Zinc-mediated allylation of aryl 2-propynyl acetates: A facile synthesis of 1,5-enynes

Article abstract of DOI:10.1246/cl.2008.954

Aryl 2-propynyl acetates undergo smooth allylation with allylzinc bromide (generated in situ from allyl bromide and zinc metal) in THF at room temperature under mild conditions to furnish the corresponding 1,5-enynes in good to excellent yields and with high selectivity. Indium metal is also found to accomplish the nucleophilic substitution of aryl 2-propynylic acetates with allyl bromide. Copyright

Full text of DOI:10.1246/cl.2008.954

954
Chemistry Letters Vol.37, No.9 (2008)
Zinc-mediated Allylation of Aryl 2-Propynyl Acetates: A Facile Synthesis of 1,5-Enynes
J. S. Yadav,ꢀ B. V. Subba Reddy, D. Chandrakanth, and B. Prashant
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received May 26, 2008; CL-080532; E-mail: yadavpub@iict.res.in)
Aryl 2-propynyl acetates undergo smooth allylation with
OAc
Zinc
allylzinc bromide (generated in situ from allyl bromide and
zinc metal) in THF at room temperature under mild conditions
to furnish the corresponding 1,5-enynes in good to excellent
yields and with high selectivity. Indium metal is also found
to accomplish the nucleophilic substitution of aryl 2-propynylic
acetates with allyl bromide.
Br
+
THF, rt
3I
1I
2
Scheme 2.
(Entries K and L, Table 1). Simple alkyl acetates failed to under-
go allylation under the reaction conditions. This method was
successful only with aryl 2-propynyl acetates. It is noteworthy
to mention that 2-propynyl acetates bearing methoxy groups
on aromatic ring gave comparatively high yields than non-me-
thoxy 2-propynyl acetates. No additives or acidic promoters
are required for the reaction to proceed. As solvent, dichloro-
methane gave the best results. All products were characterized
by 1H, 13C NMR, IR, and mass spectrometry, and also by com-
parison with authentic samples.4–15 However, in the absence of
zinc metal, the reaction did not proceed even after an extended
reaction time (12 h). Although, the reaction was successful with
indium metal, the isolated yields (20–40%) were very low even
after longer reaction times (12–18 h). In contrast to indium, zinc
metal is readily available at low cost and is highly efficient in
promoting allylation. It should be noted that the allylation of
all substrates led exclusively to the formation of 2-propynylic
products and no traces of allenic side products were detected.
The scope of this process is illustrated with respect to various
aryl 2-propynyl acetates and the results are presented in
Table 1.16
The stereoselective addition of allylmetal reagents to alde-
hydes referred to as the Barbier reaction has been recognized
as one of the most efficient methods for carbon–carbon bond
formation and has been extensively used in organic synthesis, es-
pecially in natural products synthesis.1 Aryl 2-propynyl alcohols
or acetates are well-known carbon electrophiles capable of
reacting with various nucleophiles and their ability to undergo
nucleophilic substitution reactions contributes largely to their
synthetic value.2,3 The Nicholas reaction has been widely used
as a powerful tool for the substitution of 2-propynylic alcohols.2
However, this method generally requires a stoichiometric
amount of Co2(CO)8 and several steps are necessary to obtain
the 2-propynylic product from 2-propynylic alcohols through
cationic 2-propynylic complexes.4–6 Subsequently, several tran-
sition-metal-catalyzed 2-propynylic substitutions have been re-
ported using ruthenium, rhenium(V), and gold(III) catalysts.7–12
Recently, boron(III) and bismuth(III) reagents have also been
used to accomplish this transformation.13–15 However, there
have been no reports on the allylation of aryl 2-propynylic
acetates with allyl bromide using zinc metal.
Herein, we report a simple and convenient method for the
allylation of aryl 2-propynyl acetates using allylzinc bromide
to produce 1,5-enynes. Initially, we attempted the allylation of
1-(4-methoxyphenyl)-3-phenylprop-2-ynyl acetate (1A) with allyl
bromide (2) in the presence of metallic zinc in THF. The reaction
went to completion in 25 min at room temperature and the
desired product 3A was obtained in 85% yield (Scheme 1).
Similarly, various aryl 2-propynyl acetates underwent
smooth allylation with allylzinc bromide to afford the corre-
sponding pent-4-en-2-yl benzene derivatives in high yields
(Entries B–H, Table 1). In all cases, the reactions proceeded rap-
idly at room temperature. Interestingly, doubly activated aryl
2-propynyl acetates reacted effectively with allylzinc bromide
to furnish 1,5-enynes in high yields (Entries I and J, Table 1,
Scheme 2).
In summary, we have demonstrated a simple, convenient,
and efficient protocol for the allylation of aryl 2-propynyl ace-
tates using allylzinc bromide. In addition to its efficiency, and
mild reaction conditions, this method provides high yields of
products with high selectivity, which makes it a useful and
attractive process for the synthesis of 1,5-enynes from aryl
propargyl acetates.
References and Notes
1
Z. Zha, S. Qiao, J. Jiang, Y. Wang, Q. Miao, Z. Wang,
Tetrahedron 2005, 61, 2521; F. Rubsam, S. Seck, A.
Giannis, Tetrahedron 1997, 53, 2823.
2
K. M. Nicholas, M. Mulvaney, M. Bayer, J. Am. Chem. Soc.
1980, 102, 2508; K. M. Nicholas, Acc. Chem. Res. 1987,
20, 207; Y. Nishibayashi, M. D. Milton, Y. Inada, M.
Yoshikawa, I. Wakiji, M. Hidai, S. Uemura, Chem.—Eur.
J. 2005, 11, 1433; Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y.
Cui, R.-F. Yang, W.-Z. Yang, J.-P. Li, J. Org. Chem.
2006, 71, 8298.
Furthermore, the acetate derived from 3-phenyl-1-(thio-
phen-2-yl)prop-2-yn-1-ol also participated in this reaction
3
Z. Liu, L. Liu, Z. Shafiq, Y.-C. Wu, D. Wang, Y.-J. Chen,
Tetrahedron Lett. 2007, 48, 3963; T. Schwier, M. Rubin,
V. Gevorgyan, Org. Lett. 2004, 6, 1999; R. Sanz, D. Miguel,
OAc
Zinc
THF, rt
Br
+
´
A. Martꢀnez, J. M. Alvarez-Gutierrez, F. Rodrıguez, Org.
MeO
MeO
Lett. 2007, 9, 727.
J. R. Green, Curr. Org. Chem. 2001, 5, 809.
B. J. Teobald, Tetrahedron 2002, 58, 4133.
3A
1A
2
4
5
Scheme 1.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.9 (2008)
955
Table 1. Zinc-mediated allylation of aryl 2-propynyl acetates
6
7
8
9
O. Kuhn, D. Rau, H. Mayr, J. Am. Chem. Soc. 1998, 120,
900.
Y. Nishibayashi, A. Shinoda, Y. Miyake, H. Matsuzawa,
M. Sato, Angew. Chem., Int. Ed. 2006, 45, 4835.
M. R. Luzung, F. D. Toste, J. Am. Chem. Soc. 2003, 125,
15760.
Entry
A
2-propynyl alcohol
OAc
Allyl bromide
ZnBr
Producta
Time/min
Yield/%b
25
85
Ph
Ph
Ph
MeO
MeO
MeO
MeO
OAc
B. D. Sherry, A. T. Radosevich, F. D. Toste, J. Am. Chem.
Soc. 2003, 125, 6076.
ZnBr
ZnBr
20
35
B
82
80
Ph
OMe
OMe
10 J. J. Kennedy-Smith, L. A. Young, F. D. Toste, Org. Lett.
2004, 6, 1325.
11 M. Georgy, V. Boucard, J. M. Campagne, J. Am. Chem. Soc.
2005, 127, 14180.
12 Y. Kuninobu, E. Ishii, K. Takai, Angew. Chem., Int. Ed.
2007, 46, 3296.
13 Z.-P. Zhan, W.-Z. Yang, R.-F. Yang, J.-L. Yu, J.-P. Li,
H.-J. Liu, Chem. Commun. 2006, 3352.
14 Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang,
W.-Z. Yang, J.-P. Li, J. Org. Chem. 2006, 71, 8298.
15 G. W. Kabalka, M.-L. Yao, S. Borella, J. Am. Chem. Soc.
2006, 128, 11320.
16 General procedure. A mixture of aryl 2-propynyl acetate
(5 mmol), allyl bromide (10 mmol), and zinc powder
(10 mmol) in THF (10 mL) was stirred at room temperature
for an appropriate time (Table 1). After completion of the
reaction as indicated by TLC, the reaction mixture was
quenched with saturated ammonium chloride (15 mL) and
extracted with ethyl acetate (2 ꢁ 15 mL). Evaporation of
the solvent followed by purification on silica gel (Merck,
100–200 mesh, ethyl acetate–hexane, 0.5–9.5) afforded pure
1,5-enyne. Spectral data for selected products: 3A: liquid, IR
(Neat): ꢀ 3070, 2928, 2839, 2198, 1603, 1510, 1446, 1250,
OAc
Ph
MeO
MeO
MeO
MeO
C
D
Ph
Ph
OAc
MeO
MeO
MeO
MeO
ZnBr
ZnBr
20
35
86
80
Ph
OMe
OMe
OAc
E
MeO
MeO
MeO
MeO
OAc
F
ZnBr
ZnBr
35
40
83
79
OMe
OMe
OMe
OAc
MeO
MeO
G
OMe
OAc
MeO
MeO
MeO
MeO
82
35
ZnBr
ZnBr
H
OMe
OMe
OAc
1
1175, 1032, 916, 830, 756, 691 cmꢂ1; H NMR (300 MHz,
30
30
80
78
I
Ph
Ph
CDCl3): ꢁ 7.34–7.29 (m, 2H), 7.23–7.14 (m, 5H), 6.73 (d,
J ¼ 8:3 Hz, 2H), 5.86–5.71 (m, 1H), 5.04–4.94 (m, 2H),
3.74 (t, J ¼ 7:1 Hz, 1H), 3.69 (s, 3H), 2.50–2.42 (m, 2H);
13C NMR (75 MHz, CDCl3): ꢁ 158.4, 135.4, 133.4, 131.5,
128.4, 128.1, 127.6, 123.6, 116.9, 113.7, 91.2, 83.5, 55.1,
42.7, 37.6; LCMS: m=z: [M + H]þ: 263; HRMS calcd for
C19H19O: 263.1435. Found: 263.1447. 3F: Liquid, IR
(Neat): ꢀ 2935, 2865, 1497, 1458, 1217, 1046, 914, 801,
OAc
ZnBr
ZnBr
ZnBr
J
Ph
Ph
K
25
30
83
80
S
S
S
S
OAc
709 cmꢂ1
;
1H NMR (300 MHz, CDCl3): ꢁ 7.06 (d, J ¼
L
3:0 Hz, 1H), 6.71–6.60 (m, 2H), 5.90–5.75 (m, 1H), 5.03–
4.95 (m, 2H), 4.08–4.00 (m, 1H), 3.76 (s, 3H), 3.75
(s, 3H), 2.47–2.27 (m, 2H), 2.26–2.18 (m, 2H), 1.58–1.39
(m, 4H), 0.93 (t, J ¼ 7:1 Hz, 3H); 13C NMR (75 MHz,
CDCl3): ꢁ 153.5, 150.4, 136.2, 131.7, 116.1, 114.9, 111.8,
111.3, 83.1, 81.1, 55.9, 55.5, 41.1, 31.4, 31.2, 21.8, 18.4,
13.5; LCMS: m=z: [M + H]þ: 273; HRMS calcd for
C18H24O2Na: 295.1673. Found: 295.1662. 3K: liquid, IR
(Neat): ꢀ 3075, 2926, 2856, 1641, 1597, 1489, 1439, 1310,
OAc
OAc
720c
58
65
M
ZnBr
OAc
60
N
O
ZnBr
ZnBr
MeO
MeO
MeO
MeO
MeO
OAc
OAc
1227, 993, 917, 755, 693 cmꢂ1
;
1H NMR (200 MHz,
30
45
70
75
Ph
Ph
Ph
CDCl3): ꢁ 7.53–7.44 (m, 2H), 7.38–7.29 (m, 3H), 7.22
(dd, J ¼ 1:4, 5.1 Hz, 1H), 7.08 (dd, J ¼ 1:4, 3.6 Hz, 1H),
7.01–6.90 (m, 1H), 6.12–5.89 (m, 1H), 5.29–5.14 (m, 2H),
4.24 (t, J ¼ 6:9 Hz, 1H), 2.80–2.70 (m, 2H); 13C NMR
(75 MHz, CDCl3): ꢁ 144.8, 134.8, 131.6, 128.2, 127.9,
126.5, 124.4, 123.9, 123.3, 117.5, 90.1, 83.4, 42.7, 33.;
LCMS: m=z: [M + H]þ: 239.
Ph
P
Ph
ZnBr
Ph
MeO
aAll products were characterized by NMR, IR, and mass spectrometry. bYield
refers to pure products after chromatography. cReaction was performed in
refluxing THF.
Published on the web (Advance View) August 9, 2008; doi:10.1246/cl.2008.954