Propargyl-allenyl isomerizations and electrocyclizations for the functionalization of phosphonium salts: One-pot synthesis of polysubstituted vinylbenzenes and naphthalenes

Article abstract of DOI:10.1002/adsc.201300573

Phosphonium salts are widely used in organic synthesis as the precursor of Wittig reagents but highly functionalized phosphonium salts are not readily available. We have developed a sequence of propargyl-allenyl isomerizations and electrocyclizations for the functionalization of phosphonium salts via simple starting materials, which may provide an efficient one-pot synthesis of polysubstituted vinylbenzenes and naphthalenes. Copyright

Full text of DOI:10.1002/adsc.201300573

UPDATES
DOI: 10.1002/adsc.201300573
Propargyl–Allenyl Isomerizations and Electrocyclizations for the
Functionalization of Phosphonium Salts: One-Pot Synthesis of
Polysubstituted Vinylbenzenes and Naphthalenes
Guoqing Zhao,a Qianyun Zhang,a and Hongwei Zhoua,*
a
Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, Peopleꢀs Republic of China
Fax : (+ 86)-571-8892-0271; e-mail: zhouhw@zju.edu.cn
Received: June 27, 2013; Revised: September 26, 2013; Published online: November 14, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300573.
Abstract: Phosphonium salts are widely used in or-
ganic synthesis as the precursor of Wittig reagents
but highly functionalized phosphonium salts are not
readily available. We have developed a sequence of
propargyl–allenyl isomerizations and electrocycliza-
tions for the functionalization of phosphonium salts
via simple starting materials, which may provide an
efficient one-pot synthesis of polysubstituted vinyl-
benzenes and naphthalenes.
involvement of the Nazarov cyclization,[5a] thio-Clais-
en rearrangement,[5b] Diels–Alder cycloaddition[5c] and
electrocyclization.[5d–f] It is a reasonable assumption
that the phosphonium species could assist the prop-
argyl–allenyl isomerization and trigger the electrocy-
AHCTUNGTREGcNNUN lization of phosphonium salts, which may provide an
efficient protocol for the construction of a new ben-
zene ring. On the basis of this knowledge, we pro-
posed a propargylphosphonium species A, in which
the methylene group adjacent to the phosphonium,
having considerably acidic protons, might undergo
propargyl–allenyl isomerization in the presence of
a suitable base and produce allenylphosphonium spe-
cies B. The electrocyclization of B may offer a func-
tionalized phosphonium salt C, which could afford vi-
nylbenzenes via a one-pot Wittig reaction (Scheme 1).
Stimulated by this proposal, we prepared triphen-
Keywords: electrocyclizations; naphthalenes; phos-
phonium salts; propargyl–allenyl isomerizations; vi-
nylbenzenes
Phosphonium salts, as the precursors of Wittig re- yl(4-phenylhepta-4,6-dien-2-ynyl)phosphonium bro-
agent, are widely used in organic synthesis[1] and gen- mide (1a) as the starting material, which could be syn-
erally, they are prepared via the reaction of a halide thesized in situ via the treatment of Z-(7-bromohepta-
and triarylphosphine/trialkylphosphine.[2] However, 1,3-dien-5-yn-4-yl)benzene[6] with triphenylphosphine.
this protocol might encounter difficulty when the de- We initiated our study by testing the propargyl–allen-
sired halide is not so readily available, because of the yl isomerization of 1a in the presence of various bases
effect of the substituent(s). For instance, the highly- and examined the solvent and temperature effects.
substituted benzyl bromide derivatives, which are TEA (triethylamine) and DIEA (N,N-diisopropyl-
used as the starting material for phosphonium salts,
could not be easily prepared from highly-substituted
toluene derivatives and the corresponding benzyl al-
cohol derivatives are not so readily available. Hypo-
thetically, the functionalization of phosphonium salts
may offer an efficient method to obtain complex
phosphonium salts from simple, readily available
starting materials. To the best of our knowledge, the
corresponding reactions are not well documented.[3]
Allene-mediated reactions have attracted much at-
tention by the organic community, and the propargyl–
allenyl isomerization has been a useful and efficient
method to afford allenes in situ.[4] Recently, our group
reported several kinds of cyclizations promoted by
Scheme 1. Proposal for the functionalization of phosphoni-
sulfur-participated propargyl–allenyl isomerizations,[5] um salts.
3492
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3492 – 3496

Propargyl–Allenyl Isomerizations and Electrocyclizations for the Functionalization of Phosphonium Salts
Table 1. Base, solvent and temperature effects.[a]
Table 2. Synthesis of polysubstituted vinylbenzenes.[a]
Entry
Base
Solvent
T [oC]
t [h]
Yield [%]
1
2
3
4
5
6
7
8
t-BuOK
DBU
DBN
DIEA
TEA
DIEA
TEA
DIEA
TEA
DIEA
TEA
DIEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
benzene
benzene
benzene
benzene
benzene
DMF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t
40
60
80
60
60
60
60
6
6
6
0
0
0
35
42
0
0
0
12
12
12
12
12
12
12
12
12
12
12
12
12
6
DMF
MeCN
MeCN
THF
9
0
10
11
12
13
14
15
16
17
18
19
20
10
12
48
52
58
69
62
32
60
69
65
THF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
9
15
18
[a]
Conditions: 1a (0.5 mmol) and base (1.5 mmol) in solvent
(3 mL) under an N2 atmosphere, then t-BuOK
(0.75 mmol) and p-bromobenzaldehyde (0.4 mmol).
ACHTUNGTRENNUNG
With this result in hand, we examined the scope of
the reaction and obtained polysubstituted vinylben-
zenes in moderate to good yields under mild condi-
tions (Table 2). Notably, the expected substituent
effect in the 6-p electrocyclization process is not ob-
served[5d] and the reaction is compatible with alkyl
(entries 3, 4, and 10), aryl (entry 5) and ester groups
(entry 2), probably because the allenylphosphonium
species, as an electron-deficient allene intermediate,
might be more active than the ordinary allenes.
Then our attention was diverted to the synthesis of
vinylnaphthalenes. Because of the orientation effect
of the naphthalene ring, the direct introduction of
substituent to naphthalenes on the inactive position
could be difficult and functionalization to the highly
substituted naphthalenes may offer complicated by-
products.[7] Thus, construction of a new naphthalene
ring using building blocks represents an efficient way
to access polysubstituted naphthalenes. We prepared
a series of (2-vinylphenyl)propargylphosphonium salts
as substrates and obtained the expected polysubstitut-
[a]
Conditions: 1 (0.5 mmol) and base (1.5 mmol) in solvent
(3 mL) under an N2 atmosphere, then t-BuOK
(0.75 mmol) and aldehyde (0.4 mmol).
[b]
1
E/Z ratio based on H NMR.
The functionalized naphthalenylmethylphosphoni-
ed vinylnaphthalenes in moderate to good yields um prepared via propargyl–allenyl isomerizations and
(Table 3).
electrocyclizations may undergo an intramolecular
Adv. Synth. Catal. 2013, 355, 3492 – 3496
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3493

Guoqing Zhao et al.
UPDATES
Table 3. Synthesis of polysubstituted vinylnaphthalenes.[a]
Scheme 2. Synthesis of 3-ethoxy-1,2-dihydroanthracene.
presence of triethylamine and, after work-up, ob-
served 36% deuterium on the new benzene ring,
which might come from the propargyl–allene isomeri-
zation; on the other hand, we observed 24% deuteri-
um on the carbon adjacent to the naphthalene ring, il-
lustrating a base-assisted isomerization of the inter-
mediate
isotoluene
after
electrocyclization
(Scheme 3).
In summary, we developed a sequence of proparg-
yl–allenyl isomerizations and electrocyclizations for
the functionalization of phosphonium salts, which
may provide an efficient one-pot synthesis of polysub-
stituted vinylbenzenes and vinylnaphthalenes. Studies
on the application and expansion of the propargyl–al-
lenyl isomerization in organic synthesis are currently
in progress.
Experimental Section
Typical Procedure for the Synthesis of 2a
Z-(7-Bromohepta-1,
3-dien-5-yn-4-yl)benzene
(124 mg,
0.5 mmol) was added to
a
solution of PPh3 (144 mg,
0.55 mmol) in dry toluene (3 mL) under an N2 atmosphere.
The reaction mixture was stirred at 708C for 12 h before it
was cooled to room temperature. Et3N (152 mg, 1.5 mmol)
was added to the reaction mixture, and the reaction mixture
was stirred for 12 h at 608C. After the reaction mixture had
been allowed to cool to room temperature, potassium tert-
butoxide (84 mg, 0.75 mmol) and the corresponding alde-
hyde (0.4 mmol) were added. Upon completion, the reaction
mixture was quenched by saturated aqueous NH4Cl solu-
tion, extracted with ethyl acetate, and dried over anhydrous
Na2SO4. After evaporation, chromatography on silica gel
(eluent: petroleum ether) of the crude product afforded 2a;
yield: 69%.
[a]
Conditions: 3 (0.5 mmol) and base (1.5 mmol) in solvent
(3 mL) under an N2 atmosphere, then t-BuOK
(0.75 mmol) and aldehyde (0.4 mmol).
[b]
1
E/Z ratio based on H NMR.
Wittig reaction. We prepared phosphonium salts 5
and treated it with triethylamine to give intermediates
6; and the following one-pot Wittig process offered
products 7 in moderate yields. This protocol may be
used as a simple synthesis for 1,2-dihydroanthracenes
or 1,2-dihydronaphthalenes (Scheme 2).[8]
Although we did not isolate the allenylphosphoni-
um intermediate, we conducted a control experiment
to support the propargyl–allenyl isomerization path-
(E)-3-(4-Bromostyryl)biphenyl (E-2a): amorphous solid;
1
yield: 51 mg (38%). H NMR (400 MHz, CDCl3): d =7.72
(s, 1H), 7.64 (d, J=7.2 Hz, 2H), 7.45–7.53 (m, 7H), 7.40 (d,
J=8.4 Hz, 3H), 7.17 (d, J=16.4 Hz, 1H), 7.10 (d, J=
way. We treated 3b with 5 equiv. of MeOH-d4 in the 16.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=141.7, 141.0,
3494
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3492 – 3496

Propargyl–Allenyl Isomerizations and Electrocyclizations for the Functionalization of Phosphonium Salts
Scheme 3. Proposed mechanism.
137.4, 136.2, 131.8, 129.3, 129.1, 128.8, 128.0, 127.7, 127.4,
127.2, 126.8, 125.44, 125.39, 121.4; IR (neat): n=1590, 1484,
1071, 1010, 970, 897, 857, 812 cmÀ1; HR-MS (EI-TOF):
m/z=334.0354, calcd. for C20H15Br (M+): 334.0357.
M. Oelwegaard-Halvarsson, V. Shcherbuchin, T. Elebr-
ing, J. Sjoestroem, J. Med. Chem. 2002, 45, 4282.
[4] a) Y. Xing, Y. Wei, H. Zhou, Curr. Org. Chem. 2012, 16,
1594; b) I. Nakamura, D. Zhang, M. Terada, J. Am.
Chem. Soc. 2010, 132, 7884; c) A. S. Dudnik, A. W.
Sromek, M. Rubina, J. T. Kim, A. V. Kel’in, V. Gevorgy-
an, J. Am. Chem. Soc. 2008, 130, 1440; d) A. W. Sromek,
V. Gevorgyan, Top. Curr. Chem. 2007, 274, 77; e) J. T.
Kim, A. V. Kel’in, V. Gevorgyan, Angew. Chem. 2003,
115, 102; Angew. Chem. Int. Ed. 2003, 42, 98; f) V. Srini-
vas, K. V. Sajna, K. C. K. Swamy, Chem. Commun. 2011,
47, 5629; g) K. V. Sajna, K. C. K. Swamy, J. Org. Chem.
2012, 77, 5345; h) S. Braverman, Y. Zafrani, H. E. Got-
tlieb, Tetrahedron 2001, 57, 9177; i) S. Braverman, M.
Cherkinsky, M. L. Birsa, Y. Zafrani, Eur. J. Org. Chem.
2002, 18, 3198.
(Z)-3-(4-Bromostyryl)biphenyl (Z-2a): amorphous solid;
1
yield: 42 mg (31%). H NMR (400 MHz, CDCl3): d=7.44–
7.47 (m, 5H), 7.37–7.42 (t, J=9.0 Hz, 3H), 7.30–7.35 (q, J=
7.5 Hz, 2H), 7.21 (d, J=7.6 Hz, 1H), 7.17 (d, J=8.4 Hz,
2H), 6.70 (d, J=12.0 Hz, 1H), 6.57 (d, J=12.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=141.2, 140.8, 137.2, 136.1,
131.4, 130.9, 130.5, 129.3, 128.7, 128.2, 127.7, 127.6, 127.3,
127.0, 126.1, 121.0; IR (neat): n=1597, 1486, 1071, 1010,
898, 838, 802 cmÀ1; HR-MS (EI-TOF): m/z=334.0358, calcd.
for C20H15Br (M+): 334.0357.
[5] a) H. Zhou, Y. Xie, L. Ren, K. Wang, Adv. Synth. Catal.
2009, 351, 1289; b) H. Zhou, Y. Xie, L. Ren, R. Su, Org.
Lett. 2010, 12, 356; c) H. Zhou, D. Zhu, Y. Xie, H.
Huang, K. Wang, J. Org. Chem. 2010, 75, 2706; d) H.
Zhou, Y. Xing, J. Yao, J. Chen, Org. Lett. 2010, 12, 3674;
e) H. Zhou, Y. Xing, J. Yao, Y. Lu, J. Org. Chem. 2011,
76, 4582; f) H. Zhou, L. Liu, S. Xu, J. Org. Chem. 2012,
77, 9418.
[6] The bromide could be easily prepared by a three-step
process with (Z)-3-iodo-3-phenylacrylaldehyde and
propargyl alcohol as the materials: to a suspension of
triphenylmethylphosphonium iodide (25 mmol) and t-
BuOK (25 mmol) in dry THF (50 mL) was charged (Z)-
3-iodo-3-phenylacrylaldehyde (20 mmol) at room tem-
perature under an N2 atmosphere. After 5 h, the reac-
tion mixture was quenched with saturated aqueous
NH4Cl solution, extracted with ethyl ether, and dried
over anhydrous Na2SO4. After evaporation, chromatog-
raphy on silica gel (eluent: petroleum ether) to afford
(Z)-1-iodo-1-phenylbuta-1, 3-diene in 76% yield. To
the solution of (Z)-(1-iodobuta-1,3-dienyl)benzene
(10 mmol) and propargyl alcohol (12 mmol) in 50 mL of
THF were added CuI (40 mg. 0.2 mmol) and PdCl2
Acknowledgements
Financial support from Natural Science Foundation of China
(No. 20972134) is greatly appreciated.
References
[1] a) T. Wada, Y. Sato, F. Honda, S. Kawahara, M. Sekine,
J. Am. Chem. Soc. 1997, 119, 12710; b) H. J. Cristau,
Chem. Rev. 1994, 94, 1299; c) D. G. Gilheany, Chem.
Rev. 1994, 94, 1339.
[2] a) K. Y. Amsharov, M. A. Kabdulov, M. Jansen, Angew.
Chem. 2012, 124, 4672; Angew. Chem. Int. Ed. 2012, 51,
4594; b) T. E. Long, X. Lu, M. Galizzi, R. Docampo, J.
Gut, P. J. Rosenthal, Bioorg. Med. Chem. Lett. 2012, 22,
2976; c) P. Das, M. K. Kesharwani, A. K. Mandal, E.
Suresh, B. Ganguly, A. Das, Org. Biomol. Chem. 2012,
10, 2263; d) P. Das, M. K. Kesharwani, A. K. Mandal, E.
Suresh, B. Ganguly, A. Das, Org. Biomol. Chem. 2012,
10, 2263; e) N. Takenaka, R. S. Sarangthem, B. Captain,
Angew. Chem. 2008, 120, 9854; Angew. Chem. Int. Ed.
2008, 47, 9708.
[3] a) G. A. Kraus, H. Guo, J. Org. Chem. 2009, 74, 5337;
b) G. A. Kraus, H. Guo, Org. Lett. 2008, 10, 3061; c) M.
Tao, C. H. Park, R. Bihovsky, G. J. Wells, J. Husten,
M. A. Ator, R. L. Hudkins, Bioorg. Med. Chem. Lett.
2006, 16, 938; d) T. C. Kuehler, M. Swanson, B. Christen-
son, A. Klintenberg, B. Lamm, J. Faegerhag, R. Gatti,
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
temperature for 1 h. The reaction mixture was quenched
with water, extracted with Et2O, and dried over anhy-
drous Na2SO4. After evaporation of the Et2O, chroma-
tography on silica gel (eluent: EtOAc/petroleum ether=
1:8) of the crude product afforded (Z)-4-phenyl-
Adv. Synth. Catal. 2013, 355, 3492 – 3496
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3495

Guoqing Zhao et al.
UPDATES
hepta-4,6-dien-2-yn-1-ol, in 88% yield. Treatment of the
[7] a) E. A. Dixon, A. Fischer, F. P. Robinson, Can. J.
Chem. 1981, 59, 2629; b) S. S. Hecht, M. Loy, R. Mazzar-
ese, D. Hoffmann, J. Med. Chem. 1978, 21, 38.
(Z)-4-phenylhepta-4,6-dien-2-yn-1-ol
with
CBr4
(1.2 equiv.) and Ph3P (1.5 equiv.) in DCM at 08C fur-
[8] a) A. Camacho-Davila, L. S. R. Gamage, Z. Wang, J. W.
Herndon, Tetrahedron 2010, 66, 4954; b) J. F. Collins, H.
Smith, J. Chem. Soc. 1956, 4308.
nished the bromide in 65% yield.
3496
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3492 – 3496