Mild Pd/Cu-catalyzed sila-sonogashira coupling of (hetero)aryl bromides with (hetero)arylethynylsilanes under PTC conditions

Article abstract of DOI:10.1055/s-0031-1290601

The palladium/copper cocatalyzed sila-Sonogashira reaction of (hetero)arylethynysilanes with (hetero)aryl bromides in toluene and water at 40 C under PTC conditions gave the required di(hetero)arylethynes in moderate to high yields. Activated, deactivated and ortho-substituted (hetero)aryl bromides are well tolerated. This protocol also allowed the preparation of symmetrical diarylethynes by double arylation of 1,2-bis(trimethylsilyl)ethyne. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290601

LETTER
773
Mild Pd/Cu-Catalyzed Sila-Sonogashira Coupling of (Hetero)aryl Bromides
with (Hetero)arylethynylsilanes under PTC Conditions
S
ila-Sonogash
a
ir
a
Reactio
b
C
i
Condit
o
ions Bellina,* Marco Lessi
Dipartimento di Chimica e Chimica Industriale, University of Pisa, Via Risorgimento 35, 56126 Pisa, Italy
Fax +39(050)2219260; E-mail: bellina@dcci.unipi.it
Received 26 December 2011
above, are typical byproducts of classical Sonogashira
Abstract: The palladium/copper cocatalyzed sila-Sonogashira re-
action of (hetero)arylethynysilanes with (hetero)aryl bromides in
toluene and water at 40 °C under PTC conditions gave the required
di(hetero)arylethynes in moderate to high yields. Activated, deacti-
protocols.7,15 However, these methods are generally limit-
ed to the use of (hetero)aryl iodides16a–c,f–j,m,n or activated
(hetero)aryl bromides16i as coupling partners and require
vated and ortho-substituted (hetero)aryl bromides are well tolerat- high reaction temperatures,16b,d,e,j–m or the use of commer-
cially unavailable palladium precatalysts.16j–k
ed. This protocol also allowed the preparation of symmetrical
diarylethynes by double arylation of 1,2-bis(trimethylsilyl)ethyne.
In this paper, we report a mild protocol for the Pd/Cu co-
Key words: Sonogashira reaction, palladium, alkynylsilanes, di-
catalyzed sila-Sonogashira cross-coupling reaction of
arylethynes, copper, phase-transfer catalysis
(hetero)arylethynylsilanes and BTSE with a variety of ac-
tivated and deactivated (hetero)aryl bromides in a mixture
of toluene and water in the presence of benzyl(tri-n-
Symmetrical and unsymmetrical di(hetero)arylethynes
butyl)ammoniun chloride which acts as a phase-transfer
represent important scaffolds for the assembly of new ma-
catalyst (PTC).18 Our need for an efficient synthesis of
terials such as molecular electronic devices,1 dendrimers,2
di(hetero)arylethynes was dictated by our very recent in-
foldamers,3 or polymers.4 The most important synthetic
terest in preparing new organic fluorophores for nonlinear
strategies for the preparation of this class of molecules are
optical (NLO) materials.
undoubtedly based on the palladium/copper cocatalyzed
At the onset of our studies, we tested a diverse array of
cross-coupling reactions of (hetero)aryl halides or
bases as promoters for the sila-Sonogashira coupling reac-
pseudohalides with terminal alkynes in the presence of a
tion of trimethyl(phenylethynyl)silane (1a) with 2-bro-
mothiophene (2a, 1.1 equiv) in the presence of
PdCl2(PhCN)2 (5 mol%), CuI (10 mol%) as the cocatalyst,
t-Bu3PHBF4 (10 mol%) as the palladium ligand, and
Bn(n-Bu)3NCl (20 mol%) as the phase-transfer catalyst in
a mixture of toluene and water (Scheme 1).
base (Sonogashira reaction).5 The original protocol pub-
lished by Sonogashira, Tohda, and Hagihara in 1975,6
which required a Pd/Cu(I) catalyst system for the Csp–
Csp2 coupling, has been repeatedly modified and im-
proved to overcome several drawbacks.7 In particular,
copper-free (Cassar–Heck alkynylation),8,9 silver10 or
zinc11 cocatalyzed, the use of palladacycles as precata-
lysts,12 the use of ionic liquids as reaction media,13 or mi-
crowave heating14 have been reported to increase the
efficiency of this reaction by limiting the undesired for-
mation of alkyne homocoupling Glaser-type products.15
However, despite these improvements the use of Sono-
SiMe3
PdCl2(PhCN)2
t-Bu3PHBF4
S
+
S
CuI, Bn(n-Bu)3NCl
base, toluene/H2O
Br
1a
2a
3a
gashira reactions to prepare di(hetero)aryl alkynes often Scheme 1
requires systematic silane protection–deprotection to af-
ford the terminal alkyne coupling partner, and this stage
The choice of these specific reaction conditions deserves
comment. In particular, we decided to perform the reac-
tion in a biphasic system because we guessed that the high
temperatures frequently reported in the literature for sim-
ilar sila-Sonogashira reactions may be, at least in part, a
result of the poor solubility of inorganic bases in common
organic solvents. Moreover, t-Bu3P (as its air-stable phos-
phonium tetrafluoroborate salt) was selected because it
has been reported to be an effective ligand for palladium
when aryl bromides are employed as electrophiles in clas-
sical Sonogashira reactions.19
generally precedes the cross-coupling step.5,7 In order to
overcome the necessity of protecting-group removal and
to avoid the use of acetylene, trimethylsilylalkynes and si-
lylated acetylene equivalents such as ethynyltrimethylsi-
lane (ETS) or 1,2-bis(trimethylsilyl)ethyne (BTSE) have
been directly used as nucleophilic partners in the so-called
sila-Sonogashira reaction.16,17 A further distinct advan-
tage of the use of TMS-protected alkynes instead of un-
protected terminal alkynes resides in the suppression of
the formation of diynes and enynes, which, as stated
As shown in Table 1, the use of three equivalents of KF or
K2CO3 did not gave any of the required 2-(phenylethy-
nyl)thiophene (3a, Table 1, entries 1 and 2), and even af-
SYNLETT 2012, 23, 773–777
Advanced online publication: 28.02.2012
DOI: 10.1055/s-0031-1290601; Art ID: D80911ST
x
x.
x
x.
2
0
1
2
© Georg Thieme Verlag Stuttgart · New York

774
F. Bellina, M. Lessi
LETTER
ter four days at 80 °C the GLC yields of 3a were Pd/Ag cocatalyzed base-promoted sila-Sonogashira pro-
unsatisfactory (Table 1, entries 3 and 4). No reaction was tocol,16g cannot be totally ruled out.
also observed when the amount of KF or K2CO3 was in-
Having successfully demonstrated the feasibility of the
creased to ten equivalents (Table 1, entries 5 and 6). It is
Pd/Cu-catalyzed sila-Sonogashira cross-coupling under
worth mentioning that 1a was quantitatively recovered
PTC conditions of 1a with 2a, we then tested the scope
from the crude reaction mixtures when KF or K2CO3 were
and limitations of this coupling by applying the reaction
employed at 40 °C (Table 1, entries 1, 2, 5, and 6), even
conditions of entry 8 (Table 1) to the synthesis of com-
pounds 3 starting from (hetero)arylethynyltrimethylsi-
though these bases have been routinely used for the depro-
tection of trimethylsilylalkynes in organic solvents.20 In
lanes 1 and commercially available (hetero)aryl bromides
contrast, when three equivalents of NaOH were used to
promote the coupling of 1a with 2a, compound 3a was ob-
2 (Scheme 2).22–24
tained in 47% GC yield (Table 1, entry 7). We were then
PdCl2(PhCN)2
t-Bu3PHBF4, CuI
SiMe3
Ar2
pleased to find that when ten equivalents of NaOH were
used, the coupling of 1a with 2a afforded 3a in a satisfac-
tory 88% isolated yield (Table 1, entry 8).
+
Ar2Br
Ar1
Ar1
Bn(n-Bu)3NCl, NaOH
toluene/H2O, 40 °C
1
2
3
Interestingly, when the reaction was carried out without
copper, no reaction was observed, and only ethynylben-
zene was detected in the crude reaction mixture (Table 1,
entry 9).
Scheme 2
The reactions involving (hetero)arylethynyltrimethylsi-
lanes 1a–e and (hetero)aryl bromides 2a–e and 2g–l
proved to be clean and, as shown in Table 2, gave the re-
quired diaryl substituted ethynes 3a–e and 3g–m in mod-
erate to high yields (Table 2, entries 1–5 and 7–13).
Table 1 Effect of the Base on the Sila-Sonogashira Cross-Coupling
of 1a with 2a
Entrya Base (equiv)
Temp (°C) Time (h) Yield of 3a (%)b
In particular, yields higher than 90% were observed when
activated aryl bromides were used as electrophilic part-
ners (Table 2, entries 2 and 8), but the reaction also
worked well when alkynyltrimethylsilanes 1 were cou-
pled with unactivated or deactivated (hetero)aryl bro-
mides (Table 2, entries 1, 3–5, 7, and 10). This system
also proves to be tolerant of sterically hindered substrates
and 2-substituted aryl bromides 2h and 2j smoothly react-
ed with TMS-protected alkynes 1c and 1e affording the
desired cross-coupled products 3i and 3k in 63% and 64%
yield, respectively (Table 2, entries 9 and 11), while a
lower yield was observed when a typical deactivated
ortho-substituted bromide, 2-bromoanisole (2l), was used
as the coupling partner (Table 2, entry 13). A low chemi-
cal yield also resulted from the coupling involving the
strongly deactivated 4-bromoveratrole (2k, Table 2, entry
12). Remarkably, base-sensitive groups such as the
formyl or the carboxyalkyl groups are well tolerated
(Table 2, entries 7–9), and the presence of basic pyridyl or
amino groups did not interfere with the outcome of the
coupling (Table 2, entries 3 and 10–13). Nevertheless, the
Pd/Cu cocatalyzed cross coupling of 1a with 4-bromophe-
nol (2e) did not produce the required alkyne 1f (Table 2,
entry 5); on the contrary, a small amount of the Glaser-
type homocoupled diyne and of ethynylbenzene were ob-
served in the crude reaction mixture. In our opinion, this
lack of reaction could be ascribed at least in part to the
quantitative conversion of 2e into the corresponding sodi-
um salt which is probably confined into the aqueous phase
and is unable to give an efficient oxidative addition to the
Pd(0)Ln catalyst.
1
2
3
4
5
6
7
8
9d
KF (3)
40
40
80
80
40
40
40
40
40
48
24
96
96
48
48
24
17
17
0c
0c
K2CO3 (3)
KF (3)
20
38
0c
0c
47
K2CO3 (3)
KF (10)
K2CO3 (10)
NaOH (3)
NaOH (10)
NaOH (10)
93 (88)
0e
a Unless otherwise mentioned, the reactions were carried out using 1a
(1.0 mmol), 2a (1.1 equiv), PdCl2(PhCN)2 (5 mol%), t-Bu3PHBF4 (10
mol%), CuI (10 mol%), Bn(n-Bu)3NCl (20 mol%), toluene/H2O (1:1,
8 mL).
b GC yield. Isolated yield is given in parentheses.
c Trimethyl(phenylethynyl)silane (1a) was quantitatively recovered
from the crude reaction mixture.
d This reaction was carried out in the absence of CuI.
e Only ethynylbenzene was detected by GC and GC–MS analyses of
the crude reaction mixture.
Taking into account these results and previous reports in
the literature,16 we proposed that the mechanism should
feature an in situ NaOH-promoted protiodesilylation,21 af-
fording reactive silicon-free alkyne intermediates in low
concentrations and thus suppressing the formation of
Glaser-type dimerization byproducts. This step should
then be followed by a classical Pd/Cu-cocatalyzed Sono-
gashira-type coupling. However, from our data, a direct
silicon-to-copper transmetalation promoted by NaOH, in
analogy to that suggested by Halbes and Pale for their
Having secured good access to compounds 3, we then
turned our attention to the preparation of some typical
symmetrically substituted diarylethynes 4 starting from
1,2-bistrimethylsilylethyne (BTSE). We were pleased to
Synlett 2012, 23, 773–777
© Thieme Stuttgart · New York

LETTER
Sila-Sonogashira Reaction under PTC Conditions
775
Table 2 Synthesis of 1,2-Diarylethynes 3 from Arylethynyltrimethylsilanes 1 and Aryl Bromides 2
Entrya
1
Ar1
2
Ar2
Time (h)b
17
3c
Yield of 3 (%)d
1
2
1a
1a
1a
1a
1a
1a
1b
1c
1c
1d
1e
1e
1e
Ph
2a
2b
2c
2d
2e
2f
2-thienyl
3a
3b
3c
3d
3e
3f
88
98
65
78
82
0e
Ph
4-O2NC6H4
4-H2NC6H4
4-ClC6H4
22
3
Ph
22
4
Ph
22
5
Ph
5-acetyl-2-thienyl
4-HOC6H4
2-thienyl
22
6
Ph
22
7
4-OHCC6H4
4-MeOC6H4
4-MeOC6H4
4-F3CC6H4
3-pyridyl
3-pyridyl
3-pyridyl
2a
2g
2h
2i
15
3g
3h
3i
40
91
63
64
64
32
32
8
4-EtOOCC6H4
2-MeOOCC6H4
2-pyridyl
22
9
22
10
11
12
13
22
3j
2j
2-MeC6H4
22
3k
3l
2k
2l
3,4-(MeO)2C6H3
2-MeOC6H4
22
22
3m
a The reactions were carried out at 40 °C (oil bath) using 1 (1.0 mmol), 2 (1.1 equiv), PdCl2(PhCN)2 (5 mol%), t-Bu3PHBF4 (10 mol%), CuI
(10 mol%), Bn(n-Bu)3NCl (20 mol%), 2.5 M aq NaOH solution (4 mL), toluene (4 mL).
b Unless otherwise mentioned, the conversion of the reported reactions was quantitative after the indicated reaction times.
c All compounds gave satisfactory spectroscopic and analytical data.23
d Isolated chemical yield.
e Only low amounts of ethynylbenzene and of 1,4-diphenylbuta-1,3-diyne were observed by GC–MS analysis in the crude reaction mixture after
the indicated reaction time.
find that the reaction conditions of entry 8 (Table 1) also lyst and NaOH in a biphasic toluene/water reaction medi-
proved to be suitable for the double arylation of BTSE um. Sterically hindered bromides are tolerated, as well as
with aryl bromides 2.22 As shown in Scheme 3, a molar base-labile functional groups such as formyl and carboxy-
excess of representative deactivated, activated, and ortho- alkyl groups. Moreover, symmetrical diarylethynes can
substituted aryl bromides was successfully reacted with be prepared in good isolated yields by reaction of aryl bro-
BTSE under Pd/Cu cocatalysis in toluene and water at mides with BTSE. It is proposed that the coupling pro-
40 °C for 22 hours, furnishing the required alkynes 4 in ceeds by a mechanism involving a NaOH-promoted
good yields.
protiodesilylation and a subsequent classical Pd/Cu cocat-
alyzed Sonogashira coupling. Studies on the application
of this simple protocol, which compares favorably with
those previously described in the literature,16 to the prep-
aration of highly conjugated (hetero)arylethynes are now
in progress.
PdCl2(PhCN)2
t-Bu3PHBF4, CuI
SiMe3
+ ArBr
Ar
Bn(n-Bu)3NCl, NaOH
toluene/H2O, 40 °C, 22 h
2
Ar
Me3Si
4
(2.2 equiv)
4
Ar
Yield (%)
Acknowledgment
4a
4b
4c
4-O2NC6H4
4-MeOC6H4
2-MeC6H4
67
69
84
The Fondazione Cassa di Risparmio di Pisa is acknowledged for the
financial support under ‘POLOPTEL’ project n. 167/09.
References and Notes
Scheme 3
(1) Tour, J. M. Acc. Chem. Res. 2000, 33, 791.
(2) Pugh, V. J.; Hu, Q.-S.; Zuo, X.; Lewis, F. D.; Pu, L. J. Org.
Chem. 2001, 66, 6136.
In conclusion, in this study we have demonstrated that un-
symmetrical di(hetero)arylethynes can be efficiently pre-
pared in moderate to good yields by the Pd/Cu-
cocatalyzed cross coupling of activated and deactivated
(hetero)aryl bromides with (hetero)arylethynylsilanes in
the presence of Bn(n-Bu)3NCl as the phase-transfer cata-
(3) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore,
J. S. Chem. Rev. 2001, 101, 3893.
(4) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605.
(5) Jenny, N. M.; Mayor, M.; Eaton, T. R. Eur. J. Org. Chem.
2011, 4965.
© Thieme Stuttgart · New York
Synlett 2012, 23, 773–777

776
F. Bellina, M. Lessi
LETTER
(6) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467.
(15) (a) Hay, A. S. J. Org. Chem. 1960, 25, 1275. (b) Hay, A. S.
J. Org. Chem. 1962, 27, 3320. (c) Siemsen, P.; Livingston,
R. C.; Diederich, F. Angew. Chem. Int. Ed. 2000, 39, 2632.
(16) (a) Rossi, R.; Carpita, A.; Lezzi, A. Tetrahedron 1984, 40,
2773. (b) Shultz, D.; Gwaltney, K. P.; Lee, H. J. Org. Chem.
1998, 63, 4034. (c) Pak, J. J.; Weakley, T. J. R.; Haley, M.
M. J. Am. Chem. Soc. 1999, 121, 8182. (d) Nishihara, Y.;
Ikegashira, K.; Hirabayashi, K.; Ando, J.-I.; Mori, A.;
Hiyama, T. J. Org. Chem. 2000, 65, 1780. (e) Yang, C.;
Nolan, S. P. Organometallics 2002, 21, 1020. (f) Mio, M.
J.; Kopel, L. C.; Braun, J. B.; Gadzikwa, T. L.; Hull, K. L.;
Brisbois, R. G.; Markworth, C. J.; Grieco, P. A. Org. Lett.
2002, 4, 3199. (g) Halbes, U.; Pale, P. Tetrahedron Lett.
2002, 43, 2039. (h) Li, G.; Wang, X.; Wang, F. Tetrahedron
Lett. 2005, 46, 8971. (i) Sørensen, U.; Pombo-Villar, E.
Tetrahedron 2005, 61, 2697. (j) Gil-Moltó, J.; Nájera, C.
Adv. Synth. Catal. 2006, 348, 1874. (k) Sommer, W. J.;
Weck, M. Adv. Synth. Catal. 2006, 348, 2101.
(7) Selected reviews: (a) Rossi, R.; Carpita, A.; Bellina, F. Org.
Prep. Proced. Int. 1995, 27, 127. (b) Sonogashira, K. In
Metal-Catalyzed Reactions; Diederich, F.; Stang, P. J., Eds.;
Wiley-VCH: New York, 1998, 203–229. (c) Sonogashira,
K. J. Organomet. Chem. 2002, 653, 46. (d) Negishi, E.;
Anastasia, L. Chem. Rev. 2003, 103, 1979. (e) Nicolaou, K.
C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44,
4442. (f) Yin, L.; Liebscher, J. Chem. Rev. 2007, 107, 874.
(g) Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874.
(h) Doucet, H.; Hierso, J.-C. Angew. Chem. Int. Ed. 2007,
46, 834. (i) Plenio, H. Angew. Chem. Int. Ed. 2008, 47,
6954. (j) McGlacken, G. P.; Fairlamb, I. J. S. Eur. J. Org.
Chem. 2009, 4011. (k) Pal, M. Synlett 2009, 2896.
(8) (a) Cassar, L. J. Organomet. Chem. 1975, 93, 253.
(b) Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93,
259.
(9) For recent examples of Cassar–Heck alkynylation reactions,
see: (a) Kawanami, H.; Matsushima, K.; Sato, M.; Ikushima,
Y. Angew. Chem. Int. Ed. 2007, 46, 5129. (b) Shi, S.;
Zhang, Y. Synlett 2007, 1843. (c) Ljungdahl, T.; Bennur, T.;
Dallas, A.; Emtenaes, H.; Maartensson, J. Organometallics
2008, 27, 2490. (d) Komáromi, A.; Tolnai, G. L.; Novák, Z.
Tetrahedron Lett. 2008, 49, 7294. (e) Lipshutz, B. H.;
Chung, D. W.; Rich, B. Org. Lett. 2008, 10, 3793.
(f) Carpita, A.; Ribecai, A. Tetrahedron Lett. 2009, 50, 204.
(g) Bakherad, M.; Amin, A. H.; Keinvanloo, A.; Bahramian,
B.; Raeissi, M. Tetrahedron Lett. 2010, 51, 5653. (h) Saha,
D.; Dey, R.; Ranu, B. C. Eur. J. Org. Chem. 2010, 6067.
(i) de Carné-Carnavalet, B.; Archambeau, A.; Meyer, C.;
Cossy, J.; Folléas, B.; Brayer, J.-L.; Demoute, J.-P. Org.
Lett. 2011, 13, 956. (j) Prabakaran, K.; Khan, F. N.; Jin, J. S.
Tetrahedron Lett. 2011, 52, 2566.
(l) Nishihara, Y.; Inoue, E.; Okada, Y.; Takagi, K. Synlett
2008, 3041. (m) Nishihara, Y.; Inoue, E.; Ogawa, D.;
Okada, Y.; Noyori, S.; Takagi, K. Tetrahedron Lett. 2009,
50, 4643. (n) Severin, R.; Reimer, J.; Doye, S. J. Org. Chem.
2010, 75, 3518.
(17) Recently, a Pd-free, Cu-catalyzed sila-Sonogashira cross-
coupling protocol involving aryl iodides was published:
Nishihara, Y.; Noyori, S.; Okamoto, T.; Suetsugu, M.;
Iwasaki, M. Chem. Lett. 2011, 40, 972.
(18) For a discussion on phase-transfer catalysis in cross-
coupling reactions, see: (a) Dehmlow, E. W. In Aqueous-
Phase Organometallic Catalysis, 2nd ed.; Cornils, B.;
Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 2004, 272.
(b) Mąkosza, M.; Fedoryński, M. ARKIVOC 2006, (iv), 7.
(19) Hundertmart, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C.
Org. Lett. 2000, 2, 1729.
(10) (a) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.;
Hirabayshi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935.
(b) Kobayashi, K.; Sugie, A.; Takahashi, M.; Masui, K.;
Mori, A. Org. Lett. 2005, 7, 5083.
(20) See, for example: Wuts, P. G. M.; Greene, T. W. In Greene's
Protective Groups in Organic Synthesis, 4th ed.; John Wiley
and Sons: Hoboken, 2007, 928–929.
(21) For an example of protiodesilylation of
(11) (a) Crisp, G. T.; Turner, P. D.; Stephens, K. A.
J. Organomet. Chem. 1998, 570, 219. (b) Eberhard, M. R.;
Wang, Z.; Jensen, C. M. Chem. Commun. 2002, 818.
(12) (a) Herrmann, W. A.; Böhm, V. P. W.; Reisinger, C. P.
J. Organomet. Chem. 1998, 576, 23. (b) Alonso, D. A.;
Nájera, C.; Pacheco, M. C. Org. Lett. 2000, 2, 1283.
(c) Alonso, D. A.; Nájera, C.; Pacheco, M. C. Tetrahedron
Lett. 2002, 43, 9365. (d) Alonso, D. A.; Nájera, C.; Pacheco,
M. C. Adv. Synth. Catal. 2003, 345, 1146. (e) Alacid, E.;
Alonso, D. A.; Botella, L.; Nájera, C.; Pacheco, M. C. Chem.
Rec. 2006, 6, 117.
(13) Selected papers on Sonogashira coupling reactions in ionic
liquids: (a) Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K.
V. Chem. Commun. 2001, 1544. (b) Fukuyama, T.;
Shinmen, M.; Nishitani, S.; Sato, M.; Ryu, I. Org. Lett. 2002,
4, 1691. (c) Park, S. B.; Alper, H. Chem. Commun. 2004,
1306. (d) Gholap, A. R.; Venkatesan, K.; Pasricha, R.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem.
2005, 70, 4869. (e) Rahman, M. T.; Fukuyama, T.; Ryu, I.;
Suzuki, K.; Yinoemura, K.; Hughes, P. F.; Nokihara, K.
Tetrahedron Lett. 2006, 47, 2703. (f) Hierso, J.-C.; Boudon,
J.; Picquet, M.; Meunier, P. Eur. J. Org. Chem. 2007, 583.
(g) de Lima, P. G.; Antunes, O. A. C. Tetrahedron Lett.
2008, 49, 2506. (h) Fukuyama, T.; Rahman, Md. T.;
Maetani, S.; Ryu, I. Chem. Lett. 2011, 40, 1027.
alkynyltrimethylsilanes with NaOH under PTC conditions,
see: Roser, J.; Eberbach, W. Synth. Commun. 1986, 16, 983.
(22) General Procedure for the Synthesis of
Di(hetero)arylethynes 3
To a mixture of alkynyltrimethylsilane 1 (1 mmol),
(hetero)aryl bromide 2 (1.1 mmol), PdCl2(PhCN)2 (19.8 mg,
0.05 mmol), t-Bu3PHBF4 (29.0 mg, 0.1 mmol), CuI (19.0
mg, 0.1 mmol), and Bn(n-Bu)3NCl (62.4 mg, 0.2 mmol) in
toluene (8 mL) was added a 2.5 M aq solution of NaOH (10
mmol, 4 mL), and the resulting biphasic mixture was stirred
under argon at 40 °C for the period of time reported in
Table 2. The degree of completion of the reaction and the
composition of the reaction mixture were established by GC
and GC–MS analyses of a sample of the crude reaction
mixture after it had been treated with a sat. aq NH4Cl
solution and extracted with EtOAc. After being cooled to r.t.,
the reaction mixture was diluted with EtOAc (15 mL) and
poured into a sat. aq NH4Cl solution (15 mL), and the
resulting mixture was stirred in the open air for 0.5 h and
then extracted with EtOAc (4 × 10 mL). The organic extracts
were washed with H2O (2 × 5 mL), dried and concentrated
under reduced pressure, and the residue was purified by flash
cromatography on silica gel. This procedure was employed
to prepare di(hetero)arylethynes 3a–e,g–m (Table 2, entries
1–5 and 7–10,). The same procedure, but employing BTSE
(0.23 mL, 0.17 g, 1.0 mmol) and aryl bromide 2 (2.2 mmol),
was also applied to the synthesis of symmetrically
substituted diarylethynes 4a–c (Scheme 3).
(14) (a) Kabalka, G. W.; Wang, L.; Namboodiri, V.; Pagni, R. M.
Tetrahedron Lett. 2000, 41, 5151. (b) Erdélyi, M.; Gogoll,
A. J. Org. Chem. 2001, 66, 4165.
Synlett 2012, 23, 773–777
© Thieme Stuttgart · New York

LETTER
Sila-Sonogashira Reaction under PTC Conditions
777
(23) Representative Data for New Compounds
4-(Thiophen-2-ylethynyl)benzaldehyde (3g)
6 H), 6.83 (d, J = 9 Hz, 1 H), 7.05 (s, 1 H), 7.16 (d, J = 6 Hz,
1 H), 7.25 (m, 1 H), 7.77 (d, J = 9 Hz, 1 H), 8.55 (s, 1 H),
8.79 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 55.67, 55.70,
84.48, 92.75, 110.83, 113.99, 114.40, 120.57, 122.91,
124.94, 137.98, 148.06, 148.46, 149.67, 151.85. MS: m/z
(%) = 239 (100) [M+], 224 (18), 196 (16), 167 (27), 1543
(12), 127 (12). Anal. Calcd for C15H13NO2 (239.27): C,
75.30; H, 5.48. Found: C, 75.61; H, 5.52.
Mp 110–112 °C. 1H NMR (300 MHz, CDCl3): d = 7.03 (dd,
J = 3.7, 5.0 Hz, 1 H), 7.34 (m, 2 H), 7.63 (d, J = 9.0 Hz, 2 H),
7.84 (d, J = 9.0 Hz, 2 H), 9.99 (s, 1 H). 13C NMR (75 MHz,
CDCl3): d = 86.87, 92.37, 122.43, 127.40, 128.43, 129.20,
129.62 (2 C), 131.79 (2 C), 132.93, 135.40, 191.39. MS:
m/z (%) = 212 (100) [M+], 211 (60), 183 (13), 139 (35), 91
(6). Anal. Calcd for C13H8OS (212.27): C, 73.56; H, 3.80.
Found: C, 73.84; H, 3.78.
(24) Recently, a classical Sonogashira cross-coupling protocol
for the synthesis of compounds 3 was published: Moulton,
B. E.; Whitwood, A. C.; Duhme-Klair, A. K.; Lynam, J. M.;
Fairlamb, I. J. S. J. Org. Chem. 2011, 76, 5320.
3-[(3,4-Dimethoxyphenyl)ethynyl]pyridine (3l)
Mp 53–55 °C. 1H NMR (300 MHz, CDCl3): d = 3.89 (m,
© Thieme Stuttgart · New York
Synlett 2012, 23, 773–777

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.