¨bsamen-Waigmann, H.
Science 2003, 299, 893.
(14) Stadler, A.; Kappe, C. O. J. Comb. Chem. 2001, 3, 624.
(15) Attempted cross-coupling of thioamides with alkylboronic acids (cy-
clohexylboronic acid and 2-phenyl-1-ethylboronic acid) or boronic esters
(phenylboronic acid pinacol- and propane diol ester) was unsuccessful.
(16) (a) Damm, M.; Kappe, C. O. J. Comb. Chem. 2009, 11, 460.
(12) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250.
J. Org. Chem. Vol. 74, No. 14, 2009 5119

TABLE 3. Carbon-Carbon Cross-Coupling of Pyrimidine-2(1H)-
thione 1b with Tributylorganostannanes 6a-d and
Trimethoxyphenylsilane 7
Finally, we have also attempted to utilize trimethoxyphenyl-
silane as a nucleophilic coupling partner in this transformation.
Organosilicon derivatives are becoming increasingly popular as
environmentally safe and nontoxic reaction partners in cross-
coupling chemistry (Hiyama coupling).18 Stimulated by a recent
report by Van der Eycken and co-workers describing the Pd-
catalyzed, Cu(I)-mediated desulfitative cross-coupling of thio-
ethers and thioesters with arylsiloxanes,5 cross-coupling between
pyrimidine-2(1H)-thione (1b) and trimethoxyphenylsilane was
performed employing 1 equiv of CuI, 2 equiv of TBAF, and 5
mol % of Pd(PPh3)4 in THF as solvent.5 In our hands, a 60%
yield of cross-coupling product 8a was obtained using micro-
wave heating at 100 °C for 40 min followed by an extractive
workup and silica gel chromatography.
In conclusion, we have shown that thioamide fragments
embedded in heterocyclic ring systems can be cross-coupled
under comparatively mild and nonbasic conditions with a variety
of alkenylboronic acids, vinyl- and (het)arylstannanes, and
arylsiloxanes. Employing modified Liebeskind-Srogl Pd(0)-
catalyzed, Cu(I)-mediated conditions, desulfitative C-C cross-
coupling with concomitant extrusion of sulfur occurs in
moderate to good overall yields.
entry
organometallic reagent
yielda (%)
1
2
3
4
5
6a (R ) Ph)
80 (8a)
72 (8b)
69 (8c)
63 (8d)
60 (8a)
6b (R ) 2-pyridyl)
6c (R ) 2-furyl)
6d (R ) vinyl)
7 (R ) Ph)
a Yields of pure product after column chromatography.
the effectiveness of magnetic stirring of the strongly heteroge-
neous reaction mixture (3 equiv of CuTC) and the possibility
of performing chemistry under inert conditions (argon) has been
demonstrated.
As an alternative to the use of boronic acids as nucleophilic
organometallic reagents, Liebeskind and others have reported
successful cross-couplings of a variety of thioorganic substrates
with organostannane reagents, in particular with trin-butylor-
ganostannanes (Figure 1a).4 The method relies on the same base-
free Pd(0)-catalyzed, Cu(I)-mediated methodology applied with
boronic acids.7 The variant with tin reagents is particularly
attractive in cases where stannanes are more accessible than
boronic acids, or in such instances where specific boronic acids
(for example heteroarylboronic acids with an R-heteroatom) are
problematic substrates.4,7 For Liebeskind-Srogl-type C-C
couplings involving thioamide building blocks containing a
latent free thiol functionality we are aware of only one recent
report by the group of Tatiboue¨t, where a specific set of 1,3-
oxazolidine- and 1,3-oxazoline-2-thiones were demonstrated to
undergo Pd(0)-catalyzed cross-coupling with 2-(tri-n-butylstan-
nyl)thiophene in the presence of a Cu(I) salt.17
In order to explore the feasibility of Liebeskind-Srogl-type
C-C couplings of cyclic thioamides with organostannanes in
more detail, we have investigated the cross-coupling of pyri-
midine-2(1H)-thione (1b) with four different tri-n-butylorga-
nostannane reagents (6a-d). In our hands, the Stille-type
couplings proved to be somewhat easier to perform compared
to the closely related Suzuki-type couplings involving boronic
acids.9 Therefore, 5 mol % of Pd at 100 °C reaction temperature
for 60 min (2.2 equiv of stannane) was sufficient to provide
moderate to high isolated product yields of the corresponding
2-functionalized pyrimidines 8a-d, essentially using otherwise
unaltered reaction conditions (Table 3). Longer reaction times
resulted in diminished yields of the desired coupling products
and unclean reaction profiles (homocoupling of stannane
reagents was also observed). The initial optimization experi-
ments were performed with (tri-n-butyl)phenylstannane (6a),
but good yields were subsequently also obtained with 2-(tri-n-
butylstannyl)pyridine (6b) and 2-(tri-n-butylstannyl)furan (6c).
Importantly, tri-n-butyl(vinyl)stannane (6d) provided a 63%
yield of 2-vinylpyrimidine, which was otherwise not accessible
via the boronic acid route.
Experimental Section
General Procedure for the Carbon-Carbon Cross-Coupling
of Thioamides with (E)-ꢀ-Styrylboronic Acid 2a (Table 1). A
dry microwave process vial was charged with the corresponding
thioamide 1a-h (0.5 mmol), (E)-ꢀ-styrylboronic acid 2a (111 mg,
0.75 mmol), CuTC (300 mg, 1.5 mmol), and Pd(PPh3)4 (28 mg,
0.024 mmol, 5 mol %). The reaction vessel was sealed and flushed
with Ar. Through the septum anhydrous and degassed THF (2.8
mL) was added. The mixture was subsequently heated in a
microwave reactor at 100 °C for 90 min. After this period, an
additional amount of Pd catalyst (28 mg, 0.024 mmol, 5 mol %)
was added, and the reaction mixture was again heated at 100 °C
for 90 min. After cooling, the solvent was evaporated, and EtOAc/
CHCl3 (3:1) (250 mL) was added. The crude reaction mixture was
subsequently washed with 25% aqueous ammonia (3 × 80 mL).
The aqueous ammonium layer was reextracted again with EtOAc/
CHCl3 (3:1) (3 × 80 mL). The combined organic phase was dried
over MgSO4 and the residue after evaporation purified by flash
chromatography. Characterization data for products 3a-h are given
in the Supporting Information.
General Procedure for Carbon-Carbon Cross-Coupling
of Dihydropyrimidines (4a-c) with Alkenylboronic Acids
2a-c (Table 2). (A) Single-Mode Conditions. A dry microwave
process vial was charged with the corresponding dihydropyrimidine
(DHPM) 4a-c (0.21 mmol), the corresponding alkenylboronic acid
2a-c (0.315 mmol), CuTC (120 mg, 0.63 mmol), and Pd(PPh3)4
(24 mg, 10 mol %). The reaction vessel was sealed and flushed
with Ar. Through the septum anhydrous and degassed THF (1.5
mL) was added. The mixture was stirred for 5 min and then
subsequently heated in a microwave reactor at 100 °C for 60 min.
After cooling, the solvent was evaporated, and EtOAc/CHCl3 (3:
1) (120 mL) was added. The crude reaction mixture was subse-
quently washed with 25% aqueous ammonia (3 × 40 mL). The
aqueous ammonium layer was reextracted again with EtOAc/CHCl3
(3:1) (3 × 40 mL). The combined organic phase was dried over
MgSO4, and the residue after evaporation was purified by flash
chromatography on silica gel (acetone/petroleum ether 1:3) to
provide the desired 2-substituted dihydropyrimidines 5a-i as pale
1
yellow oils. Data for 5a: H NMR (360 MHz, DMSO-d6) δ 9.21
(brs, 1H), δ 7.56- 7.52 (m, 3H), 7.41-7.26 (m, 8H), 6.63 (d, J )
(17) (a) Silva, S.; Tardy, S.; Routier, S.; Suzenet, F.; Tatiboue¨t, A.; Rauter,
A. P.; Rollin, P. Tetrahedron Lett. 2008, 49, 5583. (b) For related cross-couplings
using terminal alkynes, see: Silva, S.; Sylla, B.; Suzenet, F.; Tatiboue¨t, A.; Rauter,
A. P.; Rollin, P. Org. Lett. 2008, 10, 853.
(18) (a) Hiyama, T. J. Organomet. Chem. 2002, 653, 58. (b) Denmark, S. E.
Aldrichim. Acta 2003, 36, 75.
5120 J. Org. Chem. Vol. 74, No. 14, 2009

16.2 Hz, 1H), 5.52 (s, 1H), 4.00 (q, J ) 6.8 Hz, 2H), 2.33 (s, 3H),
1.11 (t, J ) 6.84 Hz, 3H); 13C NMR (90 MHz, DMSO-d6) δ 166.7,
146.5, 135.7, 129.7, 129.4 (3C), 128.7 (3C), 127.7 (3C), 127.4,
127.2 (3), 122.7 (2C), 59.5, 14.6 (2C); MS (pos APCI) m/z 346;
HRMS (APCI+) m/z calcd for C22H22N2O2 [M + H]+ 347.1754,
found 347.1753.
ammonium layer was reextracted again with CHCl3 (3 × 40 mL).
The combined organic phase was dried over MgSO4 and the residue
after evaporation purified by flash chromatography to yield
2-substituted pyrimidines 8a-d (Table 3). Characterization data
for products 8a-d are given in the Supporting Information.
General Procedure for the Carbon-Carbon Cross-Coupling
of Thioamide 1b with Trimethoxyphenylsilane 7 (Table 3). A
dry microwave process vial was charged with pyrimidine-2(1H)-
thione 1b (39.3 mg, 0.35 mmol), Pd(PPh3)4 (20 mg, 0.017 mmol,
5 mol %), and CuI (67 mg, 0.35 mmol). The reaction vessel was
sealed and flushed with Ar. Through the septum anhydrous and
degassed THF (1 mL) was added, and the mixture was stirred for
2 min, after which the siloxane reagent (170 µL, 0.42 mmol, 1.2
equiv) followed by tetrabutylammonium fluoride (TBAF) (183 mg,
0.7 mmol dissolved in 1 mL of THF) was added in one shot by
syringe. The reaction mixture was subsequently heated in a
microwave reactor for 40 min at 100 °C. After cooling, the reaction
mixture was poured into water and extracted with dichloromethane
(2 × 75 mL). The combined organic layers were washed with water
and dried over MgSO4. The solvent was evaporated, and the residue
was purified by flash chromatography on silica gel (EtOAc/
cyclohexane 1:7) to yield 32.8 mg (60%) of 2-phenylpyrimidine
8a.
(B) Multimode Silicon Carbide Plate Conditions. The indi-
vidual dry HPLC/GC vials containing a small stir bar fitted inside
the SiC plate were flushed with Ar and charged with the corre-
sponding dihydropyrimidine (DHPM) 4a-c (0.21 mmol), the
corresponding alkenylboronic acid 2a-c (0.315 mmol), CuTC (120
mg, 0.63 mmol), and Pd(PPh3)4 (24 mg, 10 mol %). The reaction
vessel was sealed with an aluminum crimp top employing PTFE-
coated silicon septa and flushed with Ar. Through the septum
anhydrous and degassed THF (1.0 mL) was added and the resulting
mixture stirred for 5 min. For the assembly, the SiC plate was
covered with an aluminum top plate and was fixed finger tight with
the six hex bolts.16 The whole assembly was placed on a dedicated
plate rotor inside the microwave reactor and irradiated for 60 min
at 100 °C (ramp time of 5 min and hold times 55 min) with
maximum stirring. After cooling, all individual vials were treated
as described above. Characterization data for products 5b-i are
given in the Supporting Information.
General Procedure for the Carbon-Carbon Cross-Coupling
of Thioamide 1b with Organostannanes 6a-d (Table 3). A dry
microwave process vial was charged with pyrimidine-2(1H)-thione
1b (39.3 mg, 0.35 mmol), CuTC (200 mg, 1.05 mmol), and
Pd(PPh3)4 (20 mg, 0.017 mmol, 5 mol %). The reaction vessel was
sealed and flushed with Ar. Through the septum anhydrous and
degassed THF (2 mL) was added, followed by the corresponding
stannane 6a-d (2.2 equiv, 0.77 mmol) after 5 min of stirring at
room temperature. After an additional stirring period of 5 min, the
mixture was subsequently heated in a microwave reactor at 100
°C for 60 min. After cooling, the solvent was evaporated, and CHCl3
(120 mL) was added. The crude reaction mixture was subsequently
washed with 25% aqueous ammonia (3 × 40 mL). The aqueous
Acknowledgment. N.A. and J.H. thank the Higher Education
Commission of Pakistan for Ph.D. scholarships. We thank
Marketa Bernaskova and Markus Damm for their experimental
help and Synthonix for the donation of reagents.
Supporting Information Available: Analytical data and
copies of 1H and 13C NMR spectra of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO900848S
J. Org. Chem. Vol. 74, No. 14, 2009 5121