Iodine-catalyzed 1,4-addition of 2-(trimethylsilyloxy)furan to α,β-unsaturated ketones: a facile synthesis of γ-butenolides

Article abstract of DOI:10.1016/j.tetlet.2009.02.128

The α,β-unsaturated compounds undergo smooth conjugate addition with 2-(trimethylsilyloxy)furan (TMSF) in the presence of 10 mol % of iodine under mild and neutral conditions to afford the corresponding γ-substituted butenolides in high yields and with go

Full text of DOI:10.1016/j.tetlet.2009.02.128

Tetrahedron Letters 50 (2009) 3760–3762
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Iodine-catalyzed 1,4-addition of 2-(trimethylsilyloxy)furan to a,b-unsaturated
ketones: a facile synthesis of c-butenolides
*
J. S. Yadav , B. V. Subba Reddy, G. Narasimhulu, N. Sivasankar Reddy, P. Janardhan Reddy
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
(TMSF) in the presence of 10 mol % of iodine under mild and neutral conditions to afford the correspond-
ing -substituted butenolides in high yields and with good diastereoselectivity. The use of iodine makes
this procedure simple, convenient and cost effective.
a,b-unsaturated compounds undergo smooth conjugate addition with 2-(trimethylsilyloxy)furan
Received 9 January 2009
Revised 9 February 2009
Accepted 18 February 2009
Available online 21 February 2009
c
Ó 2009 Published by Elsevier Ltd.
Keywords:
1,4-Addition
Molecular iodine
Chalcones
Silyloxyfuran
c
-Lactones
Butenolides (
a
,b-unsaturated-
c
-lactones) are versatile building
Following our interest in the catalytic uses of molecular io-
dine,10 we herein report a simple, convenient and metal free syn-
blocks for the synthesis of biologically active natural products such
as mitomycins,1 cavernosine,2 A26771B3 and many others.4 They
also serve as precursors for the synthesis of highly substituted chi-
thesis of
c-substituted butenolides by means of addition of 2-
(trimethylsilyloxy)furan onto
a,b-unsaturated systems. Thus,
ral
c
-lactones.5 Lewis acid promoted Michael addition is one of the
treatment of chalcone (1), with 2-(trimethylsilyloxy)furan (2) in
the presence of 10 mol % of I2 at À78 °C gave the corresponding
5-(3-oxo-1,3-diphenylpropyl)furan-2(5H)-one in 89% yield as a
mixture of syn:anti-isomers (3a:4a, 90:10; Scheme 1).
most important carbon–carbon bond forming reactions in organic
synthesis. In particular, acid-catalyzed addition of 2-(trimethylsi-
lyloxy)furan to
a,b-unsaturated ketone is very attractive as it pro-
vides -substituted butenolides which are key intermediates in
c
This result provided the incentive for further study with various
natural products synthesis.6 Typically, Lewis acids such as SnCl4,
Sc(OTf)3, Cu(OTf)2 and lanthanide triflates have been utilized to
accomplish this reaction under strictly anhydrous conditions.6,7
However, Diels–Alder adduct was the major side product in these
acid-catalyzed Michael additions. Alternatively, TBAF has been
used to catalyze this reaction at low temperature (À78 °C).8 How-
ever, the high cost, stringent conditions and moisture sensitivity of
these reagents limit their use in large scale synthesis. Therefore,
the development of new reagents that are more efficient leading
to convenient procedures with improved yields and selectivity is
desirable.
Recently, molecular iodine has received considerable attention
in organic synthesis because of its low cost, non-toxicity and ready
availability. The mild Lewis acidity associated with iodine has en-
hanced its use in organic synthesis to perform several organic
transformations using stoichiometric levels to catalytic amounts.9
a,b-unsaturated ketones. Interestingly, several substrates derived
from both aromatic and aliphatic aldehydes or ketones partici-
pated well in this reaction (Table 1, entries b–h). Other conjugated
ketones such as methylvinylketone and cyclohexenone were also
effective for this transformation (Table 1, entries i and j).
Next, we attempted the conjugate addition of 2-(trimethylsilyl-
oxy)furan with other unsaturated systems such as b-nitrostyrene
and 2-benzylidenemalononitrile. Interestingly, these substrates
Ph
O
O
O
O
3a
Ph
syn (major)
+
10 mol% I2
Ph
+
OTMS
O
Ether, -78 ºC
Ph
Ph
1
2
O
O
O
Ph
4a
anti (minor)
* Corresponding author. Tel.: +91 40 27193434; fax: +91 40 27160512.
E-mail address: yadav@iict.res.in (J.S. Yadav).
Scheme 1. Preparation of 3a and 4a from chalcone and 2-(trimethylsilyloxy) furan.
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.02.128

J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 3760–3762
3761
Table 1
Iodine-catalyzed preparation of butenolides from
a,b-unsaturated ketones and 2-(trimethylsiloxy)furan
Entry
Aldehyde
Producta
Time (h)
3.0
Yieldb (%)
89
syn:antic
O
O
O
Ph
O
O
Ph
O
O
O
a
90:10
O
O
O
O
Me
Me
O
b
c
3.0
2.0
3.5
4.0
91
93
88
85
90:10
87:13
89:11
85:15
O
Me
MeO
Cl
OMe
OMe
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Cl
Br
Cl
Br
O
d
e
O
O
O
O
O
Br
O
O
O
O
f
2.5
3.0
92
90
89:11
80:20
O
O
O
O
OMe
MeO
MeO
O
O
g
Me
O
O
Me
Me
Me
O
O
O
O
O
h
i
3.5
2.5
3.0
91
93
92
75:25
—
O
O
Me
O
O
Me
O
O
O
O
Me
Me
O
O
O
j
70:30
O
O
O
O
Ph
Ph
NO2
CN
O
O
k
4.0
4.0
85
82
92:8
O2N
NC
O2N
NC
O
O
Ph
Ph
O
O
O
O
l
60:40
CN
CN
CN
a
The products were characterized by 1H NMR, IR and mass spectrometry.
Yield refers to pure products after chromatography.
b
c
syn and anti Ratio was determined by 1H NMR spectroscopy of the crude products.
also underwent smooth 1,4-addition under similar reaction condi-
tions (Table 1, entries k and l). In all cases, the reactions proceeded
smoothly at À78 °C under extremely mild and neutral conditions.
In most cases, the products were obtained as a mixture of syn-
and anti-isomers, favouring the syn isomer, which could be easily
separated by column chromatography. The stereochemistry (syn
and anti) of the products was assigned on the basis of the coupling
constants of the protons in the 1H NMR spectra of the products and

3762
J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 3760–3762
also by comparison with authentic samples.6–8 The product ratio
was determined by 1H NMR spectroscopy of the crude products.
However, in the absence of iodine, the reaction did not proceed
even after a long reaction time. The combination of 2-(trimethylsi-
lyloxy)furan and iodine is a useful method for the addition of TMSF
to activated unsaturated systems. A catalytic amount of TMSI was
also found to be an equally effective catalyst for this conversion. No
additives or activators were required for the activation of enones.
In general, the reactions proceeded smoothly under the influence
of 10 mol % of molecular iodine, and the yields were generally high
to excellent. The advantages of this method are high conversions,
ready availability of the catalyst, high efficiency, no salt formation
and avoidance of heavy transition metal catalysts. The scope of this
methodology is illustrated with respect to various activated unsat-
urated systems, and the results are presented in Table 1.11
A.; Ward, S. R.; Jones, M. D.; Maddocks, P. J. Chem. Soc., Perkin Trans. 1 1993,
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In summary, molecular iodine has proved to be an effective cat-
alyst in promoting conjugate addition of 2-(trimethylsilyl-
11. General procedure: To a stirred solution of
a,b-unsaturated compound (1 mmol)
oxy)furan with various
a,b-unsaturated systems to produce
and 2-(trimethylsilyloxy)furan (1.5 mmol) in diethyl ether (10 mL), iodine
(10 mol %) was added at À78 °C, and the resulting mixture was allowed to stir
at the same temperature for the appropriate time (Table 1). After complete
conversion as indicated by TLC, the reaction mixture was quenched with water
(10 mL) and extracted with dichloromethane (3 Â 15 mL). The combined
extracts were washed with a 15% solution of aqueous sodium thiosulfate,
dried over anhydrous Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (Merck 100–200 mesh, ethyl acetate–hexane,
1:9) to afford pure butenolide. Spectral data for selected products: Compound
functionalized butenolides.
Acknowledgement
G.N and P.J.R thank CSIR, New Delhi for the award of
fellowships.
3b:
furanone: Solid, mp 129–131 °C; IR (KBr)
1674, 1596, 1513, 1372, 1264, 1101, 1015, 893, 814, 756 cmÀ1
(5R)-5-[(1R)-1-(4-methylphenyl)-3-oxo-3-phenylpropyl]-2,5-dihydro-2-
max: 3092, 3027, 2921, 1790, 1750,
1H NMR
References and notes
m
;
(300 MHz, CDCl3): d 2.31 (s, 3H), 3.33–3.65 (m, 3H), 5.17–5.21 (m, 1H), 6.02
(dd, J = 2.6, 5.2 Hz, 1H), 7.02–7.57 (m, 8H), 7.85 (d, J = 7.5 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d 20.9, 40.1, 43.9, 85.8, 121.7, 127.8, 128.1, 128.5, 129.1,
129.4, 133.1, 136.5, 137.1, 156.5, 172.6, 197.3; ESI-MS: m/z: 329 (M+Na);
HRMS calcd for C20H18O3Na: 329.1153, found: 329.1168. Compound 3i: (5S)-5-
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1712, 1602, 1420, 1362, 1164, 1105, 1015, 918, 819, 772 cmÀ1
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1H NMR
(300 MHz, CDCl3): d 1.66–1.82 (m, 1H), 2.08–2.26 (m, 4H), 2.49–2.74 (m, 2H),
5.07 (dd, J = 1.5, 8.3 Hz, 1H), 6.08 (d, J = 6.0 Hz, 1H), 7.43 (dd, J = 1.5, 6.0 Hz,
1H); 13C NMR (75 MHz, CDCl3): d 26.4, 29.8, 37.8, 81.9, 121.3, 156.1, 172.6,
207.0; ESI-MS: m/z: 177 (M+Na); HRMS calcd for C8H10O3Na: 177.0527, found:
177.0535. Compound 3j: (5R)-5-[(1R)-3-oxocyclohexyl]-2,5-dihydro-2-furanone:
Liquid, IR (KBr)
mmax: 2933, 1752, 1709, 1451, 1422, 1312, 1163, 1097, 1023,
;
901, 819, 753 cmÀ1
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J = 1.5, 3.7 Hz, 1H), 6.16 (dd, J = 2.2, 6.0 Hz, 1H), 7.42 (dd, J = 1.5, 6.0 Hz, 1H); 13C
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209.3; ESI-MS: m/z: 203 (M+Na); HRMS calcd for C10H12O3Na: 203.0684,
found: 203.0694.