IBX/Sc(OTf)3-promoted one-pot oxidative conjugate addition of allyltrimethylsilane to Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2007.07.198

Baylis-Hillman adducts undergo smooth one-pot oxidative Michael addition with allyltrimethylsilane in the presence of 2-iodoxybenzoic acid (IBX)/Sc(OTf)₃ under mild conditions to afford homoallyl β-ketoesters in good yields with high 1,4-select

Full text of DOI:10.1016/j.tetlet.2007.07.198

Tetrahedron Letters 48 (2007) 7546–7548
IBX/Sc(OTf)3-promoted one-pot oxidative conjugate
addition of allyltrimethylsilane to Baylis–Hillman adducts
J. S. Yadav,* B. V. Subba Reddy, Ashutosh Pratap Singh and A. K. Basak
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 23 June 2007; revised 23 July 2007; accepted 30 July 2007
Available online 2 August 2007
Abstract—Baylis–Hillman adducts undergo smooth one-pot oxidative Michael addition with allyltrimethylsilane in the presence of
2-iodoxybenzoic acid (IBX)/Sc(OTf)3 under mild conditions to afford homoallyl b-ketoesters in good yields with high 1,4-selectivity.
ꢀ 2007 Published by Elsevier Ltd.
The stereoselective addition of allylmetal reagents to
carbon electrophiles is an important carbon–carbon
bond forming reaction in organic synthesis.1 In particu-
lar, Lewis acid catalyzed carbon–carbon bond forming
reactions are of great significance in organic synthesis
because of their high reactivity, selectivity and mild reac-
tion conditions.2 Baylis–Hillman adducts are well
known carbon electrophiles capable of reacting with
various nucleophiles and their ability to undergo nucle-
ophilic substitution reactions contributes largely to their
synthetic value.3–6 The versatility of the functionality in
such Baylis–Hillman adducts makes them valuable syn-
thetic intermediates for the synthesis of a variety of het-
erocycles such as quinolines, pyrimidones, isoxazolines,
pyrazolones, pyrrolidines, indolizines, azetidinones,
diazacyclophanes and chromanones as well as biologi-
cally active natural products including a-alkylidene-b-
lactams, a-methylene-c-butyrolactones and mikanecic
acids, frontalin, trimethoprim, sarkomycin, ilmofosine
nuciferol and many others.7 However, there have been
no reports on the conjugate addition of allyltrimethylsi-
lane to Baylis–Hillman adducts via an oxidative
addition.
agent due to its high efficiency, easy availability, mild
reaction conditions and its stability to moisture and
air.9 A wide functional group tolerance and high-yield-
ing reactions, without over oxidation have made IBX
very familiar for the oxidation of alcohols even in the
presence of olefins, thioethers and amino groups,10 and
in other elegant oxidative transformations.11
In this Letter, we report a direct, one-pot oxidative Mi-
chael reaction of Baylis–Hillman adducts with allyltri-
methylsilane using IBX/Sc(OTf)3 as a novel catalytic
system. Initially, we examined the oxidative Michael
reaction of ethyl 2-[hydroxyl(phenyl)methyl] acrylate
(1) with allyltrimethylsilane (2) in the presence of 1.2
equiv of IBX and 10 mol % Sc(OTf)3 in acetonitrile.
The reaction proceeded smoothly at room temperature
and the product, ethyl 2-benzoylhex-5-enoate (3a) was
obtained in 84% yield (Scheme 1).
This result encouraged us to examine other substituted
Baylis–Hillman adducts (Table 1). Interestingly, this
method worked well with substrates derived from both
aliphatic and aromatic aldehydes. The starting materials
were prepared by using a known procedure.12 In all
cases, the reactions were clean and afforded the Michael
adducts in good yields. The reaction conditions were
compatible with various functionalities such as halides,
aryl methyl ethers, esters and alkenes (Table 1). All
Recently, the use of hypervalent iodine reagents as oxi-
dants in organic synthesis has attracted increasing inter-
est due to their mild, selective and environmentally
benign oxidizing properties.8 IBX is a versatile oxidizing
1
the products were characterized by H NMR, IR and
mass spectroscopy. Of the various hypervalent iodine re-
agents examined, including iodosobenzene (PhIO), iod-
obenzene diacetate (PhI(OAc)2) and Dess–Martin
periodinane (DMP), 2-iodoxybenzoic acid (IBX) was
found to be the best in terms of conversion. Other
Keywords: Baylis–Hillman adducts; Hypervalent iodine; Allylsilane;
Conjugate addition.
*
Corresponding author. Tel.: +91 40 27193030; fax: +91 40
27160512; e-mail: yadav@iict.res.in
0040-4039/$ - see front matter ꢀ 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.07.198

J. S. Yadav et al. / Tetrahedron Letters 48 (2007) 7546–7548
7547
O
OH
CO2Et
CO2Et
IBX/Sc(OTf)3
CH3CN, r.t.
Si
+
1
2
3a
Scheme 1.
Table 1. Oxidative allylation of Baylis–Hillman adducts using the IBX/Sc(OTf)3 system
Entry
Substrate
Producta
Reaction time (h)
24
Yieldb
OH
O
a
84
CO2Me
CO2Me
OH
O
CO2Me
CO2Me
b
c
20
22
82
78
F
F
O
OH
CO2Me
CO2Me
CO2Me
Cl
Cl
O
OH
CO2Me
d
30
76
MeO
Br
MeO
Br
OH
O
CO2Et
OH
CO2Et
O
e
f
22
24
36
79
70
82
CO2Me
CO2Me
O
OH
CO2Me
g
CO2Me
OH
O
CO2Me
OH
CO2Me
h
i
26
26
83
82
OPh
OPh
O
CO2Me
CO2Me
Me
Me
O
OH
MeO
CO2Me
MeO
CO2Me
j
30
88
OMe
OMe
O
O
OH
OH
CO2Me
CO2Me
CN
k
l
32
26
80
78
CN
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Yield refers to pure products after column chromatography.
oxidants such as Oxoneꢁ, CAN, MnO2 and KBrO3
failed to produce the desired product. The oxidation
of secondary alcohols was only observed when using
IBX alone. In the absence of Sc(OTf)3, no allyl addition
occurred with IBX even after long reaction times (9–
13 h) under reflux conditions. Various catalytic systems

7548
J. S. Yadav et al. / Tetrahedron Letters 48 (2007) 7546–7548
Dharma Rao, P.; Suguna, H. R. Tetrahedron 1996, 52,
8001–8062; (c) Drewes, S. E.; Roos, G. H. P. Tetrahedron
1988, 44, 4653–4670.
such as IBX/InCl3, IBX/InBr3 and IBX/CeCl3Æ7H2O
were screened but none gave satisfactory yields of prod-
ucts. As solvent, acetonitrile gave the best results. The
by-product, iodosobenzoic acid was separated by a sim-
ple filtration and could be reoxidized to IBX. The scope
of the IBX promoted oxidative Michael reaction was
investigated with respect to various Baylis–Hillman
adducts and the results are presented in Table 1.13
8. (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: San Diego, 1997; (b) Wirth, T.; Hirt, U.
H. Synthesis 1999, 1271–1287; (c) Wirth, T. Angew. Chem.,
Int. Ed. 2001, 40, 2812–2814.
9. (a) Hartman, C.; Meyer, V. Chem. Ber. 1893, 26, 1727; (b)
Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123–
1178; (c) Kitamura, T.; Fujiwara, Y. Org. Prep. Proced.
Int. 1997, 29, 409–458.
10. (a) Wirth, T. Angew. Chem., Int. Ed. 2001, 40, 2812–2814;
(b) Ladziata, U.; Zhdankin, V. V. Arkivoc 2006, ix, 26–
58.
11. (a) Nicolaou, K. C.; Montagnon, T.; Baran, P. S. Angew.
Chem., Int. Ed. 2002, 41, 993–996; (b) Nicolaou, K. C.;
Barn, P. S.; Zhong, Y.-L.; Barluenga, S.; Hunt, K. W.;
Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124,
2233–2244.
In conclusion, we have described an efficient protocol
for the one-pot oxidative conjugate addition of allyltri-
methylsilane to Baylis–Hillman adducts using IBX/
Sc(OTf)3 as a novel catalytic system. The method offers
several advantages such as operational simplicity, mild
reaction conditions, cleaner reaction profiles, simple
work-up procedure and the use of inexpensive and read-
ily available reagents, which makes it a useful and
attractive strategy for the preparation of homoallyl
b-ketoesters in a single step operation.
12. Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418.
13. Experimental procedure: A mixture of Baylis–Hillman
adduct (1 mmol) and IBX (1.2 mmol) in acetonitrile
(10 ml) was stirred at room temperature until complete
oxidation took place. Allyltrimethylsilane (1.5 mmol) and
Sc(OTf)3 (10 mol %) were added sequentially and the
reaction stirred at room temperature. The reaction mix-
ture was then diluted with saturated aqueous NaHCO3
solution (15 ml) and extracted with EtOAc (3 · 10 ml).
The combined organic layers were washed with brine
(1 · 10 ml), dried over anhydrous Na2SO4 and evaporated
under reduced pressure. The resulting product was puri-
fied by silica gel column chromatography using a gradient
mixture of hexane/ethyl acetate (9.5:0.5) as eluent to afford
the pure Michael adduct. Spectral data for selected
compounds: 3e: Colourless oil: IR (neat): t 3072, 2925,
2853, 1737, 1690, 1565, 1418, 1287, 1191, 1023, 915,
Acknowledgement
A.P.S. and A.K.B. thank CSIR, New Delhi, for the
award of fellowships.
References and notes
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207–
2293; (b) Marshall, J. A. Chemtracts 1992, 5, 75–106; (c)
Ramachandran, P. V. Aldrichim. Acta 2002, 35, 23–35; (d)
Colvin, E. Silicon in Organic Synthesis; Butterworth:
London, 1981, pp 97; (e) Hosomi, A. Acc. Chem. Res.
1988, 21, 200.
2. Kobayashi, S. Eur. J. Org. Chem. 1999, 15–27.
3. (a) Lee, K. Y.; Kim, J. M.; Kim, J. N. Tetrahedron Lett.
2003, 44, 6737–6740; (b) Lee, K. Y.; Kim, J. M.; Kim, J.
N. Tetrahedron 2003, 59, 385–390; (c) Im, Y. J.; Lee, K.
Y.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2002, 43,
4675–4678.
758 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.19 (t, 3H,
.
J = 6.8 Hz), 2.01–2.16 (m, 4H), 4.07–4.30 (m, 2H), 4.97–
5.05 (m, 2H), 5.69–5.83 (m, 1H), 7.34 (t, 1H, J = 8.3 Hz),
7.68 (d, 1H, J = 8.3 Hz), 7.87 (d, 1H, J = 8.3 Hz), 8.04 (s,
1H), 8.02 (s, 1H). ESIMS: m/z: 325 (M+H)+, 347
(M+Na)+. HRMS calcd for C15H17O3NaBr: 347.0258.
Found: 347.0266. 3g: Colourless oil: IR (neat): t 2955,
2930, 2860, 1744, 1715, 1640, 1438, 1355, 1248, 1167, 915,
746 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.89 (t, 3H,
.
4. (a) Kim, J. N.; Kim, J. M.; Lee, K. Y. Synlett 2003, 821–
824; (b) Kim, J. N.; Kim, H. S.; Gong, J. H.; Chung, Y.
M. Tetrahedron Lett. 2001, 42, 8341–8344.
J = 6.8 Hz), 1.20–1.44 (m, 6H), 1.47–1.63 (m, 2H), 1.86–
2.04 (m, 2H), 2.34–2.58 (m, 2H), 3.40 (t, 1H, J = 6.8 Hz),
3.71 (s, 3H), 4.95–5.05 (m, 2H), 5.64–5.80 (m, 1H). ESIMS
m/z: 227 (M+H)+. HRMS calcd for C13H22O3Na:
249.1466. Found: 249.1478. 3j: Colourless oil: IR (neat):
t 2925, 1740, 1670, 1593, 1492, 1274, 1221, 1164, 1042,
5. (a) Drewes, S. E.; Emslie, N. D. J. Chem. Soc., Perkin
Trans. 1 1982, 2079–2083; (b) Hoffmann, H. M. R.; Rabe,
J. Helv. Chim. Acta 1984, 67, 413–415; (c) Hoffmann, H.
M. R.; Rabe, J. J. Org. Chem. 1985, 50, 3849–3859.
6. (a) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed.
Engl. 1985, 24, 94–110; (b) Buchholz, R.; Hoffmann, H.
M. R. Helv. Chim. Acta 1991, 74, 1213–1220; (c) Ameer,
F.; Drewes, S. E.; Hoole, R. F. A.; Kaye, P. T.; Pitchford,
A. T. J. Chem. Soc., Perkin Trans. 1 1985, 2713–2717.
7. (a) Basavaiah, D.; Jaganmohan Rao, A.; Satyanarayana,
T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah, D.;
1
761 cmÀ1. H NMR (CDCl3, 200 MHz): d 1.73–2.00 (m,
4H), 3.49 (s, 3H), 3.63 (s, 3H), 3.67 (s, 3H), 4.10 (t, 1H,
J = 6.6 Hz), 4.75–4.89 (m, 2H), 5.49–5.71 (m, 1H), 6.69 (d,
1H, J = 9.1 Hz), 6.84 (dd, 1H, J = 2.4 and 8.3 Hz), 7.13
(d, 1H, J = 2.4 Hz). ESIMS: m/z: 293 (M+H)+, 315
(M+Na)+. HRMS calcd for C16H20O5Na: 315.1208.
Found: 315.1203.