Iodine as a versatile catalyst for the hydroalkylation of vinyl arenes with 1,3-diketones

Article abstract of DOI:10.1016/j.tetlet.2010.03.024

The vinyl arenes undergo smooth hydroalkylation with 1,3-diketones in the presence of 10 mol % of iodine to afford phenethyl diketones and ketoesters in good yields in short reaction times. The use of inexpensive and readily available molecular iodine makes this method quite simple, more convenient and practical.

Full text of DOI:10.1016/j.tetlet.2010.03.024

Tetrahedron Letters 51 (2010) 2622–2624
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Iodine as a versatile catalyst for the hydroalkylation of vinyl arenes with
1,3-diketones
*
J. S. Yadav , B. V. Subba Reddy, T. Srinivasa Rao, K. Bhavani, A. Raju
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The vinyl arenes undergo smooth hydroalkylation with 1,3-diketones in the presence of 10 mol % of
iodine to afford phenethyl diketones and ketoesters in good yields in short reaction times. The use of
inexpensive and readily available molecular iodine makes this method quite simple, more convenient
and practical.
Received 6 January 2010
Revised 4 March 2010
Accepted 7 March 2010
Available online 11 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Hydroalkylation
Vinyl arenes
Molecular iodine
1,3-Diketones
The hydroalkylation of alkenes by 1,3-dicarbonyl compounds is
one of the most common methods for C–C bond formation.1 Conse-
quently, there have been some reports on intermolecular hydro-
alkylation of alkenes using AuCl3/AgOTf, AgOTf, cis-[Ru(6,60-
Cl2bipy)2(H2O)2](ClO4)2, Bi(OTf)3, FeCl3, PWA, [bmim]OTf/Cu(OTf)2
or SnBr4.2–4 A few intramolecular hydroalkylation of olefins have
also been reported using PdCl2(CH3CN)2, Pd(acac)2 and [PtCl2(CH2
@CH2)]2/EuCl3.5 Besides hydroalkyation of olefins, there have been
some reports on hydroalkylation of alkynes employing (PPh3)-
AuOTf6 and Ni(acac)2.7 However, many of these reports involve
the use of expensive noble metal catalysts and require tedious
work-up procedures which limit their use in large-scale synthesis.
Since b-diketones and their derivatives have become increasingly
useful and important in the synthesis of biologically active hetero-
cycles, the hydroalkylation of alkenes remains an important and
challenging strategy.
uct 3-(1-phenylethyl)-2,4-pentanedione (3a) was isolated in 92%
yield (Scheme 1).
This result provided the incentive for further study of reactions
with different olefins and b-diketones. Interestingly, various vinyl
arenes such as p-methyl-, p-t-butyl-, p-chloro-, p-methoxy-, o-bro-
mo and b-naphthyl underwent smooth hydroalkylation with ace-
tylacetone under identical conditions (Table 1, entries b–g). The
reactions proceeded smoothly by 10 mol % iodine in refluxing
toluene under neutral conditions to afford the corresponding prod-
ucts in excellent yields. In all cases, the products were formed by
the selective addition of 1,3-diketones at benzylic position.
Furthermore, the cyclic olefin, for example, indene (4) also partic-
ipated well in this reaction to give the corresponding 3-(2,3-dihy-
dro-1H-1-indenyl)-2,4-pentanedione (3h) in good yield (Table 1,
entry h, Scheme 2).
Subsequently, we studied the reaction of alkenes with different
b-diketones such as 3-methylacetylacetone, dibenzoylmethane
and 1-phenylbutane-1,3-dione (Table 1). Interestingly, 3-methyl-
pentane-2,4-dione also underwent smooth addition onto styrenes
under similar conditions (Table 1, entry i). Furthermore, b-ketoest-
ers, for example, methyl acetoacetate also reacted smoothly with
styrene to produce methyl 2-acetyl-3-phenylbutanoate (Table 1,
entry n). The yields are generally high and the reaction times are
Recently, molecular iodine has received considerable attention
in organic synthesis because of its low cost and ready availability.
The mild Lewis acidity associated with iodine has enhanced its use
in organic synthesis to perform several organic transformations
using stoichiometric levels to catalytic amounts.8
Following our interest in the catalytic uses of molecular iodine,9
we herein report a mild and practical method for the hydroalkyla-
tion of vinyl arenes with 1,3-diketones using molecular iodine. Ini-
tially, we attempted the hydroalkylation of a readily available
styrene (1) with acetylacetone (2) in the presence of 10 mol % of
I2. The reaction proceeded well in toluene at 110 °C and the prod-
I2 (10 mol%)
O
O
O
+
toluene, 110 ºC
O
1
2
3a
* Corresponding author. Tel.: +91 40 27193535; fax: +91 40 27160512.
E-mail address: yadavpub@iict.res.in (J.S. Yadav).
Scheme 1. Reaction between styrene and acetyl acetone.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.024

J. S. Yadav et al. / Tetrahedron Letters 51 (2010) 2622–2624
2623
Table 1
Iodine-catalyzed intermolecular addition of 1,3-diketones to vinyl arenes
Entry
Alkene
1,2-Diketones
Producta
Time (h)
6.0
Yieldb (%)
O
O
O
O
O
O
O
a
92
94
O
O
O
b
c
4.5
3.5
Me
O
O
Me
96
O
O
O
O
O
O
O
d
e
5.5
6.5
86
85
Cl
O
Cl
O
MeO
O
MeO
Br
O
f
6.0
5.5
80
90
Br
O
O
O
O
O
O
O
g
O
O
h
7.0
65
O
O
O
i
j
6.0
5.5
75
88
Me
Me
O
Me
O
O
O
O
O
O
Ph
Ph
Ph
Ph
O
Ph
Ph
Ph
Ph
O
Ph
O
k
l
7.0
6.0
90
92
Ph
Ph
O
Me
O
Ph
Ph
O
O
O
Ph
O
Ph
O
m
n
6.5
8.0
6.5
88
Ph
O
OMe
O
OMe
O
O
80 (48:52)
86 (45:55)
O
Ph
O
O
O
Ph
o
a
The products were characterized by 1H NMR, IR and mass spectrometry.
Yield refers to pure products after chromatography.
b
quite reasonable. In general, the hydroalkyation was clean and no
by-products such as iodo derivatives were detected under these
conditions. As a solvent, toluene appeared to give the best results.
In the absence of catalyst, the reaction did not proceed even after a
long reaction time (10–24 h). To realize the reaction mechanism,
we have performed hydroalkylation of styrene with acetyl acetone
using equimolar amounts of iodine and triethyl amine (10 mol %
each). However, no reaction was observed in the presence of base.

2624
J. S. Yadav et al. / Tetrahedron Letters 51 (2010) 2622–2624
O
References and notes
O
I2 (10 mol%)
O
O
1. (a) Stetter, H. In Methoden Org. Chem., 4th ed.; Houben-Weyl, 1952; Vol. 7/2b, p
1423.; (b) Barton, D. H. R.; Ollis, W. D. Comprehensive Organic Chemistry;
Pergamon Press: Oxford, 1979. p 1058.
+
toluene, 110 ºC
2. (a) Yao, X. Q.; Li, C.-J. J. Am. Chem. Soc. 2004, 126, 6884; (b) Nguyen, R.-V.; Yao,
X. Q.; Bohle, D. S.; Li, C.-J. Org. Lett. 2005, 7, 673; (c) Yao, X. Q.; Li, C.-J. J. Org.
Chem. 2005, 70, 5752.
3. (a) Liu, P. N.; Zhou, Z.-Y.; Lau, C.-P. Chem. Eur. J. 2007, 13, 8610; (b) Rueping, M.;
Nachtsheim, B. J.; Kuenkel, A. Synlett 2007, 1391; (c) Duan, Z.; Xuan, X.; Wu, Y.
Tetrahedron Lett. 2007, 48, 5157; (d) Kischel, J.; Michalik, D.; Zapf, A.; Beller, M.
Chem. Asian J. 2007, 2, 909.
4
2
3h
Scheme 2. Reaction between indene and acetyl acetone.
But the reaction proceeds well in the presence of 10 mol % of HI.
This clearly indicates that HI is responsible for the hydroalkylation,
which may be generated in situ from iodine and 1,3-diketone. This
method does not require the use of expensive or corrosive reagents
and no precautions need to be taken to exclude moisture from the
reaction medium. The scope and generality of this process are illus-
trated with respect to various olefins and 1,3-diketones and the re-
sults are presented in Table 1.10
In summary, we have described a simple and efficient protocol
for the intermolecular hydroalkylation of vinyl arenes with 1,3-
diketones using iodine as a catalyst under neutral conditions. The
remarkable features of this procedure are atom efficiency, high
conversions, operational simplicity and ready availability of re-
agents at low cost.
4. (a) Wang, G.-W.; Shen, Y. -B.; Wu, X. -L.; Wang, L. Tetrahedron Lett. 2008, 49,
5090; (b) Lanman, H. E.; Nguyen, R.-V.; Yao, X.; Chan, T. -H.; Li, C.-J. J. Mol. Catal.
A: Chem. 2008, 279, 218.
5. (a) Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125, 2056; (b) Pei, T.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2001, 123, 11290; (c) Liu, C.; Widenhoefer,
R. A. Tetrahedron Lett. 2005, 46, 285.
6. (a) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem., Int. Ed. 2004, 43,
5350; (b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004,
126, 4526.
7. Gao, Q.; Zheng, B.-F.; Li, J.-H.; Yang, D. Org. Lett. 2005, 7, 2185.
8. (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Lin, X.-F.; Cui, S.-L.; Wang, Y. G.
Tetrahedron Lett. 2006, 47, 4509; (c) Chen, W.-Y.; Lu, J. Synlett 2005, 1337; (d)
Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595; (e) Banik, B. K.;
Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46, 2479; (f) Wang, S.-Y.
Synlett 2004, 2642; (g) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett.
2005, 46, 5771; (h) Pukan, P. Synth. Commun. 2004, 34, 1065; (i) Zhou, Y.; Yan,
P. F.; Li, G. M.; Chen, Z. J. Chin. J. Org. Chem. 2009, 29, 1719; (j) Stavber, S.; Jereb,
M.; Zupan, M. Synthesis 2008, 1487.
9. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem. Soc., Perkin Trans. 1 2000,
3025; (b) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy, T. Tetrahedron Lett.
2005, 46, 2687; (c) Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K.
Synthesis 2000, 1532; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.;
Prasad, A. R. Synlett 2001, 1638; (e) Yadav, J. S.; Reddy, B. V. S.; Rao, T. S.;
Krishna, B. B. M. Tetrahedron Lett. 2009, 50, 5351.
Acknowledgement
T.S.R., K.B. and A.R. thank the CSIR, New Delhi, for the award of
fellowships.
10. Experimental procedure, spectral data for new compounds and copies of 13C
NMR spectra are provided in Supplementary data.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.03.024.