Synthesis of 1-[(Triisopropylsilyl)ethynyl]-1λ3,2- benziodoxol-3(1 H)-one and alkynylation of indoles, thiophenes, and anilines

Article abstract of DOI:10.1055/s-0031-1290589

An efficient procedure was developed for the synthesis of 1-[(triisopropylsilyl)ethynyl]-1³,2-benziodoxol-3(1H)-one on a 100-mmol (36-g) scale. The benziodoxolone can be used for the gold-catalyzed direct alkynylation of indole, 2-hexylthiophene, or N,N-dibenzylaniline on a 5- to 10-mmol scale. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0031-1290589

SPECIAL TOPIC
▌1155
3
special topic
Synthesis of 1-[(Triisopropylsilyl)ethynyl]-1λ ,2-benziodoxol-3(1H)-one and
Alkynylation of Indoles, Thiophenes, and Anilines
Jonathan P. Brand, Jérôme Waser*
Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne
EPFL SB ISIC LCSO, BCH 4306, 1015 Lausanne, Switzerland
Fax +41(21)69397 00; E-Mail: jerome.waser@epfl.ch
PSP
Received: 19.01.2012; Accepted after revision: 24.02.2012
No224
Abstract: An efficient procedure was developed for the synthesis of 1-[(triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one on a 100-
mmol (36-g) scale. The benziodoxolone can be used for the gold-catalyzed direct alkynylation of indole, 2-hexylthiophene, or N,N-diben-
zylaniline on a 5- to 10-mmol scale.
Key words: alkynes, arenes, catalysis, heterocycles, iodine
TMS
TIPS
HO
I
O
TIPS
I
O
Het
H
TfOTMS
Het
TIPS
AuCl, r.t.
O
O
MeCN, py
2
1
Scheme 1 Synthesis of 1-[(triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (2) and its use in the direct alkynylation of (hetero)arenes
In addition to their use in oxidation reactions, hypervalent The discovery of the reactivity of 1-[(triisopropylsi-
iodine reagents have become increasingly important as re- lyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (2; TIPS-
actants in C–C bond-formation processes.1 Togni and co- EBX) has also made an impact in the growing field of di-
workers2 have demonstrated the use of the cyclic benzio- rect alkynylation of heterocycles and aromatics.7,8 Al-
doxol(on)e structure in the transfer of trifluoromethyl kynyl aromatics are normally synthesized by means of the
groups, whereas we have demonstrated the use of benzio- Sonogashira reaction.9 An alternative strategy is based on
doxolones in alkyne transfer.3 Togni showed that benzio- the use of an electrophilic alkyne and a nonfunctionalized
doxol(on)es 3 and 4 (Figure 1) can be used for transfer of nucleophilic arene in the presence of a metal catalyst. Re-
a trifluoromethyl group to malonates, nitro esters, or agent 2 has been shown to have unique properties for the
arenes.2 We demonstrated that benziodoxolones 5 and 2 gold-catalyzed alkynylation of indoles, pyrroles, thio-
are superior to classical alkynyliodoniums salts4 as re- phenes, and anilines.8 Here, we report a practical proce-
agents for the ethynylation of β-keto esters, β-nitro esters, dure for its synthesis together with its use in the direct
β-cyano esters,5 as well as for the oxy- and aminoalkynyl- alkynylation of indole, 2-hexylthiophene, and N,N-diben-
ation of alkenes.6
zylaniline (Scheme 1).
In 1996, Zhdankin and co-workers reported the first syn-
thesis of TIPS-EBX (2) on a 1.5-mmol scale.10 This re-
agent was not used in organic synthesis until our recent
work. To synthesize TIPS-EBX (2) in larger quantities,
we first investigated the scaling up of the originally pub-
lished procedure. The quality of the 2-iodosylbenzoic acid
(1) precursor was crucial for the efficiency and reproduc-
ibility of the reaction. The protocol of Kraszkiewicz and
Skulski11 for preparing the acid 1 gave the best results in
this respect (Scheme 2). Air drying gave a better quality
of reagent than did drying under high vacuum. This syn-
thesis was scaled up to 0.3 mol. Because of the thermal in-
stability of hypervalent iodine compounds, the reaction
must be carried out behind a safety shield.
F3C
I
O
F3C
I
O
O
O
4
3
TMS
I
O
TIPS
I
O
O
2
5
Figure 1
transfer reactions
Benziodoxoles for trifluoromethyl and alkyne group
SYNTHESIS 42170012, 44,81155–1158
Advanced online publication: 22.03.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290589; Art ID: SS-2012-C0065-ST
© Georg Thieme Verlag Stuttgart · New York

1156
J. P. Brand, J. Waser
SPECIAL TOPIC
acid to give product 12 in 81% isolated yield (2.8 g)
(Scheme 5);8c 97% of the 2-iodobenzoic acid (6) was re-
covered. Product 12 is useful as a building block for or-
ganic materials.
I
OH
HO
I
O
NaIO4
AcOH (30 w%)
O
O
361 mmol, 81%
6
1
TIPS
I
O
Scheme 2 Synthesis of 2-iodosylbenzoic acid (1)
O
2
The other precursor, the bis-silylated alkyne 8, was syn-
thesized by using a reported procedure (Scheme 3).12
TIPS
AuCl (1 mol%), MeCN
TFA (1.2 equiv), r.t.
S
S
Hex
Hex
11
12
n-BuLi, TIPSCl
10 mmol, 81%
TMS
TIPS
TMS
H
THF, –78 °C to r.t.
Scheme 6 Gold-catalyzed direct alkynylation of 2-hexylthiophene
(11)
7
8
231 mmol, 95%
Scheme 3 Synthesis of trimethylsilyl(triisopropylsilyl)ethyne (8)
Finally, N,N-dibenzylaniline (13) was successfully para-
alkynylated on a 5 mmol scale in 79% yield (1.97 g) at
room temperature (Scheme 7);8d 13% of the starting mate-
rial 13 and 72% of 2-iodobenzoic acid (6) were recovered.
Zhdankin’s procedure was then modified for scale up
(Scheme 4). On the larger scale, removal of pyridine by
treatment with acid and removal of 2-iodobenzoic acid (6)
by treatment with base were essential for efficient and re-
producible purification. A single recrystallization from
acetonitrile gave highly pure crystals that did not show
any sign of decomposition after several months at room
temperature in air.13 When the procedure was scaled up to
100 mmol, it gave 36 g of compound 2 (85% yield).
TIPS
I
O
O
2
Bn2N
Bn2N
TIPS
AuCl (5 mol%)
i-PrOH, r.t.
13
14
5 mmol, 79%
TMS
TIPS
HO
I
O
TIPS
I
O
TfOTMS
MeCN, py
100 mmol, 85%
Scheme 7 Gold-catalyzed direct alkynylation of N,N-dibenzylani-
line (13)
O
O
1
2
In conclusion, we have developed an improved synthesis
of TIPS-EBX (2) on a 100-mmol scale. Both indole (9)
and 2-hexylthiophene (11) were successfully alkynylated
in the presence of 1 mol% of gold(I) chloride under mild
conditions on a 10-mmol scale whereas N,N-dibenzylani-
line (13) was alkynylated in the presence 5 mol% of
gold(I) chloride on a 5-mmol scale. Further investigations
on synthetic applications of TIPS-EBX (2) are currently
underway in our laboratory.
Scheme 4 Synthesis of TIPS-EBX (2) from 2-iodosylbenzoic acid
(1)
We then used TIPS-EBX (2) in the direct alkynylation of
indole (9) by following our previously reported procedure
(Scheme 5).8a The process is highly C3-regioselective and
can be carried out under air and without drying of the sol-
vent. On a 10-mmol scale, the use of 1 mol% of gold(I)
chloride gave product 10 in 82% yield (2.4 g) after 36 h.
2-Iodobenzoic acid (6) could be recovered in 73% yield
by acidification of the aqueous layer and extraction with
ethyl acetate. The recycled compound can be converted
back into TIPS-EBX (2) in two steps.
All reactions were carried out in oven-dried glassware under N2, un-
less otherwise stated. AuCl was purchased from Aldrich or Alfa Ae-
sar and kept in desiccator under anhydrous condition. The catalyst
showed a decrease in reactivity on prolonged exposure to air (~1
month). All chemicals were purchased and used as received, unless
stated otherwise. Solvents were evaporated under reduced pressure
at 40 °C on a Büchi Rotavapor. Melting points were measured on a
calibrated Büchi B-540 melting-point apparatus in open glass cap-
illaries. 1H NMR spectra were recorded on a Brucker DPX-400 400-
MHz spectrometer in CDCl3 or DMSO-d6. All signals are reported
in ppm with the internal chloroform signal at 7.26 ppm or the inter-
nal DMSO signal at 2.50 ppm as standard. 13C NMR spectra were
recorded with 1H-decoupling on a Brucker DPX-400 100-MHz
spectrometer in CDCl3 or DMSO-d6. All signals are reported in ppm
with the internal chloroform signal at 77.0 ppm or the internal
DMSO signal at 39.5 ppm as standard. IR spectra were recorded on
a JASCO FT-IR B4100 spectrophotometer with an ATR PRO410-
S and a ZnSe prism. High-resolution mass spectrometric measure-
ments were performed by the mass spectrometry service of ISIC at
the EPFL on a MicroMass (ESI) Q-TOF Ultima API.
TIPS
TIPS
I
O
O
2
AuCl (1 mol%)
Et2O, r.t.
N
N
H
H
10
9
10 mmol, 82%
Scheme 5 Gold-catalyzed direct alkynylation of indole (9)
The C2-selective direct alkynylation of 2-hexylthiophene
(11) was scaled up to a 10-mmol scale by using 1 mol%
of gold(I) chloride and 1.2 equivalents of trifluoroacetic
Synthesis 2012, 44, 1155–1158
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
1-[(Triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one as an Alkynylating Agent
1157
1-Hydroxy-1λ3,2-benziodoxol-3(1H)-one (1)
ers were washed with sat. aq NaHCO3 (2 × 250 mL), dried
Caution: This reaction should be carried out behind a safety shield!
(MgSO4), filtered, and concentrated under reduced pressure. The re-
sulting solid (44.8 g) was recrystallized from MeCN (110 mL). The
colorless solid that formed on cooling was filtered off, washed with
hexanes (2 × 40 mL), and dried for 1 h at 40 °C at 5 mbar to give
white crystals; yield: 36.2 g (84.5 mmol, 85%); mp 173–177 °C
(dec).
In accordance with a reported procedure,11 NaIO4 (77.2 g, 0.361
mol, 1.0 equiv) and 2-iodobenzoic acid (6; 89.5 g, 0.361 mmol, 1.0
equiv) were suspended in 30 vol% aq AcOH (700 mL) under air in
a four-necked sulfonation flask equipped with a mechanical stirrer,
a thermometer, and a condenser. The mixture was vigorously stirred
and refluxed for 4 h then diluted with cold H2O (500 mL) and al-
lowed to cool to r.t. in darkness. After 45 min, the suspension was
added to H2O (1.5 L) and the crude product was collected by filtra-
tion, washed with ice-water (3 × 300 mL) and cold acetone (3 × 300
mL), and then air-dried in darkness overnight to give a colorless sol-
id; yield: 77.3 g (0.292 mol, 81%).
1H NMR (400 MHz, CDCl3): δ = 8.37 (m, 1 H, ArH), 8.28 (m, 1 H,
ArH), 7.72 (m, 2 H, ArH), 1.13 (m, 21 H, TIPS).
13C NMR (101 MHz, CDCl3): δ = 166.4, 134.5, 132.3, 131.4, 131.4,
126.1, 115.6, 113.9, 64.7, 18.4, 11.1.10
3-[(Triisopropylsilyl)ethynyl]-1H-indole (10)
TIPS-EBX (2; 5.14 g, 12.0 mmol, 1.2 equiv) was added to a stirred
solution of AuCl (23 mg, 0.10 mmol, 0.01 equiv) and indole (9; 1.17
g, 10.0 mmol, 1.0 equiv) in Et2O14 (200 mL) under air in a 500-mL
flask. The flask was sealed and the mixture was stirred at r.t. for 36
h. Additional Et2O (250 mL) was added and the organic layer was
washed twice with 0.1 M aq NaOH (250 mL). The aqueous layers
were combined and extracted with Et2O (250 mL). The organic lay-
ers were combined, washed successively with sat. aq NaHCO3 (250
mL) and brine (250 mL), dried (MgSO4), and concentrated under re-
duced pressure. The residue was purified by flash chromatography
[PE–Et2O (8:2)] to give a brown solid: yield: 2.43 g (8.17 mol,
82%); mp 55–58 °C; Rf = 0.4 (PE–Et2O, 7:3).
IR (neat): 3083 (w), 3060 (w), 2867 (w), 2402 (w), 1601 (m), 1585
(m), 1564 (m), 1440 (m), 1338 (s), 1302 (m), 1148 (m), 1018 (w),
834 (m), 798 (w), 740 (s), 694 (s), 674 (m), 649 (m) cm–1.11
1H NMR (400 MHz, DMSO-d6): δ = 8.02 (dd, J = 7.7, 1.4 Hz, 1 H,
ArH), 7.97 (m, 1 H, ArH), 7.85 (dd, J = 8.2, 0.7 Hz, 1 H, ArH), 7.71
(td, J = 7.6, 1.2 Hz, 1 H, ArH).
13C NMR (100 MHz, DMSO-d6): δ = 167.7, 134.5, 131.5, 131.1,
130.4, 126.3, 120.4.
Trimethylsilyl(triisopropylsilyl)ethyne (8)
In a modification of a reported procedure,12 HC≡CTMS (7; 30.3 ml,
213 mmol, 1 equiv) was placed in a four-necked 500-mL flask
equipped with a thermometer, a dropping funnel, an magnetic stir-
rer, and a N2 inlet. THF (330 mL) was added from a dropping funnel
and the mixture was cooled to –78 °C. BuLi (86 mL, 0.21 mmol,
0.98 equiv) was added and the mixture was stirred for 5 min at –78 °C
then warmed to 0 °C and stirred for 5 min. The mixture was then
cooled again to –78 °C and TIPSCl (45.5 mL, 213 mmol, 1 equiv)
was added dropwise from a dropping funnel. The mixture was al-
lowed to warm to r.t. and stirred overnight. Sat. aq NH4Cl (300 mL)
was added and the mixture was extracted with Et2O (2 × 300 mL).
The organic layer was dried (MgSO4), filtered, and concentrated.
Distillation of the crude product (55 °C, 1.4 mbar) gave a colorless
liquid; yield: 51.4 g (203 mmol, 95%).
IR (neat): 3407 (m), 3062 (w), 2942 (s), 2891 (m), 2864 (s), 2152
(s), 1620 (w), 1532 (w), 1457 (s), 1416 (m), 1383 (w), 1341 (w),
1325 (m), 1239 (s), 1128 (m), 1071 (m), 996 (m), 910 (m), 883 (s),
774 (s), 742 (s), 676 (s), 658 (s), 628 (s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.11 (br s, 1 H, NH), 7.79 (m, 1 H,
ArH), 7.40 (d, J = 2.7 Hz, 1 H, ArH), 7.36 (m, 1 H, ArH), 7.26 (m,
2 H, ArH), 1.22 (m, 21 H, TIPS).
13C NMR (100 MHz, CDCl3): δ = 135.1, 128.9, 128.3, 123.1, 120.8,
120.1, 111.4, 100.4, 99.3, 92.19, 18.8, 11.5.
HRMS (ESI): m/z [M + H]+ calcd for C19H28NSi: 298.1991; found:
298.2001.
2-Iodobenzoic acid (6) was recovered by adjusting the pH of the aq
NaOH fraction to 1 with concd. aq HCl and extracting the mixture
with EtOAc (2 × 300 mL). The organic layers were combined, dried
(MgSO4), and concentrated under reduced pressure to give 2-iodo-
benzoic acid (6) as a colorless solid; recovery: 2.18 g (8.79 mmol,
73% recovered).
IR (neat): 2959 (m), 2944 (m), 2896 (w), 2867 (m), 1464 (w), 1385
(w), 1250 (m), 996 (w), 842 (s), 764 (s), 675 (m), 660 (m) cm–1.12
1H NMR (400 MHz, CDCl3): δ = 1.08 (m, 21 H, TIPS), 0.18 (s, 9
H, TMS).
1-[(Triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (2;
TIPS-EBX)
[(5-Hexyl-2-thienyl)ethynyl](triisopropyl)silane (9)
Caution: This reaction should be carried out behind a safety
2-Hexylthiophene (11; 1.80 mL, 10.0 mmol, 1 equiv) was added to
a stirred soln of AuCl (23 mg, 0.10 mmol, 0.01 equiv) in MeCN14
(50 mL) under air in a 100-mL flask. After 2 min, TFA (0.891 mL,
12.0 mmol, 1.2 equiv) and TIPS-EBX (2; 5.14 g, 12.0 mmol, 1.2
equiv) were added. The flask was sealed and the mixture was stirred
at r.t. for 4 d. Et2O (250 mL) was added and the organic layer was
washed with 0.1 M aq NaOH (2 × 300 mL). The aqueous layers
were combined and extracted with Et2O (250 mL). The organic lay-
ers were combined, washed successively with sat. aq NaHCO3 (250
mL) and brine (250 mL) then dried (MgSO4) and concentrated un-
der reduced pressure. The resulting oil was purified by flash chro-
matography (pentane) and the remaining starting material was
removed by heating the oil at 70 °C and 0.5 mbar for 4 h to give a
slightly yellow oil; yield: 2.83 g (8.11 mmol, 81%); Rf = 0.6 (pen-
tane).
shield!13
In a modification of a reported procedure,10 2-iodosylbenzoic acid
(1) (26.4 g, 100 mmol, 1.0 equiv) was placed in a four-necked flat-
bottomed flask equipped with a thermometer, a dropping funnel, a
mechanical stirrer, and a N2 inlet. The system was flushed with N2
in three vacuum/N2 cycles before anhyd MeCN (350 mL) was add-
ed from a cannula. The white suspension was cooled to 4 °C and
TMSOTf (20.0 mL, 110 mol, 1.1 equiv) was added dropwise over
15 min from a dropping funnel that was finally rinsed with anhyd
MeCN (10 mL); no increase in temperature was observed. The ice
bath was removed and the mixture was stirred for 15 min.
TMSC≡CTIPS (8; 28.0 g, 110 mmol, 1.1 equiv) was added drop-
wise from a dropping funnel over 15 min and the colorless suspen-
sion changed to a yellow soln. The dropping funnel was rinsed with
anhyd MeCN (10 mL) and the mixture was stirred for 30 min. Pyr-
idine (9.9 mL, 25 mmol, 1.1 equiv) was then added dropwise from
a dropping funnel over 5 min. After 15 min, the mixture was trans-
ferred to a one-necked 1-L flask and concentrated to a solid under
reduced pressure. The solid was dissolved in CH2Cl2 (250 mL) and
transferred to a 2-L separatory funnel. The organic layer was re-
moved and washed with 1 M aq HCl (150 mL). The aqueous layer
was extracted with CH2Cl2 (250 mL) and the combined organic lay-
IR (neat): 2958 (s), 2928 (s), 2865 (s), 2143 (s), 1535 (w), 1463 (s),
1382 (w), 1367 (w), 1243 (w), 1167 (m), 1074 (w), 1018 (m), 997
(m), 920 (w), 883 (s), 800 (s), 757 (s), 736 (s), 678 (s), 658 (s), 633
(s) cm–1.
1H NMR: δ = 7.08 (d, J = 3.5 Hz, 1 H, ArH), 6.65 (d, J = 3.5 Hz, 1
H, ArH), 2.80 (t, J = 7.5 Hz, 2 H, CH2), 1.68 (m, 2 H, CH2), 1.44–
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1155–1158

1158
J. P. Brand, J. Waser
SPECIAL TOPIC
1.30 (m, 6 H, CH2), 1.15 (m, 21 H, TIPS), 0.93 (t, J = 6.1 Hz, 3 H,
CH3).
Acknowledgment
We acknowledge financial support from EPFL. We thank Liang Su
(Laboratory of Macromolecular and Organic Materials, EPFL) for
performing DSC measurements on TIPS-EBX (2).
13C NMR: δ = 148.1, 132.4, 123.9, 121.0, 99.8, 94.3, 31.7, 31.6,
30.2, 28.7, 22.6, 18.7, 14.1, 11.4.
HRMS (ESI): m/z [M + H]+ calcd for C21H37SSi: 349.2385; found:
349.2381.
References
2-Iodobenzoic acid (6) was recovered by adjusting the pH of the
NaOH fraction to 2 with 1 M HCl and extracting the mixture with
EtOAc (2 × 250 mL). The organic layers were combined, dried
(MgSO4), and concentrated under reduced pressure to give 2-iodo-
benzoic acid (6) as a gray solid; recovery: 2.91 g (11.7 mmol, 97%).
(1) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299.
(2) (a) Eisenberger, P.; Gischig, S.; Togni, A. Chem. Eur. J.
2006, 12, 2579. (b) Kieltsch, I.; Eisenberger, P.; Togni, A.
Angew. Chem. Int. Ed. 2007, 46, 754. (c) Wiehn, M. S.;
Vinogradova, E. V.; Togni, A. J. Fluorine Chem. 2010, 131,
951.
N,N-Dibenzyl-4-[(triisopropylsilyl)ethynyl]aniline (14)
AuCl (59 mg, 0.025 mmol, 0.05 equiv) was added to a stirred soln
of PhNBn2 (13; 1.36 g, 5.00 mmol, 1 equiv) and TIPS-EBX (2; 3.00
g, 7.00 mmol, 1.4 equiv) in i-PrOH14 (100 mL) under air in a 250-
mL flask and the mixture was stirred at r.t. for 24 h. EtOAc (200
mL) was added and the mixture was washed successively with 0.1
M aq NaOH (200 mL), sat. aq NaHCO3 (200 mL), and brine (200
mL) then dried (MgSO4) and concentrated in vacuo. The resulting
oil was purified by column chromatography [pentane–CH2Cl2 (95:5
to 9:1)] to give 14 as a colorless oil [yield: 1.66 g (3.66 mmol, 73%)]
together with a mixture of 14 and 13 [yield: 314 mg, (42 wt% 14 +
58 wt% 13), equivalent to 6% product 14 + 13% recovered starting
material 13] as a colorless oil; total yield = 79%; yield based on re-
covered starting material: 91%; Rf (pentane–CH2Cl2, 9:1) = 0.15.
(3) (a) Brand, J. P.; Fernández González, D.; Nicolai, S.; Waser,
J. Chem. Commun. (Cambridge) 2011, 47, 102. (b) Reagents
2, 3 and 4 are now also commercially available.
(4) For a review, see: Zhdankin, V. V.; Stang, P. J. Tetrahedron
1998, 54, 10927.
(5) Fernández González, D.; Brand, J. P.; Waser, J. Chem. Eur.
J. 2010, 16, 9457.
(6) (a) Nicolai, S.; Erard, S.; Fernández González, D.; Waser, J.
Org. Lett. 2010, 12, 384. (b) Nicolai, S.; Piemontesi, C.;
Waser, J. Angew. Chem. Int. Ed. 2011, 50, 4680.
(7) For reviews on direct alkynylation, see: (a) Dudnik, A. S.;
Gevorgyan, V. Angew. Chem. Int. Ed. 2010, 49, 2096.
(b) Messaoudi, S.; Brion, J. D.; Alami, M. Eur. J. Org.
Chem. 2010, 6495.
(8) (a) Brand, J. P.; Charpentier, J.; Waser, J. Angew. Chem. Int.
Ed 2009, 48, 9346. (b) Brand, J. P.; Chevalley, C.; Waser, J.
Beilstein J. Org. Chem. 2011, 7, 565. (c) Brand, J. P.; Waser,
J. Angew. Chem. Int. Ed. 2010, 49, 7304. (d) Brand, J. P.;
Waser, J. Org. Lett. 2012, 14, 744.
IR (neat): 3051 (w), 2943 (w), 2865 (w), 2143 (w), 1606 (m), 1516
(m), 1495 (w), 1454 (w), 1398 (w), 1360 (w), 1266 (m), 1241 (w),
1188 (w), 1075 (w), 997 (w), 955 (w), 884 (w), 841 (w), 818 (w),
737 (s), 698 (m), 677 (m) cm–1.
1H NMR (400 MHz, C6D6): δ = 7.37 (m, 2 H, ArH), 7.18–7.01 (m,
6 H, ArH), 6.95 (m, 4 H, ArH), 6.42 (m, 2 H, ArH), 4.15 (s, 4 H,
CH2), 1.21 (m, 21 H, TIPS).
(9) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467. (b) Chinchilla, R.; Najera, C. Chem.
Rev. 2007, 107, 874.
13C NMR (101 MHz, C6D6): δ = 149.3, 138.4, 133.9, 128.9, 127.3,
126.9, 112.4, 111.8, 109.6, 87.6, 53.9, 19.1, 11.9.
(10) Zhdankin, V. V.; Kuehl, C. J.; Krasutsky, A. P.; Bolz, J. T.;
Simonsen, A. J. J. Org. Chem. 1996, 61, 6547.
(11) Kraszkiewicz, L.; Skulski, L. ARKIVOC 2003, (iv), 120.
(12) Helal, C. J.; Magriotis, P. A.; Corey, E. J. J. Am. Chem. Soc.
1996, 118, 10938.
(13) Differential scanning calorimetry showed that TIPS-EBX
undergoes exothermic degradation at 187 °C.
(14) The commercial solvent was used without additional drying
or purification.
HRMS (ESI): m/z [M + H]+ calcd for C31H40NSi+: 454.2925; found:
454.2913.
2-Iodobenzoic acid (6) was recovered by adjusting the pH of the
NaOH fraction to 2 with 1 M aq HCl and extracting with EtOAc
(2 × 250 mL). The organic layers were combined, dried (MgSO4),
and concentrated under reduced pressure to give 2-iodobenzoic acid
(6) as a gray solid: recovery: 1.25 g (5.03 mmol, 72%).
Synthesis 2012, 44, 1155–1158
© Georg Thieme Verlag Stuttgart · New York