Palladium-catalyzed carbonylation of aryl bromides with n-substituted cyanamides

Article abstract of DOI:10.1055/s-0033-1341200

The palladium(0)-catalyzed three-component coupling reaction of aryl bromides, carbon monoxide, and N-alkyl cyanamides has been developed employing a two-chamber system with ex situ generation of carbon monoxide from a silacarboxylic acid. The reactions proceeded well and were complete with a reaction time of only five hours leading to the corresponding N-alkyl cyanamides in good yields. The methodology was further extended to ¹³C isotope labeling of the carbonyl group through the use of a ¹³CO produced from the corresponding ¹³C-labeled version of the silacarboxylic acid. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341200

LETTER
▌1241
letter
Palladium-Catalyzed Carbonylation of Aryl Bromides with N-Substituted
Cyanamides
Carbonylation of Aryl Bromides with N-Substituted Cyanamides
Zhong Lian,a Stig D. Friis,a Anders T. Lindhardt,*b Troels Skrydstrup*a
a
Center for Insoluble Protein Structures, Interdisciplinary Nanoscience Center, Department of Chemistry, Aarhus University, Gustav Wieds Vej
14, 8000 Aarhus C, Denmark
b
Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N, Denmark
Fax +4541893001; E-mail: lindhardt@eng.au.dk; E-mail: ts@chem.au.dk
Received: 20.02.2014; Accepted after revision: 19.03.2014
larger functional diversity, N-alkylation blocks deproton-
Abstract: The palladium(0)-catalyzed three-component coupling
ation of the base-labile cyanamide functionality. Correct-
reaction of aryl bromides, carbon monoxide, and N-alkyl cyan-
ly chosen, this would in turn allow the N-alkyl substituent
to act as a cyanamide-protecting group.
amides has been developed employing a two-chamber system with
ex situ generation of carbon monoxide from a silacarboxylic acid.
The reactions proceeded well and were complete with a reaction
time of only five hours leading to the corresponding N-alkyl cyana-
O
C
O
C
O
C
mides in good yields. The methodology was further extended to 13
C
CN
CN
CN
isotope labeling of the carbonyl group through the use of a 13CO
produced from the corresponding 13C-labeled version of the sila-
carboxylic acid.
N
Ph
N
A
N
H
H
H
O
C
O
C
CN
CN
Key words: N-alkyl cyanamides, transition-metal catalysis, isotope
labeling, aminocarbonylation, multicomponent reaction, palladium
Ph
N
O
N
H
H
A1DH inhibitors
MeO
Cyanamides occupy a special place in organic chemistry
as they are present attractive N–C–N building blocks, the
reactivity of which can be further enhanced by installing
an acyl group next to the amine nitrogen.1 Cyanamides are
widely used in the synthesis of amidines, quinazolinones,
and some N-acyl cyclic guanidines.2 In addition, there is
an increased attention to cyanamides because of their ap-
plications as potent inhibitors of aldehyde dehydrogenase
(A1DH)3a–c and their occurrence in biologically interest-
ing molecules (Figure 1).3d,e As a consequence of this,
there is a continued interest in the development of new
methodologies for their synthesis.
N
O
O
Ph
H
CN
C
N
N
N
H
O
O
BocHN
hepatitis C virus NS3 protease inhibitor
Figure 1 N-Acyl cyanamides utilized as A1DH or hepatitis C virus
NS3 inhibitors
Since the first example reported by Heck and co-workers
in 1974,4 the three-component carbonylative coupling of
an aryl halide, carbon monoxide, and a nucleophile has
been expanded to the synthesis of a series of aromatic acyl
derivatives including ketones,5 esters,6 amides,7 alde-
hydes,8 anhydrides,9 acid chlorides,10 and so on.11 Despite
the considerable attention for the application of nitrogen
nucleophiles in carbonylative reactions, there are no ex-
amples for the employment of N-substituted cyanamides.
In 2012, the group of Louie developed a palladium(0)-cat-
alyzed cross-coupling of N-alkyl cyanamides with aryl
halides.12 And just recently, while our work was in prog-
ress, Larhed and co-workers disclosed that the parent cy-
anamide is also a competent nucleophile for the
carbonylative coupling leading to synthesis of nonsubsti-
tuted N-acyl cyanamides.13 Besides providing access to a
Over the last three years, our group has developed and ex-
plored a connected two-chamber system for a number of
palladium-catalyzed carbonylative reactions14 of aryl ha-
lides and triflates using ex situ generation of CO gas from
solid CO precursors, such as COgen and SilaCOgen.15
During this work we became interested in applying alkyl-
ated cyanamides as nucleophiles in carbonylation reac-
tions with stoichiometric CO. In this manuscript we wish
to report on the development of the multicomponent reac-
tion for performing a palladium-catalyzed carbonylative
reaction providing direct access to N-substituted acyl cy-
anamides from aryl bromides (Scheme 1). The developed
method tolerates different N-alkylated cyanamides and
performs with the inherent high functional-group toler-
ance of palladium catalysis. Finally, the method was ex-
trapolated to include 13C labeling using 13CO obtained by
simple exchange of the CO precurser for the 13C-labeled
silacarboxylic acid derivative in the two-chamber system.
SYNLETT 2014, 25, 1241–1245
Advanced online publication: 11.04.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1341200; Art ID: ST-2014-D0147-L
© Georg Thieme Verlag Stuttgart · New York

1242
Z. Lian et al.
LETTER
Table 1 Selected Entries for the Optimization of the Carbonylative
Coupling of 2-Bromonaphthalene (1a) with N-Benzyl Cyanamide
(2a)a
Br
CO (2.5 equiv)
O
C
[Pd(cinnamyl)Cl]2 (5 mol%)
ligand (5–10 mol%)
base(1.5 equiv)
CN
1a
N
+
Bn
solvent (0.1 M)
90 °C, 5 h
Bn
CN
N
H
3a
2a
Scheme 1 Pd(0)-catalyzed carbonylative coupling of N-substituted
cyanamides with aryl bromides in a two-chamber reactor
Entry
Ligand
Ph3P
Base
Solvent
Yield (%)b
The initial investigation focused on the reaction of 2-bro-
monaphthalene (1a, 1.0 equiv) and N-benzyl cyanamide
(2a, 1.2 equiv) in the presence of [Pd(cinnamyl)Cl]2 (5
mol%), Ph3P (10 mol%), K3PO4 (1.5 equiv), and CO (2.5
equiv) generated from methyldiphenylsilacarboxylic acid
(SilaCOgen) in butyronitrile (0.1 M) as shown in Table
1.16 We found that the desired product 3a was obtained in
a 33% yield after five hours at 90 °C (Table 1, entry 1).
1
2
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
Cy2NMe
DIPEA
K3PO4
K3PO4
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
butyronitrile
dioxane
33
L1
DPPP
L2
L3
L1
L1
L1
L1
L1
L1
L1
83 (81)
75
3
4
11
5
35
6c
7d
8
37
Applying the more electron-rich and sterically demanding
monodentate phosphine ligand, CataCXium A (L1, Fig-
ure 2), improved the yield of 3a significantly to 83% (Ta-
ble 1, entry 2). On the other hand, employing bidentate
phosphine ligands such as dppp, DPEPhos (L2), and
XantPhos (L3) led to a reduced efficiency of the coupling
reaction (Table 1, entries 3–5). Varying the amount of
CataCXium A did not improve the yield of 3a (Table 1,
entries 6 and 7), while exchange of K3PO4 as the base for
K2CO3, Cy2NMe, or DIPEA only led to a slight reduction
of the coupling yield (Table 1, entries 8–10). Replacement
of the solvent butyronitrile with toluene or dioxane also
led to a deterioration of the coupling yield to 3a (Table 1,
entries 11 and 12).
80
74
9
77
10
11
12
74
65
toluene
42
a Chamber 1: ArBr (0.20 mmol), N-benzyl cyanamide (0.24 mmol),
[Pd(cinnamyl)Cl]2 (5 mol%), ligands (monodentate ligands 10 mol%,
bidentate ligands 5 mol%), K3PO4 (1.5 equiv), and solvent (2.0 mL);
chamber 2: methyldiphenylsilacarboxylic acid (0.50 mmol), KF (0.50
mmol), and butyronitrile (2.0 mL).
b Yield was determined by 1H NMR spectroscopic data of crude prod-
ucts using 1,3,5-trimethoxybenzene as an internal standard. Isolated
yield is given in parenthesis.
PPh2
PPh2
PPh2
PPh2
Ada
Bu
O
c Conditions: 5 mol% CataCXium A (L1) was employed.
d Conditions: 20 mol% CataCXium A (L1) was employed.
O
P
Ada
meta position did not have a significant influence on the
coupling efficiency. It is interesting to note that the thioes-
ter containing product 3n could be prepared although with
some deterioration of the yield most likely due to compet-
ing amination at the thioester bond. For successful cou-
pling with the more electron-deficient aryl bromides
containing a 4-nitro or a 4-cyano substituent as in 3q and
3r, it was necessary to reduce the reaction temperature to
80 °C, as well as increasing the loading of the catalytic
system in order to promote a reasonable conversion.
CataCXium A - L1
DPEPhos - L2
XantPhos - L3
Figure 2 Ligands used
Having identified optimal reaction conditions for the
preparation of an N-substituted acyl cyanamide, we next
set out to examine the substrate scope of this palladium-
catalyzed carbonylative reaction with various aryl bro-
mides (Scheme 2). All reactions proceeded smoothly with
N-benzyl cyanamide and were complete in five hours gen-
erating the corresponding acyl cyanamides in yields rang-
ing from 42–86%. Both aryl bromides with electron-
withdrawing and electron-donating substituents proved to
be compatible with the coupling conditions. Substrates
displaying an ortho substituent proved reactive, albeit
providing reduced yields as exemplified with acyl cyana-
mide 3g. On the other hand, substituents in the para or
Next, a few other N-alkyl-substituted cyanamides were
evaluated as coupling partners with 2-naphthyl bromide
(1a, Scheme 3). Not too surprisingly, the alkyl substituent
on the cyanamide did indeed influence the reactivity of
this particular nucleophile, however, the three examples
3s–u could all be secured in acceptable yields after col-
umn chromatography.
Synlett 2014, 25, 1241–1245
© Georg Thieme Verlag Stuttgart · New York

LETTER
Carbonylation of Aryl Bromides with N-Substituted Cyanamides
1243
CO (2.5 equiv)
[Pd(cinnamyl)Cl]2 (5 mol%)
CataCXium A (10 mol%)
O
C
CN
Bn
CN
N
Br
+
N
H
R
R
Bn
K3PO4 (1.5 equiv)
butyronitrile (0.1 M)
90 °C, 5 h
1
2
3
O
C
O
C
O
C
O
CN
CN
CN
C
CN
N
N
N
N
Bn
Bn
Bn
Bn
MeO
3b, 83%
3c, 86%
3d, 68%
3a, 81%
O
C
O
C
O
C
O
C
CN
CN
CN
N
N
N
CN
N
Bn
Bn
Bn
Ph
Bn
Ph
3g, 43%
3e, 79%
3f, 61%
3h, 87%
O
O
O
C
O
C
O
C
C
CN
CN
CN
CN
N
N
N
N
Bn
Ph
Bn
Bn
Bn
MeO
EtO2C
O
O
3j, 83%a
3i, 86%
3k, 54%
3l, 77%
O
C
O
O
O
O
C
CN
C
N
CN
t-BuO2C
C
CN
CN
O
N
N
N
N
Bn
Bn
Bn
Bn
O
O
N
SCy
3p, 78%
3o, 76%
3m, 88%
3n, 42%
O
O
C
CN
C
CN
N
Bn
Bn
O2N
NC
3q, 45%a,b
3r, 61%a,b
Scheme 2 Scope of the Pd(0)-catalyzed carbonylative coupling of N-benzyl cyanamide with aryl bromides. (a) 80 °C. (b) [Pd(cinnamyl)Cl2]
(7.5 mol%), CataCXium A (15 mol%)
Finally, we examined the possibility for 13C isotope label- 80% yield (Scheme 4).16 Repeating the sequence in the
ing applying 13CO generated from 13C-labeled methyldi- coupling with 4-bromobiphenyl afforded 13C-3e in the
phenylsilacarboxylic acid (Scheme 1). As illustrated in yield of 77%, whereas with the n-hexyl-substituted cyan-
Scheme 4, starting from 2-bromonaphthalene, the corre- amide 13C-3t was generated in a yield of 62%.
sponding N-acyl cyanamide 13C-3a was obtained in an
CO (2.5 equiv)
O
[Pd(cinnamyl)Cl]2 (5 mol%)
Br
C
CN
R2
CN
CataCXium A (10 mol%)
N
R2
N
H
+
K3PO4 (1.5 equiv)
butyronitrile (0.1 M)
90 °C, 5 h
1a
2
3
O
O
C
O
C
CN
C
CN
CN
N
N
N
Pr
Hex
Cy
3s, 68%
3t, 64%
3u, 56%
Scheme 3 Examination of other N-alkyl cyanamides in the Pd(0)-catalyzed carbonylative coupling with aryl bromides
© Georg Thieme Verlag Stuttgart · New York Synlett 2014, 25, 1241–1245

1244
Z. Lian et al.
LETTER
Ph
Ph Si13COOH
Me
KF
butyronitrile
O
13C
[Pd(cinnamyl)Cl]2 (5 mol%)
CataCXium A (10 mol%)
Br
CN
R2
CN
N
R2
13CO
R1
R1
+
+
N
H
K3PO4 (1.5 equiv)
butyronitrile (0.1 M)
90 °C, 5 h
3
O
O
O
13C
CN
13C
CN
13C
CN
N
N
N
Bn
13C-3a, 80%
Bn
n-Hex
13C-3t, 62%
Ph
13C-3e, 77%
Scheme 4 Synthesis of various 13C-labeled N-acyl cyanamides
1870. (c) Kwon, C.-H.; Nagasawa, H. T.; De Master, E. G.;
Shirota, N. F. J. Med. Chem. 1986, 29, 1922. (d) Ronn, R.;
Gossas, T.; Sabnis, Y. A.; Daoud, H.; Akerblom, E.;
Danielson, U. H.; Sandstrom, A. Bioorg. Med. Chem. 2007,
15, 4057. (e) Larraufie, M.-H.; Maestri, G.; Malacria, M.;
Ollivier, C.; Fensterbank, L.; Lacôte, E. Synthesis 2012, 44,
1279.
In summary, a protocol for the direct transformation of a
variety of aryl bromides into N-acyl cyanamides via a pal-
ladium-catalyzed carbonylative protocol has been devel-
oped using our previously described two-chamber system
with a slight excess of ex situ generated carbon monoxide.
Both electron-deficient and electron-rich aryl bromides
could be transformed into the desired product, and fur-
thermore, the process tolerates a wide variety of function-
al groups while an example with an ortho substituent
provide slightly reduced yields. Lastly, isotope labeling
with 13CO proved the corresponding 13C-labeled N-acyl
cyanamides.
(4) (a) Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem.
1974, 39, 3318. (b) Schoenberg, A.; Heck, R. F. J. Org.
Chem. 1974, 39, 3327.
(5) (a) Ahmed, M. S. M.; Mori, A. Org. Lett. 2003, 5, 3057.
(b) Ishiyama, T.; Kizaki, H.; Hayashi, T.; Suzuki, A.;
Miyaura, N. J. Org. Chem. 1998, 63, 4726.
(6) (a) Albaneze, J.; Bazaral, C.; Leavey, T.; Dormer, P. G.;
Murry, J. A. Org. Lett. 2004, 6, 2097. (b) Munday, R. H.;
Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008,
130, 2754. (c) Hu, Y.; Liu, J.; Lu, Z.; Luo, X.; Zhang, H.;
Lan, Y.; Lei, A. J. Am. Chem. Soc. 2010, 132, 3153.
(d) Lapidus, A. L.; Eliseev, O. L.; Bondarenko, T. N.; Sizan,
O. E.; Ostapenko, A. G.; Beletskaya, I. P. Synthesis 2002,
317.
(7) (a) Kumar, K.; Zapf, A.; Michalik, D.; Tillack, A.; Heinrich,
T.; Arlt, M.; Beller, M. Org. Lett. 2004, 6, 7. (b) Liang, D.;
Hu, Z.; Peng, J.; Huang, J.; Zhu, Q. Chem. Commun. 2013,
173. (c) Xie, P.; Xia, C.; Huang, H. Org. Lett. 2013, 15,
3370. (d) Fang, W.; Deng, Q.; Xu, M.; Tu, T. Org. Lett.
2013, 15, 3678. (e) Iizuka, M.; Kondo, Y. Chem. Commun.
2006, 16, 1739. (f) Nielsen, D. U.; Taaning, R.; Lindhardt,
A.; Gøgsig, T. M.; Skrydstrup, T. Org. Lett. 2011, 13, 4454.
(8) Klaus, S.; Neumann, H.; Zapf, A.; Almena, J.; Riermeier, T.;
Groâ, P.; Sarich, M.; Krahnert, W.-R.; Rossen, K.; Beller,
M. Angew. Chem. Int. Ed. 2006, 45, 154.
(9) Pri-Bar, I.; Alper, H. J. Org. Chem. 1989, 54, 36.
(10) Quesnel, J. S.; Arndtsen, B. A. J. Am. Chem. Soc. 2013, 135,
16841.
(11) For recent carbonylative reaction review, see: (a) Wu, X. F.;
Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1. (b) Wu,
X. F.; Neumann, H.; Beller, M. Chem. Soc. Rev. 2011, 40,
4986. (c) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111,
2177. (d) Grigg, R.; Mutton, S. P. Tetrahedron 2010, 66,
5515. (e) Brennfuhrer, A. H.; Neumann, H.; Beller, M.
Angew. Chem. Int. Ed. 2009, 48, 4114.
Acknowledgment
We are deeply appreciative of generous financial support from the
Danish National Research Foundation (grant no. DNRF59), the Vil-
lum Foundation, the Danish Council for Independent Research:
Technology and Production Sciences, the Lundbeck Foundation,
the Carlsberg Foundation, and Aarhus University for generous fi-
nancial support of this work. Furthermore, we thank the Chinese
Scholarship Council for a grant to Z.L.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett. Included are
general methods, an experimental section and copies of 1H and 13
C
NMR spectra for all products. SunogIpintfrmiratouSpIg
n
pifom
i
References and Notes
(1) Larraufie, M.-H.; Maestri, G.; Malacria, M.; Ollivier, C.;
Fensterbank, L.; Lacôte, E. Synthesis 2012, 44, 1279.
(2) (a) Nekrasov, D. D. Russ. J. Org. Chem. 2004, 40, 1387.
(b) Nekrasov, D. D. Chem. Heterocycl. Compd. 2004, 40,
1107. (c) Maestri, G.; Larraufie, M. H.; Ollivier, C.;
Malacria, M.; Fensterbank, L.; Lacôte, E. Org. Lett. 2012,
14, 5538. (d) Larraufie, M.-H.; Courillon, C.; Ollivier, C.;
Lacôte, E.; Malacria, M.; Fensterbank, L. J. Am. Chem. Soc.
2010, 132, 4381. (e) Hu, Z.; Li, S.-d.; Hong, P.-Z. ARKICOV
2010, (ix), 171.
(12) Stolley, R. M.; Guo, W.-X.; Louie, J. Org. Lett. 2012, 14,
322.
(13) Mane, R. S.; Nordeman, P.; Odell, L. R.; Larhed, M.
Tetrahedron Lett. 2013, 54, 6912.
(3) (a) Guay, D.; Beaulieu, C.; Percival, M. D. Curr. Top. Med.
Chem. 2010, 10, 708. (b) Shirota, F. N.; Stevens, J. M.;
DeMaster, E. G.; Nagasawa, H. T. J. Med. Chem. 1997, 40,
Synlett 2014, 25, 1241–1245
© Georg Thieme Verlag Stuttgart · New York

LETTER
Carbonylation of Aryl Bromides with N-Substituted Cyanamides
1245
(14) (a) Hermange, P.; Lindhardt, A.; Taaning, R.; Bjerglund, K.;
Lupp, D.; Skrydstrup, T. J. Am. Chem. Soc. 2011, 133, 6061.
(b) Hermange, P.; Gøgsig, T.; Lindhardt, A.; Taaning, R.;
Skrydstrup, T. Org. Lett. 2011, 13, 2444. (c) Xin, Z.;
Gøgsig, T.; Lindhardt, A.; Skrydstrup, T. Org. Lett. 2012,
14, 284. (d) Nielsen, D. U.; Neumann, K.; Taaning, R.;
Lindhardt, A.; Modvig, A.; Skrydstrup, T. J. Org. Chem.
2012, 77, 6155. (e) Bjerglund, K.; Lindhardt, A.;
Skrydstrup, T. J. Org. Chem. 2012, 77, 3793. (f) Burhardt,
M.; Taaning, R.; Skrydstrup, T. Org. Lett. 2013, 15, 948.
(15) (a) Friis, S.; Taaning, R.; Lindhardt, A.; Skrydstrup, T.
J. Am. Chem. Soc. 2011, 133, 18114. (b) Friis, S.; Andersen,
T. L.; Skrydstrup, T. Org. Lett. 2013, 15, 1378.
benzyl cyanamide (31 mg, 0.24 mmol) in butyronitrile (1.0
mL) was added to chamber 1. Lastly butyronitrile (2.0 mL)
was added to chamber 2. This reaction was stirred at 90 °C
for 5 h and was then cooled to r.t. The solids were filtrated
off, and the reaction was concentrated under vacuum. The
crude residue was subjected to flash chromatography using
pentane–EtOAc (10:1) as eluent. This resulted in 46 mg
(81%) of 3a as white solid. 1H NMR (400 MHz, CDCl3): δ =
8.43 (s, 1 H), 7.94–7.98 (m, 2 H), 7.91 (d, J = 8.4 Hz, 1 H),
7.85 (d, J = 8.4 Hz, 1 H), 7.44–7.84 (m, 7 H), 4.98 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 135.3, 133.8, 131.9,
130.0, 129.2, 129.1 (2 C), 129.0 (2 C), 128.8, 128.7, 128.6,
127.9, 127.8, 127.2, 124.3, 111.1, 51.4. HRMS: m/z calcd for
C19H15N2O [M + H]+: 287.1184; found: 287.1178.
(16) General Procedure for the Synthesis of N-Benzyl-N-
cyano-2-naphthamide (3a)
13C-Labeled N-Benzyl-N-cyano-2-naphthamide (13C-3a)
According to the general procedure. Flash chromatography
using pentane–EtOAc (10:1) as eluent resulted in 46 mg
(80% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ
= 8.40 (d, J = 4.4 Hz, 1 H), 7.81–7.96 (m, 4 H), 7.41–7.64
(m, 7 H), 4.96 (d, J = 2.8 Hz, 2 H). 13C NMR (0100 MHz,
CDCl3): δ = 168.1 (13C-enriched), 135.4, 133.9, 132.0 (d, J
= 5.1 Hz), 130.1 (d, J = 2.2 Hz), 129.3 (2 C), 129.1 (d, J =
2.9 Hz, 2 C), 128.8, 128.7, 128.6, 128.4, 127.9, 127.7, 127.3,
124.3 (d, J = 2.2 Hz), 111.1 (d, J = 3.6 Hz), 51.5. HRMS: m/z
calcd for C1813CH15N2O [M + H]+: 288.1218; found:
288.1213.
In an argon-filled glovebox to chamber 1 of the two-chamber
system was added 2-bromonaphthalene (42 mg, 0.20 mmol),
[Pd(cinnamyl)Cl]2 (5.0 mg, 0.01 mmol), CataCXium A (8.0
mg, 0.02 mmol), K3PO4 (65 mg, 0.3 mmol), and
butyronitrile (1.0 mL) in that order. The chamber was closed
with a screwcap fitted with a Teflon seal. To chamber 2 of
the two-chamber system was added methyldiphenylsila-
carboxylic acid (122 mg, 0.50 mmol) and KF (30 mg, 0.50
mmol). The chamber was closed with a screwcap fitted with
a Teflon seal. The loaded two-chamber system was removed
from the glovebox and heated to 30 °C for 15 min. Then N-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1241–1245

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.