Metal-free sequential reaction via a propargylation, annulation and isomerization sequence for the one-pot synthesis of 2,3-disubstituted benzofurans

Article abstract of DOI:10.1039/c4ra05503a

A metal-free one-pot synthesis of 2,3-disubstituted benzofurans is described, which allows for the reactions to be performed under ambient conditions with readily accessible propargyl alcohols and general phenols, including phenols substituted with an ele

Full text of DOI:10.1039/c4ra05503a

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Metal-free sequential reaction via a propargylation,
annulation and isomerization sequence for the
one-pot synthesis of 2,3-disubstituted
benzofurans†
Cite this: RSC Adv., 2014, 4, 34774
Received 9th June 2014
Accepted 28th July 2014
*
Wen-Tao Li, Wen-Hui Nan and Qun-Li Luo
DOI: 10.1039/c4ra05503a
www.rsc.org/advances
A metal-free one-pot synthesis of 2,3-disubstituted benzofurans is internal alkynes, or olens.6 Nevertheless, all these methods
described, which allows for the reactions to be performed under require the use of metals or their salts as catalysts for the
ambient conditions with readily accessible propargyl alcohols and annulation reactions.
general phenols, including phenols substituted with an electron
A sequential reaction, incorporating two or more different
transformations in a facile “one-pot” operation, holds great
promise for the rapid buildup of molecular complexity and
diversity.7 In contrast to traditional “step-by-step” operations,
such transformations allow for reactions to be carried out with
readily accessible starting materials in a single reaction vessel
without purication between steps, and hence efficiently
improve atom economy and lower energy and raw materials
consumption.8 Accordingly, Chen et al. reported a one-pot
synthetic method of benzofurans from phenols with propargyl
acetates catalyzed by InCl3,9a and Tian et al. disclosed a similar
method from phenols with benzylic propargylic sulfonamides
catalyzed by ZnCl2.9b
withdrawing group or a nitrogen-containing group.
Benzofuran derivatives are ubiquitous in both natural products
and articial compounds with interesting biological activities
and photochromic properties.1 Particularly, the 2,3-disubsti-
tuted benzofurans are widely distributed in bioactive struc-
tures.2 The common strategies for the synthesis of 2,3-
disubstituted benzofurans relied mainly on metal-catalyzed
intra/intermolecular annulations, in which the pre-prepared
ortho-alkynylated
phenol
derivatives,
ortho-hydroxy-
benzophenones, ortho-hydroxy-a-arylstyrenes, or ortho-disub-
stituted halogenated arenes were used as the substrates.3,4 For
the reason that metal-based protocols have inherent restric-
tions, including costly metal catalysts, fastidious reaction
installations, troublesome metal residue in the synthetic prod-
ucts and difficulties in the disposal of metal waste, metal-free
intramolecular annulations of ortho-alkynylated phenol deriva-
tives have also been disclosed.5 Although the above strategies
are synthetically viable, they suffered from some limitations
such as multistep syntheses, inaccessible starting materials,
tedious procedures, or requirement for using metals,
frequently, noble metals as catalysts. Therefore, the develop-
ment of mild, convenient, highly selective and atom economic
methods to afford substituted benzofurans is still highly
desirable. Recently, a few elegant methodologies have been
reported, enabling the single-step synthesis of substituted
benzofurans from readily available phenols with b-keto esters,
However, these methods require the use of metals as cata-
lysts and pre-prepared acetates or sulfonamides as substrates in
addition to the use of different solvents between steps for the
former and the requirement of heating for the latter. To the best
of our knowledge, there is only one example that involved the
one-pot synthesis of 2,3-disubstituted benzofurans via
a
sequential reaction from phenols and readily accessible prop-
argyl alcohols,10 but it still requires the use of transition metals
as catalysts, and heating in sealed tubes is necessary for the
annulation reactions. To expand the concept of sequential
reaction for the rapid buildup of polysubstituted benzofurans,
we here report a metal-free one-pot synthesis of 2,3-disubsti-
tuted benzofurans from phenols and secondary propargyl
alcohols. Our method represents the rst example of metal-free
one-pot synthesis for such transformations, allowing for the
reactions to be performed at room temperature in the ambient
atmosphere without any metal catalysts while it holds the
advantages of the above method (Scheme 1).
Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry
and Chemical Engineering, Southwest University, Chongqing, 400715, China. E-mail:
qlluo@swu.edu.cn
Our studies began with the propargylation between phenol
1a and propargyl alcohol 2a, with screening of various Brønsted
acids in different solvents. As shown in Table 1, several strong
Brønsted acids efficiently catalyzed the propargylation to yield
† Electronic supplementary information (ESI) available: Experimental procedures,
1H and 13C NMR spectra for products, and HRMS spectra for new compounds. See
DOI: 10.1039/c4ra05503a
34774 | RSC Adv., 2014, 4, 34774–34779
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Brønsted acid systems, 4-toluenesulphonic acid monohydrate–
dichloromethane (TsOH/DCM) was proved to be most efficient
(entry 8), and organic weak acid, e.g., acetic acid, chloroacetic
acid, and benzoic acid, was incapable of catalyzing this trans-
formation (results not shown).
To investigate the annulation process of ortho-propargyl
phenols, several bases were screened by taking the reaction of
3a to yield benzofuran 4aa in various solvent (Table 2). The
results demonstrated that the relatively weak bases, such as
tertiary amines (results not shown), carbonates (entry 1), or
hydroxides (entry 2), were incapable of promoting the annula-
tion of 3a at room temperature, whereas t-BuOK was suitable
(entries 3, 4, 8 & 9). When t-BuOK was used as base, the choice of
solvent was also important (entries 3–9). The solvents with weak
acidity (entries 5, 6 & 10) or with large dipole moment (entries 6
& 7) were unsuitable, while the common halogenated solvents
(except chloroform) and ether solvents were workable (entries 3,
4, 8 & 9). Among the tested base catalytic systems, t-BuOK/DCM
and t-BuOK/dioxane were efficient (entries 3 & 9).
Aer the optimized conditions for the two steps were
established, we focused on the screening of an appropriate
combination of Brønsted acid catalyst, base, and solvent that
enables the propargylation and the following annulation to
occur efficiently through a one-pot operation. Some represen-
tative results are summarized in Table 3. A screening of base
amount showed that it was necessary to employ 2 equiv. or more
of t-BuOK for the annulation (entries 2–4 vs. 1). When TsOH was
used in the rst step, it was better to add 2.5 equiv. of t-BuOK in
the following step because 0.2 equiv. of water from mono-
hydrate TsOH could transform a certain amount of t-BuOK to
KOH and thus reduce the efficacy of t-BuOK. Based on an overall
consideration of the investigated parameters, we could
Scheme
commercial phenols.
1 One-pot sequential synthesis of benzofurans from
Table 1 Propargylations between 1a and 2a catalyzed by Brønsted
acid
Entrya
Acid
Solvent
Yieldb
1
2
3
4
5
6
7
8
HClO4
HClO4
HClO4
TFA
TFA
TFA
DCE
74%
76%
83%
89%
NR
NR
94%
99%
Dioxane
CH3CN
CH3CN
DMF
Dioxane
DCM
Table 2 Annulations of ortho-propargyl phenol 3a promoted by base
TFA
TsOH
DCM
a
Reaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), acid (0.1 mmol) and
solvent (4 mL). Ar ¼ p-CH3O–C6H4. TFA: triuoroacetic acid. TsOH:
4-toluenesulphonic acid monohydrate. DCE: 1,2-dichloroethane. DCM:
dichloromethane. DMF: N,N-dimethylformamide. NR: no reaction.
The product was isolated by chromatographic purication on silica
column.
Entrya
Base
Solvent
Yieldb
b
1
2
3
4
5
6
7
8
9
K2CO3
NaOH
DCE
DCM
DCM
DCE
CHCl3
CH3CN
DMF
THF
Dioxane
MeOH
Trace
Trace
93%
66%
NR
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
3a in common solvent at room temperature. However, solvents
with large polarity strongly inhibited this reaction when the
acidity of Brønsted acid was decreased (entries 5 & 6 vs. 4 & 7),
which was possibly attributed to that the catalytic species of the
propargylation, protons, were bound by the solvents when the
acidity of Brønsted acid was not strong enough, since these
solvents can be looked as Lewis bases, and are strong H-bond
0c
NR
67%
99%
Trace
10
a
Reaction conditions: 3a (0.5 mmol), base (1 mmol) and solvent (4 mL).
b
THF: tetrahydrofuran. The product was isolated by chromatographic
c
acceptors. Thus, Brønsted acid–solvent matching was very purication on silica column. 3a was totally transformed, but no
important toward the propargylation. Among the tested
target product (4aa) was generated, as monitored by thin-layer
chromatography (TLC).
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 34774–34779 | 34775

View Article Online
RSC Advances
Communication
alkylacetylene-derived a-aryl propargyl alcohols (R2 ¼ alkyl)
were more difficult and required higher reaction temperatures
than that of the arylacetylene-derived counterparts (entries 27
and 28 vs. 1–21). Gratifyingly, phenols substituted with an
amido or an alkoxyformamido were workable (entries 24–27),
which is very interesting because using such substrates helps to
conveniently introduce nitrogen-containing groups into the
products, which makes the method useful in the eld of
medicinal chemistry. For comparison, two experiments parallel
to entries 26 and 27 were conducted by using the literature
method,10 but the reactions were messy and unidentiable
mixtures were observed instead. Therefore, our method selec-
tively afforded the target products in yields that were compa-
rable to the above method, whereas showed more generality of
substrates than it.
Table 3 One-pot sequential synthesis of benzofuran 4aa from phenol
1a with propargyl alcohol 2a
Entrya
Solvent 1
Solvent 2
Acid
t-BuOK
Yieldb
1
2
DCM
DCM
DCM
DCM
DCM
DCM
DCM
Dioxane
TFA
TFA
TsOH
TFA
1.2 equiv.
2.2 equiv.
2.5 equiv.
2.0 equiv.
Trace
62%
90%
81%
3
4c
a
Reaction conditions: unless noted otherwise, the mixture of 1a
(1.0 mmol), 2a (0.5 mmol), acid (0.1 mmol) and DCM (4 mL) was
stirred at room temperature for 2 h, then indicated amount of base
was added to it, and the reaction mixture was stirred at room
b
temperature for 5 h. The product was isolated by chromatographic
purication on silica column. Aer the completion of the rst step,
c
Unfortunately, neither the propargyl alcohols containing a
strongly EWG on the benzene ring, such as nitro, nor the a-alkyl
propargyl alcohols gave the expected products,11 which indi-
cated that the a-aromatic rings of propargyl alcohols played an
extremely important role in stabilizing the carbocation and
initiating the propargylation step.
the solvent (DCM) was removed via rotary evaporation, and the
residual was diluted with 4 mL of dioxane, followed by the addition of
t-BuOK (1 mmol).
establish the optimized conditions for the one-pot synthesis of
benzofuran 4aa from phenol 1a and propargyl alcohol 2a, i.e., 1a
and 2a in the presence of 20 mol% of TsOH catalyst at room
temperature in DCM for 2 h, then t-BuOK (2.5 equiv.) was
recharged in situ and the reaction mixture was stirred at room
temperature for an additional 5 h. Under these conditions, 4aa
could be isolated in 90% yield (entry 3).
Under the optimized conditions for the one-pot process, we
examined the substrate scope of this methodology. The results,
summarized in Table 4, demonstrated the generality of this
method. Sequential reactions of common phenols bearing
alkyl, alkoxy or aryl with phenylacetylene-derived a-aryl prop-
argyl alcohols smoothly afforded the expected benzofuran 4
mostly in good to very good yields (entries 1–21), which is
comparable to that of the literature method.10 In all these
transformations, the corresponding benzopyran derivatives
were not isolated. Furthermore, this protocol gave acceptable
yields with deactivated phenols (entries 22 & 23). In compar-
ison, the yield of benzofuran 4gc from 4-chlorophenol (1g) was
only 14% by using the literature method (entry 23).10 Generally,
electron donating groups (EDGs) on both phenols and prop-
argyl alcohols were favorable to the sequential reaction, whereas
electron withdrawing groups (EWGs) unfavorable because an
EWG on a phenol reduced the phenol's nucleophilicity and that
on the aromatic ring, Ar of 2 decreased the stability of the cor-
responding carbocation. Both effects were unfavorable to the
propargylation of the phenol. Relatively, an EWG on phenol 1
inuenced the propargylation more than that on the aromatic
ring, Ar of 2. For example, the substitution at the aromatic ring,
Ar of 2 with an EWG (2e) only slightly decreased the yields of
benzofuran 4 and the reactions could be achieved at room
temperature (entries 5 & 18), but when a phenol substituted
with an EWG (1g) was employed as a substrate, it was necessary
to elevate the reaction temperature to 40 ꢀC and the yields were
To establish the mechanism of the metal-free annulation of
ortho-propargyl phenol 3, we envisioned two possible pathways
(Scheme 2). Path A, an ionic mechanism, consists of an isom-
erization of 3a catalyzed by t-BuOK to form allene 3a2 and an
intramolecular annulation via nucleophilic addition of pheno-
late anion to allenyl carbon. Alternatively, path B, a radical
mechanism, is also conceivable, which consists of a radical
annulation (3b1 to 3b2), one time of intermolecular proton
transfer (3b3 + 3a / 3b4 + 3b1) and two intramolecular isom-
erizations (3b2 to 3b3 & 3b4 to 4aa). In principle, path A seems
to be reasonable because (1) the connection of two aryl groups
lower (entries 22
& 23). In addition, the reactions of
34776 | RSC Adv., 2014, 4, 34774–34779
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Table 4 Substrate scope of the one-pot synthesis of benzofuran 4 from phenol 1 with propargyl alcohol 2
Entrya
1 (R1)
2 (R2, Ar)
T1/T2 (h)
4
Yieldb
1
2
3
4
5
6
7
8
1a (4-t-Bu)
1a
1a
1a
2a (Ph, 4-MeO-C6H4)
2b (Ph, 4-Me-C6H4)
2c (Ph, Ph)
2d (Ph, 1-naphthyl)
2e (Ph, 4-Br-C6H4)
2a
2b
2c
2a
2b
2c
2d
2a
2b
2c
2b
2c
2e
2a
2b
2c
2a
2c
2a
2/5
10/10
5/6
3/5
10/7
8/9
5/10
4/7
4/7
4/7
4/6
6/10
5/6
6/9
8/6
4/7
4aa
4ab
4ac (ref. 10)
4ad
4ae (ref. 10)
4ba
4bb
4bc (ref. 10)
4ca
4cb (ref. 3e)
4cc (ref. 10)
4cd
4da
4db
4dc (ref. 10)
4eb
4ec
4ee
4fa
4
4fc (ref. 10)
4ga
90%
74%
79%
86%
63%
80%
75%
74%
70%
80%
81%
73%
72%
75%
74%
70%
70%
60%
77%
70%
68%
45%
55%
49%
50%
52%
56%
51%
1a
1b (4-MeO)
1b
1b
1c: 2-naphthalenol
1c
1c
1c
1d (4-Me)
1d
1d
1e (3,5-diMe)
1e
1e
1f (4-Ph)
9
10
11
12
13
14
15
16
17
18
19
20
21
22c
23c
24c
25c
26d
27e
28f
3/8
11/9
7/11
5/5
1f
1f
4/6
1g (4-Cl)
1g
1h (4-AcNH)
1h
1i (4-BocNH)
1i
1c
16/11
12/11
9/13
15/11
18/20
24/14
9/12
4gc (ref. 10)
4ha
4hc
4ia
4if
2c
2a
2f (n-C4H9, 4-MeO-C6H4)
2f
4cf
a
Reaction conditions: unless noted otherwise, the mixture of 1 (1.0 mmol), 2 (0.5 mmol), TsOH$H2O (0.1 mmol) and DCM (4 mL) was stirred at
room temperature until 2 had disappeared as monitored by TLC, then t-BuOK (1.25 mmol) was recharged in situ and the reaction mixture was
continually stirred at room temperature until the new component that generated at the rst stage had fully transformed as monitored by TLC.
b
c
d
Isolated yield aer silica-gel column chromatography. The reaction was conducted at 40 ꢀC in the whole process. Phenol 1i was dissolved
e
in acetonitrile (1 mL) and then added to the reaction mixture. The mixture of 1i (1.0 mmol), 2f (0.5 mmol), triic acid (0.1 mmol) was
dissolved in THF (4 mL) instead of DCM, and stirred at room temperature until 2f had disappeared as monitored by TLC, then the solvent was
evaporated. To the residue were added DMF (4 mL) and NaOH (1.25 mmol). The reaction mixture was stirred at 60 ꢀC until the new component
f
that generated at the rst stage had fully transformed as monitored by TLC. At the stage of annulation, the reaction temperature was elevated
to 40 ꢀC.
1
and an alkynyl group makes the methine proton of 3a rather equiv. of t-BuOK to the CDCl3 solution of 3a overnight, the H
acidic, and (2) it has been known for the catalytic isomerization NMR signal of methine proton remained unchangeable, and
of propargyl to allenyl by t-BuOK.12 A typical feature of path A that of hydroxyl was totally disappeared, whereas that of CHCl3
lies in that two times of intermolecular proton transfer (3a1 to largely increased (eqn (2)). This result indicated that the acidity
3a2 & 3a3 to 4aa) are involved, while for path B, there are one of the methine proton of 3a was weaker than that of CHCl3, and
time of intermolecular and two times of intramolecular proton implied that the catalytic isomerization of 3a to allene 3a2 by
transfer instead. To this end, a hydrogen–deuterium exchange t-BuOK via deprotonation–protonation was difficult under the
experiment was performed (eqn (1)).13 The result indicated that reaction conditions (Scheme 2, path A).14 Furthermore, the para-
as high as 96.5% of product (4aa + D-4aa) retained one H atom propargyl substituted counterpart 3b failed to isomerize to
at the benzylic position against the hydrogen–deuterium allene 3c even with more amount of base and at higher
exchange, which is consistent with path B, i.e., one H atom at temperature (eqn (3)), which disapproves of the pathway from
the benzylic position of 4aa is difficult to be exchanged with a 3a to 3a2. To further validate the mechanism of radical annu-
deuterium atom in which intramolecular proton transfer is lation, extra control experiments were conducted (eqn (4) & (5)).
involved and the other one is possible to be done in which The results demonstrated that (1) under inert atmosphere, the
intermolecular proton transfer is involved. By the addition of 2 annulation step was remarkably sluggish,11 and (2) under
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 34774–34779 | 34777

View Article Online
RSC Advances
Communication
Scheme 2 Possible mechanisms for the metal-free annulation of ortho-propargyl phenol 3.
aerobic
atmosphere,
2,2,6,6-tetramethylpiperidine-1-oxyl
2009, 11, 1329–1331; (d) X. Xu, J. Liu, L. Liang, H. Li and
Y. Li, Adv. Synth. Catal., 2009, 351, 2599–2604; (e) J. Hu,
L. Liu, X. Wang, Y. Hu, S. Yang and Y. Liang, Green
Sustainable Chem., 2011, 1, 165–169; (f) M. J. Moure,
R. SanMartin and E. Dominguez, Angew. Chem., Int. Ed.,
2012, 51, 3220–3224.
4 For selected examples, see: (a) R. C. Larock, E. K. Yum,
M. J. Doty and K. K. C. Sham, J. Org. Chem., 1995, 60,
3270–3271; (b) B. Lu, B. Wang, Y. Zhang and D. Ma, J. Org.
Chem., 2007, 72, 5337–5341; (c) M. Yamaguchi,
H. Katsumata and K. Manabe, J. Org. Chem., 2013, 78,
9270–9281.
(TEMPO, a radical scavenger) greatly inhibited this step.
Therefore, path B is more appropriate than path A.
In conclusion, a metal-free one-pot synthesis of 2,3-disub-
stituted benzofurans from phenols and secondary propargyl
alcohols is described. The transformations are high yielding,
atom-efficient, and environmentally benign in terms of the
substrates and reagents being used and the water as the only by-
product. The control experiments support the transformations
undergo the sequence of propargylation, radical annulation and
isomerization.
5 For selected examples, see: (a) J. Hu, L.-Y. Wu, X.-C. Wang,
Y.-Y. Hu, Y.-N. Niu, X.-Y. Liu, S. Yang and Y.-M. Liang, Adv.
Synth. Catal., 2010, 352, 351–356; (b) M. Xu, X.-H. Zhang
and P. Zhong, Tetrahedron Lett., 2011, 52, 6800–6804; (c)
N. Yadav, M. K. Hussain, M. I. Ansari, P. K. Gupta and
K. Hajela, RSC Adv., 2013, 3, 540–544; (d) T. B. Grimaldi,
D. F. Back and G. Zeni, J. Org. Chem., 2013, 78, 11017–11031.
6 For selected examples, see: (a) J. X. Guo, R. Yu, H. Li and
Z. Li, J. Am. Chem. Soc., 2009, 131, 17387–17393; (b)
D.-H. Lee, K.-H. Kwon and C. S. Yi, J. Am. Chem. Soc., 2012,
134, 7325–7328; (c) M. R. Kuram, M. Bhanuchandra and
A. K. Sahoo, Angew. Chem., Int. Ed., 2013, 52, 4607–4612;
(d) U. Sharma, T. Naveen, A. Maji, S. Manna and D. Maiti,
Angew. Chem., Int. Ed., 2013, 52, 12669–12673; (e) R. Zhu,
J. Wei and Z. Shi, Chem. Sci., 2013, 4, 3706–3711; (f)
D. Kundu, M. Samim, A. Majee and A. Hajra, Chem. – Asian
J., 2011, 6, 406–409.
7 X. Zeng, Chem. Rev., 2013, 113, 6864–6900.
8 J.-C. Wasilke, S. J. Obrey, R. T. Baker and G. C. Bazan, Chem.
Rev., 2005, 105, 1001–1020.
9 (a) Y.-C. Wu, L. Liu, Z. Shaq, Y.-C. Wu, D. Wang and
Y.-J. Chen, Synthesis, 2007, 1961–1969; (b) C.-R. Liu,
M.-B. Li, C.-F. Yang and S.-K. Tian, Chem.–Eur. J., 2009, 15,
793–797.
10 F.-Q. Yuan and F.-S. Han, Adv. Synth. Catal., 2013, 355, 537–547.
11 We thank one of the reviewers for pointing us towards this
work.
Acknowledgements
We are grateful to Prof. Fa-Jun Nan and Dr Min Gu (Shanghai
Institute of Materia Medica, CAS, China) for help with HRMS
analysis. The authors thank the nancial support from the
National Natural Science Foundation of China (no. 20971105)
and the Fundamental Research Funds for the Central Univer-
sities (XDJK2012B011).
Notes and references
1 For selected examples, see: (a) B. Walker, A. B. Tomayo,
X. D. Dang, P. Zalar, J. H. Seo, A. Garcia, M. Tantiwiwat
and T. Q. Nguyen, Adv. Funct. Mater., 2009, 19, 3063–3069;
(b) Y. Liu, M. Kubo and Y. Fukuyama, J. Nat. Prod., 2012,
75, 2152–2157; (c) P. Lan, M. G. Banwell and A. C. Willis, J.
Org. Chem., 2014, 79, 2829–2842.
2 For selected reviews, see: (a) D. A. Horton, G. T. Bourne and
M. L. Smythe, Chem. Rev., 2003, 103, 893–930; (b)
M. E. Welsch, S. A. Snyder and B. R. Stockwell, Curr. Opin.
Chem. Biol., 2010, 14, 347–361; (c) S. B. Bharate,
S. D. Sawant, P. P. Singh and R. A. Vishwakarma, Chem.
Rev., 2013, 113, 6761–6815.
3 For selected examples, see: (a) I. Nakamura, Y. Mizushima
and Y. Yamamoto, J. Am. Chem. Soc., 2005, 127, 15022–
15023; (b) Y. Liao, J. Smith, R. Fathi and Z. Yang, Org. Lett.,
2005, 7, 2707–2709; (c) N. Isono and M. Lautens, Org. Lett.,
34778 | RSC Adv., 2014, 4, 34774–34779
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
12 For selected examples, see: (a) L. K. McConachie and 13 Protic solvents inhibited the annulation of ortho-propargyl
A. L. Schwan, Tetrahedron Lett., 2000, 41, 5637–5641; (b)
J. M. Motto, A. Castillo, A. Greer, L. K. Montemayer,
E. E. Sheepwash and A. L. Schwan, Tetrahedron, 2011, 67,
phenol 3 (Table 2, entry 10). In the presence of MeOD, the
amount of t-BuOK was increased to 7 equivalents in order
to promote the annulation.
1002–1010; (c) S. Hoff, L. Brandsma and J. F. Arens, Recl. 14 The solvent environment of chloroform is close to that of
Trav. Chim. Pays-Bas, 1968, 87, 916–924.
dichloromethane, while the annulation of 3a was
unsuccessful in the former solvent (Table 2, entry 5).
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 34774–34779 | 34779