Metal-free synthesis of ynones via direct C-H alkynylation of aldehydes with ethynylbenziodoxolones

Article abstract of DOI:10.1016/j.tet.2015.06.091

Abstract A metal-free synthesis of ynones via direct alkynlyation of C-H bonds in aldehydes with ethynylbenziodoxolones is described. A variety of unactivated aldehydes undergo this transformation, affording ynones in good yields. These ynones could be fu

Full text of DOI:10.1016/j.tet.2015.06.091

Tetrahedron xxx (2015) 1e7
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Tetrahedron
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Metal-free synthesis of ynones via direct CeH alkynylation of
aldehydes with ethynylbenziodoxolones
*
*
Ruo-Yi Zhang, Long-Yi Xi, Lei Zhang, Shan-Yong Chen , Xiao-Qi Yu
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A metal-free synthesis of ynones via direct alkynlyation of CeH bonds in aldehydes with ethy-
nylbenziodoxolones is described. A variety of unactivated aldehydes undergo this transformation, af-
fording ynones in good yields. These ynones could be further transformed into important heterocycles
without purification.
Received 14 May 2015
Received in revised form 19 June 2015
Accepted 24 June 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Ynones
Ethynylbenziodoxolones
CeH alkynlyation
1. Introduction
transition metal impurities in final products, the development of
transition-metal-free cross-coupling reactions is of special impor-
Alkynones are abundant structural motifs found in numerous
biologically active molecules.1 More importantly, they are often
employed as important key intermediates in the organic synthesis.
They are precursors to valuable organic functional groups, such as
pyrimidines,2 quinolones,3 furans,4 pyrazoles,5 pyrroles,6 iso-
xazoles,7 benzodiazepines,8 flavones,9 oximes,10 chiral propargylic
alcohols.11 Therefore, developing new strategies for the synthesis of
ynones is of significance.
tance. In view of previous successful radical-induced alkynylation
reactions of ethynylbenziodoxolones,18 we envisioned that acyl
radicals generated from aldehydes could be trapped by suitable
alkynylating reagents, providing an efficient synthesis of ynones
from easily available aldehydes. Herein, we describe a metal-free
direct alkynylation of common aldehydes with ethynylbenziodox-
olones to afford ynones (Scheme 1, Eq. 4).19
Several approaches have been reported for the preparation of
ynones. Classical methods involve the addition of acetylide anion to
aldehydes followed by further oxidization (Scheme 1, Eq. 1),12
transition metal-catalyzed Sonogashira coupling of terminal al-
kynes with activated carboxylic acid derivatives, or carbonylative
Sonogashira coupling of alkynes with aryl halides (Scheme 1, Eq.
2).1b,2bed,13 Other methods, including Au-catalyzed decarbonylative
alkynylation of aldehydes with ethynylbenziodoxolones,14 Lewis
acid-promoted alkynylation of acyl chlorides with alkynyltri-
fluoroborate salts,15 homogeneous gold-catalyzed MeyereSchuster
rearrangement of propargylicpivalates followed by oxidation,16
have also been reported. Very recently, Zhou et al. developed the
first Rh(III)- or Ir(III)- catalyzed direct alkynylation from aldehydes
via chelation-assisted CeH bond activation with suitable directing
group for the synthesis of ynones (Scheme 1, Eq. 3).17 However, the
largest part of these methods required the use of transition metals.
To avoid the drawbacks of metal usage such as toxicity and heavy
2. Results and discussion
Initially, benzaldehyde and 1-[(triisopropylsilyl)-ethynyl]-1,2-
benziodoxol-3(1H)-one (TIPS-EBX) (2a) were utilized to optimize
the reaction conditions. With tert-butylhydroperoxide (TBHP) as the
initiator, the desired product 3a was isolated in 56% yield (Table 1,
entry 1). Then, several solvents were tested, but the yield got no
further increase (Table 1, entries 2e4). When the reaction temper-
ature was raised to 100 ꢀC with the reaction time shortened to 12 h,
the yield increased to 61% (Table 1, entries 1, 5e7). Several different
initiators were also screened in an effort to promote the reaction.
Unfortunately, these initiators were not effective (Table 1, entries
8e10). After optimization of the ratio of 1a and 2a, we are pleased to
obtain the desired product in 80% yield (Table 1, entry 16).
The substrate scope was subsequently investigated under the
optimized conditions. First, various substituted aldehydes were
applied to the direct coupling with TIPS-EBX. As shown in Fig. 1,
various benzaldehydes bearing electron-donating (3be3d, 3ie3j,
3l, 3n, 3o) and electron-withdrawing (3ee3h, 3k) substituents at
different positions furnished the corresponding ynones in moder-
ate to good yields, and the electron-donating substituents resulted
* Corresponding authors. Tel./fax: þ86 28 85415886; e-mail addresses: chensy@
scu.edu.cn (S.-Y. Chen), xqyu@scu.edu.cn (X.-Q. Yu).
http://dx.doi.org/10.1016/j.tet.2015.06.091
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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R.-Y. Zhang et al. / Tetrahedron xxx (2015) 1e7
Scheme 1. Methods for the synthesis of ynones.
Table 1
Optimization of reaction conditionsa
Entry
1a:2a (equiv)
Initiators (equiv)
Solvent
t (h)/T (ꢀC)
Yield (%)b
1
2
3
4
5
6
7
8
4:1
4:1
4:1
4:1
4:1
4:1
4:1
4:1
4:1
4:1
4:1
4:1
2:1
1:2
1:3
1:3
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
DTBP (4)
m-CPBA (4)
H2O2 (4)
TBHP (3)
TBHP (5)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (3)
DCE
24/80
24/80
24/80
24/80
56
53
18
18
41
46
61
40
Trace
13
58
59
51
53
75
80
MeCN
Toluene
1,4-Dioxane
DCE
DCE
DCE
DCE
DCE
DCE
DCE
12/80
24/100
12/100
12/100
12/100
12/100
12/100
12/100
12/100
12/100
12/100
12/100
9
10
11
12
13
14
15
16
DCE
DCE
DCE
DCE
DCE
a
All reactions were carried out on a 0.2 mmol scale in 1 mL of solvent under an argon atmosphere. TBHP (anhydrous, 5.5 M in decane) was used.
Yield of isolated product.
b
in comparatively better yields. The reaction was not sensitive to
through oxidation/alkynylation cascade reaction (Scheme 3).
Moreover, we performed one-pot syntheses of pyrazoles starting
from inexpensive readily available aldehydes. Here, tosylhydrazide
or phenylhydrazine was added after the coupling reaction without
isolation of ynones, and pyrazole products were successfully ob-
tained in good yield (Scheme 4).5
steric effects. High yields were observed for both para- and ortho-
substituted benzaldehydes derivatives (3b vs 3j). To our delight, the
phenolic hydroxyl group was survived in this transformation under
oxidation conditions (3l). Subsequently, we found that other aro-
matic aldehydes (3m, 3p, 3q, 3r), such as 2-naphthaldehyde, thio-
phene-2-carbaldehyde,
thiophene-3-carbaldehyde,
To investigate the mechanism, a series of controlled experi-
ments were conducted (Scheme 5). The addition of radical scav-
enger 2, 2, 6, 6-tetramethylpiperidine N-oxide (TEMPO) or 1, 1-
diphenylethylene decreased the yield of the model reaction obvi-
ously. This results indicate that this reaction most likely proceeds
via a radical pathway, and the reaction may proceed through
a similar mechanism as proposed in our previous work.18a Firstly,
the benzoyl radicals are generated from aldehydes in the presence
of TBHP. Then, the addition of the radical species to the triple bond
picolinaldehyde, etc. were also suitable for this transformation.
Interestingly, unprotected 1H-indole-3-carbaldehyde was also
good substrate for this coupling reaction (3s), providing a conve-
nient synthetic method for important indole derivatives.
Several ethynylbenziodoxolones were then prepared20 to
widen the reaction scope. As shown in Fig. 2, most of the corre-
sponding products were obtained in moderate to good yields. In
addition to silyl substituted EBX reagents, aryl and alkyl
substituted EBX reagents were also good substrates for this
transformation.
forms new radical intermediates (Scheme 6, B). Subsequently, b-
elimination of the adduct radicals occurs to afford the final product
with the formation of a benziodoxolonyl radical, which is further
transformed to 2-iodobenzoic acid via a reduction-protonation
sequence (see Scheme 6).
Addtionally, the reaction could be carried out smoothly on water
affording product 3a in moderate yield (Scheme 2). It is worth
mentioning that a series of benzyl alcohols could afford ynones
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R.-Y. Zhang et al. / Tetrahedron xxx (2015) 1e7
3
Fig. 1. Scope of aldehydes 1.a
Fig. 2. Scope of ethynylbenziodoxolones 2.a
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R.-Y. Zhang et al. / Tetrahedron xxx (2015) 1e7
Scheme 2. The synthesis of ynone on water.
Scheme 3. Oxidation/alkynylation cascade reaction for the synthesis of ynones.
Scheme 4. One-pot synthesis of pyrazoles from aldehydes with ethynylbenziodoxolones.
Scheme 5. The radical inhibition experiments.
Scheme 6. Proposed reaction mechanism.
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R.-Y. Zhang et al. / Tetrahedron xxx (2015) 1e7
5
3. Conclusion
97.46, 35.44, 31.21, 18.73, 11.27. HRMS (ESI) calcd for C22H35OSiþ
[MþH]þ: 343.2452, found: 343.2455.
In conclusion, we have developed a simple and convenient
metal-free synthesis of ynones from readily available starting ma-
terials under mild conditions. The reaction proceeds via direct CeH
alkynylation with ethynylbenziodoxolones. A series of (hetero) ar-
omatic aldehydes were alkynylated smoothly to provide targets
ynones in moderate to good yields. Based on the control experi-
ments, a radical mechanism was proposed. Here, our work repre-
4.2.5. 1-(4-Bromophenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3e). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.03e8.01 (m, 2H),
7.65e7.63 (m, 2H), 1.16e1.14 (m, 21H). 13C NMR (100 MHz, CDCl3)
d
176.55, 135.68, 132.11, 131.04, 129.69, 102.74, 99.07, 26.74, 18.70,
11.21. HRMS (ESI) calcd for C18H25BrNaOSiþ [MþNa]þ: 387.0750,
found: 387.0748.
sents
a worthy supplement and development over existing
4.2.6. 1-(4-Chlorophenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
methods for the synthesis of the valuable ynones.
(3f). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.11e8.09 (m, 2H),
7.48e7.46 (m, 2H), 1.16e1.15 (m, 21H). 13C NMR (100 MHz, CDCl3)
4. Experimental section
4.1. General information
d
176.35,140.84,135.33,130.97,129.13,102.82, 99.98, 26.75,18.71,11.25.
HRMS (ESI) calcd for C18H26ClOSiþ [MþH]þ: 321.1436, found: 321.1442.
4.2.7. 1-(4-Fluorophenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
1H NMR, 13C NMR spectra were measured on a Bruker AM400
NMR spectrometer (1H 400 MHz, 13C 100 MHz) with CDCl3 as sol-
vent and recorded in parts per million (ppm) relative to internal
tetramethylsilane (TMS) standard. ESI-MS spectral data were
recorded on a Finnigan LCQDECA mass spectrometer. Unless oth-
erwise noted, all reagents were purchased from commercial sup-
(3g). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.21e8.18 (m, 2H),
7.18e7.14 (m, 2H), 1.16e1.15 (m, 21H). 13C NMR (100 MHz, CDCl3)
d
176.07, 166.57 (d, J¼254.8 Hz), 133.42, 132.33 (d, J¼9.6 Hz), 115.98
(d, J¼22.2 Hz), 102.86, 98.59, 26.74, 18.71, 11.23. HRMS (ESI) calcd
for C18H25FNaOSiþ [MþNa]þ: 327.1551, found: 327.1556.
4.2.8. 1-(4-(Trifluoromethyl)phenyl)-3-(triisopropylsilyl)prop-2-yn-
pliers
and
used
without
further
purification.
1-one (3h). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.29e8.27 (m,
2H), 7.78e7.76 (m, 2H), 1.17e1.15 (m, 21H). 13C NMR (100 MHz,
CDCl3)
Ethynylbenziodoxolones were prepared according to the literature
procedure.
d
176.39, 139.34, 135.47 (t, J¼32.2 Hz), 129.92, 125.86 (q,
J¼3.6 Hz), 123.67 (d, J¼271.0 Hz), 102.67, 100.11, 18.71, 11.23. HRMS
4.2. General procedure for ynones
(ESI) calcd for C19H26F3OSiþ [MþH]þ: 355.1700, found: 355.1695.
In a sealed 25 mL Schlenk tube equipped with a magnetic stir
bar were added aldehydes (0.2 mmol), ethynylbenziodoxolones
(0.6 mmol, 3.0 equiv), TBHP (anhydrous, 5.5 M in decane, 3.0 equiv),
DCE (1 mL), and the reaction mixture was heated under argon at-
mosphere at 100 ꢀC for 12 h. Then, the reaction mixture was
allowed to cool to ambient temperature, and diluted with 20 mL of
ethyl acetate, and washed with brine (15 mL), water (15 mL). The
organic layer was separated and dried over Na2SO4. After concen-
trated in vacuo, the crude product was purified by column chro-
matography. The identity and purity of the product was confirmed
by 1H NMR, 13C NMR, GCeMS and HRMS.
4.2.9. 1-(m-Tolyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3i). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.00e7.97 (m, 2H),
7.43e7.36 (m, 2H), 2.42 (s, 3H), 1.17e1.16 (m, 21H). 13C NMR
(100 MHz, CDCl3) 177.91, 138.55, 136.93, 135.01, 130.21, 128.62,
d
127.05, 103.29, 97.96, 21.42, 18.72, 11.26. HRMS (ESI) calcd for
C
19H28NaOSiþ [MþNa]þ: 323.1802, found: 323.1804.
4.2.10. 1-(o-Tolyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3j). Colorless oil. 1H NMR (400 MHz, CDCl3)
8.30e8.28 (m, 1H),
7.47e7.43 (m, 1H), 7.35e7.31 (m, 1H), 7.26e7.24 (m, 1H), 2.64 (s, 3H),
1.15e1.14 (m, 21H).13C NMR (100 MHz, CDCl3)
179.41,140.81,135.51,
d
d
133.58,133.03,132.27,125.97,104.62, 94.46, 22.16,18.72,11.26. HRMS
(ESI) calcd for C19H28NaOSiþ [MþNa]þ: 323.1802, found: 323.1801.
4.2.1. 1-Phenyl-3-(triisopropylsilyl)prop-2-yn-1-one (3a). Colorless
oil. 1H NMR (400 MHz, CDCl3)
d
8.19e8.17 (m, 2H), 7.63e7.59 (m,
1H), 7.51e7.47 (m, 2H), 1.17e1.15 (m, 21H). 13C NMR (100 MHz,
4.2.11. 1-(3-Bromophenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3k). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.33e8.32 (m, 1H),
8.10e8.08 (m, 1H), 7.75e7.72 (m, 1H), 7.39e7.36 (m, 1H), 1.17e1.14
(m, 21H). 13C NMR (100 MHz, CDCl3)
176.13, 138.57, 136.96, 132.77,
CDCl3)
d 177.70, 136.88, 134.21, 129.70, 128.73, 103.17, 98.20, 18.72,
11.25. HRMS (ESI) calcd for C18H27OSiþ [MþH]þ: 287.1826, found:
287.1835.
d
130.33, 128.07, 122.98, 102.59, 99.65, 18.71, 11.23. HRMS (ESI) calcd
for C18H26BrOSiþ [MþH]þ: 365.0931, found: 365.0939.
4.2.2. 1-(p-Tolyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3b). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.08e8.06 (m, 2H),
7.30e7.28 (m, 2H), 2.43 (s, 3H), 1.16e1.15 (m, 21H). 13C NMR
4.2.12. 1-(4-Hydroxyphenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3l). White solid. 1H NMR (400 MHz, CDCl3)
d
8.12e8.10 (m, 2H),
(100 MHz, CDCl3)
d 177.42, 145.29, 134.68, 129.84, 129.46, 103.35,
6.57 (s, 2H), 1.14e1.13 (m, 21H). 13C NMR (100 MHz, CDCl3)
d
177.49,
97.53, 21.95, 18.72, 11.28. HRMS (ESI) calcd for C19H29OSiþ [MþH]þ:
162.85, 132.83, 129.50, 115.96, 103.04, 99.11, 18.66, 11.21. HRMS (ESI)
301.1982, found: 301.1978.
calcd for C18H26NaO2Siþ [MþNa]þ: 325.1594, found: 325.1604.
4.2.3. 1-(4-Methoxyphenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3c). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.15e8.13 (m, 2H),
6.97e6.95 (m, 2H), 3.89 (s, 3H), 1.16e1.15 (m, 21H). 13C NMR
(100 MHz, CDCl3) 176.37, 164.56, 132.09, 130.36, 113.98, 103.33,
4.2.13. 1-(Naphthalen-2-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3m). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.80e8.79 (m, 1H),
8.17e8.15 (m, 1H), 7.97e7.95 (m, 1H), 7.92e7.89 (m, 2H), 7.65e7.56
(m, 2H), 1.21e1.20 (m, 21H). 13C NMR (100 MHz, CDCl3)
177.65,
d
97.05, 55.74, 18.73, 11.26. HRMS (ESI) calcd for
C
19H29O2Siþ
d
[MþH]þ: 317.1931, found: 317.1940.
136.27, 134.50, 133.22, 132.52, 130.00, 129.18, 128.62, 128.05, 127.09,
123.93, 103.30, 98.15, 18.77, 11.30. HRMS (ESI) calcd for C22H29OSiþ
[MþH]þ: 337.1982, found: 337.1991.
4.2.4. 1-(4-(tert-Butyl)phenyl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3d). Colorless oil. 1H NMR (400 MHz, CDCl3)
8.12e8.10 (m, 2H),
7.52e7.50 (m, 2H), 1.35 (s, 9H), 1.17e1.15 (m, 21H). 13C NMR
(100 MHz, CDCl3) 177.38, 158.20, 134.50, 129.70, 125.74, 103.35,
d
4.2.14. 1-([1,10-Biphenyl]-4-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3n). Colorless oil. 1H NMR (400 MHz, CDCl3)
d 8.26e8.24 (m, 2H),
d
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6
R.-Y. Zhang et al. / Tetrahedron xxx (2015) 1e7
7.73e7.71 (m, 2H), 7.66e7.64 (m, 2H), 7.50e7.46 (m, 2H), 7.43e7.40
(m, 1H), 1.18e1.17 (m, 21H). 13C NMR (100 MHz, CDCl3)
177.27,
(m, 4H), 7.37e7.36 (m, 3H), 7.32e7.29 (m, 2H), 2.40 (s, 3H), 1.39 (s,
9H), 1.16e1.15 (m, 21H). 13C NMR (100 MHz, CDCl3)
144.43,136.06,
d
d
146.89, 139.86, 135.75, 130.29, 129.13, 128.56, 127.47, 127.39, 103.27,
98.16, 18.74, 11.26. HRMS (ESI) calcd for C24H31OSiþ [MþH]þ:
363.2139, found: 363.2144.
135.76, 133.75, 130.27, 129.88, 128.58, 127.98, 126.67, 110.12, 94.14,
21.73, 18.78, 11.17. HRMS (ESI) calcd for C25H35N2O2SSiþ [MþH]þ:
455.2183, found: 455.2184.
4.2.15. 3-(Triisopropylsilyl)-1-(4-(1,2,2-triphenylvinyl)phenyl)prop-
4.2.24. 1,3-Diphenyl-5-(triisopropylsilyl)-1H-pyrazole (7). Colorless
2-yn-1-one (3o). Colorless oil. 1H NMR (400 MHz, CDCl3)
oil. 1H NMR (400 MHz, CDCl3)
d
8.83 (s, 1H), 7.96e7.94 (m, 2H),
7.42e7.38 (m, 2H), 7.34e7.30 (m, 3H), 7.19e7.17 (m, 2H), 6.96e6.92
(m, 1H), 1.24e1.21 (m, 21H). 13C NMR (100 MHz, CDCl3)
143.69,
d
7.92e7.89 (m, 2H), 7.12e7.11 (m,11H), 7.04e7.00 (m, 6H),1.14e1.13
(m, 21H). 13C NMR (100 MHz, CDCl3)
d
177.16, 150.32, 143.28, 143.16,
d
143.12, 139.94, 134.85, 131.65, 131.45, 131.39, 129.18, 128.07, 128.05,
127.86, 127.18, 126.98, 126.95, 103.37, 97.70, 29.85, 18.72, 11.27.
135.68, 129.55, 128.51, 128.22, 126.12, 125.49, 121.17, 113.48, 107.70,
96.16, 18.90, 11.32. HRMS (ESI) calcd for C24H32N2NaSiþ [MþNa]þ:
399.2227, found: 399.2231.
HRMS (ESI) calcd for
541.2922.
C
38H41OSiþ [MþH]þ: 541.2921, found:
Acknowledgements
4.2.16. 1-(Pyridin-2-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3p). Colorless oil. 1H NMR (400 MHz, CDCl3)
8.78e8.77 (m, 1H),
8.17e8.15 (m, 1H), 7.87e7.84 (m, 1H), 7.50e7.47 (m, 1H), 1.17e1.16
(m, 21H). 13C NMR (100 MHz, CDCl3)
177.46, 153.20, 150.21, 136.97,
d
This work was supported financially by the National Program on
Key Basic Research Project of China (973 Program, 2013CB328900)
and the National Science Foundation of China (Grant No. 21202107,
21321061 and J1103315).
d
127.44, 124.06, 103.85, 100.95, 18.70, 11.29. HRMS (ESI) calcd for
C
17H26NOSiþ [MþH]þ: 288.1778, found: 288.1787.
Supplementary data
4.2.17. 1-(Thiophen-2-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3q). Colorless oil. 1H NMR (400 MHz, CDCl3)
7.94e7.93 (m, 1H),
7.71e7.69 (m, 1H), 7.17e7.15 (m, 1H), 1.16e1.15 (m, 21H). 13C NMR
d
Supplementary data (The detailed experimental procedures and
compounds characterization can be found in the online version)
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2015.06.091.
(100 MHz, CDCl3)
d 169.40, 145.15, 135.33, 135.10, 128.49, 102.79,
96.71, 18.71, 11.24. HRMS (ESI) calcd for C16H25OSSiþ [MþH]þ:
293.1390, found: 293.1392.
References and notes
4.2.18. 1-(Thiophen-3-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3r). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.28e8.27 (m, 1H),
1. (a) Xu, B. H.; Kehr, G.; Frohlich, R.; Wibbeling, B.; Schirmer, B.; Grimme, S.;
Erker, G. Angew. Chem., Int. Ed. 2011, 50, 7183; (b) D’Souza, D. M.; Muller, T. J. J. J.
€
7.63e7.62 (m, 1H), 7.34e7.32 (m, 1H), 1.17e1.14 (m, 21H). 13C NMR
Nat. Protoc. 2008, 3, 1660; (c) Nicolaou, K. C.; Sarlahand, D.; Shaw, D. M. Angew.
Chem., Int. Ed. 2007, 46, 4708; (d) Forsyth, C. J.; Xu, J.; Nguyen, S. T.; Samdal, I. A.;
Briggs, L. R.; Rundberget, T.; Sandvik, M.; Miles, C. O. J. Am. Chem. Soc. 2006, 128,
15114; (e) Marco-Contelles, J.; de Opazo, E. J. Org. Chem. 2002, 67, 3705; (f)
Quesnelle, C. A.; Gill, P.; Dodier, M.; St Laurent, D.; Serrano-Wu, M.; Marinier, A.;
Martel, A.; Mazzucco, C. E.; Stickle, T. M.; Barrett, J. F.; Vyas, D. M.; Balasu-
bramanian, B. N. Bioorg. Med. Chem. Lett. 2003, 13, 519; (g) Fawcett, C. H.; Firn,
R. D.; Spencer, D. M. Physiol. Plant Pathol. 1971, 1, 163; (h) Imai, K.; Ikeda, N.;
Tanaka, K.; Sugawara, S. J. Pharm. Soc. Jpn. 1956, 76, 405.
(100 MHz, CDCl3) d171.06, 143.16, 135.52, 126.92, 103.74, 96.08,
18.72, 11.24. HRMS (ESI) calcd for C16H25OSSiþ [MþH]þ: 293.1390,
found: 293.1397.
4.2.19. 1-(1H-Indol-3-yl)-3-(triisopropylsilyl)prop-2-yn-1-one
(3s). White solid. 1H NMR (400 MHz, CDCl3)
d
9.22 (s, 1H),
8.42e8.40 (m, 1H), 8.09e8.08 (m, 1H), 7.46e7.44 (m, 1H), 7.31e7.29
(m, 2H), 1.14e1.13 (m, 21H). 13C NMR (100 MHz, CDCl3)
171.87,
ꢀ
ꢀ
€
2. (a) Bannwarth, P.; Valleix, A.; Gree, D.; Gree, R. J. Org. Chem. 2009, 74, 4646; (b)
Karpov, A. S.; Merkul, E.; Rominger, F.; Muller, T. J. J. Angew. Chem., Int. Ed. 2005,
d
€
44, 6951; (c) Karpov, A. S.; Muller, T. J. J. Org. Lett. 2003, 5, 3451; (d) Karpov, A.
136.81, 135.46, 125.12, 124.34, 123.24, 122.50, 120.14, 111.82, 104.47,
91.93, 18.75, 11.29. HRMS (ESI) calcd for C20H28NOSiþ [MþH]þ:
326.1935, found: 326.1937.
€
S.; Muller, T. J. J. Synthesis 2003, 2815.
3. (a) Arcadi, A.; Aschi, M.; Marinelli, F.; Verdecchia, M. Tetrahedron 2008, 64,
5354; (b) Arcadi, A.; Marinelli, F.; Rossi, E. Tetrahedron 1999, 55, 13233.
4. (a) Jiang, H. F.; Pan, X. Y.; Huang, L. B.; Zhao, J.; Shi, D. B. Chem. Commun. 2012,
4698; (b) Lee, C. G.; Lee, K. Y.; Lee, S.; Kim, J. Tetrahedron 2005, 61, 8705; (c)
Kel’in, A. V.; Gevorgyan, V. J. Org. Chem. 2002, 67, 95.
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49, 3805; (b) Kel’in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem. Soc. 2001,
123, 2074; (c) Utimoto, K.; Miwa, H.; Nozaki, H. Tetrahedron Lett. 1981, 22, 4277.
7. Hojo, M.; Tomita, K.; Hosomi, A. Tetrahedron Lett. 1993, 34, 485.
8. Willy, B.; Dallos, T.; Rominger, F.; Schonhaber, J.; Muller, T. J. J. Eur. J. Org. Chem.
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Org. Chem. 2012, 77, 3627.
4.2.20. 1,3-Diphenylprop-2-yn-1-one (4b). Yellow oil. 1H NMR
(400 MHz, CDCl3)
d
8.24e8.22 (m, 2H), 7.70e7.62 (m, 3H), 7.54e7.41
178.18, 137.06, 134.27, 133.23,
(m, 5H). 13C NMR (100 MHz, CDCl3)
d
130.95, 129.74, 128.84, 128.78, 120.30, 93.26, 87.04. HRMS (ESI)
calcd for C15H11Oþ [MþH]þ: 207.0804, found: 207.0806.
4.2.21. 1-Phenyl-3-(o-tolyl)prop-2-yn-1-one (4c). Yellow oil. 1H
€
€
NMR (400 MHz, CDCl3)
7.55e7.51 (m, 2H), 7.38e7.36 (m, 1H), 7.31e7.29 (m, 1H), 7.26e7.24
(m, 1H), 2.60 (s, 3H). 13C NMR (100 MHz, CDCl3)
178.21, 142.33,
d 8.25e8.23 (m, 2H), 7.67e7.62 (m, 2H),
d
137.20, 134.18, 133.82, 130.95, 130.03, 129.70, 128.78, 126.09, 120.17,
92.32, 90.91, 21.04. HRMS (ESI) calcd for C16H13Oþ [MþH]þ:
221.0961, found: 221.0964.
11. (a) Matsumura, K.; Hashigushi, S.; Ikarya, T.; Noyori, R. J. Am. Chem. Soc. 1997,
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4.2.22. 4,4-Dimethyl-1-phenylpent-2-yn-1-one (4e). Colorless oil.
1H NMR (400 MHz, CDCl3)
d
8.13e8.11 (m, 2H), 7.62e7.58 (m, 1H),
7.50e7.46 (m, 2H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3)
d
178.55,
133.95, 130.16, 129.67, 128.62, 104.15, 78.27, 30.33, 26.44. HRMS
13. (a) Neumann, K. T.; Laursen, S. R.; Lindhardt, A. T.; Bang-Andersen, B.;
(ESI) calcd for C13H15Oþ [MþH]þ: 187.1117, found: 187.1116.
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€
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4.2.23. 3-Phenyl-1-tosyl-5-(triisopropylsilyl)-1H-pyrazole
(6). Colorless oil. 1H NMR (400 MHz, CDCl3)
d
8.58 (s,1H), 7.87e7.82
Please cite this article in press as: Zhang, R.-Y.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.091

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