Synthesis of 3-Substituted 3-Bromo-1-phenylallenes from Alkynylcycloheptatrienes

Article abstract of DOI:10.1021/acs.joc.8b01498

A new method has been developed for the preparation of 3-bromo-1-phenylallenes from 7-alkynylcycloheptatrienes and N-bromosuccinimide. Trisubstituted bromoallenes were obtained at room temperature in moderate to excellent yields. Functionalization of the carbon-bromine bond via Pd- or Cu-catalyzed cross-coupling reactions easily provided substituted allenes.

Full text of DOI:10.1021/acs.joc.8b01498

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Note
Synthesis of 3-Substituted 3-Bromo-1-
phenylallenes from Alkynylcyclohepta-trienes
Marie VAYER, Régis Guillot, Christophe Bour, and Vincent Gandon
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01498 • Publication Date (Web): 25 Jul 2018
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Synthesis of 3-Substituted 3-Bromo-1-phenylallenes from Alkynylcycloheptatrienes.
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Marie Vayer, Régis Guillot, Christophe Bour,* and Vincent Gandon*
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Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS UMR 8182, Université ParisꢀSud, Université
ParisꢀSaclay, Bâtiment 420, 91405 Orsay cedex, France.
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Abstract: A new method has been developed for the preparation of 3ꢀbromoꢀ1ꢀphenylallenes from 7ꢀ
alkynylcycloheptatrienes and Nꢀbromosuccinimide. Trisubstituted bromoallenes were obtained at room
temperature in moderate to excellent yields. Functionalization of the carbonꢀbromine bond via Pdꢀ or
Cuꢀcatalyzed crossꢀcoupling reactions easily provided substituted allenes.
Bromoallenes constitute an important class of compounds. Their framework can be found in a
1
variety of biologically active molecules. Besides, they have been used on many occasions as key
2
intermediates in organic synthesis. However, only a few methods to synthesize bromoallenes
have been reported. For instance, bromopropadiene can be prepared by isomerization of 3ꢀ
,
3 4
bromopropyne in the presence of copper(I) bromide. It can also be obtained by flash vacuum
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pyrolysis (400 °C) of 1ꢀbromocyclopropene. Substituted bromoallenes have been synthesized by
,
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7 8
SN2’ reaction of propargyl methanesulfonates with a bromocuprate (Scheme 1a).
Scheme 1. Synthesis of Bromoallenes
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Bromination of aryl propargyl alcohols using Nꢀbromosuccinimide (NBS) or HBr has been reꢀ
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ported (Scheme 1bꢀc).9 10 Finally, bromoallenes can also be reached by bromolactonization of conꢀ
,
,
13 14
11 12
jugated enynes,
or bromoetherification of enynes (Scheme 1d),
an approach used for the
,
15 16
total synthesis of (±)ꢀpanacene.
Our approach to bromoallenes is very different and complementary to the existing ones
(Scheme 1e). In our case, starting materials are based on the 7ꢀalkynylcycloheptatriene moiety.
Such compounds have been used previously as substrates in goldꢀcatalyzed transformations for
17
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the synthesis of indenes, barbaralones and bullvalenes, as precursors of cumulenes and barꢀ
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baralanes, and of arylallenes or endoperoxides. They are stable and can be easily synthesized
in one operational steps from an alkyne and the commercially available tropylium tetrafluoroboꢀ
rate salt. We have used 7ꢀalkynylcycloheptatriene derivatives as tools to reveal the πꢀacidity of
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Lewis acids (Scheme 2). For instance, depending on the softness or hardness of the Lewis acid
catalysts used, compound 1a may transform into distinct cycloisomerization products.
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Scheme 2. Divergent Reaction Pathways in the Lewis AcidꢀCatalyzed Skeletal Reorganization of
1a (E = CO2Me)
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We have found that the reaction of these species with electrophilic bromination agents yields
3ꢀsubstituted 3ꢀbromoꢀ1ꢀphenylallenes (Scheme 1d). In addition to being a new way of making
such compounds, this transformation is appealing because it forms trisubstituted bromoallenes
which have been rarely synthesized.7,9,11,12,14 Because of the lack of availability of substituted
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tropylium cations, the reaction is so far limited to 3ꢀbromoꢀ1ꢀphenylallenes, yet phenylallenes
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are themselves key reagents in a number of important transformations.
Based on our experience with 7ꢀalkynylcycloheptatrienes derived from arenynes,21 we began
our investigations with compound 1a (Table 1). Treatment with 1.1 equiv of NBS in MeNO2 reꢀ
sulted in a complex mixture of products. In toluene, a low conversion was obtained. In 1,2ꢀ
dichloroethane (DCE), bromoallene 2a could be isolated in 56% yield (Entry 1). Full conversion
was reached with at least 3 equiv of NBS, allowing to isolate 2a in 68% yield after removal of
unidentified side products by silica gel chromatography (Entry 2). Other sources of electrophilic
bromine were also tested. When employing 1.1 equiv of Br2, pyridinium tribromide, 1,3ꢀ
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dibromoꢀ5,5ꢀdimethylhydantoin (DBDMH)
or 2,4,4,6ꢀtetrabromoꢀ2,5ꢀcyclohexadienꢀ1ꢀone
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(TBCD),24 only complex mixtures or low conversions were observed. On the other hand,
Nꢀbromophthalimide led to 2a in 60% yield (Entry 3). Increasing the amount of
Nꢀbromophthalimide to 3 equiv resulted in the formation of sideꢀproducts (Entry 4).
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Table 1. Optimization of the Reaction Conditions (E = CO2Me)
Entry
[Br+] source
NBS
x
Yield of 2aa
56 (83)
1
2
3
1.1
3
NBS
68 (100)
60 (100)
Nꢀbromophthalimide
Nꢀbromophthalimide
1.1
3
4
ꢀ (100)c
a
b
Isolated yield after flash chromatography, conversion indicated in parentheses. Complex mixꢀ
ture. c 2a observed but contaminated by a large amount of sideꢀproducts.
O
O
O
O
Br
Br
Br
N
N
Br
N
Br
O
-
N
N
Br3
H
Br
O
O
Br Br
TBCD
-bromophthalimide
NBS
pyridinium
tribromide
DBDMH
When the reaction of 1a was carried out during an extended reaction time of 24 h (instead of 6
h) and at a higher temperature of 80 °C (instead of 25 °C), the bromoallene 2a was not isolated
(Scheme 3). We observed instead the formation of the brominated enone 3a. Its structure was
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ascertained by Xꢀray crystallography (see the Supporting Information). It presumably arises from
the reaction of 2a with NBS to give a bromonium intermediate which is trapped by adventitious
water. From the less hindered bromonium ion, this results in the formation of a E bromoenone
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which isomerizes into the thermodynamic Z product 3a. Alternatively, opening of the bromoniꢀ
um ion, rotation of the vinyl cation and bromonium reformation leads, through the most hindered
isomer, to the Z olefin directly.
Scheme 3. Formation of the Z bromoenone 3a
In spite of this possible side reaction, we decided to use 3 equiv of NBS with other malonates
(Scheme 4). With a meta methoxyphenyl (1b) or a 3,5ꢀdimethylphenyl group (1c), the reaction
were faster than with 1a (3 h instead of 6 h), with still full conversion. The rate was even higher
when the phenyl group was replaced by naphthalene, which gave rise to 2d in 68% yield in only
1 h. The presence of an alkene instead of a phenyl group proved also compatible with our condiꢀ
tions. However, the transformations of 1e and 1f were slower at 25 °C (~ 40% conversion after 6
h). The yields could be markedly increased to 78% and 71% for 2e and 2f respectively at 80 °C in
1 h, without enone formation.
Scheme 4. Substrate Scope with Dimethyl Malonates (E = CO2Me)
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a
b
100% conversion (NMR), yields of isolated products are given. Full conversion was not obꢀ
served at 25 °C. c E/Z 80:20.
We then studied the formation of bromoallenes with substrates synthesized from simple comꢀ
mercially available alkynes (Scheme 5). With these, the amount of NBS could be decreased to 2
or even 1.1 equiv to reach full conversion. Substrates displaying nꢀpropyl and nꢀhexyl groups
were first tested, leading to 5a and 5b as major products with 2 equiv of NBS, although some
impurities could not be eliminated from these nonꢀpolar products. With a phenethyl substituent
and only 1.1 equiv of NBS, the desired bromoallene 5c was isolated in 85% yield by simple filꢀ
tration on silica gel. Bromoallene 5d exhibiting a tꢀbutyl group was obtained with an excellent
96% yield. This reaction was scaled up to 1 g of substrate, with still a very good yield of 88%.
With alkoxy groups in the alkyl chain, the products were isolated in yields around 50% (5e, 5f,
5h). On the other hand, using a free alcohol as in 4g resulted in decomposition. The same pheꢀ
nomenon was observed with substrate 4i bearing a conjugated alkene group. The reason for the
instability of 4g and 4i under the reaction conditions could not be rationalized. Of particular inꢀ
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terest, a silylated alkyne could be efficiently converted into a bromosilylallene in 78% yield (5j).
Such compounds are not easily prepared by conventional methods and have yet proven to be useꢀ
ful intermediates.2a,26
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Scheme 5. Substrate Scope with Simple 7ꢀAlkynylcycloheptatrienes
a
b
Presence of impurities, the yield corresponds to a maximum. ~ 40ꢀ70% conversion with 1.1
d
equiv. c 88% yield on a 1 g scale. 87% conversion. e After flash chromatography. f Decomposiꢀ
tion.
A mechanistic rationale is shown in Scheme 6.20a,c The substrate A is in equilibrium with the
norcaradiene form B after 6π electrocyclization.27 Bromination of the alkyne moiety of B gives
rise to the vinyl carbocation C. The allene framework is then formed by ring opening of the cyꢀ
clopropane to give D. Proton elimination finally leads to the bromoallene E.
Scheme 6. Postulated Mechanism
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Of note, no reaction took place when NCS was used instead of NBS. With NIS, in sharp conꢀ
trast with NBS, compound 1a transformed into 6 (Scheme 7). This product presumably arises
from the hydroarylation and oxidation of an iodoindene intermediate. As mentioned above, 7ꢀ
alkynylcycloheptatrienes can be readily isomerized into indenes under gold catalysis.17 The soft
I+ cation behaves in this case as a soft Au+ ion and triggers a nonꢀclassical carbocation pathway.28
However, this takes place only because the intermediate iodoindene can be trapped by hydroaryꢀ
lation. With the simple substrate 5d, the expected iodoallene 7 could be isolated in 70% yield.
Scheme 7. Reactions with NIS (E = CO2Me)
To illustrate the utility of our methodology, we carried out functionalizations of bromoallene
5d
(Scheme
8).
A
copperꢀcatalyzed
CꢀN
coupling2f
involving
Nꢀallylꢀ4ꢀ
methylbenzenesulfonamide enabled the formation of 8 with an uncompleted conversion and a
moderate yield of 25%. A SuzukiꢀMiyaura crossꢀcoupling2g was also performed and proved more
efficient, as compound 9 could be isolated in 65% yield. Finally, the Sonogashira crossꢀcoupling2l
was studied and provided the 1,3ꢀallenynes 10a-f with a large tolerance on the alkyne moiety and
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excellent yields without purification by column chromatography.29 As above, the products were
simply isolated by filtration on silica gel. The conjugated allenyne scaffold is actually commonly
found in natural products and is a useful building block in organic synthesis.1,30
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Scheme 8. Derivatization of Bromoallene 5d
In conclusion, an efficient and straightforward procedure for the synthesis of trisubstituted 3ꢀ
bromoꢀ1ꢀphenylallenes from 7ꢀalkynylcycloheptatrienes and NBS has been developed. The prodꢀ
ucts can then be used to easily introduce allene moiety by crossꢀcoupling reactions.
EXPERIMENTAL SECTION
General Information. All reactions were performed in ovenꢀdried flasks. Unless otherwise statꢀ
ed, products were purified by flash chromatography on silica gel. Reactions in overheated solvent
were performed in 10 mL reaction tubes sealed with a Teflonꢀcoated Rodaviss® stopper and imꢀ
mersed in a preꢀheated oil bath when necessary. Reactions were monitored using thinꢀlayer
chromatography (TLC) on silica gel plates (0.25 mm) preꢀcoated with a fluorescent indicator.
The spots were visualized with ultraviolet light and/or pꢀanisaldehyde stain with heat as revealing
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agent. Flash column chromatography was performed on CombiFlash System with silica gel.
NMR characterization data was collected at 296 K on a AM 250, AV 300, AV 360 Bruker specꢀ
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trometers, operating at 250, 300, and 360 MHz respectively for H NMR. H NMR chemical
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shifts are reported in ppm using residual solvent peak as reference (CHCl3: δ = 7.27 ppm). Data
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for H NMR are presented as follows: chemical shift δ (ppm), multiplicity (s = singlet, d = douꢀ
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blet, t = triplet, m = multiplet, br = broad), coupling constant J (Hz) and integration; C NMR
spectra were recorded at 296 K on AM 250, AV 300, AV 360 Bruker spectrometers, operating at
63, 75, and 90 MHz respectively, using broadband proton decoupling. Chemical shifts are reportꢀ
ed in ppm using residual solvent peaks as reference (CHCl3: δ = 77.16 ppm). Melting points were
determined using a Reichert melting point apparatus. IR characterization data were recorded on a
FTꢀIR spectrometer (PerkinꢀElmer). HRMS was performed on a MicrOTOFq Bruker spectromeꢀ
ter (ESI) or on a QꢀTOF Agilent (APPI). Deprotonated molecular ions [M − H]−, protonated moꢀ
lecular ions [M + H]+, or sodium adducts [M + Na]+ were used for empirical formula confirmaꢀ
tion. Compounds 4f, 5b, 5h, 10d and 10f proved too apolar and too sensitive to allow massꢀ
spectroscopy analysis.
Materials. Reagents were purchased from commercially suppliers (Alfa Aesar, Sigma Aldrich or
Strem) and used as received, unless stated otherwise. Solvents were dried by distillation under
argon from the followings: tetrahydrofuran (sodium/benzophenone); toluene (sodium); 1,2ꢀ
dichloroethane (calcium hydride). Organic extracts were, in general, dried over anhydrous magꢀ
31c
nesium sulfate (MgSO4). 1,6ꢀArenynes S1a-d,31aꢀd1,6ꢀenynes S1e-f,32, 1,6ꢀarenyne S4f,
compounds 1a,21 1f,17a 4c,17a 4j,17a were synthetized according to the literature.
and
Procedure for the synthesis of the 7-alkynylcycloheptatrienes.
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The alkyne (1 equiv) was placed in an ovenꢀdried 250 mL screwꢀcap tube fitted with a septum
under a nitrogen atmosphere. Dry THF (0.1 M) was added and the resulting solution was cooled
to ꢀ78 ºC before adding nꢀBuLi (1.5 equiv) and stirred for 1 h at this temperature. Tropylium tetꢀ
rafluoroborate (1.2 equiv) was added, and then, the cooling bath was removed. After stirring the
mixture at RT for 20 h, the reaction was quenched with a saturated aqueous solution of NH4Cl
(30 mL) and the aqueous layer was extracted with Et2O (3 x 40 mL). The combined organic exꢀ
tracts were washed with brine (20 mL), dried over MgSO4 and concentrated under reduced presꢀ
sure. The crude reaction mixture was purified by chromatography on silica gel (80 g of silica,
Cy/AcOEt, 100:0 to 97:3) to afford the desired product.
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Compound 1b. Following the general procedure, 1b was obtained from S1b (1.39 g, 4.8 mmol,
1
1 equiv) as a colorless oil (0.9 g, 2.4 mmol, 49%). H NMR (360 MHz, CDCl3): δ 7.19 (t,
J = 8.0 Hz, 1H), 6.80ꢀ6.77 (m, 1H), 6.76ꢀ6.72 (m, 2H), 6.66 (dd, J = 3.7, 2.7 Hz, 2H), 6.18 (dddd,
J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.34 (dd, J = 8.8, 5.5 Hz, 2H), 3.76 (s, 6H), 3.40 (s, 2H), 2.73 (d,
J = 2.4 Hz, 2H), 2.57ꢀ2.51 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 170.4 (2 C=O), 159.7 (C),
137.3 (C), 131.2 (2 CH), 129.5 (CH), 124.9 (2 CH), 123.8 (2 CH), 122.3 (CH), 115.8 (CH), 112.6
(CH), 85.9 (C), 75.4 (C), 58.7 (C), 55.2 (CH3), 52.8 (2 CH3), 37.7 (CH2), 31.8 (CH), 22.7 (CH2).
FTꢀIR (neat, cmꢀ1): 3024, 2956, 1737, 1641, 1610, 1490, 1434, 1304, 1282, 1263, 1242, 1208,
1180, 1053. HRMS (ESI) m/z: [M + Na]+ Calcd for C23H24O5Na 403.1516; Found 403.1502.
Compound 1c. Following the general procedure, 1c was obtained from S1c (1.3 g, 4.5 mmol) as
1
a yellow oil (0.82 g, 2.2 mmol, 48%). H NMR (300 MHz, CDCl3): δ 6.87 (s, 1H), 6.76 (s, 2H),
6.67 (dd, J = 3.7, 2.7 Hz, 2H), 6.19 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.35 (dd, J = 8.8, 5.5 Hz,
2H), 3.75 (s, 6H), 3.34 (s, 2H), 2.71 (d, J = 2.4 Hz, 2H), 2.58ꢀ2.52 (m, 1H), 2.27 (s, 6H). 13C
NMR (63 MHz, CDCl3): δ 170.5 (2 C=O), 137.9 (2 C), 135.6 (C), 131.2 (2 CH), 128.9 (CH),
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127.8 (2 CH), 124.9 (2 CH), 123.8 (2 CH), 85.7 (C), 75.5 (C), 58.8 (C), 52.7 (2 CH3), 37.6 (CH2),
31.8 (CH), 22.6 (CH2), 21.5 (2 CH3). FTꢀIR (neat, cmꢀ1): 3026, 2952, 1738, 1642, 1606, 1435,
1334, 1296, 1275, 1241, 1206, 1067, 1051. HRMS (ESI) m/z: [M + Na]+ Calcd for C24H26O4Na
401.1723; Found 401.1723.
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Compound 1d. Following the general procedure, 1d was obtained from S1d (1.8 g, 5.8 mmol) as
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a yellow oil (1.2 g, 3.0 mmol, 52%). H NMR (360 MHz, CDCl3): δ 7.83ꢀ7.74 (m, 3H), 7.65 (s,
1H), 7.47ꢀ7.43 (m, 2H), 7.28 (dd, J = 8.1 Hz, J = 2.0 Hz, 1H), 6.69 (dd, J = 3.7, 2.7 Hz, 2H), 6.22
(dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.39 (dd, J = 8.8, 5.5 Hz, 2H), 3.77 (s, 6H), 3.59 (s, 2H),
2.75 (d, J = 2.4 Hz, 2H), 2.62ꢀ2.57 (m, 1H). 13C NMR (90 MHz, CDCl3): δ 170.5 (2 C=O), 133.5
(C), 133.3 (C), 132.7 (C), 131.2 (2 CH), 128.9 (CH), 128.2 (CH), 128.0 (CH), 127.8 (CH), 127.8
(CH), 126.2 (CH), 125.9 (CH), 125.0 (2 CH), 123.8 (2 CH), 85.9 (C), 75.4 (C), 58.9 (C), 52.9 (2
CH3), 37.9 (CH2), 31.8 (CH), 22.7 (CH2). FTꢀIR (neat, cmꢀ1): 3025, 2652, 1738, 1601, 1436,
1330, 1288, 1243, 1204, 1065, 1050. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H24O4Na
423.1567; Found 423.1547.
Compound 1e. Following the general procedure, 1e was obtained from S1e (1.0 g, 4.8 mmol, 1
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equiv) as a pale yellow oil (0.77 g, 2.6 mmol, 54%). H NMR (300 MHz, CDCl3): δ 6.64 (dd,
J = 3.7, 2.3 Hz, 2H), 6.19ꢀ6.11 (m, 2H), 5.65 (ddt, J = 17.0, 10.0, 7.4 Hz, 1H), 5.26 (dd, J = 9.3,
5.7 Hz, 2H), 5.22ꢀ5.10 (m, 2H), 3.74 (s, 6H), 2.85ꢀ2.81 (m, 4H), 2.48ꢀ2.41 (m, 1H). 13C NMR (90
MHz, CDCl3): δ 170.5 (2 C=O), 132.0 (CH), 131.1 (2 CH), 124.8 (2 CH), 123.9 (2 CH), 119.9
(CH2), 85.1 (C), 74.9 (C), 57.4 (C), 52.9 (2 CH3), 36.8 (CH2), 31.8 (CH), 23.1 (CH2). FTꢀIR
(neat, cmꢀ1): 2953, 1739, 1437, 1327, 1291, 1250, 1218, 1141. HRMS (ESI) m/z: [M + Na]+
Calcd for C18H20O4Na 323.1254; Found 323.1248.
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Compound 4a. Following the general procedure, 4a was obtained from 1ꢀpentyne (1.0 ml,
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10.1 mmol, 1 equiv) as a yellow oil (1.5 g, 9.5 mmol, 94%). H NMR (360 MHz, CDCl3): δ 6.65
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(dd, J = 3.7, 2.7 Hz, 2H), 6.16 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.33 (dd, J = 8.8, 5.5 Hz, 2H),
2.48ꢀ2.42 (m, 1H), 2.21 (td, J = 7.2, 2.4 Hz, 2H), 1.61ꢀ1.51 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H). 13C
NMR (90 MHz, CDCl3): δ 131.1 (2 CH), 124.5 (4 CH), 81.8 (C), 80.6 (C), 31.9 (CH), 22.5
(CH2), 20.9 (CH2), 13.6 (CH3). FTꢀIR (neat, cmꢀ1): 3014, 2963, 1933, 1873, 1635, 1453, 1390,
1329, 1281. HRMS (APPI) m/z: [M – H]– Calcd for C12H13 157.1023; Found 157.1012.
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Compound 4b. Following the general procedure, 4b was obtained from 1ꢀoctyne (1.0 ml, 6.7
mmol, 1 equiv) as a yellow oil (1.18 g, 5.9 mmol, 88%). 1H NMR (360 MHz, CDCl3): δ 6.64 (dd,
J = 3.7, 2.7 Hz, 2H), 6.15 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.32 (dd, J = 8.8, 5.5 Hz, 2H),
2.47ꢀ2.41 (m, 1H), 2.22 (td, J = 7.2, 2.4 Hz, 2H), 1.58ꢀ1.48 (m, 2H), 1.46ꢀ1.38 (m, 2H), 1.35ꢀ1.26
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(m, 4H), 0.90 (t, J = 7.2 Hz, 3H). C NMR (63 MHz, CDCl3): δ 131.1 (2 CH), 124.5 (4 CH),
81.6 (C), 80.8 (C), 32.0 (CH), 31.5 (CH2), 29.1 (CH2), 28.7 (CH2), 22.8 (CH2), 18.9 (CH2), 14.2
(CH3). FTꢀIR (neat, cmꢀ1): 3052, 3023, 3013, 2954, 2932, 2856, 1466, 1390, 1279. HRMS
(APPI) m/z: [M]+ Calcd for C15H21 201.1643; Found 201.1640.
Compound 4d. Following the general procedure, 4d was obtained from 3,3ꢀdimethylꢀ1ꢀbutyne
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(1.0 ml, 8.0 mmol, 1 equiv) as a yellow oil (1.22 g, 7.1 mmol, 88%). H NMR (360 MHz,
CDCl3): δ 6.64 (dd, J = 3.7, 2.7 Hz, 2H), 6.14 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.31 (dd, J =
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8.8, 5.5 Hz, 2H), 2.39ꢀ2.43 (m, 1H), 1.25 (s, 9H). C NMR (90 MHz, CDCl3): δ 131.0 (2 CH),
124.8 (2 CH), 124.4 (2 CH), 89.3 (C), 80.0 (C), 31.9 (CH), 31.4 (3 CH3), 27.5 (C). FTꢀIR (neat,
cmꢀ1): 3027, 2968, 2867, 1698, 1601, 1475, 1457, 1390, 1361, 1284, 1204, 1094. HRMS (APPI)
m/z: [M – H]– Calcd for C13H15 171.1168; Found 171.1168.
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Compound 4e. Following the general procedure, 4e was obtained from 3ꢀmethoxypropꢀ1ꢀyne
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(0.7 g, 10.0 mmol, 1 equiv) as a yellow oil (1.17 g, 7.3 mmol, 73%). H NMR (360 MHz,
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CDCl3): δ 6.65 (dd, J = 3.7, 2.7 Hz, 2H), 6.17 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.34 (dd, J =
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8.8, 5.5 Hz, 2H), 4.16 (d, J = 2.0 Hz, 2H), 3.41 (s, 3H), 2.57ꢀ2.51 (m, 1H). C NMR (90 MHz,
CDCl3): δ 131.1 (2 CH), 124.7 (2 CH), 123.2 (2 CH), 88.2 (C), 76.1 (C), 60.2 (CH2), 57.6 (CH3),
31.8 (CH). FTꢀIR (neat, cmꢀ1): 3027, 2934, 2820, 2236, 1699, 1602, 1464, 1449, 1391, 1377,
1357, 1278, 1187, 1142, 1099. MS (IE) m/z: [M]+ Calcd for C11H12O 160.09; Found 160.00.
Compound 4f. Following the general procedure, 4f was obtained from S4f (2.0 g, 13.7 mmol) as
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a dark yellow oil (2.5 g, 10.6 mmol, 77%). H NMR (360 MHz, CDCl3): δ 7.40ꢀ7.34 (m, 4H),
7.33ꢀ7.28 (m, 1H), 6.67 (dd, J = 3.7, 2.2 Hz, 2H), 6.21ꢀ6.15 (m, 2H), 5.35 (dd, J = 9.0, 5.5 Hz,
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2H), 4.63 (s, 2H), 4.24 (d, J = 2.2 Hz, 2H), 2.60ꢀ2.54 (m, 1H). C NMR (75 MHz, CDCl3): δ
137.7 (C), 131.1 (2 CH), 128.6 (2 CH), 128.3 (2 CH), 128.0 (CH), 124.9 (2 CH), 123.2 (2 CH),
88.3 (C), 76.2 (C), 71.6 (CH2), 57.8 (CH2), 31.9 (CH). FTꢀIR (neat, cmꢀ1): 3028, 2853, 1698,
1603, 1593, 1495, 1454, 1390, 1354, 1260. HRMS (ESI) m/z: [M + Na]+ C17H16ONa 259.1093;
Found 259.1094.
Compound 4h. Following the general procedure, 4h was obtained from (butꢀ3ꢀynꢀ1ꢀyloxy)(tertꢀ
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butyl)dimethylsilane33 (2.0 g, 10.9 mmol, 1 equiv) as a yellow oil (1.2 g, 4.4 mmol, 41%). H
NMR (360 MHz, CDCl3): δ 6.64 (dd, J = 3.7, 2.7 Hz, 2H), 6.15 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz,
2H), 5.31 (dd, J = 8.8, 5.5 Hz, 2H), 3.75 (t, J = 7.1 Hz, 2H), 2.48ꢀ2.41 (m, 3H), 0.91 (s, 9H), 0.09
(s, 6H). 13C NMR (90 MHz, CDCl3): δ 131.1 (2 CH), 124.6 (2 CH), 124.2 (2 CH), 82.8 (C), 77.4
(C), 62.4 (CH2), 31.9 (CH), 36.1 (3 CH3), 23.3 (CH2), 18.5 (C), ꢀ5.1 (2 CH3). FTꢀIR (neat, cmꢀ1):
3029, 2955, 2929, 2857, 1471, 1463, 1390, 1255, 1105, 1058. HRMS (ESI) m/z: [M + Na]+
C17H26OSiNa 297.1645; Found 297.1642.
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Compound 4i. Following the general procedure, 4i was obtained from 1ꢀ(propꢀ2ꢀynꢀ1ꢀ
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yl)cyclohexꢀ1ꢀene (1.0 g, 8.3 mmol, 1 equiv) as a yellow oil (1.69 g, 8.3 mmol, 97%). H NMR
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(360 MHz, CDCl3): δ 6.68 (dd, J = 3.7, 2.7 Hz, 2H), 6.17 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H),
6.11 (tt, J = 4.1, 2.0 Hz, 1H), 5.34 (dd, J = 8.8, 5.5 Hz, 2H), 2.58 (tt, J = 5.6, 1.5 Hz, 1H), 2.17ꢀ
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2.12 (m, 2H), 2.12ꢀ2.06 (m, 2H), 1.68ꢀ1.54 (m, 5H). C NMR (90 MHz, CDCl3): δ 134.3 (CH),
131.1 (2 CH), 124.6 (2 CH), 123.9 (2 CH), 120.8 (C), 88.3 (C), 82.5 (C), 32.3 (CH), 29.6 (CH2),
25.7 (CH2), 22.5 (CH2), 21.7 (CH2). FTꢀIR (neat, cmꢀ1): 3026, 2929, 2858, 2835, 1697, 1633,
1601, 1447, 1435, 1390, 1347, 1285, 1266, 1136, 1076, 1051. HRMS (APPI): m/z: [M + H]+
Calcd for C15H16 197.1330; Found 197.1322.
Synthesis of 7-alkynylcycloheptatriene 4g. In a 100 mL round bottom flask, 4h (1.4 g, 5.1
mmol, 1 equiv) and THF (20 mL) was introduced. Tetrabutylammonium fluoride solution (5.1
mL, 5.1 mmol, 1 M in THF) was added slowly and the resulting solution was stirred at RT during
1 hour. Then, H2O was added and the mixture was stirred for 30 min. The aqueous layer was exꢀ
tracted with Et2O (3 x 40 mL). The combined organic extracts were washed with brine (20 mL),
dried over MgSO4 and concentrated under reduced pressure. The crude reaction mixture was puꢀ
rified by chromatography on silica gel (80 g of silica, Cy/AcOEt, 100:0 to 80:20) to afford 4g
(0.67 g, 4.2 mmol, 82%) as a yellow liquid. 1H NMR (360 MHz, CDCl3): δ 6.65 (dd, J = 3.7, 2.7
Hz, 2H), 6.16 (dddd, J = 8.8, 3.7, 2.7, 1.5 Hz, 2H), 5.31 (dd, J = 8.8, 5.5 Hz, 2H), 3.77ꢀ3.70 (m,
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2H), 2.53ꢀ2.48 (m, 3H), 1.90 (brs, 1H). C NMR (90 MHz, CDCl3): δ 131.1 (2 CH), 124.8 (2
CH), 123.7 (2 CH), 83.9 (C), 76.9 (C), 61.4 (CH2), 31.7 (CH), 23.3 (CH3). FTꢀIR (neat, cmꢀ1):
3344, 3026, 2938, 1391, 1282, 1182. HRMS (ESI) m/z: [M + H]+ Calcd for C11H12ONa
183.0776; Found 183.0780.
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Procedure for the Formation of Compounds 2a-f. In air, substrate 1b-f (1 equiv), NBS (3
equiv) and dry DCE (0.2 M) were charged in a 10 mL tube equipped with a Teflonꢀcoated magꢀ
netic stir bar. The tube was sealed with a plastic stopper and the mixture was stirred at the indiꢀ
cated temperature during the indicating time with TLC reaction progress monitoring. Then, the
reaction was quenched with a saturated aqueous solution of Na2S2O4 (5 mL) and the aqueous
layer was extracted with Et2O (3 x 10 mL). The combined organic extracts were washed with
brine (10 mL), dried over MgSO4 and concentrated under reduced pressure. The crude product
was purified by flash chromatography (12 g of SiO2 previously treated by 5% of Et3N,
Cy/EtOAc, 100:0 to 95:5) to afford bromoallene 2b-f.
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Compound 2a. The general procedure was followed with 1a (30 mg, 0.09 mmol) to afford 2a as
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a colorless oil (24.5 mg, 0.06 mmol, 68%). H NMR (300 MHz, CDCl3): δ 7.39 (s, 2H), 7.38ꢀ
7.37 (m, 2H), 7.32ꢀ7.24 (m, 4H), 7.15ꢀ7.11 (m, 2H), 6.34 (dd, J = 3.2, 3.2 Hz, 1H), 3.69 (s, 3H),
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3.55 (s, 3H), 3.38 (s, 2H), 3.25 (dd, J = 16.6, 3.2 Hz, 1H), 3.08 (dd, J = 16.6, 3.2 Hz, 1H). C
NMR (75 MHz, CDCl3): δ 200.7 (C), 170.1 (C=O), 170.0 (C=O), 135.7 (C), 132.1 (C), 130.0 (2
CH), 129.0 (2 CH), 128.8 (CH), 128.5 (2 CH), 128.3 (2 CH), 127.3 (CH), 102.3 (CH), 89.8 (C),
58.8 (C), 52.8 (2 CH3), 39.5 (CH2), 37.5 (CH2). FTꢀIR (neat, cmꢀ1): 2949, 2620, 1952, 1736,
1603, 1437, 1335, 1273, 1239, 1215, 1065. HRMS (ESI) m/z: [M + Na]+ Calcd for
C22H21O4BrNa 451.0515; Found 451.0497.
Compound 2b. The general procedure was followed with 1b (40 mg, 0.11 mmol) to afford 2b as
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a colorless oil (30.0 mg, 0.07 mmol, 62%). H NMR (360 MHz, CDCl3): δ 7.38ꢀ7.35 (m, 4H),
7.32ꢀ7.26 (m, 1H), 7.17 (t, J = 8.1 Hz, 1H), 6.77 (dd, J = 8.1, 2.6 Hz, 1H), 6.69ꢀ6.65 (m, 2H),
6.32 (dd, J = 3.2, 3.2 Hz, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 3.54 (s, 3H), 3.33 (s, 2H), 3.24 (dd,
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J = 16.6, 3.2 Hz, 1H), 3.07 (dd, J = 16.6, 3.2 Hz, 1H). C NMR (90 MHz, CDCl3): δ 200.8 (C),
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170.2 (C=O), 170.0 (C=O), 159.7 (C), 137.2 (C), 132.2 (C), 129.5 (CH), 129.1 (2 CH), 128.9
(CH), 128.3 (2 CH), 122.3 (CH), 115.5 (CH), 113.1 (CH), 102.3 (CH), 89.9 (C), 58.8 (C), 55.3
(CH3), 52.9 (CH3), 52.8 (CH3), 39.5 (CH2), 37.5 (CH2). FTꢀIR (neat, cmꢀ1): 2952, 2836, 1950,
1738, 1600, 1584, 1489, 1452, 1434, 1282, 1263, 1203, 1181, 1054, 1043. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C23H23O5BrNa 481.0621; Found 481.0621.
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Compound 2c. The general procedure was followed with 1c (40 mg, 0.11 mmol) to afford 2c as
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a colorless oil (25.1 mg, 0.05 mmol, 52%). H NMR (360 MHz, CDCl3): δ 7.39ꢀ7.35 (m, 4H),
7.32ꢀ7.28 (m, 1H), 6.85 (s, 1H), 6.70 (s, 2H), 6.32 (dd, J = 3.2, 3.2 Hz, 1H), 3.69 (s, 3H), 3.54 (s,
3H), 3.28 (s, 2H), 3.21 (dd, J = 16.6, 3.2 Hz, 1H), 3.04 (dd, J = 16.6, 3.2 Hz, 1H), 2.23 (s, 6H).
13C NMR (90 MHz, CDCl3): δ 201.0 (C), 170.3 (C=O), 170.2 (C=O), 137.8 (2 C), 135.3 (C),
132.2 (C), 128.9 (2 CH), 128.8 (CH), 128.7 (CH), 128.2 (2 CH), 127.7 (2 CH), 102.1 (CH), 89.8
(C), 58.7 (C), 52.6 (CH3), 52.6 (CH3), 39.3 (CH2), 37.3 (CH2), 21.3 (2 CH3). FTꢀIR (neat, cmꢀ1):
2951, 2621, 1950, 1739, 1605, 1434, 1333, 1275, 1236, 1212, 1068. HRMS (ESI) m/z: [M + Na]+
Calcd for C24H25O4BrNa 479.0828; Found 479.0826.
Compound 2d. The general procedure was followed with 1d (50 mg, 0.12 mmol) to afford 2d as
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a colorless oil (40.7 mg, 0.08 mmol, 68%). H NMR (300 MHz, CDCl3): δ 7.79 (dd, J = 6.0,
3.3 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.69 (dd, J = 6.0, 3.3 Hz, 1H), 7.59 (s, 1H), 7.46ꢀ7.42 (m,
2H), 7.41ꢀ7.34 (m, 4H), 7.33ꢀ7.29 (m, 1H), 7.21 (dd, J = 8.5, 1.8 Hz, 1H), 6.37 (dd, J = 3.2, 3.2
Hz, 1H), 3.69 (s, 3H), 3.55 (s, 3H), 3.53 (s, 2H), 3.26 (dd, J = 16.6, 3.2 Hz, 1H), 3.09 (dd, J =
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16.6, 3.2 Hz, 1H). C NMR (90 MHz, CDCl3): δ 201.1 (C), 170.2 (C=O), 170.1 (C=O), 133.5
(C), 133.3 (C), 132.6 (C), 132.3 (C), 129.2 (CH), 129.1 (2 CH), 128.9 (CH), 128.4 (2 CH), 128.1
(CH), 127.9 (CH), 127.8 (CH), 127.7 (CH), 126.3 (CH), 125.9 (CH), 102.3 (CH), 89.8 (C), 59.0
(C), 52.9 (2 CH3), 39.7 (CH2), 37.8 (CH2). FTꢀIR (neat, cmꢀ1): 2951, 1949, 1738, 1434, 1332,
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1286, 1215, 1068. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H23O4BrNa 501.0672; Found
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501.0682.
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Compound 2e.The general procedure was followed with 1e (50 mg, 0.17 mmol) to afford 2e as a
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colorless oil (49.2 mg, 0.13 mmol, 78%). H NMR (360 MHz, CDCl3): δ 7.39ꢀ7.35 (m, 1H),
7.34ꢀ7.32 (m, 2H), 7.31ꢀ7.27 (m, 2H), 6.21 (dd, J = 3.2, 3.2 Hz, 1H), 5.70ꢀ5.58 (m, 1H), 5.12ꢀ
5.05 (m, 2H), 3.69 (s, 3H), 3.60 (s, 3H), 3.24 (dd, J = 16.6, 3.2 Hz, 1H), 3.16 (dd, J = 16.6, 3.2
Hz, 1H), 2.99 (d, J = 7.6 Hz, 2H). 13C NMR (63 MHz, CDCl3): δ 201.4 (C), 170.4 (C=O), 170.3
(C=O), 132.2 (C), 132.1 (CH), 129.0 (2 CH), 128.8 (CH), 128.3 (2 CH), 119.9 (CH2), 101.4
(CH), 89.0 (C), 57.7 (C), 52.8 (2 CH3), 40.3 (CH2), 36.5 (CH2). FTꢀIR (neat, cmꢀ1): 3029, 2972,
2950, 2868, 1950, 1738, 1604, 1494, 1430, 1382, 1254, 1205, 1116, 1074. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C18H19O4BrNa 401.0364; Found 401.0355.
Compound 2f. The general procedure was followed with 1f (50 mg, 0.13 mmol) to afford 2f as a
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colorless oil (43.0 mg, 0.09 mmol, 71%, mixture of isomers, E/Z : 80/20). H NMR (300 MHz,
CDCl3, major isomer): δ 7.25ꢀ7.18 (m, 4H), 7.17ꢀ7.10 (m, 6H), 6.30 (d, J = 15.7 Hz, 1H), 6.16
(dd, J = 3.2, 3.2 Hz, 1H), 5.97ꢀ5.82 (m, 1H), 3.68 (s, 3H), 3.61 (s, 3H), 3.27 (dd, J = 16.6, 2.6 Hz,
1H), 3.19 (dd, J = 16.6, 2.6 Hz, 1H), 2.80 (d, J = 7.2 Hz, 2H). 13C NMR (90 MHz, CDCl3, major
isomer): δ 201.5 (C), 170.4 (C=O), 170.3 (C=O), 137.0 (C), 134.7 (CH), 132.2 (C), 129.0 (2 CH),
128.8 (CH), 128.6 (2 CH), 128.3 (2 CH), 126.4 (CH), 126.3 (2 CH), 123.4 (CH), 101.3 (CH),
88.9 (C), 57.9 (C), 52.9 (2 CH3), 40.5 (CH2), 35.8 (CH2). FTꢀIR (neat, cmꢀ1): 3029, 2971, 2951,
2870, 1948, 1738, 1601, 1492, 1433, 1382, 1254, 1205, 1116, 1076. HRMS (ESI) m/z: [M + Na]+
Calcd for C24H23O4BrNa 477.0672; Found 477.0637.
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Procedure for formation of compounds 5a-j (Scheme 5). In air, substrate 5a-j (1 equiv), NBS
(1.1ꢀ2 equiv) and dry DCE (0.2 M) were charged in a 10 mL tube equipped with a Teflonꢀcoated
magnetic stir bar. The tube was sealed with a plastic stopper and the mixture was stirred at RT
during 6 h. Then, the crude mixture was filtrated over a pad of silica previously treated by 5% of
Et3N (unless otherwise stated) and rinsed with cyclohexane to afford bromoallene 5a-j after
evaporation.
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Compound 5a. The general procedure was followed with 4a (50 mg, 0.32 mmol) to afford 5a as
1
a colorless oil (55.7 mg, 0.24 mmol, 74%). H NMR (250 MHz, CDCl3): δ 7.38ꢀ7.34 (m, 4H),
7.31ꢀ7.27 (m, 1H), 6.22 (dd, J = 2.7, 2.7 Hz, 1H), 2.53 (td, J = 7.2, 2.4 Hz, 2H), 1.72ꢀ1.56 (m,
2H), 0.99 (t, J = 7.2 Hz, 3H). 13C NMR (90 MHz, CDCl3): δ 200.0 (C), 133.1 (C), 128.9 (2 CH),
128.3 (CH), 127.9 (2 CH), 100.5 (CH), 96.0 (C), 40.2 (CH2), 21.5 (CH2), 13.4 (CH3). FTꢀIR
(neat, cmꢀ1): 2960, 2930, 2870, 1949, 1494, 1459, 1380, 1233, 1195, 1103, 1073. HRMS (APPI):
m/z: [M – H]– Calcd for C12H12Br 235.0112; Found 235.0116.
Compound 5b. The general procedure was followed with 4b (50 mg, 0.25 mmol) to afford 5b as
1
a colorless oil (57.8 mg, 0.21 mmol, 83%). H NMR (360 MHz, CDCl3): δ 7.38ꢀ7.34 (m, 4H),
7.31ꢀ7.26 (m, 1H), 6.23 (dd, J = 2.7, 2.7 Hz, 1H), 2.56 (td, J = 7.2, 2.4 Hz, 2H), 1.68ꢀ1.56 (m,
2H), 1.43ꢀ1.28 (m, 6H), 0.90 (t, J = 7.2 Hz, 3H). 13C NMR (90 MHz, CDCl3): δ 199.9 (C), 133.1
(C), 128.9 (2 CH), 128.3 (CH), 127.9 (2 CH), 100.5 (CH), 96.3 (C), 38.2 (CH2), 31.6 (CH2), 28.4
(CH2), 28.1 (CH2), 22.7 (CH2), 14.2 (CH3). FTꢀIR (neat, cmꢀ1): 2959, 2932, 2872, 1952, 1496,
1457, 1379, 1235, 1193, 1101, 1072.
Compound 5c. The general procedure was followed with 4c (50 mg, 0.23 mmol) to afford 5c as
1
a colorless oil (57.7 mg, 0.19 mmol, 85%). H NMR (300 MHz, CDCl3): δ 7.38ꢀ7.25 (m, 8H),
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7.15ꢀ7.11 (m, 2H), 6.18 (dd, J = 2.7, 2.7 Hz, 1H), 3.01ꢀ2.95 (m, 2H), 2.92ꢀ2.85 (m, 2H). 13C
NMR (63 MHz, CDCl3): δ 200.3 (C), 140.4 (C), 132.8 (C), 128.8 (3 CH), 128.6 (2 CH), 128.3
(CH), 128.0 (2 CH), 126.3 (CH), 100.8 (CH), 95.0 (C), 39.8 (CH2), 34.2 (CH2). FTꢀIR (neat, cmꢀ
1): 3587, 3567, 3423, 3057, 3027, 2919, 1948, 1601, 1494, 1453, 1194, 1075, 1027, 1015. HRMS
(APPI): m/z: [M]+ Calcd for C17H15Br 298.0357; Found 298.0349.
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Compound 5d. The general procedure was followed with 4d (50 mg, 0.29 mmol) to afford 5d as
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a colorless oil (69.4 mg, 0.28 mmol, 96%). H NMR (300 MHz, CDCl3): δ 7.39ꢀ7.32 (m, 4H),
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7.31ꢀ7.24 (m, 1H), 6.22 (s, 1H), 1.29 (s, 9H). C NMR (75 MHz, CDCl3): δ 198.5 (C), 133.3
(C), 128.9 (2 CH), 128.2 (CH), 127.7 (2 CH), 108.5 (C), 100.4 (CH), 37.8 (C), 29.3 (3 CH3). FTꢀ
IR (neat, cmꢀ1): 2967, 2928, 1947, 1474, 1457, 1362, 1242, 1143, 1025. HRMS (APPI): m/z: [M
+ H]+ Calcd for C13H15Br 251.0435; Found 251.0429.
Compound 5e. The general procedure was followed with 4e (50 mg, 0.31 mmol) to afford 5e as
1
a colorless oil (36.7 mg, 0.15 mmol, 49%). H NMR (360 MHz, CDCl3): δ 7.37ꢀ7.34 (m, 4H),
7.37ꢀ7.34 (m, 1H), 6.36 (dd, J = 2.7, 2.7 Hz, 1H), 4.24 (d, J = 2.4 Hz, 2H), 3.42 (s, 3H). 13C
NMR (63 MHz, CDCl3): δ 200.9 (C), 132.1 (C), 128.9 (2 CH), 128.6 (CH), 128.1 (2 CH), 101.8
(CH), 91.7 (C), 74.5 (CH2), 57.9 (CH3). FTꢀIR (neat, cmꢀ1): 2968, 2930 1948, 1651, 1494, 1459,
1352, 1193, 1105, 1026. HRMS (ESI) m/z: [2M + Na]+ Calcd for C22H22O2Br2Na 498.9879;
Found 498.9869.
Compound 5f. The general procedure was followed with 4f (40 mg, 0.17 mmol) to afford 5f as a
1
colorless oil (55.5 mg, 0.08 mmol, 49%). H NMR (300 MHz, CDCl3): δ 7.38ꢀ7.32 (m, 8H),
7.31ꢀ7.27 (m, 2H), 6.37 (dd, J = 2.4, 2.4 Hz, 1H), 4.61 (d, J = 4.0 Hz, 2H), 4.33 (d, J = 2.4 Hz,
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2H). C NMR (63 MHz, CDCl3): δ 201.2 (C), 137.6 (C), 132.2 (C), 129.1 (2 CH), 128.8 (CH),
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128.6 (2 CH), 128.2 (4 CH), 128.0 (CH), 102.0 (CH), 92.0 (C), 72.2 (CH2), 72.1 (CH2). FTꢀIR
(neat, cmꢀ1): 2968, 2930 1948, 1651, 1494, 1459, 1352, 1193, 1105, 1026. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C17H15OBrNa 337.0198; Found 337.0190.
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Compound 5h. The general procedure was followed with 4h (100 mg, 0.36 mmol) to afford 5h
1
as a colorless oil (62 mg, 0.18 mmol, 48%). H NMR (300 MHz, CDCl3): δ 7.36ꢀ7.30 (m, 4H),
7.29ꢀ7.26 (m, 1H), 6.19 (dd, J = 2.7, 2.7 Hz, 1H), 3.83 (td, J = 6.3, 2.7 Hz, 2H), 2.72 (dt, J = 6.3,
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2.7 Hz, 2H), 0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H). C NMR (75 MHz, CDCl3): δ 200.9 (C),
132.9 (C), 128.9 (2 CH), 128.4 (CH), 128.1 (2 CH), 100.4 (CH), 92.7 (C), 61.0 (CH2), 41.4
(CH2), 26.1 (3 CH3), 18.5 (C), ꢀ5.1 (CH3), ꢀ5.2 (CH3). FTꢀIR (neat, cmꢀ1): 2950, 2929, 2859,
1949, 1651, 1472, 1462, 1255, 1106, 1076.
Compound 5j.The general procedure was followed with 4j (50 mg, 0.27 mmol) to afford 5j as a
colorless oil (55.3 mg, 0.21 mmol, 78%). 1H NMR (360 MHz, CDCl3): δ 7.36ꢀ7.32 (m, 4H),
7.29ꢀ7.26 (m, 1H), 6.10 (s, 1H), 0.27 (s, 9H). 13C NMR (90 MHz, CDCl3): δ 204.7 (C), 132.8
(C), 129.0 (2 CH), 128.1 (CH), 127.5 (2 CH), 98.0 (CH), 89.9 (C), ꢀ1.5 (3 CH3). FTꢀIR (neat,
cmꢀ1): 3061, 3330, 2960, 1941, 1495, 1456, 1250, 1185, 1046, 1027. HRMS (APPI): m/z: [M –
Br]+ Calcd for C12H15Si 187.0943; Found 187.0939.
Compound 3a (Scheme 3). In air, substrate 1a (50 mg, 0.14 mmol, 1 equiv), NBS (76.2 mg,
0.064 mmol, 3 equiv) and DCE (0.7 mL) were charged in a 10 mL tube equipped with a Teflonꢀ
coated magnetic stir bar. The tube was sealed with a plastic stopper and the mixture was stirred at
80 °C during 24 h. Then, the reaction was quenched with a saturated aqueous solution of Na2S2O4
(5 mL) and the aqueous layer was extracted with Et2O (3 x 10 mL). The combined organic exꢀ
tracts were washed with brine (10 mL), dried over MgSO4 and concentrated under reduced presꢀ
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sure. The crude product was purified by flash chromatography (12 g of SiO2 previously treated
by 5% of Et3N, Cy/EtOAc, 100:0 to 95:5) to afford the bromoenone 3a (28.6 mg, 0.06 mmol,
45%) as a yellow oil. The structure was confirmed by Xꢀray diffraction of crystals of 3a (see
Supporting Information).1H NMR (360 MHz, CDCl3): δ 7.99 (s, 1H), 7.91ꢀ7.83 (m, 2H), 7.46ꢀ
7.43 (m, 2H), 7.34 (dd, J = 5.3, 2.1 Hz, 1H), 7.24 (dd, J = 2.1, 1.2 Hz, 2H), 7.19 (dd, J = 5.3, 2.8
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Hz, 1H), 6.96 (dd, J = 7.5, 2.0 Hz, 2H), 3.79 (s, 6H), 3.71 (s, 2H), 3.48 (d, J = 2.8 Hz, 2H). C
NMR (90 MHz, CDCl3): δ 192.7 (C=O), 170.7 (2 C=O), 140.2 (CH), 140.0 (C), 136.1 (C), 130.8
(3 CH), 130.2 (2 CH), 128.7 (2 CH), 128.6 (2 CH), 127.4 (CH), 122.2 (C), 57.1 (C), 53.1 (2
CH3), 41.2 (CH2), 38.6 (CH2). FTꢀIR (neat, cmꢀ1): 2952, 2097, 1736, 1642, 1494, 1446, 1434,
1277, 1242, 1179, 1152, 1080, 1057. HRMS (ESI) m/z: [M + Na]+ Calcd for C22H21O5BrNa
467.0470; Found 467.0443.
Compound 6 (Scheme 7). In air, substrate 1a (50 mg, 0.14 mmol, 1 equiv), NIS (35.3 mg, 0.16
mmol, 1.1 equiv) and DCE (0.7 mL) were charged in a 10 mL tube equipped with a Teflonꢀ
coated magnetic stir bar. The tube was sealed with a plastic stopper and the mixture was stirred at
RT during 1 hour. Then, the reaction was quenched with a saturated aqueous solution of Na2S2O4
(5 mL) and the aqueous layer was extracted with Et2O (3 x 10 mL). The combined organic exꢀ
tracts were washed with brine (10 mL), dried over MgSO4 and concentrated under reduced presꢀ
sure. The crude product was purified by flash chromatography (12 g of SiO2, Cy/EtOAc, 100:0 to
1
95:5) to afford 6 (30.4 mg, 0.06 mmol, 45%) as a yellow oil. H NMR (300 MHz, CDCl3): δ
7.30ꢀ7.26 (m, 3H), 7.08ꢀ7.03 (m, 2H), 7.02ꢀ6.97 (m, 3H), 4.59 (dd, J = 2.3, 2.3 Hz, 1H), 3.74 (s,
3H), 3.71 (s, 3H), 3.45 (dd, J = 16.0, 3.6 Hz, 1H), 3.39 (dd, J = 16.0, 3.6 Hz, 1H), 3.19 (dd, J =
16.4, 2.3 Hz, 1H), 3.09 (dd, J = 16.4, 2.3 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 171.2 (C=O),
171.0 (C=O), 147.3 (C), 143.3 (C), 140.1 (C), 138.4 (C), 128.9 (2 CH), 128.5 (2 CH), 127.5
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(CH), 126.6 (CH), 125.4 (CH), 122.2 (CH), 99.0 (C), 63.7 (CH), 55.7 (C), 53.2 (CH3), 53.1
(CH3), 33.9 (CH2), 33.4 (CH2). FTꢀIR (neat, cmꢀ1): 3030, 2952, 2917, 2849, 1737, 1685, 1599,
1493, 1447, 1433, 1396, 1279, 1245, 1202, 1183, 1158, 1080, 1061, 1035. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C22H19O4INa 497.0226; Found 497.0230.
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Compound 7 (Scheme 7). In air, substrate 1d (40 mg, 0.23 mmol, 1 equiv), NIS (58 mg, 0.26
mmol, 1.1 equiv) and dry DCE (1.1 mL) were charged in a 10 mL tube equipped with a Teflonꢀ
coated magnetic stir bar. The tube was sealed with a plastic stopper and the mixture was stirred at
RT during 5 h. Then, the reaction was filtrated over a pad of silica (unless otherwise stated) preꢀ
viously treated by 5% of Et3N and rinsed with cyclohexane to afford iodoallene 7 (48.2 mg, 0.16
1
mmol, 70%) as a colorless oil. H NMR (300 MHz, CDCl3): δ 7.40ꢀ7.25 (m, 5H), 5.96 (s, 1H),
1.27 (s, 9H). 13C NMR (90 MHz, CDCl3): δ 201.0 (C), 133.3 (C), 129.0 (2 CH), 127.9 (CH),
127.6 (2 CH), 96.0 (CH), 83.2 (C), 38.0 (C), 29.9 (3 CH3). FTꢀIR (neat, cmꢀ1): 2968, 2931, 2868,
2211, 1685, 1648, 1599, 1492, 1476, 1453, 1393, 1363, 1271, 1071. HRMS (APPI): m/z: [M – I]+
Calcd for C13H15 171.1174; Found 171.1174.
Compound 8 (Scheme 8). Following the procedure reported by Bäckvall,2q Nꢀallylꢀ4ꢀ
methylbenzenesulfonamide (33.7 mg, 0.16 mmol, 1.0 equiv), copper(I) thiopheneꢀ2ꢀcarboxylate
(CuTC) (4.6 mg, 0.02 mmol, 0.15 equiv), Cs2CO3 (104 mg, 0.32 mmol, 2.0 equiv) and dry toluꢀ
ene (0.9 mL) were charged in a 10 mL tube equipped with a Teflonꢀcoated magnetic stir bar. The
resulting mixtures was stirred for 2ꢀ3 minutes and then N,N'ꢀdimethylethylenediamine (DMEDA)
(4.2 mg, 0.05 mmol, 0.30 equiv) and bromoallene 5d (100 mg, 0.40 mmol, 2.5 equiv) were addꢀ
ed. The tube was sealed, wrapped in aluminum foil and stirred at 80 °C for 24 h. The reaction
was cooled to RT, filtrated over a pad of celite and rinsed with Et2O. The resulting mixture was
then purified by flash chromatography (12 g of SiO2 previously treated by 5% of Et3N,
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Cy/EtOAc, 100:0 to 95:5) to afford coupling product 8 (15.0 mg, 0.04 mmol, 25%) as a yellow
oil. 1H NMR (360 MHz, CDCl3): δ 7.67 (dd, J = 8.3, 1.4 Hz, 2H), 7.56 (tt, J = 7.3, 1.3 Hz, 1H),
7.48ꢀ7.41 (m, 4H), 6.96 (s, 1H), 6.84 (d, J = 8.3 Hz, 2H), 6.17 (dddd, J = 17.2, 10.1, 7.6, 6.1 Hz,
1H), 5.25ꢀ5.16 (m, 2H), 4.43 (ddt, J = 15.3, 6.1, 1.5 Hz, 1H), 4.12 (ddt, J = 15.3, 7.6, 1.5 Hz,
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1H), 2.18 (s, 3H), 1.36 (s, 9H) . C NMR (90 MHz, CDCl3): δ 189.5 (C), 161.0 (C), 143.0 (C),
137.8 (C), 137.1 (C), 135.4 (CH), 133.2 (CH), 129.3 (2 CH), 128.5 (2 CH), 128.4 (2 CH), 127.9
(2 CH), 126.4 (CH), 118.5 (CH2), 57.8 (CH2), 39.4 (C), 31.4 (3 CH3), 21.5 (CH3). FTꢀIR (neat,
cmꢀ1): 2962, 1914, 1669, 1601, 1506, 1448, 1344, 1249, 1222, 1159, 1090, 1053. HRMS (ESI)
m/z: [M + H]+ Calcd for C23H27NO2SNa 404.1655; Found 404.1632.
Compound 9 (Scheme 8). Following a modified procedure reported by Burke,2r in air,
PhB(OH)2 (31.6 mg, 0.26 mmol, 1.0 equiv), Ag2O (120.0 mg, 0.52 mmol, 2.0 equiv), bromoꢀ
allene 5d (65 mg, 0.26 mmol, 1.0 equiv), THF (1.2 mL) and distillated water (0.12 mL) were
charged in a 10 mL tube equipped with a Teflonꢀcoated magnetic stir bar. Argon was bubbled
into the mixture during 10 min and Pd(PPh3)4 (15 mg, 0.01 mmol, 0.05 equiv) was added. The
tube was sealed with a plastic stopper and the mixture was stirred at RT during 2 h. Then, the
reaction was filtrated over a pad of celite and rinsed with Et2O. The resulting mixture was puriꢀ
fied by flash chromatography (12 g of SiO2 previously treated by 5% of Et3N, Cy/EtOAc, 100:0
to 95:5) to afford coupling product 9 (42.0 mg, 0.17 mmol, 65%) as a colorless oil. 1H NMR (360
MHz, CDCl3): δ 7.41ꢀ7.35 (m, 5H), 7.35 (s, 2H), 7.33ꢀ7.27 (m, 2H), 7.22 (tt, J = 6.9, 1.7 Hz, 1H),
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6.28 (s, 1H), 1.27 (s, 9H). C NMR (90 MHz, CDCl3): δ 203.2 (C), 137.4 (C), 135.6 (C), 129.4
(2 CH), 128.7 (2 CH), 128.0 (2 CH), 127.0 (CH), 126.7 (CH), 126.5 (2 CH), 119.9 (C), 95.3
(CH), 35.4 (C), 30.1 (3 CH3). FTꢀIR (neat, cmꢀ1): 3060, 2963, 2900, 1944, 1597, 1491, 1475,
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249.1643; Found 249.1635.
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Procedure for Sonogashira cross-coupling reactions. In air, bromoallene 5d (1.0 equiv) was
dissolved in a 3:1 mixture of triethylamine and toluene (0.2 M) in a 10 mL tube equipped with a
Teflonꢀcoated magnetic stir bar. PdCl2(Ph3)2 (0.06 equiv), CuI (0.03 equiv) and the alkyne (1.1
equiv) was added. The tube was sealed with a plastic stopper and the mixture was stirred at 50 °C
during 3 h. Then, the reaction was filtrated over a pad of silica (previously treated by 5% of Et3N
in Et2O) and rinsed with cyclohexane to afford coupling product 10a-f.
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Compound 10a. The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10a
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as a yellow solid (43.7 mg, 0.16 mmol, 81%). m.p. (°C): 83ꢀ85. H NMR (360 MHz, CDCl3): δ
7.53ꢀ7.48 (m, 2H), 7.39ꢀ7.36 (m, 4H), 7.36ꢀ7.32 (m, 3H), 7.31ꢀ7.24 (m, 1H), 6.50 (s, 1H), 1.33
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(s, 9H). C NMR (90 MHz, CDCl3): δ 209.8 (C), 134.0 (C), 131.6 (2 CH), 128.9 (2 CH), 128.4
(2 CH), 128.2 (CH), 127.4 (CH), 127.2 (2 CH), 123.7 (C), 105.2 (C), 97.6 (CH), 93.2 (C), 83.1
(C), 35.8 (C), 29.5 (3 CH3). FTꢀIR (neat, cmꢀ1): 2967, 2929, 1929, 1729, 1669, 1598, 1489, 1456,
1392, 1362, 1234, 1072. HRMS (APPI): m/z: [M + H]+ Calcd for C21H21 273.1631; Found
273.1638.
Compound 10b.The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10b
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as a yellow solid (49.1 mg, 0.16 mmol, 82%). m.p. (°C): 81ꢀ83. H NMR (360 MHz, CDCl3): δ
7.44 (d, J = 8.7 Hz, 2H), 7.38 (s, 2H), 7.36 (s, 2H), 7.30ꢀ7.24 (m, 1H), 6.88 (d, J = 8.7 Hz, 2H),
6.48 (s, 1H), 3.84 (s, 3H), 1.32 (s, 9H). 13C NMR (60 MHz, CDCl3): δ 209.7 (C), 159.6 (C),
134.2 (C), 133.0 (2 CH), 128.8 (2 CH), 127.4 (CH), 127.2 (2 CH), 115.9 (C), 114.4 (2 CH),
105.4 (C), 97.5 (CH), 93.2 (C), 81.6 (C), 55.4 (CH3), 35.8 (C), 29.5 (3 CH3). FTꢀIR (neat, cmꢀ1):
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3030, 2962, 2931, 2902, 2206, 1929, 1604, 1509, 1457, 1441, 1362, 1288, 1247, 1173, 1148,
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1057, 1030. HRMS (APPI): m/z: [M + H]+ Calcd for C22H22O 303.1749; Found 303.1749.
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Compound 10c. The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10c
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as a yellow oil (52.6 mg, 0.18 mmol, 88%). H NMR (300 MHz, CDCl3): δ 7.37ꢀ7.29 (m, 5H),
7.29ꢀ7.20 (m, 5H), 6.37 (s, 1H), 2.90 (t, J = 7.4, 2H), 2.67 (t, J = 7.4, 2H), 1.17 (s, 9H). 13C NMR
(90 MHz, CDCl3): δ 209.5 (C), 140.8 (C), 134.3 (C), 128.8 (2 CH), 128.6 (2 CH), 128.5 (2 CH),
127.2 (CH), 127.1 (2 CH), 126.4 (CH), 105.2 (C), 97.1 (CH), 97.4 (C), 74.5 (C), 35.4 (C), 35.3
(CH2), 29.3 (3 CH3), 22.0 (CH2). FTꢀIR (neat, cmꢀ1): 3028, 2959, 2948, 2215, 1936, 1600, 1495,
1473, 1454, 1361, 1203, 1114, 1074, 1026. HRMS (APPI): m/z: [M + H]+ Calcd for C23H24
301.1951; Found 301.1945.
Compound 10d. The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10d
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as a yellow oil (46.0 mg, 0.18 mmol, 92%). H NMR (300 MHz, CDCl3): δ 7.34ꢀ7.27 (m, 4H),
7.23ꢀ7.16 (m, 1H), 6.34 (s, 1H), 2.35 (t, J = 7.1, 2H), 1.58ꢀ1.37 (m, 4H), 1.18 (s, 9H), 0.92 (t,
J = 7.1, 3H). 13C NMR (90 MHz, CDCl3): δ 209.4 (C), 134.4 (C), 128.8 (2 CH), 127.2 (CH),
127.1 (2 CH), 105.4 (C), 97.1 (CH), 94.4 (C), 73.7 (C), 35.5 (C), 31.1 (CH2), 29.3 (3 CH3), 22.2
(CH2), 19.5 (CH2), 13.8 (CH3). FTꢀIR (neat, cmꢀ1): 3029, 2960, 2929, 2869, 1936, 1600, 1495,
1474, 1457, 1362, 1246, 1202, 1116.
Compound 10e.The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10e
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as a yellow oil (36.9 mg, 0.16 mmol, 78%). H NMR (300 MHz, CDCl3): δ 7.37ꢀ7.32 (m, 1H),
7.32ꢀ7.27 (m, 3H), 7.26ꢀ7.18 (m, 1H), 6.36 (s, 1H), 1.45ꢀ1.67 (m, 1H), 1.20 (s, 9H), 0.83ꢀ0.73
(m, 4H). 13C NMR (90 MHz, CDCl3): δ 209.7 (C), 134.4 (C), 128.8 (2 CH), 127.2 (CH), 127.1 (2
CH), 105.3 (C), 97.4 (C), 97.1 (CH), 68.8 (C), 35.5 (C), 29.3 (3 CH3), 8.8 (2 CH2), 0.57 (CH).
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FTꢀIR (neat, cmꢀ1): 3030, 2961, 2930, 2869, 1932, 1603, 1493, 1473, 1457, 1361, 1247, 1202,
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1114. HRMS (APPI): m/z: [M + H]+ Calcd for C18H20 237.1643; Found 237.1641.
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Compound 10f. The general procedure was followed with 5d (50 mg, 0.20 mmol) to afford 10f
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as a yellow oil (61.7 mg, 0.17 mmol, 87%). H NMR (300 MHz, CDCl3): δ 7.34ꢀ7.27 (m, 4H),
7.23ꢀ7.17 (m, 1H), 6.34 (s, 1H), 3.75 (t, J = 7.1, 2H), 2.57 (td, J = 7.1, 0.9 Hz, 2H), 1.18 (s, 9H),
0.89 (s, 9H), 0.06 (s, 6H). 13C NMR (90 MHz, CDCl3): δ 209.6 (C), 134.3 (C), 128.8 (2 CH),
127.2 (CH), 127.1 (2 CH), 105.2 (C), 97.2 (CH), 91.1 (C), 74.8 (C), 62.1 (CH2), 35.5 (C), 29.3 (3
CH3), 26.0 (3 CH3), 24.2 (CH2), 18.4 (C), ꢀ5.1 (2 CH3). FTꢀIR (neat, cmꢀ1): 3028, 2958, 2928,
2858, 1936, 1600, 1495, 1472, 1460, 1361, 1254, 1106, 1056.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on ACS Publications website at DOI:
XXXX
Xꢀray diffraction analysis of compound 3a. Copies of H NMR and 13C NMR spectra of the
1
products.
AUTHOR INFORMATION
Corresponding Author
* vincent.gandon@uꢀpsud.fr; christophe.bour@uꢀpsud.fr.
ORCID
Vincent Gandon: 0000ꢀ0003ꢀ1108ꢀ9410
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Christophe Bour: 0000ꢀ0001ꢀ6733ꢀ5284
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENT
We thank CNRS, MESR, Université ParisꢀSud and Institut Universitaire de France (IUF) for the
support of this work.
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