Ionic liquid-promoted one-pot oxidative Michael addition of TMSCN to Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2008.08.072

The first example of ionic liquid-promoted one-pot oxidative conjugate hydrocyanation of Baylis-Hillman adducts with trimethylsilyl cyanide (TMSCN) is reported. The oxidation of Baylis-Hillman adducts with IBX/[bmim]Br or isomerization-oxidation with NaNO

Full text of DOI:10.1016/j.tetlet.2008.08.072

Tetrahedron Letters 49 (2008) 6360–6363
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Tetrahedron Letters
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Ionic liquid-promoted one-pot oxidative Michael
addition of TMSCN to Baylis–Hillman adducts
*
Lal Dhar S. Yadav , Chhama Awasthi, Ankita Rai
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The first example of ionic liquid-promoted one-pot oxidative conjugate hydrocyanation of Baylis–Hill-
man adducts with trimethylsilyl cyanide (TMSCN) is reported. The oxidation of Baylis–Hillman adducts
with IBX/[bmim]Br or isomerization-oxidation with NaNO3/[Hmim]HSO4 systems affords b-ketomethyl-
Received 15 June 2008
Revised 17 August 2008
Accepted 21 August 2008
Available online 24 August 2008
ene compounds or [E]-cinnamaldehydes, respectively. These
a,b-unsaturated carbonyl compounds
undergo Michael addition with TMSCN in the same vessel to afford the corresponding thermodynami-
cally more stable b-cyanated products. Thermodynamically less stable 1,2-addition products were not
formed. The present regioselective reactions are promoted by ionic liquids, which can be recycled easily
for further use without any loss of efficiency.
Keywords:
Baylis–Hillman adducts
Ionic liquids
Hypervalent iodine
Oxidation
Ó 2008 Elsevier Ltd. All rights reserved.
Michael addition
TMSCN
Continuing development in synthetic organic chemistry relies
on discovering new, high yielding and selective reactions. The Mi-
functionality including allylic hydroxyl and Michael acceptor units,
are valuable starting materials for the synthesis of various com-
pounds of chemical and pharmaceutical importance.10 Regioselec-
tive introduction of nucleophiles, viz. C-, S-, N-, O-centred
chael addition of cyanide to
is a useful C–C bond forming reaction because the resulting b-cya-
no adducts can be converted into -aminobutyric acids (GABA ana-
a,b-unsaturated carbonyl derivatives
c
nucleophiles, at either the a- or c-position of the BH adduct have
logues) under reducing conditions. GABA is the chief inhibitory
neurotransmitter in the central nervous system.1 b-Cyanocarbonyl
derivatives are also valuable synthons for a variety of compounds,
and thereby enhance the versatility of molecules containing cyano
become powerful tools in synthetic organic chemistry.10–12 How-
ever, there has been no report on the oxidative conjugate hydrocy-
anation of BH adducts.
Amongst various hypervalent iodine reagents,13 2-iodoxyben-
zoic acid (IBX) has become a reagent of choice due to its easy han-
dling, low cost, tolerance to moisture,14 mild reaction conditions
and zero toxic waste generation. IBX selectively oxidizes alcohols
in the presence of olefins, thioethers and amino groups,15 and is
also useful for other elegant oxidative transformations.16 Similarly,
ionic liquids (ILs) have gained considerable interest as environ-
mentally benign reaction media, catalysts and reagents, and are
easy to recycle.17 Recently, Brønsted acidic ionic liquids have been
deemed as promising alternatives for acid-catalyzed reactions, and
play a dual solvent—catalyst role in a variety of reactions including
esterification of carboxylic acids, protection of alcohols and car-
bonyl groups, oxidation of alcohols, alcohol dehydrodimerization,
pinacol/benzopinacol rearrangement in Mannich reactions and
for cleavage of ethers.18
functionalities.2 Thus, the development of
a convenient and
efficient methodology for the synthesis of b-cyanocarbonyl
compounds is an interesting target for investigation.
One of the best methods for the introduction of a cyanide group
involves the reaction of carbonyl compounds with trimethylsilyl
cyanide (TMSCN),3 in contrast to other reagents such as Et2AlCN,4
NaCN,5 KCN6 and HCN.7 It is reported that the reaction of
a,b-
unsaturated carbonyls with TMSCN in the presence of a base as
catalyst affords 1,2-adducts.8 In contrast, on employing Lewis acids
such as Et2AlCN, Et3Al, AlCl3 and SnCl2, regioselective 1,4-addition
takes place.9 These metallated catalysts have drawbacks such as
toxicity, difficult handling and work up, which we have overcome
by using ionic liquids as both the reaction media and reaction
promoters in the present work.
The Baylis–Hillman reaction is a useful C–C bond forming
reaction. The Baylis–Hillman (BH) adducts, which possess dense
One-pot sequential multistep reactions are of increasing aca-
demic, economical and ecological interest because they address
fundamental principles of synthetic efficiency and reaction design.
The continued interest of synthetic chemists in the BH reaction,
and our ongoing efforts to devise one-pot protocols involving
* Corresponding author. Tel.: +91 5322500652; fax: +91 5322460533.
E-mail address: ldsyadav@hotmail.com (L. D. S. Yadav).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.072

L. D. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6360–6363
6361
O
O
Br
COOMe
COOMe
CN
N
N
TMSCN
rt, 2-3 h
IBX, rt, 1 h
OH
2
3
COOMe
CN
HSO4
H
NaNO3, 80 oC, 1-2 h
COOMe
O
1
COOMe
O
N
N
TMSCN
rt, 2-3 h
5
4
Scheme 1. Ionic liquid-promoted oxidative conjugate addition of TMSCN to BH adducts.
conjugate addition19 have encouraged us to develop the present
ionic liquid-promoted one-pot oxidative hydrocyanation of BH
adducts (Scheme 1), which opens up a new aspect of their
synthetic utility.
Initially, we examined the reaction in six different ILs, 1-butyl-
3-methylimidazolium (bmim) tetrafluoroborate ([bmim]BF4),
[bmim]PF6, [bmim]Br, butylpyridinium (bpy) tetrafluoroborate
(bpyBF4), bpyPF6 and bpyBr.
Among these ILs, [bmim]Br dissolved IBX at rt and gave the best
result in the one-pot oxidative hydrocyanation leading to 3
(Scheme 1). The other five ILs tested did not dissolve IBX even
when heated to 80 °C in the presence of a small amount of water
and did not give satisfactory yields of 3. Thus, to achieve the oxida-
tive conjugate addition of TMSCN to BH adducts in one-pot, we oxi-
dized BH adducts 1 to the corresponding carbonyl compounds 2
with IBX in [bmim]Br at rt for 1 h followed by the addition of
TMSCN and stirring at rt for a further 2–3 h to afford the corre-
sponding hitherto unknown b-cyanated ketones 3 in 79–89% yields
(Scheme 1, Table 1). A plausible mechanism for the hydrocyanation
of 2 to afford 3 is depicted in Scheme 2. Other hypervalent iodine
reagents such as DMP, PhI(OAc)2 and PhIO gave unsatisfactory
results. IBX was found to be the best reagent in terms of conversion.
In order to investigate the substrate scope of the reaction, we
converted BH adducts 1 into [E]-cinnamaldehyde derivatives 4 via
isomerization-oxidation with NaNO3 in the protic ionic liquid
[Hmim]HSO4 employing the known method.20 Hydrocyanation
of 4 with TMSCN in the same vessel afforded new b-cyanated
aldehydes 5 in 84–91% yields. The present procedure in its
entirety involves stirring of an equimolar mixture of BH adduct 1
and NaNO3 in 1-methylimidazolium hydrogen sulfate [Hmim]H-
SO4 for 1–2 h at 80 °C followed by the addition of TMSCN and
stirring for a further 2–3 h at rt to afford b-cyanated aldehydes
5 (Scheme 3, Table 1). The formation of 5 was highly diastereo-
selective in favour of the syn isomers. The diastereomeric ratios
in the crude ratio isolates of 5 were determined by 1H NMR spec-
troscopy to note any inadvertent alteration of these ratios during
subsequent purification. As determined by 1H NMR spectroscopy,
the crude isolates of 5 were found to be diastereomeric mixtures
containing 94–97% of the syn isomer. The syn stereochemistry of
molecules 5 was conclusively assigned on the basis of 1H NMR
spectra and literature precedent,21 as the coupling constant
(J2,3 = 4.0 Hz) for syn 5 was lower than that for the minor anti iso-
mer (J2,3 = 7.9 Hz).
The oxidative conjugate hydrocyanation was also attempted
with NaNO3–[Hmim]NO3 and NaNO3–[Hmim]H2PO4 systems
under the same reaction conditions. The reaction was unsuccessful
in the former case indicating the need for an acidic hydrogen which
is absent in [Hmim]NO3 to catalyze the oxidation of the BH adducts
into cinnamaldehydes 4 (Scheme 3). However, the reaction pro-
ceeded with the NaNO3–[Hmim]H2PO4 system, but relatively low
Table 1
One-pot oxidative conjugate addition of TMSCN to BH adducts 1
Entry
BH aduct 1
OH
Oxidized adduct 2 or 4
Final product 3 or 5a
Reaction time (h)
4
Yieldb,c (%)
83
O
O
COOMe
COOMe
3a
COOMe
CN
O
OH
O
CN
CN
O
CN
OH
CN
3b
3.5
85
O
COOMe
COOMe
COOMe
CN
3c
3.5
86
89
O2N
O2N
O2N
O2N
O2N
O2N
OH
OH
O
O
O
CN
CN
CN
CN
3d
3
O
COOMe
CN
COOMe
COOMe
3e
4
79
MeO
MeO
MeO
(continued on next page)

6362
L. D. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6360–6363
Table 1 (continued)
Entry
BH aduct 1
Oxidized adduct 2 or 4
Final product 3 or 5a
Reaction time (h)
4
Yieldb,c (%)
82
O
OH
O
CN
CN
CN
CN
3f
MeO
MeO
MeO
CN
OH
OH
COOMe
O
COOMe
COOMe
5a
5b
5c
5d
5e
3.5
3.5
3
86
87
89
91
84
85
O
CN
CN
O
CN
O
CN
OH
CN
COOMe
COOMe
O
COOMe
O
O2N
O2N
MeO
MeO
O2N
O2N
O2N
O2N
MeO
MeO
CN
OH
OH
CN
O
CN
O
CN
3
CN
COOMe
O
COOMe
COOMe
O
3.5
3.5
MeO
MeO
CN
OH
CN
O
CN
CN
O
5f
a
Syn/anti representation proposed by Masamune and coworkers has been followed.27
Yield of pure products 3 or 5 after column chromatography.
b
c
All compounds gave C, H and N analyses within 0.38% and satisfactory spectral (IR, 1 H NMR, 13C NMR and EIMS) data.
SiMe3
O
Br
EWG
N
N
Ar
H2O
O
CN
EWG
Br
N
Ar
N
SiMe3OH
Ar
2
H
OH
EWG = COOMe, CN
O
O
EWG
CN
TMSCN
EWG
CN
EWG
Ar
Ar
3
Scheme 2. A plausible mechanism for the conjugate addition of TMSCN to a,b-unsaturated ketone 2 to afford 3.
yields of 5 (30–37%) were obtained probably due to the lower
Brønsted acidity associated with [H2PO4]. Thus, [Hmim]HSO4 plays
a dual role, that is, as an acid catalyst and solvent for both oxida-
tion and hydrocyanation.
In conclusion, we have presented a novel example of ionic
liquid-promoted one-pot oxidative conjugate hydrocyanation of
BH adducts. The present method involves an efficient regioselec-
tive addition of TMSCN to b-keto-a-methylenes and [E]-cinnamal-
The requisite BH adducts and ILs were prepared by employing
known methods.22–24 After isolation of products 3 and 5, the ionic
liquids could be recycled for four times up to 73% recovery and
reused without any loss of efficiency.25,26
dehydes, obtained from oxidation and isomerization-oxidation of
BH adducts, respectively, to afford the corresponding b-cyanated
products, which opens up a new aspect for the synthetic utility
of BH adducts.

L. D. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6360–6363
6363
46, 1489–1491; (h) Earle, M. J.; Katdare, S. P.; Seddon, K. R. Org. Lett. 2004, 6,
707–710.
OH
OH2
O
N
COOMe
18. (a) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver, K. J.; Forbes, D. C.;
Davis, J. H., Jr J. Am. Chem. Soc. 2002, 124, 5962–5963; (b) Welton, T. Chem.
Rev. 1999, 99, 2071–2084; (c) Sheldon, R. Chem. Commun. 2001, 23, 2399–
2407; (d) Zhu, H. P.; Yang, F.; Tang, J.; He, M. Y. Green Chem. 2003, 5, 38–39; (e)
Zhao, G.; Jiang, T.; Gao, H.; Han, B.; Huang, J.; Sun, D. Green Chem. 2004, 6, 75–
77.
19. (a) Yadav, L. D. S.; Awasthi, C.; Rai, V. K.; Rai, A. Tetrahedron Lett. 2007, 48,
4899–4902. and 8037–8039; (b) Yadav, L. D. S.; Patel, R.; Rai, V. K.; Srivastava,
V. P. Tetrahedron Lett. 2007, 48, 7793–7795; (c) Yadav, L. D. S.; Rai, A.; Rai, V. K.;
Awasthi, C. Synlett 2007, 1905–1908; (d) Yadav, L. D. S.; Yadav, S.; Rai, V. K.
Green Chem. 2006, 8, 455–458; (e) Yadav, L. D. S.; Rai, V. K.; Yadav, S.
Tetrahedron 2006, 62, 5464–5468.
20. Yadav, L. D. S.; Srivastava, V. P.; Patel, R. Tetrahedron Lett. 2008, 49, 3142–3146.
21. (a) Kamimura, A.; Mitsudera, H.; Asano, S.; Kidera, S.; Kakehi, A. J. Org. Chem.
1999, 64, 6353–6360; (b) Albertshofer, K.; Thayumanavan, R.; Utsumi, N.;
Tanaka, F.; Barbas, C. F., III. Tetrahedron Lett. 2007, 48, 693–696.
22. Cai, J.; Zhou, Z.; Zhao, G.; Tang, C. Org. Lett. 2002, 4, 4723–4725.
23. Lancaster, N. L.; Salter, P. A.; Welton, T.; Young, G. B. J. Org. Chem. 2002, 67,
8855–8861.
COOMe
[Hmim]HSO4
NaNO3
O
O
1
COOMe
COOMe
O
TMSCN
-HNO2
O
4
H
N
O
O
CN
COOMe
O
5
Scheme 3. A plausible mechanism for the formation of 5.
24. Mehdi, H.; Bodor, A.; Lantos, D.; Horváth, I. T.; de Vas, D. E.; Binnemans, K. J.
Org. Chem. 2007, 72, 1517–1524.
Acknowledgement
25. General procedure for the synthesis of b-cyano ketones 3: To
a mixture of
[bmim]Br (3 mL) and water (0.5 mL) was added IBX (1 mmol). The resulting
mixture was stirred at rt for 5–10 min, and BH adduct 1 (1 mmol) was added.
The reaction mixture was stirred at rt for 1 h. After complete oxidation
(monitored by TLC), TMSCN (1.5 mmol) was added and the reaction mixture
was further stirred at rt for 2–3 h (Table 1). Then, it was diluted with saturated
aqueous NaHCO3 solution (10 mL) and extracted with ether (3 Â 10 mL). The
combined organic layers were washed with brine solution, dried over MgSO4
and evaporated under reduced pressure. The resulting product was purified by
silica gel column chromatography using hexane/ethyl acetate (9:1) as eluent to
afford an analytically pure sample of 3. After isolation of the product, the
remaining aqueous layer containing the ionic liquid was washed with ether
(2 Â 10 mL) to remove any organic impurity and filtered. The filtrate was
extracted with CH2Cl2 (3 Â 10 mL), dried over MgSO4 and evaporated under
reduced pressure to afford [bmim]Br, which was used in subsequent runs
without further purification. Physical data of representative compounds.
Compound 3a: Yellowish solid, yield 83%, mp 95–97 °C. IR (KBr) mmax 3060,
We sincerely thank SAIF, Punjab University, Chandigarh, for
providing microanalyses and spectra.
References and notes
1. (a) Martin, D. L.; Olsen, R. W. GABA in the Nervous System: The View at Fifty
Years; Lippincott Williams & Wilkins: Philadelphia, 2000; (b) Alger, B. E.;
Möhler, H. Pharmacology of GABA and Glycine Neurotransmission; Springer:
Berlin, New York, 2001; (c) Krogsgaard-Larsen, P.; Froelund, B.; Kristiansen, U.;
Frydenvang, K.; Ebert, B. Eur. J. Pharm. Sci. 1997, 5, 355–384; (d) Krogsgaard-
Larsen, P.; Froelund, B.; Joergensen, F. S.; Schousboe, A. J. Med. Chem. 1994, 37,
2489–2505.
2. Ros, F. J. Chem. Res. 2000, 2000, 124–125.
.
2862, 2238, 1743, 1691, 1602, 1584, 1455, 695, 760 cmÀ1 1H NMR (400 MHz;
3. (a) Hayashi, M.; Kawabata, H.; Inoue, K. Carbohydr. Res. 2000, 325, 68–71; (b)
Hayashi, M.; Kawabata, H.; Shimono, S.; Kakehi, A. Tetrahedron Lett. 2000, 41,
2591–2594; (c) Tanaka, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2008, 130,
6072–6073; (d) Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2004,
126, 9928; (e) Mita, T.; Sasaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
2005, 127, 514–515.
4. (a) Dahuron, N.; Langlois, N. Synlett 1996, 51–52; (b) Benedetti, F.; Berti, F.;
Garau, G.; Martinuzzi, I.; Norbedo, S. Eur. J. Org. Chem. 2003, 1973–1982.
5. Gerrits, P. G.; Marcus, J.; Birikaki, L.; vander Gen, A. Tetrahedron: Asymmetry
2001, 12, 971–974.
CDCl3/TMS): d 2.91 (dd, 1H, J = 12.8, 8.4 Hz, b-H), 3.19 (dd, 1H, J = 12.8, 3.5 Hz,
b-H), 4.10 (dd, 1H, J = 8.4, 3.5 Hz,
a-H), 3.68 (s, 3H, COOMe), 7.32-7.94 (m,
5Harom). 13C NMR (100 MHz; CDCl3/TMS): d 14.5, 50.1, 52.2, 116.5, 128.1, 129.1,
130.8, 138.2, 169.8, 198.8. EIMS (m/z): 217 (M+). Anal. Calcd for C12H11NO3: C,
66.35; H, 5.10; N, 6.45. Found C, 65.97; H, 4.80; N, 6.76. Compound 3f:
Yellowish solid, yield 82%, mp 142–144 °C. IR (KBr) mmax 2993, 2851, 2248,
2240, 1697, 1605, 1540, 1343, 853 cmÀ1 1H NMR (400 MHz; CDCl3/TMS): d
.
2.85 (dd, 1H, J = 12.9, 8.5 Hz, b-H), 3.12 (dd, 1H, J = 12.9, 3.5 Hz, b-H), 3.61 (s,
3H, OMe), 4.10 (dd, 1H, J = 8.5, 3.5 Hz, a-H), 7.10 (d, 2H, J = 7.9 Hz, Harom), 7.68
(d, 2H, J = 7.9 Hz, Harom). 13C NMR (100 MHz; CDCl3/TMS): d 11.9, 36.4, 57.6,
115.0, 117.3, 118.2, 129.4, 130.3, 168.0, 198.2. EIMS (m/z): 214 (M+). Anal.
Calcd for C12H10N2O2: C, 67.28; H, 4.71; N, 13.08. Found C, 67.58; H, 4.38; N,
13.40.
6. Utsugi, M.; Kamada, Y.; Miyamoto, H.; Nakada, M. Tetrahedron Lett. 2007, 48,
6868–6872.
7. Nagata, W.; Yoshioka, M.; Murakami, M. J. Am. Chem. Soc. 1972, 94, 4654–4672.
8. (a) Baeza, A.; Najera, C.; Retamosa, M de G.; Sansano, J. M. Synthesis 2005,
2787–2797; (b) He, B.; Li, Y.; Feng, X.; Zhang, G. Synlett 2004, 1776–1778; (c)
Higuchi, K.; Onaka, M.; Izumi, Y. Bull. Chem. Soc. Jpn. 1993, 66, 2016–2032.
9. Iida, H.; Moromizata, T.; Hamana, H.; Matsumoto, K. Tetrahedron Lett. 2007, 48,
2037–2039.
10. (a) Aggarwal, V. K.; Patin, A.; Tisserand, S. Org. Lett. 2005, 7, 2555–2557; (b)
Wasnaire, P.; Wiaux, M.; Touillaux, R.; Markó, I. E. Tetrahedron Lett. 2006, 47,
985–989; (c) Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Tetrahedron Lett. 2005, 46,
5387–5391; (d) Luo, S.; Wang, P. G.; Cheng, J.-P. J. Org. Chem. 2004, 69, 555–
558; (e) Yeo, J. E.; Yang, X.; Kim, H. J.; Koo, S. Chem. Commun. 2004, 236–237; (f)
Racker, R.; Doring, K.; Reiser, O. J. Org. Chem. 2000, 65, 6932–6939; (g) Lee, K.
Y.; Gowrisankar, S.; Kim, N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (h)
Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645.
11. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–892;
(b) Basavaiah, D.; Rao, V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581–1582.
12. (a) Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. Synthesis 2008, 469–473;
(b) Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. Tetrahedron Lett. 2007,
48, 4169–4172. and 7546–7548.
13. (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic Press: San
Diego, 1997; (b) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271–1287.
14. (a) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123–1178; (b) Kitamura,
T.; Fujiwara, Y. Org. Prep. Proced. Int. 1997, 29, 409–458.
15. (a) Wirth, T. Angew. Chem., Int. Ed. 2001, 40, 2812–2814; (b) Ladziata, U.;
Zhdankin, V. V. Arkivoc 2006, ix, 26–58.
16. (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.
17. (a) Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63, 2363–2389;
(b) Bao, W.; Wang, Z. Green Chem. 2006, 8, 1028–1033; (c) Zhao, D.; Wu, M.;
Kou, Y.; Min, E. Catal. Today 2002, 74, 157–189; (d) Dupont, J.; de Souza, R. F.;
Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667–3692; (e) Qiao, K.; Yakoyama, C.
Chem. Lett. 2004, 33, 472–473; (f) Sun, W.; Xia, C.-G.; Wang, H.-W. Tetrahedron
Lett. 2003, 44, 2409–2411; (g) Kamal, A.; Chouhan, G. Tetrahedron Lett. 2005,
26. General procedure for the synthesis of b-cyano cinnamaldehydes 5: A mixture of
BH adduct 1 (1 mmol) and NaNO3 (1 mmol) was stirred in 1 mL of [Hmim]-
HSO4 at 80 °C for 1–2 h. After complete oxidation (monitored by TLC), the
reaction mixture was cooled to rt, TMSCN (1.5 mmol) was added and the
mixture was further stirred at rt for 2–3 h (Table 1). Then, water (10 mL) was
added and the product was extracted with ether (3 Â 10 mL). The combined
ether extracts were dried over MgSO4, filtered, concentrated under reduced
pressure and purified by silica gel column chromatography (hexane/ethyl
acetate 9.3:0.7) to afford the desired product 5. After isolation of the product,
the remaining aqueous layer containing the ionic liquid was washed with ether
(2 Â 10 mL) to remove any organic impurity, then H2SO4 (2.5 mmol) was
added, the mixture was stirred at 80 °C for 1 h, and cooled to about À5 °C in an
ice-salt bath. The precipitated solid was filtered off and the filtrate was dried
under vacuum to afford the IL [Hmim]HSO4 which was used in subsequent
runs. Physical data of representative compounds. Compound 5a: Yellowish
solid, yield 86%, mp 68–69 °C. IR (KBr) mmax 3028, 2856, 2241, 1748, 1720,
1605, 1577, 1455, 1284, 766, 712 cmÀ1 1H NMR (400 MHz; CDCl3/TMS): d 3.72
.
(dd, 1H, J = 4.0, 2.2 Hz, 2-H), 3.86 (s, 3H, COOMe), 4.48 (d, 1H, J = 4.0 Hz, 3-H),
7.13–7.34 (m, 5Harom), 9.58 (s, 1H, J = 2.2 Hz, CHO). 13C NMR (100 MHz; CDCl3/
TMS): d 18.5, 49.9, 57.9, 116.9, 127.7, 127.9, 129.0, 130.5, 171.8, 198.6. EIMS
(m/z): 217 (M+). Anal. Calcd for C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found C,
66.63; H, 5.43; N, 6.13. Compound 5f: Yellowish solid, yield 85%, mp 104–
106 °C. IR (KBr) mmax 2998, 2851, 2240, 1730, 1607, 1579, 1386, 847 cmÀ1 1H
.
NMR (400 MHz; CDCl3/TMS): d 3.70 (dd, 1H, J = 4.0, 2.2 Hz, 2-H), 3.71 (s, 3H,
OMe), 4.45 (d, 1H, J = 4.0 Hz, 3-H), 6.89 (d, 2H, J = 7.8 Hz, Harom), 7.3 (d, 2H,
J = 7.8 Hz, Harom), 9.54 (d, 1H, J = 2.2 Hz, CHO). 13C NMR (100 MHz; CDCl3/TMS):
d 22.1, 42.8, 56.2, 112.6, 117.1, 118.1, 124.0, 131.1, 162.5, 198.7. EIMS (m/z):
214 (M+). Anal. Calcd for C12H10N2O2: C, 67.28; H, 4.71; N, 13.08. Found C,
66.98; H, 5.09; N, 12.74.
27. Masamune, S.; Ali, S. K. A.; Snitman, D. L.; Garvey, D. S. Angew. Chem., Int. Ed.
Engl. 1980, 19, 557–558.