TfOH-catalyzed allylation of alkynes with cyclic Baylis-Hillman alcohols

Article abstract of DOI:10.1016/j.tetlet.2009.04.012

The substitution reaction of cyclic Baylis-Hillman alcohols with arylacetylenes was achieved under the catalysis of TfOH in nitromethane. The γ,δ-unsaturated ketones were obtained in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2009.04.012

Tetrahedron Letters 50 (2009) 3786–3789
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TfOH-catalyzed allylation of alkynes with cyclic Baylis–Hillman alcohols
*
*
Chen Wu, Li Liu , Dong Wang, Yong-Jun Chen
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The substitution reaction of cyclic Baylis–Hillman alcohols with arylacetylenes was achieved under the
Received 10 February 2009
Revised 31 March 2009
Accepted 3 April 2009
Available online 9 April 2009
catalysis of TfOH in nitromethane. The
yields.
c
,d-unsaturated ketones were obtained in moderate to good
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Baylis–Hillman alcohols
Alkynes
TfOH
Ketones
Allylation
The chemical behavior of alkynes is one of the most important
and useful subjects in organic chemistry.1 The terminal alkyne
could be used as a nucleophile in addition reactions with various
electrophiles such as carbonyl compounds and imines, as well as
Michael acceptors.1,2 The direct reaction of terminal alkynes with
alcohols should be another attractive process for C–C bond forma-
tion and the only byproduct is water. However, the catalytic nucle-
ophilic substitution of alcohols with terminal alkynes is rarely
reported.3 In most cases, terminal alkynes should be transformed
to metal alkynides such as alkynylboron and alkynyllithium.4
A pioneering work on the reaction of terminal alkynes with
alcohols is the CpRu(PPh3)2Cl-catalyzed reconstitutive condensa-
tion of acetylenes and allyl alcohols reported by Trost and
to explore the versatility of the reaction between alkynes and
allylic alcohols is still desirable.
Baylis–Hillman adducts, bearing both allylic hydroxyl group
and Michael acceptor moiety, have been illustrated as valuable
starting materials for the synthesis of heterocycles and many bio-
logically active molecules.9 Herein, we wish to describe an efficient
Br/nsted acid-catalyzed allylation of terminal alkynes with Baylis–
Hillman alcohols to produce c,d-unsaturated ketones.
Initially we investigated the reaction of cyclic Baylis–Hillman
alcohol 1a derived from cyclopentenone with phenylacetylene 2a
catalyzed by Lewis acid (Scheme 1). In the presence of 10 mol %
In(OTf)3, two products were obtained: 2-(1,3-diphenylprop-2-
ynyl)cyclopent-2-enone
3a
and
2-(3-oxo-1,3-diphenylpro-
co-workers. b,
nium-vinylidene intermediates.5 On the other hand, under the
catalysis of CpRu(cod)Cl, the reaction provided ,d-unsaturated
c
-Unsaturated ketones were obtained via ruthe-
pyl)cyclopent-2-enone 4a as the relative hydration product in
18% and 24% yields, respectively (Table 1, entry 1). No Michael
addition product was observed. Under the catalysis of AgOTf, the
reaction provided similar results (entry 2). However, when AgOTf
combined with a base such as iPr2NEt was used as the catalytic sys-
tem, which could be used in the addition reactions to activate the
alkynes, the reaction did not occur (entry 3).2 With Sc(OTf)3 catal-
ysis, the reaction provided a better yield of 4a (40%) and the same
yield of 3a (18%) (entry 4).
When MeNO2 was used as the solvent, the total yield of 3a and
4a was increased under the catalysis of Sc(OTf)3 or Hf(OTf)4 (en-
tries 5 and 7).10 Whereas FeCl3Á6H2O provided only moderate
yields (3a + 4a = 53%) (entry 7).8 Fortunately, when TfOH was used
as a catalyst, the reaction was complete in 10 min to provide 10%
3a and 68% 4a, and then prolonging the reaction time to 1 h affor-
c
ketones in a totally different reaction pathway by the addition of
the alkene bond of allylic alcohol to alkynes.6 In the case of palla-
dium catalysis, allylation of alkynes with allyl alcohols provided
substituted 1,4-dienes.7 Recently, Iron(III) was used as the catalyst
for the reaction of benzylic alcohols with aryl alkynes and substi-
tuted aryl ketones were obtained in moderate yields.8 It was note-
worthy that different catalytic systems afford different products
for the allylation of alkynes. Development of new efficient catalysts
* Corresponding authors. Tel.: +86 10 62554614; fax: +86 10 62554449 (Y.-J.C.).
E-mail addresses: lliu@mail.iccas.ac.cn (L. Liu), yjchen@mail.iccas.ac.cn (Y.-J.
Chen).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.012

C. Wu et al. / Tetrahedron Letters 50 (2009) 3786–3789
3787
OH
O
O
O
O
catalyst (10 mol%)
solvent, 80oC
+
Ph
H
+
2a
1a
3a
4a
Scheme 1.
ded 4a in 76% yield (entries 8 and 9). In the absence of the catalyst,
no reaction occurred (entry 10).
Table 1
Allylation of phenylacetylene 2a with cyclic Baylis–Hillman alcohols 1aa
As shown in Table 2, various substituted Baylis–Hillman alco-
hols 1 could react with aryl alkynes 2 under the catalysis of TfOH
in nitromethane at 80 °C. The ketone products 4 were obtained
in moderate to good yields.11 The reaction showed exclusively
Entry
Catalyst
Solvent
t (h)
Yieldb of 3a (%)
Yieldb of 4a (%)
1
2
3
In(OTf)3
AgOTf
Toluene
Toluene
Toluene
Toluene
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
12
12
12
12
12
5
18
18
0
18
18
10
13
10
0
28
24
0
40
55
43
64
68
76
0
i
AgOTf Pr2NEtc
a-regioselectivity, no
c-allylic substitution products were
4
Sc(OTf)3
Sc(OTf)3
FeCl3Á6H2O
Hf(OTf)4
TfOH
5
observed. Under the optimized reaction conditions, alkyne-substi-
tuted products 3 were not isolated. Electronic effect of substituted
phenyl acetylene is not distinct (Table 2, entries 7–9). In the
reaction of 1,4-diethynylbenzene 2d with 1a, mono-substituted
product 4j was isolated in 48% yield (Table 2, entry 10).
6d
7
1
8
9
10
10 min
1
12
TfOH
—
0
Though in the model reaction, direct substituted product 3a
and relative hydration product 4a were isolated, the reaction
pathway is still not clear. One of the possible reaction pathways
could be considered for the formation of alkenyl cation by regio-
selective nucleophilic attack of phenylacetylene on allylic cation
a
Reactions were carried out on a 0.2 mmol scale in 2 mL of solvent, molar ratio of
alcohols/phenylacetylene = 1:2.
b
Isolated yield.
c
iPr2NEt 20 mol %.
d
Reaction conditions see Ref. 8.
Table 2
TfOH-catalyzed reaction of arylacetylenes with cyclic B–H alcoholsa
Ar
OH
O
O
O
TfOH (10mol%)
Ar
H
+
R
R
80oC
MeNO2
1
2
4
Entry
B–H alcohols
Alkynes
Products
Yieldb (%)
O
O
OH
O
1
76
2a
2a
1a
4a
F
OH
O
O
2
73
F
O
1b
4b
Cl
OH
O
O
3
2a
74
Cl
O
1c
4c
(continued on next page)

3788
C. Wu et al. / Tetrahedron Letters 50 (2009) 3786–3789
Table 2 (continued)
Entry
B–H alcohols
Alkynes
Products
Yieldb (%)
Br
OH
O
O
O
4
5
6
7
8
2a
70
Br
1d
4d
Ph
OH
O
O
O
2a
64
59
73
67
Ph
1e
4e
OH
O
O
O
2a
1f
4f
O
O
F
1a
F
2b
4g
O
O
Br
1a
1a
1a
Br
2a
4h
O
O
9
64
2c
4i
O
O
10
48
2d
4j
a
Reactions were carried out on a 0.2 mmol scale in 2 mL of nitromethane for 1 h at 80 °C, molar ratio of alcohols/phenylacetylene = 1:2.
Isolated yield.
b

C. Wu et al. / Tetrahedron Letters 50 (2009) 3786–3789
3789
Ph
Ph
OH2
H
O
OH
O
+H+
-H+
O
Ph
O
Ph
Ph
Ph
Ph
Ph
H2O
1a
3a
H2O, -H+
O
O
Ph
4a
Scheme 2. Proposed reaction pathway.
TfOH (10 mol%), H2O (5eq.)
O
nitromethane, 80oC,1h
O
O
yield 70%
3a
4a
Scheme 3. Coversion of alkyne 3a to ketone 4a.
5. (a) Trost, B. M.; Dyker, G.; Kulawiec, R. J. J. Am. Chem. Soc. 1990, 7809; (b) Trost,
B. M.; Kulawiec, R. J. J. Am. Chem. Soc. 1992, 5579; (c) Trost, B. M.; Flygare, J. A.
J. Am. Chem. Soc. 1992, 5416; (d) Trost, B. M.; Flygare, J. A. J. Org. Chem. 1994,
1078.
6. (a) Trost, B. M.; Martinez, J. A.; Kulawiec, R. J.; Indolese, A. F. J. Am. Chem. Soc.
1993, 10402; (b) Derien, S.; Dixneuf, P. H. J. Chem. Soc., Chem. Commun. 1994,
2551; (c) Derien, S.; Jan, D.; Dixneuf, P. H. Tetrahedron 1996, 5511.
7. Huang, J.; Zhou, L.; Jiang, H. Angew. Chem., Int. Ed. 2006, 45, 1945.
8. Jana, U.; Biswas, S.; Maiti, S. Eur. J. Org. Chem. 2008, 5798.
9. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811; (b)
Basavaiah, D.; Rao, A. J.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581; (c) Masson,
G.; Housseman, C.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 4614; (d) Shi, Y. L.;
Shi, M. Eur. J. Org. Chem. 2007, 2905.
of Baylis–Hillman adduct, and then followed either by the selec-
tive hydration of alkenyl cation to generate the ,d-unsaturated
c
ketone 4a or by deprotonation to provide alkyne-substituted
product 3a. The plausible mechanism was illustrated in Scheme
2. However, ketone 4a could also be generated by the hydration
of compound 3a.12 The conversion of alkyne-substituted product
3a to ketone product 4a was further proved. When 3a was trea-
ted with 10 mol % TfOH in MeNO2 in the presence of water
(5 equiv) at 80 °C for 1 h, 4a was obtained in 70% yield (Scheme
3). The hydration of compound 3a could not be catalyzed by
PdCl2 in MeCN–H2O which had been used in the hydration of
internal alkynes.13
10. Noji, M.; Ohno, T.; Fuji, K.; Futaba, N.; Tajima, H.; Ishii, K. J. Org. Chem. 2003, 68,
9340.
11. Typical procedure for the allylation of terminal alkynes with cyclic Baylis–Hillman
In conclusion, the reaction of cyclic Baylis–Hillman alcohols with
arylacetylenes was achieved under the catalysis of TfOH in nitro-
alcohols catalyzed by TfOH: To
a stirred solution of 2-(hydroxy(phenyl)-
methyl)cyclopent-2-enone 1a (0.2 mmol) in nitromethane (2 mL) were added
phenylacetylene 2a (0.4 mmol) and TfOH (0.02 mmol). The resulting reaction
was then heated to 80 °C and monitored by TLC. On cooling to room
temperature, saturated NaHCO3 (10 mL) was added and the organic layer
was extracted with CH2Cl2. The combined organic layers were dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (eluent: petroleum ether/
methane. The reaction provided
ate to good yields via regioselective nucleophilic attack of terminal
alkynes at -position of Baylis–Hillman alcohols, followed by the
c,d-unsaturated ketones in moder-
a
in-site hydration.
ethyl acetate = 4/1) to afford the
c,d-unsaturated ketone 4a and the
phenylacetylene-substituted product 3a.
Acknowledgments
Compound 3a: mp 83–85 °C; 1H NMR (300 MHz, CDCl3): d 7.67 (s, 1H), 7.50–
7.44 (m, 4H), 7.34–7.21 (m 6H), 4.96 (s, 1H), 2.64–2.59 (m, 2H), 2.48–2.42 (m,
2H); 13C NMR (75.4 MHz, CDCl3): d 206.76, 159.32, 146.83, 139.46, 131.70,
128.59, 128.23, 128.07, 127.78, 127.11, 123.28, 88.95, 83.56, 34.91, 34.25,
26.40; IR (KBr) 3038, 2908, 1703, 1490, 757, 694 cmÀ1; HRMS: m/z calcd for
C20H16O: 272.1201; found, 272.1204.
We thank the National Natural Science Foundation of China
(Nos. 20632010, 20872141) and the Chinese Academy of Sciences
for financial support.
Compound 4a: mp 74–76 °C; 1H NMR (300 MHz, CDCl3):
d 7.95–7.92 (d,
J = 7.2 Hz, 2H), 7.56–7.51 (t, J = 7.2 Hz, 1H), 7.45–7.40 (t, J = 7.2 Hz, 2H), 7.30–
7.25 (m, 5H), 7.22–7.19 (m, 1H), 4.48–4.43 (td, J = 7.1 Hz, 0.7 Hz, 1H), 3.86–3.77
(dd, J = 17.0 Hz, J = 7.3 Hz, 1H), 3.51–3.43 (dd, J = 17.0 Hz, J = 7.3 Hz, 1H), 2.54–
2.52 (m, 2H), 2.41–2.37 (m, 2H); 13C NMR (75.4 MHz, CDCl3): d 208.51, 197.91,
158.66, 148.05, 141.97, 136.88, 133.05, 128.58, 128.10, 127.86, 126.71, 42.54,
38.31, 35.10, 26.42; IR (KBr) 3046, 2914, 1694, 1448, 1237, 1205, 1001, 752,
698 cmÀ1; HRMS: m/z calcd for C20H18O2: 290.1307; found, 290.1310.
12. Hintermann, L.; Labonne, A. Synthesis 2007, 8, 1121.
References and notes
1. (a) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43,
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Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979; (d) Schore, N. E. Chem. Rev.
1988, 88, 1081.
2. Chen, L.; Li, C. J. Adv. Synth. Catal. 2006, 348, 1459.
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13. Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H. J. Org. Chem. 1991, 56, 5816.
4. Kabalka, G. W.; Yao, M. L.; Borella, S. Org. Lett. 2006, 879.