Regio- and stereoselective synthesis of 1-(1-halovinyl)-1H-indoles from 1-ethynyl-1H-indoles with in situ generated HX

Article abstract of DOI:10.1016/j.tetlet.2013.03.107

A facile approach to 1-(1-halovinyl)-1H-indoles from readily accessible 1-ethynyl-1H-indoles with in situ generated HX is described. The simple protocol enables a regio- and stereoselective hydrohalogenation to the triple bonds in gram-scale, and provides a general entry for novel N-alkenylindole derivatives.

Full text of DOI:10.1016/j.tetlet.2013.03.107

Tetrahedron Letters 54 (2013) 2878–2881
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regio- and stereoselective synthesis of 1-(1-halovinyl)-1H-indoles
from 1-ethynyl-1H-indoles with in situ generated HX
⇑
Akihiro H. Sato, Kazuhiro Ohashi, Kouhei Ito, Tetsuo Iwasawa
Department of Materials Chemistry, Faculty of Science and Technology, Ryukoku University, Otsu, Shiga 520-2194, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile approach to 1-(1-halovinyl)-1H-indoles from readily accessible 1-ethynyl-1H-indoles with in situ
generated HX is described. The simple protocol enables a regio- and stereoselective hydrohalogenation to
the triple bonds in gram-scale, and provides a general entry for novel N-alkenylindole derivatives.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 27 February 2013
Revised 19 March 2013
Accepted 22 March 2013
Available online 2 April 2013
Keywords:
Iodotrimethylsilane
Haloenamides
Indole
Hydroiodation
Ynamides
Enamides are valuable intermediates in organic synthesis,1–3
because of their ability to serve as building blocks in a wide variety
of functional group transformations.4 They have also been found as
a substructure in numerous bioactive natural products and phar-
maceutically interesting compounds.5 In addition, they recently
have emerged as a novel type of useful nucleophiles in stereoselec-
tive C–C and C–N bond-forming reactions.6 From the synthetic
point of view, haloenamides are versatile variants of enamides.
Reactive bond between sp2 carbon and halogen in haloenamide
is advantageous to chemical transformation, and this beneficial
point would expand the possibilities and importance of enamide
structure. Iodoenamides are especially useful, as they are readily
converted into various functional groups by halogen-metal
exchange and are significant for carbon–carbon bond forming reac-
tions by way of transition-metal catalyzed cross-coupling reac-
tions.7–9 Thus, the weakly bonded iodide and electron-rich olefin
are highly reactive and potentially useful toward the synthesized
nitrogen-containing complex molecules.10,11 Despite the utility of
iodoenamides, their synthetic availability still remains a challenge,
because of the inherent difficulty in regio- and stereoselective
hydrohalogenation.12 The stoichiometric addition of hydrogen io-
dide (HI) to ynamide is one way to prepare iodoenamides; however
the hygroscopic and gaseous HI is inconvenient, and this method
often results in poor regio- and stereochemical control, and separa-
tion of the resultant isomeric mixtures is laborious.13
The pioneering work for efficient synthesis of iodoenamide
from ynamide via addition of HI was reported by Hsung and
co-workers in 2003.14 The in situ generation of HI from MgI2 and
H2O afforded a-iodoenamides with good selectivities of E/Z ratios.
The outcome of stereoselective addition is dictated by the polariza-
tion of the triple bond caused by nitrogen.15 According to the nat-
ure of the keteniminium resonance form, the iodine automatically
unites with the a-carbon. There was still room for improvement in
the reaction efficiency, especially in terms of its scale and purity;
the prototype system worked using only 0.1 mmol of starting al-
kynes and giving the products with E/Z mixtures. On the other
hand, very recently we successfully performed a synthesis of
a-
iodoenamide as a single isomer in gram-scale (up to 2.62 g) using
in situ generated HX.16 The in situ HX (X = I, Br) was generated
from halotrimethylsilane (TMSX) and H2O, and added to ynamide
in nearly quantitative yields with perfect regio- and stereoselectiv-
ities.14,17,18 The method completes the reaction quickly under rou-
tine conditions, and showed extensive substrate compatibility.
Herein we present a facile vinyl halogenation of 1-ethynyl-
1H-indoles,19,20 which regio- and stereoselectively yields
1-(1-halovinyl)-1H-indoles through the addition of the in situ
generated HX (Scheme 1). Our previously reported method was
successfully applicable to the triple bond of 1-ethynyl-1H-indoles:
to the best of our knowledge, so far such a compound of
1-(1-halovinyl)-1H-indole has not been reported. Thus, the proto-
col provides a simple access to novel 1-(1-halovinyl)-1H-indole
moieties.
At the onset of our study, we focused on TMSI-mediated
⇑
Corresponding author. Tel.: +81 77 543 7461; fax: +81 77 543 7483.
E-mail address: iwasawa@rins.ryukoku.ac.jp (T. Iwasawa).
hydroiodation of 1,21,22 based on our previous report.16,23 The
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.107

A. H. Sato et al. / Tetrahedron Letters 54 (2013) 2878–2881
2879
Table 1
Evaluation of the reactivity of 1 conducted via Scheme 1a
Entry
TMSI (equiv)
Temp (°C)
Solvent
Yieldb (%)
(E)-2
1
1
2
3
4
5
6
1.2
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
À78
À78
À78
À45
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2/H2O (4% v/v)
CH2Cl2/H2O (4% v/v)
Toluene
CPME
THF
Hexane
CH3CN
CH2Cl2
CH2Cl2
73
99
Quant.
95
94
12
0
0
0
0
0
0
0
0
0
0
39
4
4
31
99
>99
9
0
99
Scheme 1. Hydroiodation of 1, 3, and 5.
rt
97
97
7c
8d
9f
À78
À78
0g
99 (96)e
Quant.
95
10h
11
12
13
14
15
16
17
18i
19j
20k
0g
À78
99
61
92
96
68
<1
0
88
rt
À78
À78
À78
À78
À20
À78
À78
À78
Quant.
0
CH2Cl2
a
Reaction conditions: 1 (1 mmol), solvent (8 mL), 1 M (CH3)3SiI in CH2Cl2, H2O
(20 mmol).
b
Isolated yields of 2 and recovered 1.
After addition of H2O, the reaction was conducted at 0 °C.
D2O was used instead of H2O.
% D in parenthesis.
4 mL of CH2Cl2 was used.
For dissolving 1 in CH2Cl2, the reaction was performed at 0 °C.
1 mL of CH2Cl2 was used.
CH3OH was used instead of H2O.
(CH3)3SiBr was used instead of (CH3)3SiI.
(CH3)3SiCl was used instead of (CH3)3SiI.
c
d
e
f
g
h
i
Figure 1. ORTEP drawing of 2 with thermal ellipsoids at the 50% probability
level. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å):
N(2)–C(9) = 1.415, C(9)–I(1) = 2.125, C(9)–C(10) = 1.327, C(10)–C(11) = 1.479.
j
k
mixture of 1 and TMSI24 was stirred at À78 °C for 10 min, then
water was added, and the reaction was allowed to warm to ambi-
ent temperature. After workup and purification, the product was
Table 2
Evaluation of the reactivity of 3 and 5 conducted via Scheme 1a
1
isolated without decomposition, and both H and 13C NMR analy-
Entry Substrate Solvent
Temp (°C)
Yieldb (%)
ses revealed it to be a single isomer. The molecular structure of 2
4 or 6 (E/Z) 3 or 5
was determined by crystallographic analysis as shown in Figure
1
2
3
3
5
3
5
5
3
5
3
5
3
3
5
3
3
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
À78
À78
0
0
rt
95/4
95/5
97/3
93/7
53/4
95/4
94/6
98/2
98/2
97/3
96/4
98/2
91/9
93/4
Quant./0
Trace
0
0
0
1,25 disclosing its stereochemistry as a (E)- -iodovinyl adduct.26
a
As summarized in Table 1, the reactivity of 1 conducted via
Scheme 1 was evaluated. More than 1.5 equiv of TMSI was needed
for completion (entries 1–3), and a wide range of temperature was
tolerated (entries 3–6). For entry 8, deuterioiodation of 1 was car-
ried out with D2O, and deuterium was incorporated in 96%. The
concentration was increased in entries 9 and 10, and high yielding
transformations were achieved. For entries 11 and 12, addition of
H2O to the solvent in advance yielded 99% at À78 °C and 61% at
room temperature, respectively. Other solvents of toluene, cyclo-
pentyl methyl ether, and THF gave an acceptable yield of (E)-2
although some unreacted 1 remained (entries 13–15). For entry
18, methanol was used as a proton source in place of H2O, however,
9% of the starting 1 remained. For entries 19 and 20, (CH3)3SiBr and
(CH3)3SiCl were used instead of TMSI; the former quantitatively
4
5c
0
6
7
CH2Cl2/H2O (4% v/v) À78
Trace
CH2Cl2/H2O (4% v/v) À78
0
0
0
0
0
0
0
3
0
8d
9d
10e
11f
12f
13g
14h
15h
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
0
0
0
0
À78
À78
a
Reaction conditions: 3 or 5 (0.5 mmol), solvent (4 mL), 1 M (CH3)3SiI in CH2Cl2
(2 equiv), H2O (10 mmol).
Determined by 1H NMR after column chromatography.
b
c
Compound 6 was purified with short-plug column chromatography.
yielded the corresponding (E)-a-bromovinyl, while the latter
d
CH3OH was added instead of H2O.
1.5 equiv of (CH3)3SiI was used.
2 mL of CH2Cl2 was used.
0.5 mL of CH2Cl2 was used.
resulted in 0%. The respective bond energies of Si–Cl, Si–Br, and
Si–I are 113, 96, and 77 kcal/mol:27 the obstinate bond of Si–Cl
would be difficult to activate. It is worth noting that any (Z)- or
b-isomer of 2 was not observed on NMR spectra and TLC analyses
from entry 1 through entry 20.
e
f
g
h
(CH3)3SiBr was used instead of (CH3)3SiI.
On the other hand, as shown in Table 2, the hydrohalogenation
of 3 and 5 conducted via Scheme 1 afforded the E/Z isomeric mix-
tures of 4 and 6, in high yields. For entries 1–5, small amounts of
(Z)-4 and (Z)-6 were observed at a wide range of temperatures.
Addition of 20 equiv water in advance (entries 6 and 7), and the
employment of methanol (entries 8 and 9), and the increased
concentration (entries 11–13) did not afford 4 or 6 as a single
isomer. For entry 15, surprisingly, the hydrobromination of 5
exclusively gave (E)-6 in quantitative yield. Noteworthy is
that highly stereochemical controls were achieved at all entries
in Table 2.

2880
A. H. Sato et al. / Tetrahedron Letters 54 (2013) 2878–2881
Table 3
With optimized conditions in hand for the TMSX-mediated syn-
Scope of the reactiona
thesis of 1-(1-halovinyl)-1H-indoles, we next turned our attention
to the scope of this reaction. The results are summarized in Table 3.
The reactions at gram-scale successfully performed in synthesizing
2 of 3.15 g and 8a of 1.47 g without any isomers, respectively.28,29
Recrystallization of acetyl 4 on a E/Z = 98/2 mixture afforded a
single (E)-isomer of 1.24 g in 80% yield. Methyl indole 8b as only
E-form was suitably obtained in 97% yield. The ester group at
2-position of the indole frame was accepted for the hydrohalogen-
ation in high yields (8c and 8d), and the substrate derived from ali-
phatic alkynes was converted into the corresponding halovinyls
with perfect stereo-control (8e and 8f). In the presence of func-
tional groups such as OMe and CN (8g–8j) the transformation
worked well with high stereoselectivity, although 8j was produced
along with 37% of the unreacted 7j. Notably, all the 1-(1-halovi-
nyl)-1H-indoles in Table 3 were stable without decomposition,
whereas the similar stability of the vinyl halides was not observed
in (E)-a
-haloenamides and (1-iodovinyl)arene.16
The mechanism resulting in high stereochemical control to pro-
duce predominantly (E)-adducts is not yet fully known. Prelimin-
ary mechanistic investigations were performed through the
deuterioiodation of 1 (Table 1, entry 8) and competitive reactions
(Table 4). The deuterioiodation of 1 was carried out with D2O,
and the deuterium was thoroughly incorporated for H of (E)-2.
As for competitive reactions, 5 dominated over 1 in reactivity
(run 1 and 2): 5 was quantitatively transformed into 6, while ca.
80% of 1 was unreacted. These indicate that the hydrohalogenation
does not follow a stepwise path, and carbonyl substituents such as
ester or ketone on indole did not affect the selectivities: the nitro-
gen atom of indole scaffold likely coordinate to the silicon atom,
involving the exact syn-addition of HBr.14,30–32 Actually, diphenyl-
acetylene was tested on this hydrohalogenation system, and no
reaction was observed.16a
In summary, a simple procedure for regio- and stereoselective
hydrohalogenation of 1-ethynyl-1H-indoles has been developed.
This approach afforded a variety of new and potentially useful
1-(1-halovinyl)-1H-indoles in high yields along with the practi-
cally perfect stereochemical outcomes. The method quickly com-
pletes the reaction under routine conditions, and was readily
amenable to scale-up. Mechanistically, nitrogen of indole scaffold
likely coordinates to silicon, involving the exact syn-addition of
HI. We hope this reliable methodology finds widespread use in
organic synthesis. Application and mechanistic elucidation are
ongoing for further development of this reaction and will be re-
ported in due course.
a
Reaction conditions: 7 (1 equiv), CH2Cl2 (8 mL/mmol of 7), 1 M (CH3)3SiX in
CH2Cl2 (2 equiv).
b
Recrystallization from ethanol.
c
Reaction was conducted at À20 °C.
d
Determined by 1H NMR. 37% of unreacted 7j was observed.
Table 4
Competitive experiments of hydrobromination between 1 and 5
Run
Conditions
Amount (mmol)
1
2
5
6
1
2
(1)
(2)
(1)
(2)
CH2Cl2 (8 mL), À78 °C, 10 min; then 1 M TMSBr (1.5 equiv)
H2O (0.4 mL), rt, 50 min
0.41
0.09
0
0.50
CH2Cl2 (8 mL)/H2O (0.4 mL), À78 °C, 10 min; then 1 M TMSBr (1.5 equiv)
0.40
0.10
0
0.50
rt, 50 min

A. H. Sato et al. / Tetrahedron Letters 54 (2013) 2878–2881
2881
Jouvin, K. Angew. Chem., Int. Ed. 2010, 49, 2840; (c) DeKorver, K. A.; Li, H.; Lohse,
A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev. 2010, 110, 5064; (d)
Mulder, J. A.; Kurtz, K. C. M.; Hsung, P. R. Synlett 2003, 1379.
Acknowledgments
We thank Dr. Ken-ichi Yamada at the Kyoto University for use-
ful discussion and gentle assistance with measurement of X-ray
diffraction and scattering. We are very grateful to Professor
Michael P. Schramm at the California State University of Long
Beach for helpful discussion.
16. (a) Sato, A. H.; Mihara, S.; Iwasawa, T. Tetrahedron Lett. 2012, 53, 3585–3589;
(b) Sato, A. H.; Ohashi, K.; Iwasawa, T. Tetrahedron Lett. 2013, 54, 1309–1311.
17. Kamiya, N.; Chikami, Y.; Ishii, Y. Synlett 1990, 675–676.
18. Jouvin, K.; Coste, A.; Bayle, A.; Legrand, F.; Karthikeyan, G.; Tadiparthi, K.;
Evano, G. Organometallics 2012, 31, 7933–7947.
19. (a) Gupta, L.; Talwar, A.; Chauhan, M. S. Curr. Med. Chem. 2007, 14, 1789–1803;
(b) Gul, W.; Hamann, M. T. Life Sci. 2005, 78, 442–453; (c) Aygun, A.; Pindur, U.
Curr. Med. Chem. 2003, 10, 1113–1127; (d) Skibo, E. B.; Xing, C.; Dorr, R. T. J.
Med. Chem. 2001, 44, 3545–3562; (e) McLeay, L. M.; Smith, B. L.; Munday-Finch,
S. C. Res. Vet. Sci. 1999, 66, 119–127; (f) Katritzky, A. R.; Zhang, G.; Xie, L.;
Ghiviriga, I. J. Org. Chem. 1996, 61, 7558–7563; (g) Bergman, J.; Venemalm, L.;
Gogoll, A. Tetrahedron Lett. 1990, 46, 6067–6084.
20. (a) Li, H.; Boonnak, N.; Padwa, A. J. Org. Chem. 2011, 76, 9488–9496; (b) Joshi,
M.; Patel, M.; Tiwari, R.; Verma, A. K. J. Org. Chem. 2012, 77, 5633–5645.
21. (a) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett.
2004, 6, 1151–1154; (b) Zhang, X.; Zhang, Y.; Huang, J.; Hsung, R. P.; Kurtz, K. C.
M.; Oppenheimer, J.; Petersen, M. E.; Sagamanova, I. K.; Shen, L.; Tracey, M. R. J.
Org. Chem. 2006, 71, 4170–4177.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
03.107.
References and notes
22. Our improved procedure for preparing 1-ethynyl-1H-indoles affords high
yields, see Supplementary data.
1. (a) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional
Group Preparations; Wiley-VCH: New York, 1999; (b) Rappoport, Z. The
Chemistry of Enamines. In The Chemistry of Functional Groups; John Wiley
and Sons: New York, 1994.
2. (a) Shen, R.; Porco, J. A., Jr. Org. Lett. 2000, 2, 1333; (b) Jiang, L.; Job, G. E.;
Klapars, A.; Buchwald, S. L. Org. Lett. 2003, 5, 3667.
23. Representative procedure for synthesizing (E)-2 (Table 1, entry 3): to a solution
of 1 (1 mmol) in anhydrous CH2Cl2 (8 mL) at À78 °C was added TMSI (1 M in
CH2Cl2) dropwise over 5 min, and the mixture was stirred for 10 min. Then,
H2O (20 mmol) was added, and the cooling-bath was removed to warm to
room temperature. After additional stirring for 50 min, the reaction was
quenched at 0 °C with saturated aqueous sodium thiosulfate, and stirred for
30 min, and allowed to warm to ambient temperature. To the mixture was
added CH2Cl2, and organic phases were washed with brine, and then dried over
Na2SO4, and concentrated to give a crude product. Purification by silica gel
column chromatography (eluent; toluene/EtOAc = 100/1) afforded 403 mg of
(E)-2 in quantitative yield as a pale yellow solid material. 1H NMR (400 MHz,
CDCl3) d 8.21 (dd, J = 8.1, 1.5 Hz, 1H), 7.79 (s, 1H), 7.45 (s, 1H), 7.42–7.30 (m,
3H), 7.20–7.16 (m, 1H), 7.13–7.09 (m, 2H), 6.76 (dd, J = 9.0, 1.4 Hz, 2H), 3.91 (s,
3H). 13C NMR (100 MHz, CDCl3) d 128.3, 127.0, 124.5, 123.7, 122.2, 112.3,
111.7, 84.1, 51.6. MS (EI) m/z: 403 (M+), 372 ([MÀOCH3]+), 276 ([MÀI]+). IR
(neat): 3121, 3048, 1697 (C@O), 1621 (C@C) cmÀ1. Anal. Calcd for C18H14INO2:
C, 53.62; H, 3.50; N, 3.47. Found: C, 53.46; H, 3.60; N, 3.73.
3. For reviews on enamides, see: (a) Dehli, J. R.; Legros, J.; Bolm, C. Chem. Commun.
2005, 41, 973; (b) Whitesell, J. K.; Whitesell, M. A. Synthesis 1983, 517; (c)
Hickmott, P. W. Tetrahedron Lett. 1982, 38, 1975; (d) Hickmott, P. W.
Tetrahedron Lett. 1982, 38, 3363; (e) Lenz, G. R. Synthesis 1978, 489.
4. (a) Ruan, J.; Xiao, J. Acc. Chem. Res. 2011, 44, 614–626; (b) Ma, D.; Cai, Q. Acc.
Chem. Res. 2008, 41, 1450–1460.
5. (a) Nielsene, P. H.; Anthoni, U.; Christophersen, C. Acta Chem. Scand. 1988, B42,
489–491; (b) Anthoni, U.; Bock, K.; Chevolot, L.; Larsen, C.; Nielsen, P. H.;
Christophersen, C. J. Org. Chem. 1987, 52, 5638–5639; Anthoni, U.; Chevolot, L.;
Larsen, C.; Nielsen, P. H.; Christophersen, C. J. Org. Chem. 1987, 52, 4709–4719;
(d) Chevolot, L.; Chevolot, A.-M.; Gajhede, M.; Larsen, C.; Anthoni, U. J. Am.
Chem. Soc. 1985, 107, 4542–4543; (e) Lin, X.; Weinreb, S. M. Tetrahedron Lett.
2001, 42, 2631–2633; (f) Pinder, J. L.; Weinreb, S. M. Tetrahedron Lett. 2003, 44,
4141–4143; (g) Nishikawa, T.; Kajii, S.; Isobe, M. Synlett 2004, 2025–2027; (h)
Baran, P. S.; Shenvi, R. A.; Mitsos, C. A. Angew. Chem., Int. Ed. 2005, 44, 3714–
3717; (i) Sun, C.; Camp, J. E.; Weireb, S. M. Org. Lett. 2006, 8, 1779–1781.
6. Matsubara, R.; Kobayashi, S. Acc. Chem. Res. 2008, 41, 292. and references
therein.
24. Preparation of 1 M TMSI in CH2Cl2, see Supplementary data.
25. Crystal data of (E)-2: orthorhombic, space group P212121, colorless,
a = 10.247(3) Å, b = 10.904(3) Å, c = 13.780(3) Å,
a b c
= 90°, V = 1539.7 Å3,
Z = 4, T = À180 °C, dcalcd = 1.739 g cmÀ3
, l(Mo, Ka
) = 2.09 mmÀ1, R1 = 0.0193,
wR2 = 0.0451, GOF = 1.241.
26. Compound 5 was converted to the corresponding olefin using tert-BuLi for
lithium–halogen exchange, and the (Z)-olefin was obtained in 94% yield with
typical coupling constant J = 9.2 Hz for cis-form: in brief, the compound 5 was
in (E)-fashion.
27. (a) Walsh, R. Acc. Chem. Res. 1981, 14, 246–252; (b) Doncaster, A. M.; Walsh, R.
J. Phys. Chem. 1979, 83, 3037–3040.
7. (a) Brandsma, L.; Verkruijsse, H. Preparative Polar Organometallic Chemistry 1;
Springer: Berlin, 1987; (b) Wakefield, B. J. Organolithium Methods; Academic
Press: London, 1988; (c) Brandsma, L. Preparative Polar Organometallic
Chemistry 2; Springer: Berlin, 1990; (d) Schlosser, M. In Organometallics in
Synthesis A Manual; Schlosser, M., Ed., 2nd ed.; Wiley: Chichester, UK, 2002; pp
1–352.
28. Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008–2022.
29. (a) Mullard, A. Nat. Rev. Drug Disc. 2011, 10, 643–644; (b) Prinz, F.; Schlange, T.;
Asadullah, K. Nat. Rev. Drug Disc. 2011, 10, 712.
8. (a) Neumann, H.; Seebach, D. Chem. Ber. 1978, 111, 2785; (b) Evans, D. A.;
Crawford, T. C.; Thomas, R. C.; Walker, J. A. J. Org. Chem. 1976, 41, 3947.
9. Galli, C.; Rappoport, Z. Acc. Chem. Res. 2003, 36, 580.
30. The alternative to the concerted way is synchronous mechanism, see: (a)
Fischer, J.; Steglich, W. Angew. Chem., Int. Ed. 1979, 18, 167–168; (b) Bearpark,
M.; Bernardi, F.; Olivucci, M.; Robb, M. A. J. Am. Chem. Soc. 1990, 112, 1732–
1737.
10. (a) Funk, R. L.; Hentley, R. J. Tetrahedron Lett. 2011, 52, 6671; (b) Heffernan, S.;
Carbery, D. R. Tetrahedron Lett. 2012, 53, 5180.
11. (a) Yu, Z.; Jin, Z. J. Am. Chem. Soc 2000, 122, 9840; (b) Liu, X.; Henderson, J. A.;
Sasaki, T.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 16678.
31. Ihara, M.; Taniguchi, T.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59,
8092–8100.
12. (a) Reddy, Ch. K.; Periasamy, M. Tetrahedron Lett. 1919, 1990, 31; (b) Stewart, L.
J.; Gray, D.; Pagni, R. N.; Kabalka, G. W. Tetrahedron Lett. 1987, 28, 4497; (c)
Stone, H.; Schecher, H. Org. Synth. Coll. 1963, 4, 543.
13. (a) Kropp, P. J.; Craword, S. D. J. Org. Chem. 1994, 59, 3102; (b) Hudrlik, P. F.;
Kulkarni, A. K.; Jain, S.; Hudrlik, A. M. Tetrahedron Lett. 1983, 39, 877; (c)
Griesbaum, K.; El-Abed, M. Chem. Ber. 2001, 1973, 106.
32. We have carried out some mechanistic studies with NMR experiments. The 1
H
and 13C NMR spectra for the mixture before addition of water were totally
same with the starting alkynes. In addition, the reaction after addition of water
was monitored with 1H NMR spectra; the spectra were completely identical to
the product. In brief, halosilylation of the starting alkyne did not occurred and
the addition of HX was too fast to pursuit the reaction intermediates.
14. Mulder, J. A.; Kurtz, K. C. M.; Hsung, R. P.; Coverdale, H.; Frederick, M. O.; Shen,
L.; Zificsak, C. A. Org. Lett. 2003, 5, 1547.
15. (a) Compain, G.; Jouvin, K.; Martin-Mingot, A.; Evano, G.; Marrot, J.;
Thibaudeau, S. Chem. Commun. 2012, 48, 5196; (b) Evano, G.; Coste, A.;