Copper-catalyzed tandem alkynylation, propargyl-allenyl isomerization, 6π-electrocyclization of Morita-Baylis-Hillman adducts to naphthalenes

Article abstract of DOI:10.1016/j.tetlet.2012.07.126

An expedient synthetic approach of naphthalenes was developed by the reaction of Morita-Baylis-Hillman bromides and arylacetylenes. The synthesis was carried out via a tandem copper-catalyzed alkynylation, propargyl-allenyl isomerization, and 6π-electrocyclization protocol.

Full text of DOI:10.1016/j.tetlet.2012.07.126

Tetrahedron Letters 53 (2012) 5449–5454
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Copper-catalyzed tandem alkynylation, propargyl–allenyl isomerization,
6p
-electrocyclization of Morita–Baylis–Hillman adducts to naphthalenes
⇑
Jin Woo Lim, Ko Hoon Kim, Se Hee Kim, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An expedient synthetic approach of naphthalenes was developed by the reaction of Morita–Baylis–
Hillman bromides and arylacetylenes. The synthesis was carried out via a tandem copper-catalyzed
Received 8 July 2012
Revised 23 July 2012
Accepted 30 July 2012
Available online 7 August 2012
alkynylation, propargyl–allenyl isomerization, and 6
p
-electrocyclization protocol.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Morita–Baylis–Hillman adducts
Alkynylation
Propargyl–allenyl isomerization
6p
-Electrocyclization
Naphthalenes
Recently, syntheses of a variety of acyclic and cyclic compounds
respects, we envisaged that modified MBH adducts 3 could be used
as efficient starting materials for 1,3-disubstituted naphthalenes 4.
The propargyl moiety of 3 could be isomerized to the correspond-
ing allene intermediate I, which could form naphthalene 4 via a
including various aromatic and heterocyclic compounds have been
carried out starting from the Morita–Baylis–Hillman (MBH)
adducts.1,2 Numerous synthetic approaches of naphthalene
scaffold have also been reported from the MBH adducts.2
6p-electrocyclization process.
In 2004, we have reported the synthesis of 7H-benzocyclohep-
tene derivatives from the acetate of MBH adducts, as shown in
Scheme 1.2h The synthesis was carried out via a sequential intro-
duction of phenylethynyl moiety at the primary position of the
MBH adduct and a subsequent acid-catalyzed intramolecular
Friedel–Crafts alkenylation reaction.2h The reaction involved a
selective formation of a vinyl cation at the benzylic site. Our con-
tinuous interest for the synthesis of naphthalenes prompted us
to investigate the feasibility for the synthesis of naphthalene 4a
from the acetylene derivative 3a via the allene-mediated electro-
cyclization process.3–5
Many examples of allene-mediated electrocyclization reactions
have been known,3–5 and the synthesis of naphthalene scaffold
using this protocol has also been reported,4,5 as shown in Scheme
2. Zhou and co-workers have reported a heteroatom-assisted prop-
argyl–allenyl isomerization and subsequent electrocyclization to
form naphthalenes.4 Burton and co-workers used fluoroenyne
derivatives in their base-catalyzed synthesis of 3-fluoronaphtha-
lenes.5 Although the yields of naphthalenes were good in most en-
tries,4,5 the preparation of starting materials required many steps
involving the use of transition metal-catalyzed reactions. In these
In order to examine the base-mediated propargyl–allenyl
isomerization,6 and a subsequent 6
p-electrocyclization process,
compound 3a was selected as a representative starting material.
Thus, at the outset of our experiments, compound 3a was prepared
from the acetate of MBH adduct and phenylethynylmagnesium
bromide in the presence of CuI (10%) according to the reported
method.2h,7 However, the yield of 3a was moderate (53%), thus
we decided to develop an alternative method. The reaction between
Grignard reagents and the acetates of MBH adduct has been re-
ported by Basavaiah and co-workers for the first time.7a Although
many papers have used this protocol for the alkenyl and alkynyl-
substituted MBH adducts; however, the yields of products were
low to moderate.2h,7 Copper salt-catalyzed in-situ generation of
an acetylide anion and a subsequent alkylation with MBH bromide
could be an alternative choice;8 however, there was no report using
such a strategy, to the best of our knowledge. Thus, we examined
the synthesis of 3a from the MBH bromide 1a and phenylacetylene
(2a) under copper salt-catalyzed reaction conditions in brief, and
the results are summarized in Table 1 (entries 1–4). When we used
DBU (entry 1), only a trace amount of 3a (10%) was formed. The low
yield may be due to a rapid salt formation between 1a and DBU, as
we observed before.9 The reaction in the presence of K2CO3 at 20 °C
was also ineffective (entry 2). When we elevated the reaction
temperature to 50 °C, compound 3a was obtained in moderate yield
⇑
Corresponding author.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.126

5450
J. W. Lim et al. / Tetrahedron Letters 53 (2012) 5449–5454
COOEt
COOEt
COOEt
Friedel-Crafts
alkenylation
OAc
H2SO4
Ph
MgBr
H
COOEt
Ref. 2h
Ph
Ph
3a
Ph
MBH acetate
COOEt
COOEt
(2a)
Ph
propargyl-allenyl
isomerization
COOEt
6π-electrocyclization
CuI (20 mol%)
3a
Cs2CO3 (2.0 equiv)
Br
4a
CH3CN, 50 o
This Work
C
Ph
Ph
I
MBH bromide 1a
Scheme 1.
R
R
F
R
Zhou
(X = O, S)
XR'
X
R'
XR'
F
F
Burton
R'
R'
R'
R'
COOEt
COOEt
COOEt
This Work
R'
3
4
I
R'
Scheme 2.
(49%); however, the yield was not satisfactory. To our delight, the
yield of 3a increased to 78% when the reaction was performed at
20 °C using Cs2CO3 as a base (entry 4).
Scheme 3. The reaction of 3a in CH3CN in the presence of Cs2CO3
(1.0 equiv) at 50 °C for 4 h afforded 4a in moderate yield (65%),
while the reaction with K2CO3 was sluggish at the same reaction
temperature. The use of DBU (0.3 equiv, CH3CN, 50 °C) was found
to be more effective,4,5b,e and 4a was obtained in good yield
(78%) in a short time (2 h). The acidic methylene proton of 3a could
be readily isomerized to form the allene intermediate, and a subse-
quent electrocyclization proceeded to form 4a. The yield of 4a was
slightly higher (61%; 78% for 3a and 78% for 4a) than that of the
one-pot synthesis (56%).
Encouraged by the successful results, we examined the synthe-
sis of various naphthalene derivatives under the one-pot reaction
conditions (entries 5 or 6 in Table 1), and the results are summa-
rized in Table 2. Although the yield of naphthalene was slightly
lower than that of the two-step procedure, we selected a more con-
venient one-pot condition.
As shown in Table 2, various naphthalenes 4b–d and 4f–i were
synthesized in good to moderate yields (44–81%) from the MBH
bromides 1a–d and arylacetylenes 2a–d. The yield of p-chloro
derivative 4b was similar to that of 4a (entry 2), while the yields
increased with MBH bromides bearing an electron-donating group
such as 1c and 1d (entries 3 and 4). Benzofuran derivative 4e was
synthesized in 59% by the reaction of 1e and 2a (entry 5). The reac-
tions of 1a and 1d with substituted arylacetylenes 2b–d also affor-
ded the corresponding naphthalenes 4f–i in moderate yields
(entries 6–9).
The reaction between the MBH bromide of cinnamaldehyde 1f
and 2a produced a trisubstituted benzene derivative 4j in 55% un-
der the same reaction conditions, as shown in Scheme 4. The reac-
tion of 1-naphthyl derivative 1g and 2a gave phenanthrene
derivative 4k in moderate yield (64%) along with a low yield (8%)
of cyclohepta[a]naphthalene derivative 5. This compound might
be formed via a CuBr-assisted intramolecular Friedel–Crafts type
alkenylation process.2,11 The reaction of 2-naphthyl derivative 1h
afforded 4l and 6 as an inseparable mixture (80%, 4l:6 = 3:2). Such
During the synthesis of 3a we found the formation of naphtha-
lene 4a, albeit in a low yield (3–4%), in some entries. The results
implied that naphthalene 4a could be synthesized in a one-pot
reaction. Thus we further examined the reaction conditions in or-
der to obtain 4a in a one-pot reaction, and the results are summa-
rized in Table 1 (entries 5–10). The yield of 4a increased to 56%
when we raised the reaction temperature to 50 °C (entry 5) in a
short time (5 h).10 The use of CuBr showed a similar result (entry
6) although somewhat a longer reaction time (15 h) was required.
The use of CuCl (entry 7) and other solvents such as DMF (entry 8)
or toluene (entry 9) were less effective than the conditions of en-
tries 5 and 6. The reaction at elevated temperature (entry 10) did
not increase the yield of 4a. Thus, compound 4a could be synthe-
sized in 56–57% yields (entries 5 and 6) by a one-pot procedure.
In order to compare the yield of 4a using a two-step procedure,
we examined a base-mediated synthesis of 4a from 3a, as shown in
Table 1
Optimization of copper salt-catalyzed synthesis of 3a and 4aa
Entry
CuX
Base
Solvent/temp/time (h)
3a (%)
4a (%)
1
2
3
4
5
6
7
8
9
CuI
CuI
CuI
CuI
DBU
CH3CN/20 °C/10
CH3CN/20 °C/24
CH3CN/50 °C/24
CH3CN/20 °C/10
CH3CN/50 °C/5
CH3CN/50 °C/15
CH3CN/50 °C/5
DMF/50 °C/6
10
12
49
78
0
0
5
0
5
0
0
3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
4
CuI
56
57
39
44
10
49
CuBr
CuCl
CuBr
CuBr
CuI
Toluene/reflux/15
CH3CN/reflux/2
10
0
a
Conditions: substrate 1a (0.5 mmol), 2a (2.0 equiv), base (2.0 equiv), CuX
(20 mol %).

J. W. Lim et al. / Tetrahedron Letters 53 (2012) 5449–5454
2a (2.0 equiv), CuI (20 mol%)
5451
Cs2CO3 (2.0 equiv), CH3CN, 20 °C, 10 h
CH3CN, Cs2CO3 (1.0 equiv), 50 °C, 4 h, 65%
1a
3a
4a
78% (entry 4 in Table 1)
CH3CN, DBU (0.3 equiv), 50 °C, 2 h, 78%
(two-step overall yield, 51-61%)
2a (2.0 equiv), CuI (20 mol%), Cs2CO3 (2.0 equiv), CH3CN, 50 °C, 5 h
one-pot synthesis (56%, entry 5 in Table 1)
Scheme 3.
Table 2
One-pot synthesis of naphthalene derivatives from MBH bromides
Entry
MBH bromide
Acetylene
Conditiona (h)
Product (%)
COOEt
CuI/5
CuBr/15
4a (56)
4a (57)
1
1a
2a
Ph
COOEt
Br
COOEt
CuI/3
CuBr/5
4b (54)
4b (52)
2
3
4
5
6
7
8
9
2a
2a
2a
Cl
Cl
1b
Ph
COOEt
Br
COOEt
4c (74)
CuBr/5
1c
Ph
COOEt
Br
COOEt
CuI/10
CuBr/18
4d (78)
4d (81)
MeO
MeO
O
1d
Ph
COOEt
COOEt
Br
O
4e (59)
2a
CuBr/15
CuBr/15
CuI/16
1e
Ph
Ar1
COOEt
2b
4f (44)
1a
(Ar1 = p-MeOPh)
Ar1
COOEt
Ar2
2c
4g (56)
1a
1a
1d
(Ar2 = p-MePh)
Ar2
Ar3
COOEt
2d
4h (54)
CuI/13
(Ar3 = p-FPh)
Ar3
COOEt
4i (56)
2b
CuBr/19
MeO
Ar1
a
Conditions: MBH bromide 1 (0.5 mmol), arylacetylene 2 (2.0 equiv), CH3CN, Cs2CO3 (2.0 equiv), 50 °C, copper salt (0.2 equiv).
a formation of seven-membered ring compound was not observed
during the synthesis of 4a–i, and the reason is not clear at this
stage.
Compound 5 could be prepared from 3b in an increased yield
(37%) under an acid-catalyzed intramolecular Friedel–Crafts alke-
nylation reaction condition,2h as shown in Scheme 5. The phenan-
threne 4l could also be synthesized in a high yield (81%) using a
two-step procedure via the preparation of 3c and a subsequent
DBU-mediated cyclization. We could not observe the formation
of compound 6 in the reaction of 3c.
of many intractable side products. Thus, we used a two-step
process in these entries, as shown in Scheme 6. The reaction of 1a
and ethyl propiolate afforded 3d in moderate yield (63%), and a sub-
sequent cyclization of 3d gave 4m in 71%. The use of K2CO3 was
better than that of Cs2CO3 in both steps in this reaction. However,
an introduction of 1-decyne at the primary position of 1a was
somewhat difficult. Combined use of Cs2CO3 and DBU (0.1 equiv)
in DMF afforded a low yield of 3e (35%) at best. The cyclization of
3e–4n was carried out in the presence of DBU in toluene, and the
yield of 4n was low (42%) as compared to that of the other entries.
When we used p-nitro derivative 1i the reaction pathway was
changed completely, as shown in Scheme 7. The reaction of 1i
The reactions of 1a with ethyl propiolate (2e) or 1-decyne (2f)
were not successful in a one-pot procedure due to the formation

5452
J. W. Lim et al. / Tetrahedron Letters 53 (2012) 5449–5454
COOEt
COOEt
Br
2a, CuBr, 9 h
Ph
Ph
same conditions in Table 2
1f
Ph
Ph
4j (55%)
COOEt
COOEt
COOEt
CuBr
COOEt
2a, CuBr, 12 h
+
COOEt
Br
same conditions in Table 2
Ph
5 (8%)
4k (64%)
Ph
CuBr
1g
1h
Ph
Ph
COOEt
Ph
COOEt
Br
2a, CuBr, 12 h
COOEt
+
same conditions in Table 2
4l
6
80% as a mixture (4l:6 = 3:2)
Scheme 4.
H2SO4 (1.2 equiv)
CH2Cl2, 0 °C to rt, 8 h
2a
COOEt
1g
4k (14%) + 5 (37%)
Cs2CO3, CuI
CH3CN, 20 °C, 9 h
3b (75%)
Ph
COOEt
DBU (0.3 equiv)
CH3CN, 50 °C, 2 h
2a
4l (81%)
1h
Cs2CO3, CuI
Ph
CH3CN, 20 °C, 9 h
3c (72%)
Scheme 5.
K2CO3 (0.1 equiv)
CH3CN, 70 °C, 3 h
ethyl propiolate (2e, 1.0 equiv)
COOEt
COOEt
Ph
Ph
K2CO3 (1.3 equiv)
1a
1a
CuBr (20 mol%)
CH3CN, 70 °C, 1 h
COOEt
COOEt
4m (71%)
3d (63%)
1-decyne (2f, 1.5 equiv)
Cs2CO3 (1.5 equiv)
DBU (0.1 equiv)
COOEt
DBU (0.3 equiv)
toluene, reflux, 24 h
COOEt
CuI (20 mol%)
DMF, 50 °C, 3 h
(CH2)7CH3
(CH2)7CH3
4n (42%)
3e (35%)
Scheme 6.
COOEt
COOEt
H
COOEt
Br
O2N
COOEt
E
2a
1i
[B]
Cs2CO3, CuBr
CH3CN, 20 °C, 2 h
O2N
O2N
SN2
O2N
O2N
Ph
1i
3f
7 (35%)
Ph
COOEt
COOEt
COOEt
O2N
O2N
Ph
Ph
Ph
A
B
C
three resonance structures of the anion of 3f
Scheme 7.
and phenylacetylene (2a) under the one-pot condition (CuBr,
Cs2CO3, 50 °C, 2 h) did not produce the expected naphthalene
derivative at all. Instead, compound 7 was formed unexpectedly
in low yield (25%) along with intractable side products. The
reaction produced 7 again in 35% in short time (2 h) even at low
temperature (20 °C). The reason for the formation of 7 could be

J. W. Lim et al. / Tetrahedron Letters 53 (2012) 5449–5454
5453
L.; Bosica, G.; Fiorini, D.; Mignini, E.; Palmieri, A. Tetrahedron 2004, 60, 4995–
4999.
10. Typical procedure for the synthesis of compound 4a: MBH bromides 1a–i were
explained as follows. There could be three resonance structures for
the anion of intermediate 3f, and the resonance structure B must
be the most stable one due to the presence of a stabilizing p-nitro
moiety. The anion B then reacted with bromide 1i once again in a
SN2 manner to produce 7.12
In summary, we disclosed an efficient one-pot synthetic
approach of naphthalenes by the reaction of Morita–Baylis–Hillman
bromides and arylacetylenes. The reaction involved a tandem
copper-catalyzed alkynylation, propargyl–allenyl isomerization,
prepared from the corresponding MBH adducts by treatment with aqueous HBr
2a–c,e
according to the literature procedure.
A stirred solution of MBH bromide
1a (135 mg, 0.5 mmol), phenylacetylene (2a, 102 mg, 1.0 mmol), CuI (19 mg,
0.2 equiv), and Cs2CO3 (352 mg, 2.0 equiv) in CH3CN (1.5 mL) was heated to
50 °C for 5 h. After the aqueous extractive workup and column
chromatographic purification process (hexanes/ether, 15:1) compound 4a
was obtained as
a colorless oil, 81 mg (56%). Other compounds were
synthesized similarly, and the selected spectroscopic data of 4a, 4b, 4e, 4f,
4i–n, 5, and 7 are as follows.
Compound 4a: 56%; colorless oil; IR (film) 1716, 1296, 1241, 1206 cmÀ1 1H
;
and 6p-electrocyclization.
NMR (CDCl3, 300 MHz) d 1.44 (t, J = 7.2 Hz, 3H), 4.43 (q, J = 7.2 Hz, 2H), 4.47 (s,
2H), 7.14–7.29 (m, 5H), 7.46–7.55 (m, 2H), 7.93–8.00 (m, 3H), 8.53 (s, 1H); 13
C
Acknowledgments
NMR (CDCl3, 75 MHz) d 14.37, 39.14, 61.08, 124.46, 126.15, 126.27, 126.64,
127.27, 128.26, 128.47 (2C), 130.13, 130.21, 133.12, 134.27, 136.97, 140.18,
166.83; ESIMS m/z 291 [M+H]+. Anal. Calcd for C20H18O2: C, 82.73; H, 6.25.
Found: C, 82.49; H, 6.36.
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology
(2012R1A1B3000541). Spectroscopic data were obtained from
the Korea Basic Science Institute, Gwangju branch.
Compound 4b: 54%; pale yellow solid, mp 114–116 °C; IR (KBr) 1716, 1287,
1238, 1203 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.43 (t, J = 7.2 Hz, 3H), 4.42 (s,
;
2H), 4.42 (q, J = 7.2 Hz, 2H), 7.16–7.30 (m, 5H), 7.44 (dd, J = 8.7 and 1.8 Hz, 1H),
7.88 (d, J = 8.7 Hz, 1H), 7.94–8.00 (m, 2H), 8.48 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 14.34, 38.91, 61.20, 123.59, 126.38, 127.30, 127.62, 127.64, 128.49,
128.61, 129.82, 131.38, 131.58, 134.42, 134.98, 136.41, 139.57, 166.45; ESIMS
m/z 325 [M+H]+, 327 [M+H+2]+. Anal. Calcd for C20H17ClO2: C, 73.96; H, 5.28.
Found: C, 74.11; H, 5.14.
References and notes
Compound 4e: 59%; colorless oil; IR (film) 1714, 1368, 1307, 1241 cmÀ1 1H
;
1. For the general reviews on Morita–Baylis–Hillman reaction, see (a) Basavaiah,
D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah,
D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010, 110, 5447–5674; (c) Singh, V.;
Batra, S. Tetrahedron 2008, 64, 4511–4574; (d) Declerck, V.; Martinez, J.;
Lamaty, F. Chem. Rev. 2009, 109, 1–48; (a) Ciganek, E. In Organic Reactions;
Paquette, L. A., Ed.; John Wiley & Sons: New York, 1997; Vol. 51, pp 201–350;
(f) Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (g) Lee, K. Y.;
Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (h)
Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65,
8769–8780; (i) Shi, M.; Wang, F.-J.; Zhao, M.-X.; Wei, Y. The Chemistry of the
Morita–Baylis–Hillman Reaction; RSC Publishing: Cambridge, UK, 2011.
2. For the synthesis of naphthalene derivatives from MBH adducts, see (a) Kim, S.
H.; Lee, S.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2010, 51, 6305–6309; (b) Kim,
S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2010, 51, 4267–4271; (c)
Kim, E. S.; Kim, K. H.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 5098–
5101; (d) Chen, P.-Y.; Chen, H.-M.; Chen, L.-Y.; Tzeng, J.-Y.; Tsai, J.-C.; Chi, P.-C.;
Li, S.-R.; Wang, E.-C. Tetrahedron 2007, 63, 2824–2828; (e) Lee, K. Y.; Kim, S. C.;
Kim, J. N. Tetrahedron Lett. 2006, 47, 977–980; (f) Im, Y. J.; Lee, K. Y.; Kim, T. H.;
Kim, J. N. Tetrahedron Lett. 2002, 43, 4675–4678; (g) Kim, J. N.; Im, Y. J.; Gong, J.
H.; Lee, K. Y. Tetrahedron Lett. 2001, 42, 4195–4197; (h) Gowrisankar, S.; Lee, K.
Y.; Lee, C. G.; Kim, J. N. Tetrahedron Lett. 2004, 45, 6141–6146.
3. For the selected examples on allene-mediated electrocyclization reactions, see
(a) Souto, J. A.; Perez, M.; Lopez, C. S.; Alvarez, R.; Torrado, A.; De Lera, A. R. J.
Org. Chem. 2010, 75, 4453–4462; (b) Knobloch, K.; Eberbach, W. Eur. J. Org.
Chem. 2002, 2054–2057; (c) Wang, F.; Tong, X.; Cheng, J.; Zhang, Z. Chem. Eur. J.
2004, 10, 5338–5344; (d) Tohyama, S.; Choshi, T.; Matsumoto, K.; Yamabuki,
A.; Ikegata, K.; Nobuhiro, J.; Hibino, S. Tetrahedron Lett. 2005, 46, 5263–5264;
(e) Turnbull, P.; Moore, H. W. J. Org. Chem. 1995, 60, 3274–3275.
4. For the allene-mediated electrocyclization reactions to naphthalene, see (a)
Zhou, H.; Xing, Y.; Yao, J.; Lu, Y. J. Org. Chem. 2011, 76, 4582–4590; (b) Zhou, H.;
Xing, Y.; Yao, J.; Chen, J. Org. Lett. 2010, 12, 3674–3677.
NMR (CDCl3, 300 MHz) d 1.40 (t, J = 7.2 Hz, 3H), 4.24 (s, 2H), 4.39 (q, J = 7.2 Hz,
2H), 6.69 (dd, J = 2.4 and 0.9 Hz, 1H), 7.16–7.30 (m, 5H), 7.68 (d, J = 2.4 Hz, 1H),
7.82 (m, 1H), 8.09 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 14.35, 39.45, 61.00,
105.59, 111.36, 124.35, 126.30, 126.75, 128.53, 128.65, 131.30, 133.76, 139.90,
147.40, 154.53, 166.83; ESIMS m/z 281 [M+H]+. Anal. Calcd for C18H16O3: C,
77.12; H, 5.75. Found: C, 77.35; H, 5.92.
Compound 4f: 44%; colorless oil; IR (film) 1715, 1511, 1245, 1206 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 1.44 (t, J = 7.2 Hz, 3H), 3.75 (s, 3H), 4.41 (s, 2H), 4.43
(q, J = 7.2 Hz, 2H), 6.79 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 7.46–7.56 (m,
2H), 7.92–8.01 (m, 3H), 8.52 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 14.36, 38.25,
55.17, 61.05, 113.87, 124.43, 126.22, 126.41, 127.28, 128.20, 129.41, 130.09,
130.11, 132.22, 133.12, 134.24, 137.42, 157.93, 166.83; ESIMS m/z 321 [M+H]+.
Anal. Calcd for C21H20O3: C, 78.73; H, 6.29. Found: C, 78.69; H, 6.46.
Compound 4i: 56%; colorless oil; IR (film) 1712, 1624, 1510, 1239, 1202 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.43 (t, J = 7.2 Hz, 3H), 3.74 (s, 3H), 3.79 (s, 3H),
4.34 (s, 2H), 4.42 (q, J = 7.2 Hz, 2H), 6.79 (d, J = 8.7 Hz, 2H), 7.12 (d, J = 8.7 Hz,
2H), 7.14 (dd, J = 8.7 and 2.4 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.83 (d, J = 8.7 Hz,
1H), 7.93 (s, 1H), 8.44 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 14.40, 38.75, 55.18,
55.19, 60.88, 103.30, 113.87, 118.71, 124.99, 127.04, 128.41, 129.42, 129.85,
131.61, 132.16, 135.77, 135.95, 157.94, 159.37, 166.99; ESIMS m/z 351 [M+H]+.
Anal. Calcd for C22H22O4: C, 75.41; H, 6.33. Found: C, 75.77; H, 6.24.
Compound 4j: 55%; colorless oil; IR (film) 1718, 1288, 1180, 1104 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 1.38 (t, J = 7.2 Hz, 3H), 3.99 (s, 2H), 4.37 (q, J = 7.2 Hz,
2H), 6.91–6.95 (m, 2H), 7.10–7.25 (m, 5H), 7.30–7.39 (m, 4H), 7.93–7.96 (m,
2H); 13C NMR (CDCl3, 75 MHz) d 14.31, 38.91, 60.91, 125.89, 127.32, 127.38,
128.13, 128.26, 128.64, 128.93, 129.59, 130.29, 131.61, 138.47, 140.68, 140.81,
146.81, 166.53; ESIMS m/z 317 [M+H]+. Anal. Calcd for C22H20O2: C, 83.51; H,
6.37. Found: C, 83.32; H, 6.41.
Compound 4k: 64%; white solid, mp 116–118 °C; IR (KBr) 1715, 1268,
1230 cmÀ1 1H NMR (CDCl3, 300 MHz)
; d 1.46 (t, J = 7.2 Hz, 3H), 4.47 (q,
J = 7.2 Hz, 2H), 4.50 (s, 2H), 7.13–7.26 (m, 5H), 7.55–7.60 (m, 1H), 7.64–7.69
(m, 1H), 7.72 (d, J = 9.3 Hz, 1H), 7.82 (dd, J = 7.8 and 1.8 Hz, 1H), 7.86 (d,
J = 9.3 Hz, 1H), 8.10 (d, J = 1.8 Hz, 1H), 8.78 (d, J = 7.8 Hz, 1H), 9.37 (s, 1H); 13C
NMR (CDCl3, 75 MHz) d 14.42, 39.46, 61.14, 122.61, 123.05, 124.01, 126.14,
126.98, 127.16, 127.59, 128.23, 128.41, 128.48, 128.51, 129.38, 130.35, 130.90,
131.57, 133.42, 137.28, 140.30, 166.92; ESIMS m/z 341 [M+H]+. Anal. Calcd for
5. For the similar electrocyclization of aryl enynes, see (a) Xu, J.; Wang, Y.; Burton,
D. J. Org. Lett. 2006, 8, 2555–2558; (b) Wang, Y.; Burton, D. J. Org. Lett. 2006, 8,
5295–5298; (c) Wang, Y.; Burton, D. J. Tetrahedron Lett. 2006, 47, 9279–9281;
(d) Wang, Y.; Burton, D. J. J. Fluorine Chem. 2007, 128, 1052–1057; (e) Wang, Y.;
Xu, J.; Burton, D. J. J. Org. Chem. 2006, 71, 7780–7784.
6. For the synthetic applications of propargyl–allenyl isomerizations, see (a) Zhu,
S.; Wu, L.; Huang, X. RSC Adv. 2012, 2, 132–134; (b) Cao, J.; Huang, X. Org. Lett.
2010, 12, 5048–5051; (c) Huang, X.; Zhu, S.; Shen, R. Adv. Synth. Catal. 2009,
351, 3118–3122; (d) Shen, R.; Chen, L.; Huang, X. Adv. Synth. Catal. 2009, 351,
2833–2838; (e) Shen, R.; Zhu, S.; Huang, X. J. Org. Chem. 2009, 74, 4118–4123;
(f) Zhou, H.; Zhu, D.; Xie, Y.; Huang, H.; Wang, K. J. Org. Chem. 2010, 75, 2706–
2709; (g) Xu, G.; Chen, K.; Zhou, H. Tetrahedron Lett. 2010, 51, 6240–6242.
7. For the reaction of Grignard reagents and MBH adducts, see (a) Basavaiah, D.;
Sarma, P. K. S.; Bhavani, A. K. D. J. Chem. Soc., Chem. Commun. 1994, 1091–1092;
(b) Song, Y. S.; Lee, K.-J. J. Heterocycl. Chem. 2006, 43, 1721–1724; (c)
Gowrisankar, S.; Lee, K. Y.; Kim, S. C.; Kim, J. N. Bull. Korean Chem. Soc. 2005,
26, 1443–1446; (d) Schmidt, Y.; Breit, B. Chem. Eur. J. 2011, 17, 11789–11796;
For the indium-mediated alkynylation of MBH acetates, see (e) Yadav, J. S.;
Reddy, B. V. S.; Yadav, N. N.; Singh, A. P.; Choudhary, M.; Kunar, A. C.
Tetrahedron Lett. 2008, 49, 6090–6094.
C
24H20O2: C, 84.68; H, 5.92. Found: C, 84.57; H, 6.02.
Compound 4l: 81%; white solid, mp 104–106 °C; IR (KBr) 1716, 1274, 1212,
1029 cmÀ1 1H NMR (CDCl3, 500 MHz)
1.35 (t, J = 7.0 Hz, 3H), 4.35 (q,
;
d
J = 7.0 Hz, 2H), 4.77 (s, 2H), 7.12–7.16 (m, 3H), 7.20–7.24 (m, 2H), 7.32–7.35
(m, 1H), 7.46–7.49 (m, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 9.0 Hz, 1H), 7.79
(d, J = 8.5 Hz, 1H), 8.02 (s, 1H), 8.45 (s, 1H), 8.50 (d, J = 8.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) d 14.37, 43.60, 61.11, 125.99, 126.29, 127.00, 127.40, 127.95,
127.97, 128.25, 128.58, 128.71, 128.72, 129.85, 129.92, 131.88, 133.56, 133.64,
134.15, 136.88, 140.29, 166.54; ESIMS m/z 341 [M+H]+. Anal. Calcd for
C
24H20O2: C, 84.68; H, 5.92. Found: C, 84.79; H, 5.67.
Compound 4m: 71%; white solid, mp 45–47 °C; IR (KBr) 1718, 1291, 1243, 1204,
1172 cmÀ1 1H NMR (CDCl3, 300 MHz)
1.22 (t, J = 7.2 Hz, 3H), 1.44 (t,
;
d
J = 7.2 Hz, 3H), 4.09 (s, 2H), 4.15 (q, J = 7.2 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 7.51–
7.58 (m, 1H), 7.60–7.66 (m, 1H), 7.95–8.03 (m, 3H), 8.55 (s, 1H); 13C NMR
(CDCl3, 75 MHz) d 14.11, 14.37, 39.20, 61.04, 61.11, 123.88, 126.46, 127.19,
127.27, 128.58, 130.16, 130.94, 131.17, 132.97, 134.24, 166.53, 171.17; ESIMS
m/z 287 [M+H]+. Anal. Calcd for C17H18O4: C, 71.31; H, 6.34. Found: C, 71.68; H,
6.20.
8. For the copper-catalyzed coupling of alkynes and allylic or benzylic halides, see
(a) Bieber, L. W.; Da Silva, M. F. Tetrahedron Lett. 2007, 48, 7088–7090; (b)
Davies, K. A.; Abel, R. C.; Wulff, J. E. J. Org. Chem. 2009, 74, 3997–4000; (c)
Caruso, T.; Spinella, A. Tetrahedron 2003, 59, 7787–7790; (d) Grushin, V. V.;
Alper, H. J. Org. Chem. 1992, 57, 2188–2192.
Compound 4n: 42%; colorless oil; IR (film) 2926, 1719, 1261, 1240, 1201 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 0.81 (t, J = 6.9 Hz, 3H), 1.12–1.32 (m, 12H), 1.38 (t,
J = 7.2 Hz, 3H), 1.63–1.73 (m, 2H), 3.01 (t, J = 7.8 Hz, 2H), 4.37 (q, J = 7.2 Hz, 2H),
7.41–7.47 (m, 1H), 7.50–7.56 (m, 1H), 7.83 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.99
9. For the reaction of MBH adducts and DBU, see (a) Im, Y. J.; Gong, J. H.; Kim, H. J.;
Kim, J. N. Bull. Korean Chem. Soc. 2001, 22, 1053–1055; (b) Ballini, R.; Barboni,

5454
J. W. Lim et al. / Tetrahedron Letters 53 (2012) 5449–5454
(d, J = 7.8 Hz, 1H), 8.38 (s, 1H); 13C NMR (CDCl3, 75 MHz) d 14.33, 14.64, 22.89,
7.32–7.43 (m, 7H), 7.46 (d, J = 8.7 Hz, 2H), 7.77 (s, 1H), 8.09 (d, J = 8.7 Hz, 2H),
8.14 (d, J = 8.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.82, 14.08, 28.80, 44.27,
60.90, 61.34, 85.38, 103.11, 121.81, 122.91, 123.25, 123.63, 128.56, 128.62,
128.69, 129.72, 131.78, 134.07, 138.52, 141.51, 142.20, 146.51, 147.13, 149.26,
164.75, 166.89; ESIMS m/z 569 [M+H]+. Anal. Calcd for C32H28N2O8: C, 67.60; H,
4.96; N, 4.93. Found: C, 67.93; H, 4.84; N, 4.59.
29.55, 29.75, 29.80, 30.06, 31.01, 32.11, 33.34, 61.25, 124.16, 125.16, 126.29,
127.46, 128.15, 129.59, 130.44, 133.26, 134.34, 139.81, 167.26; ESIMS m/z 327
[M+H]+. Anal. Calcd for C22H30O2: C, 80.94; H, 9.26. Found: C, 80.65; H, 9.37.
Compound 5: 8%; white solid, mp 168–170 °C; IR (KBr) 1706, 1264, 1197,
1094 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.41 (t, J = 7.2 Hz, 3H), 2.78 (br s, 2H),
;
4.35 (q, J = 7.2 Hz, 2H), 6.29 (t, J = 7.5 Hz, 1H), 7.18-7.33 (m, 5H), 7.36 (d,
J = 8.7 Hz, 1H), 7.55–7.60 (m, 1H), 7.62–7.67 (m, 1H), 7.70 (d, J = 8.7 Hz, 1H),
7.87 (dd. J = 8.1 and 1.5 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.40 (s, 1H); 13C NMR
(CDCl3, 75 MHz) d 14.38, 25.60, 61.11, 124.99, 126.44, 126.84, 127.19, 127.40,
128.18, 128.40, 128.47, 128.80, 129.03, 131.60, 131.89, 131.94, 132.10, 132.79,
137.49, 141.71, 142.58, 166.00; ESIMS m/z 341 [M+H]+. Anal. Calcd for
11. For the metal-catalyzed cyclization between aryl moiety and allenyl or
acetylenic tether, see (a) Zhang, X.; Teo, W. T.; Chan, P. W. H. Org. Lett. 2009,
11, 4990–4993; (b) Huang, W.; Zheng, P.; Zhang, Z.; Liu, R.; Chen, Z.; Zhou, X. J.
Org. Chem. 2008, 73, 6845–6848; (c) Liu, C.; Widenhoefer, R. A. Org. Lett. 2007,
9, 1935–1938.
12. The stereochemistry of the enyne moiety of compound 7 would be E based on
the chemical shift of the vinyl proton (d = 6.94 ppm) as compared to those of
similar compounds, see (a) Park, S. P.; Ahn, S.-H.; Lee, K.-J. Tetrahedron 2010, 66,
3490–3498; (b) Reddy, C. R.; Reddy, M. D.; Srikanth, B.; Prasad, K. R. Org.
Biomol. Chem. 2011, 9, 6027–6033.
C
24H20O2: C, 84.68; H, 5.92. Found: C, 84.93; H, 5.76.
Compound 7: 35%; pale yellow oil; IR (film) 2195, 1710, 1520, 1347, 1242 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H), 3.41
(ddd, J = 13.2, 5.1 and 0.9 Hz, 1H), 3.65 (dd, J = 13.2 and 9.9 Hz, 1H), 3.75–3.85
(m, 2H), 4.02–4.23 (m, 2H), 4.86 (dd, J = 9.9 and 5.1 Hz, 1H), 6.94 (s, 1H),