N-heterocyclic carbene catalyzed cross coupling of aromatic aldehydes with Baylis-Hillman bromides: An easy access to α-arylidene-γ-keto esters

Article abstract of DOI:10.1055/s-0030-1258586

N-Heterocyclic carbene catalyzed carbonyl umpolung reaction of aldehydes with Baylis-Hillman (BH) bromides as activated halides were realized for the first time. This intermolecular cross-coupling reaction features the easily available catalyst and mild reaction conditions to provide α-arylidene- γ-keto esters in excellent yields for a wide range of substrates. Thus, the present work opens up a new aspect of the synthetic utility of BH adducts via the reactivity umpolung of aldehydes. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1258586

LETTER
2649
N-Heterocyclic Carbene Catalyzed Cross Coupling of Aromatic Aldehydes
with Baylis–Hillman Bromides: An Easy Access to a-Arylidene-g-keto Esters
N
a
HC-Catalyze
a
d Synthesis
n
of
a
-Arylid
k
ene-
g
-keto
E
a
sters j Singh,a Santosh Singh,a Vijai K. Rai,a,b Lal Dhar S. Yadav*a
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Fax +91(532)2460533; E-mail: ldsyadav@hotmail.com
b
School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu & Kashmir 182 320, India
Received 25 July 2010
BH bromides under basic conditions and the development
of an efficient method to obtain a-arylidene-g-keto esters.
BH bromides are activated allylic halides which are dis-
tinct from benzyl halides in structure and reactivity. Thus,
Abstract: N-Heterocyclic carbene catalyzed carbonyl umpolung
reaction of aldehydes with Baylis–Hillman (BH) bromides as acti-
vated halides were realized for the first time. This intermolecular
cross-coupling reaction features the easily available catalyst and
mild reaction conditions to provide a-arylidene- g-keto esters in ex- it was unclear at the outset whether the NHC-catalyzed
cellent yields for a wide range of substrates. Thus, the present work
opens up a new aspect of the synthetic utility of BH adducts via the
reactivity umpolung of aldehydes.
cross-coupling of aldehydes with BH bromides would be
effective and whether it would follow the SN2 or SN2¢
pathway. Literature survey reveals that there are some re-
Key words: N-heterocyclic carbenes, umpolung, acyl anion,
Baylis–Hillman bromides, a-arylidene- g-keto esters
ports on the nucleophilic substitution reactions (SN2) of
certain carbon,17 oxygen,18 nitrogen,18b,19a and sulfur18b,19b
nucleophiles with BH bromides. However, nucleophilic
substitution reaction of BH halides with carbon nucleo-
philes, such as acyl anions, has not been studied so far.
The generation of acyl anion by N-heterocyclic carbene
(NHC), that is, reactivity umpolung is a crucial enterprise
due to the broad utility of this concept in organic synthe-
sis.1,2 This approach generally includes the reaction of
Breslow intermediate (Scheme 1) with various electro-
philic reagents such as aromatic aldehydes, namely, ben-
zoin reaction,3 and Michael acceptors, namely, Stetter
reaction.4 Recently, several electrophilic reagents such as
ketones,5 enolethers,6a epoxides,6b aziridines,7 nitroal-
kenes,8 and imines9 have been used as good acceptors for
the acyl anion during the umpolung reaction.
a-Arylidene-g-keto esters, products of the present reac-
tion, are important precursors for biologically and phar-
maceutically relevant g-butyrolactones,20 pyrroles,21
furans,22 and cyclopentadienones,23 thus, a variety of ap-
proaches have been developed for their synthesis,24 but a
general and practical methodology is still needed for
chemists to construct a-arylidene-g-keto ester skeleton
from simple and readily available starting materials. To
date, BH bromides have not been utilized for the synthesis
of a-arylidene-g-keto esters via cross-coupling reaction.
In view of applicability of the reaction, our initial efforts
were focused on the systematic examination of different
readily available NHC-precursors 3a–f to optimize the re-
action conditions. We set up a series of experiments to
check the performance of the reaction using benzaldehyde
(1a) and (Z)–2-(bromomethyl)-3-phenylprop-2-enoate
(2a) as model substrates. It was found that the reaction at
room temperature gives satisfactory yield of product 4a
(Table 1).
In recent years, Morita–Baylis–Hillman chemistry has be-
come one of the best methods to provide highly function-
alized molecules and has been widely employed for the
synthesis of various biologically active molecules and
natural products.10 Allylic structure present in Baylis–
Hillman (BH) alcohols can be further utilized by convert-
ing the hydroxyl group into a suitable leaving group like
acetate or bromide (Scheme 1) as nucleophilic acceptors
in many useful synthetic transformations.11 In many cases
the bromo group present at allylic position of BH
bromides12 directs the attack of nucleophile.11
Ph
O
O
OH
To date, only a few reports described the NHC-catalyzed
carbon–carbon bond-formation reaction using activated
halides such as p-nitrofluorobenzene13 and heteroaryl
chloride.14 Very recently, Lin et al.15 reported efficient
NHC-mediated cross-coupling of aromatic aldehydes
with benzyl halides. As intrigued by their findings and our
continuous interest in Baylis–Hillman chemistry,16 we en-
visioned the cross-coupling of Breslow intermediate with
N
N
OH
HBr, H2SO4
R2
OMe
R2
OMe
CH2Cl2
ref. 12a,b
Ph
Br
Baylis–Hillman alcohol
Baylis–Hillman bromide
Ph
Scheme 1 Baylis–Hillman bromide and Breslow intermediate
Among the tested precatalysts, 3c was found to be most
efficient for the present umpolung reaction and afforded
70% yield of the desired product 4a (Table 1, entry 3).
When the amount of the precatalyst 3c was decreased
from 25 mol% to 20 mol% relative to substrate 1a, the
SYNLETT 2010, No. 17, pp 2649–2653
x
x
.x
x
.2
0
1
0
Advanced online publication: 23.09.2010
DOI: 10.1055/s-0030-1258586; Art ID: G23110ST
© Georg Thieme Verlag Stuttgart · New York

2650
P. Singh et al.
LETTER
yield of the product 4a significantly reduced (Table 1, en- Both electron-withdrawing and electron-donating substit-
try 7), but the use of 30 mol% of 3c did not affect the yield uents on the aromatic rings of aldehydes 1 and BH bro-
(Table 1, entry 8). Optimization of solvents for the cross- mides 2 are tolerated to afford the corresponding product
coupling of 1a with 2a was also undertaken, and it was 4 in good to excellent yields (65–85%). However, under
found that among the tested solvents, THF was the best the present basic conditions aliphatic aldehydes did not
while others gave diminished yields (Table 1, entries 12 give appreciable amount of the desired product 4 probably
and 13). DBU was found to be the best base among the due to side reaction such as aldol reaction. The requisite
bases tested (Table 1, entries 3, 9–11).
BH bromides 2 were prepared employing the known
method.12a,b
Table 1 Optimization of Intermolecular Aldehyde–BH Bromide
Cross-Couplinga
Table 2 Synthesis of a-Arylidene-g-keto Esters 4 by Cross-
Coupling of Aldehydes 1 with BH Bromides 2a
O
O
O
O
3 (25 mol%)
Ph
OMe
Ph
Ph
OMe
PhCHO
+
R2
OMe
R2
OMe
R1
base (25 mol%)
solvent, r.t., N2
3c (25 mol%)
R1CHO
1a
2a
+
4a
Br
DBU (25 mol%)
THF, r.t., N2
O
Br
1
2
4
Ph
O
Ph
Mes
N
N
N
Entry R1
R2
Time
Product Yield
N
Cl–
–
Cl–
ClO4
(h)b
16
16
18
16
18
14
14
18
14
14
14
18
18
12
4
(%)c,d
70
72
65
75
70
73
75
70
85
74
75
77
72
85
N+
N+
N+
Ph
Ph
Mes
3a
Ph
1
2
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
3c
3b
4-ClC6H4
4-MeC6H4
4-MeOC6H4
3-MeC6H4
Ph
Et
Bn
Me
N
N+
N+
S
3
Cl–
Br–
Cl–
N+
S
4
Me
3d
3f
3e
5
Entry Precatalyst Solvent
(mol%)
Base
Time
(h)b
Yield 4a
6
4-ClC6H4
(%)c
7
4-ClC6H4
4-MeC6H4
4-MeOC6H4
Ph
4-ClC6H4
4g
4h
4i
1
2
3a (25)
3b (25)
3c (25)
3d (25)
3e (25)
3f (25)
3c (20)
3c (30)
3c (25)
3c (25)
3c (25)
3c (25)
3c (25)
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
MeCN
CH2Cl2
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DABCO
Et3N
48
48
16
48
48
48
16
16
48
36
30
48
48
0
0
8
4-ClC6H4
9
4-ClC6H4
3
70
25
0
10
11
12
13
14
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4j
4
4-ClC6H4
4-MeC6H4
2-ClC6H4
4-MeOC6H4
4k
4l
5
6
0
4m
4n
7
55
70
10
20
40
26
35
8
a Reaction conditions: 1/2/DBU = 1:1:0.25 mmol, in THF (5 mL) at
25 °C. For experimental procedure, see ref. 25.
b Stirring time at r.t.
9
10
11
12
13
c Yield of isolated and purified products.
d All compounds gave C and H analyses within 0.38% and satisfac-
tory spectral (IR, 1H NMR, 13C NMR- and EI-MS) data.
Cs2CO3
DBU
DBU
On the basis of the above results, a tentative mechanism is
depicted in Scheme 2. Carbene I is generated by deproto-
nation of benzimidazolium salt 3c in the presence of
DBU. Carbene I reacts with aldehyde 1 to give the
Breslow intermediate III which undergoes SN2 reaction at
the bromine-bearing sp3 carbon atom of BH bromide 2 in
the SN2 fashion. The intermediate V thus formed affords
product 4 and regenerates carbene I to complete the cata-
lytic cycle (Scheme 2). The formation of SN2¢ reaction
product through IV could not be observed at all under the
present conditions. The absence of rearranged products
a For experimental procedure, see ref. 25.
b Stirring time at r.t.
c Yield of isolated and purified product 4a.
With these optimized conditions (25 mol% of 3c, 25
mol% of DBU, in THF at r.t. under positive pressure of ni-
trogen),25 a variety of aromatic aldehydes and Baylis–
Hillman bromides have been explored to examine the gen-
erality of the reaction. The results are listed in Table 2.
Synlett 2010, No. 17, 2649–2653 © Thieme Stuttgart · New York

LETTER
NHC-Catalyzed Synthesis of a-Arylidene-g-keto Esters
2651
Ph
N+
O–
R1CHO
1
R1
H
N
Ph
II
Ph
Ph
OH
N
N
R1
N
I
N
Ph
Ph III
Br
4
MeO
Ph
O–
O
R2
SN2
N+
N
Ph
N+
Ph
N+
2
SN2'
R1
R2
OH
R1
OH
R1
MeO
MeO
O
N
Ph
MeO
O
R2
N
VI
O
R2
IV
Ph
Ph
V
Scheme 2 Tentative mechanism for the formation of 4
(2) For recent examples on NHC as umpolung catalysts, see:
(a) Phillips, E. M.; Wadamoto, M.; Chan, A.; Scheidt, K. A.
Angew. Chem. Int. Ed. 2007, 46, 3107. (b) Bode, J. W.;
Sohn, S. S. J. Am. Chem. Soc. 2007, 129, 13798.
via IV is probably because the Breslow intermediate III
does not attack the b-position due to steric effects as well
as a stronger stabilization of the double bond by an exten-
sive conjugation through the ester group and the aromatic
ring. This is in conformity with the earlier observations
where BH halides undergo SN2 reaction with carbon, ni-
trogen, sulfur, and oxygen nucleophiles.17–19
(c) Phillips, E. M.; Reynolds, T. E.; Scheidt, K. A. J. Am.
Chem. Soc. 2008, 130, 2416. (d) Seayad, J.; Patra, P. K.;
Zhang, Y.-G.; Ying, J. Y. Org. Lett. 2008, 10, 953.
(e) Wong, F. T.; Patra, P. K.; Seayad, J.; Zhang, Y.; Ying, J.
Y. Org. Lett. 2008, 10, 2333. (f) He, M.; Bode, J. W. J. Am.
Chem. Soc. 2008, 130, 418. (g) Rommel, M.; Fukuzumi, T.;
Bode, J. W. J. Am. Chem. Soc. 2008, 130, 17266. (h) He,
M.; Beahm, B. J.; Bode, J. W. Org. Lett. 2008, 10, 3817.
(i) Maki, B. E.; Scheidt, K. A. Org. Lett. 2008, 10, 4313.
(j) Chan, A.; Scheidt, K. A. J. Am. Chem. Soc. 2008, 130,
2740.
In summary, we have developed for the first time an effi-
cient NHC-catalyzed intermolecular cross-coupling of ar-
omatic aldehydes with Baylis–Hillman bromides to
provide a facile access to synthetically and pharmaceuti-
cally relevant a-arylidene-g-keto esters.
The reaction features the easily available catalyst and mild
reaction conditions. The present work opens up a new as-
pect of the synthetic utility of Baylis–Hillman adducts via
the reactivity umpolung of aldehydes.
(3) (a) Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719.
(b) Sheehan, J.; Hunneman, D. H. J. Am. Chem. Soc. 1966,
88, 3666. (c) Enders, D.; Breuer, K.; Teles, J. H. Synth.
Commun. 1999, 29, 1. (d) Enders, D.; Kallfass, U. Angew.
Chem. Int. Ed. 2002, 41, 1743. (e) Enders, D.; Han, J.
Tetrahedron 2008, 64, 1637. (f) Ma, Y.-J.; Wei, S.-P.; Wu,
J.; Yang, F.; Liu, B.; Lan, J.-B.; Yang, S.-Y.; You, J.-S. Adv.
Synth. Catal. 2008, 350, 2645. (g) Zhao, H.; Foss, F. W. Jr.;
Breslow, R. J. Am. Chem. Soc. 2008, 130, 12590.
(4) (a) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. Helv.
Chim. Acta 1996, 79, 1899. (b) Kerr, M. S.; Read de Alaniz,
J.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298. (c) Kerr,
M. S.; Rovis, T. Synlett 2003, 1934. (d) Kerr, M. S.; Rovis,
T. J. Am. Chem. Soc. 2004, 126, 8876. (e) Read de Alaniz,
J.; Rovis, T. J. Am. Chem. Soc. 2005, 127, 6284. (f)Enders,
D.; Han, J.; Henseler, A. Chem. Commun. 2008, 3989.
(g) Liu, Q.; Perreault, S.; Rovis, T. J. Am. Chem. Soc. 2008,
130, 14066. (h) Alaniz, J. R.; Kerr, M. S.; Moore, J. L.;
Rovis, T. J. Org. Chem. 2008, 130, 2033. (i) Cullen, S. C.;
Rovis, T. Org. Lett. 2008, 10, 3141. (j) Orellana, A.; Rovis,
T. Chem. Commun. 2008, 730. (k) Enders, D.; Han, J.
Synthesis 2008, 3864. (l) Hirano, K.; Biju, A. T.; Piel, I.;
Glorius, F. J. Am. Chem. Soc. 2009, 131, 14190. (m) Biju,
A. T.; Wurz, N. E.; Glorius, F. J. Am. Chem. Soc. 2010, 132,
5970.
Acknowledgment
We sincerely thank SAIF, Punjab University, Chandigarh, for pro-
viding microanalyses and spectra. P.S. thanks UGC, New Delhi and
S.S. thanks CSIR, New Delhi, for the award of a JRF and SRF, re-
spectively.
References and Notes
(1) For reviews, see: (a) Seebach, D. Angew. Chem., Int. Ed.
Engl. 1979, 18, 239. (b) Grasa, G. A.; Singh, R.; Nolan, S. P.
Synthesis 2004, 971. (c) Dalko, P. I.; Moisan, L. Angew.
Chem. Int. Ed. 2004, 43, 5138. (d) Vijay, N.; Santhamma,
B.; Vellalath, S. Angew. Chem. Int. Ed. 2004, 43, 5130.
(e) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719.
(f) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007,
107, 5606. (g) Marion, N.; Díez-González, S.; Nolan, S. P.
Angew. Chem. Int. Ed. 2007, 46, 2988. (h) Nair, V.;
Vellalath, S.; Babu, B. P. Chem. Soc. Rev. 2008, 37, 2691.
Synlett 2010, No. 17, 2649–2653 © Thieme Stuttgart · New York

2652
P. Singh et al.
LETTER
(5) (a) Hachisu, Y.; Bode, J. W.; Suzuki, K. J. Am. Chem. Soc.
2003, 125, 8432. (b) Burstein, C.; Glorius, F. Angew. Chem.
Int. Ed. 2004, 43, 6205. (c) Enders, D.; Niemeier, O.;
Balensiefer, T. Angew. Chem. Int. Ed. 2006, 45, 1463.
(d) Burstein, C.; Tschan, S.; Xie, X.; Glorius, F. Synthesis
2006, 2418. (e) Takikawa, H.; Hachisu, Y.; Bode, J. W.;
Suzuki, K. Angew. Chem. Int. Ed. 2006, 45, 3492. (f) Li,
Y.; Feng, Z.; You, S.-L. Chem. Commun. 2008, 226.
(g) Hirano, K.; Piel, I.; Glorius, F. Adv. Synth. Catal. 2008,
350, 984.
(6) (a) He, J.; Tang, S.; Liu, J.; Su, Y.; Pan, X.; She, X.
Tetrahedron 2008, 64, 8797. (b) Yadav, L. D. S.; Singh, S.;
Rai, V. K. Synlett 2010, 240.
(7) (a) Liu, Y.-K.; Li, R.; Yue, L.; Li, B.-J.; Chen, Y.-C.; Wu,
Y.; Ding, L.-S. Org. Lett. 2006, 8, 1521. (b) Yadav, L. D.
S.; Rai, V. K.; Singh, S.; Singh, P. Tetrahedron Lett. 2010,
51, 1657.
Tetrahedron Lett. 2009, 50, 1423. (h) Yadav, L. D. S.; Patel,
R.; Srivastava, V. P. Tetrahedron Lett. 2009, 50, 1335.
(i) Yadav, L. D. S.; Patel, R.; Srivastava, V. P. Synlett 2010,
1047.
(17) (a) Ameer, F.; Drewes, S. E.; Emslie, N. D.; Kaye, P. T.;
Mann, R. L. J. Chem. Soc., Perkin Trans. 1 1983, 2293.
(b) Ameer, F.; Drewes, S. E.; Houstan-Mcmillan, M. S.;
Kaye, P. T. J. Chem. Soc., Perkin Trans. 1 1985, 1143.
(c) Gowrisankar, S.; Kim, K. H.; Kim, S. H.; Kim, J. N.
Tetrahedron Lett. 2008, 49, 6241. (d) Kim, S. H.; Lee, S.
H.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2009, 50,
1696. (e) Kim, J. M.; Kim, S. H.; Lee, S. H.; Kim, J. N.
Tetrahedron Lett. 2009, 50, 1734. (f) Kim, K. H.; Kim,
E. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 5322.
(18) (a) Basavaiah, D.; Bakthadoss, M.; Pandiaraju, S. Chem.
Commun. 1998, 1640. (b) Kotti, S. R. S. S.; Xu, X.; Li, G.;
Headley, A. D. Tetrahedron Lett. 2004, 45, 1427.
(c) Bakthadoss, M.; Sivakumar, N.; Sivakumar, G.;
Murugan, G. Tetrahedron Lett. 2008, 49, 820.
(8) Mattson, A. E.; Zuhl, A. M.; Reynolds, T. E.; Scheidt, K. A.
J. Am. Chem. Soc. 2006, 128, 4932.
(9) (a) Murry, J. A.; Franz, D. E.; Soheil, A.; Tillyer, R. E.;
Grabowski, J. J.; Reider, P. J. J. Am. Chem. Soc. 2001, 123,
9696. (b) Mennen, S. M.; Gipson, J. D.; Kim, Y. R.; Miller,
S. J. J. Am. Chem. Soc. 2005, 127, 1654. (c) Li, G.-Q.; Dai,
L.-X.; You, S.-L. Chem. Commun. 2007, 852.
(19) (a) Sa, M. M.; Ramos, D. M.; Fernandes, L. Tetrahedron
2006, 62, 11652. (b) Sa, M. M.; Fernandes, L.; Ferreira, M.;
Bortoluzzi, A. J. Tetrahedron Lett. 2008, 49, 1228.
(20) (a) Ballini, R.; Bosica, G. Synlett 1996, 1115.
(b) Choudhury, P. K.; Foubelo, F.; Yus, M. Tetrahedron
Lett. 1998, 39, 3581. (c) Ballini, R.; Marcantoni, E.; Perella,
S. J. Org. Chem. 1999, 64, 2954. (d) Reddy, G. S.;
Neelakantan, P.; Iyengary, D. S. Synth. Commun. 2002, 32,
2601. (e) Ramachandran, P. V.; Garner, G.; Pratihar, D. Org.
Lett. 2007, 9, 4753. (f) Paira, M.; Banerjee, B.; Jana, S.;
Mandal, S. K.; Roy, S. C. Tetrahedron Lett. 2007, 48, 3205.
(21) Ballini, R.; Bosica, G.; Fiorini, D.; Giarlo, G. Synthesis
2001, 2003.
(22) Ballini, R.; Barboni, L.; Bosica, G.; Petrini, M. Synlett 2000,
391.
(23) Ballini, R.; Bosica, G.; Fiorini, D.; Gil, M. V.; Petrini, M.
Org. Lett. 2001, 3, 1265.
(24) (a) Ballini, R.; Fiorini, D.; Palmieri, A. Tetrahedron Lett.
2005, 46, 1245. (b) Ballini, R.; Barboni, L.; Bosica, G.;
Fiorini, D.; Palmieri, A. Pure Appl. Chem. 2006, 78, 1857.
(c) Ballini, R.; Palmieri, A.; Righi, P. Tetrahedron 2007, 63,
12099.
(10) (a) Drewes, S. E.; Emslie, N. D. J. Chem. Soc., Perkin Trans.
1 1982, 2079. (b) Roush, W. R.; Brown, B. B. J. Org. Chem.
1993, 58, 2151. (c) Jenn, T.; Heissler, D. Tetrahedron 1998,
54, 97. (d) Basavaiah, D.; Rao, A. J.; Satyanarayana, T.
Chem. Rev. 2003, 103, 811. (e) Yeo, J. E.; Yang, X.; Kim,
H. J.; Koo, S. Chem. Commun. 2004, 236. (f) Luo, S.;
Wang, P. G.; Cheng, J.-P. J. Org. Chem. 2004, 69, 555.
(g) Aggarwal, V. K.; Patin, A.; Tisserand, S. Org. Lett. 2005,
7, 2555. (h) Lee, K. Y.; Gowrisankar, S.; Kim, J. N.
Tetrahedron Lett. 2005, 46, 5387. (i) Wasnaire, P.; Wiaux,
M.; Touillaux, R.; Markó, I. E. Tetrahedron Lett. 2006, 47,
985. (j) Basavaiah, D.; Rao, K. V.; Reddy, R. J. Chem. Soc.
Rev. 2007, 36, 1581. (k) Shi, Y.-L.; Shi, M. Eur. J. Org.
Chem. 2007, 2905. (l) Masson, G.; Housseman, C.; Zhu, J.
Angew. Chem. Int. Ed. 2007, 46, 4614. (m) Singh, V.;
Yadav, G. P.; Maulik, P. R.; Batra, S. Tetrahedron 2008, 64,
2979.
(11) (a) Ribière, P.; Declerck, V.; Nédellec, Y.; Yadav-
Bhatnagar, N.; Martinez, J.; Lamaty, F. Tetrahedron 2006,
62, 10456. (b) Gowrisankar, S.; Kim, S. J.; Lee, J.-E.; Kim,
J. N. Tetrahedron Lett. 2007, 48, 4419. (c) Lee, K. Y.; Lee,
H. S.; Kim, J. N. Tetrahedron Lett. 2007, 48, 2007.
(d) Nag, S.; Yadav, G. P.; Maulik, P. R.; Batra, S. Synthesis
2007, 911. (e) Pathak, R.; Batra, S. Tetrahedron 2007, 63,
9448.
(12) (a) Buchholz, R.; Hoffmann, H. M. R. Helv. Chim. Acta
1991, 74, 1213. (b) Basavaiah, D.; Hyma, R. S.; Padmaja,
K.; Krishnamacharyulu, M. Tetrahedron 1999, 55, 6971.
(13) (a) Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita,
A. Chem. Commun. 2003, 1314. (b) Suzuki, Y.; Toyota, T.;
Miyashita, A.; Sato, M. Chem. Pharm. Bull. 2006, 54, 1653.
(14) Miyashita, A.; Matsuda, H.; Iijima, C.; Higashino, T. Chem.
Pharm. Bull. 1990, 38, 1147.
(25) General Procedure for the Synthesis of a-Arylidene-g-
keto Esters 4
A flame-dried round-bottom flask was charged with
benzimidazolium salt 3c (0.25 mmol), aldehyde 1 (1.0
mmol), and THF (5 mL) under positive pressure of nitrogen
followed by addition of DBU (0.25 mmol) with a syringe.
After stirring for 10 min at r.t., BH bromide 2 (1.0 mmol)
was added. The reaction mixture was stirred at r.t. for 12–18
h (Table 2). After completion of the reaction (the
disappearance of 2, monitored by TLC), the reaction mixture
was concentrated under reduce pressure. The residue was
purified by flash column chromatography using hexane–
EtOAc as eluent to afford product 4 in 65–85% yield.
Characterization Data of Representative Compounds 4
Compound 4a: IR (film) : nmax = 1714, 1642 cm–1. 1H NMR
(400 MHz, CDCl3): d = 3.84 (s, 3 H, OMe), 5.20 (s, 2 H,
CH2), 7.57–7.25 (m, 8 Harom, Ph), 7.88–7.80 (m, 2 Harom, Ph),
8.02 (s, 1 H, C = CH). 13C NMR (100 MHz, CDCl3/TMS):
d = 40.6, 52.5, 126.1, 127.2, 128.1, 128.9, 129.7, 130.6,
133.4, 135.6, 137.2, 138.5, 166.5, 193.4. MS (EI): m/z = 280
[M+]. Anal. Calcd for C18H16O3: C, 77.12; H, 5.75. Found:
77.44; H, 5.96.
(15) Lin, L.; Li, Y.; Du, W.; Deng, W. P. Tetrahedron Lett. 2010,
51, 3571.
(16) (a) Yadav, L. D. S.; Srivastava, V. P.; Patel, R. Tetrahedron
Lett. 2008, 49, 3142. (b) Yadav, L. D. S.; Srivastava, V. P.;
Patel, R. Tetrahedron Lett. 2008, 49, 5652. (c) Yadav, L. D.
S.; Patel, R.; Srivastava, V. P. Synlett 2008, 1789.
(d) Yadav, L. D. S.; Awasthi, C. Tetrahedron Lett. 2009, 50,
3801. (e) Yadav, L. D. S.; Rai, V. K. Tetrahedron Lett. 2009,
50, 2414. (f) Yadav, L. D. S.; Rai, V. K.; Singh, S. Synlett
2009, 1423. (g) Yadav, L. D. S.; Srivastava, V. P.; Patel, R.
Compound 4c: IR (film): nmax = 1712, 1640 cm–1. 1H NMR
(400 MHz, CDCl3): d = 2.30 (s, 3 H, Me), 3.86 (s, 3 H,
OMe), 5.14 (s, 2 H, CH2), 7.50–7.19 (m, 5 Harom, Ph), 7.90–
7.77 (m, 4 Harom, 4-MePh), 7.96 (s, 1 H, C = CH). 13C NMR
Synlett 2010, No. 17, 2649–2653 © Thieme Stuttgart · New York

LETTER
(100 MHz, CDCl3/TMS): d = 25.4, 41.5, 53.1, 126.2, 127.1,
NHC-Catalyzed Synthesis of a-Arylidene-g-keto Esters
2653
191.2. MS (EI): m/z = 310 [M+]. Anal. Calcd for C19H18O4:
C, 73.52; H, 5.85. Found: C, 73.18; H, 5.50.
127.9, 128.7, 129.4, 130.2, 134.34, 135.41, 138.2, 143.3,
167.3, 193.2.MS (EI): m/z = 294 [M+]. Anal. Calcd for
C19H18O3: C, 77.53; H, 6.16. Found: C, 77.86; H, 6.54.
Compound 4d: IR (film): nmax = 1709, 1638 cm–1. 1H NMR
(400 MHz, CDCl3): d = 3.80 (s, 3 H, OMe), 3.84 (s, 3 H,
OMe), 5.20 (s, 2 H, CH2), 7.55–7.22 (m, 5 Harom, Ph),
Compound 4k: IR (film): nmax = 1711, 1636 cm–1. 1H NMR
(400 MHz, CDCl3): d = 3.80 (s, 3 H, OMe), 3.83 (s, 3 H,
OMe), 5.15 (s, 2 H, CH2), 7.32–7.22 (m, 4 Harom, 4-ClPh),
7.37–7.30 (m, 2 Harom, 4-MeOPh), 7.85–7.80 (m, 2 Harom
4-MeOPh), 7.98 (s, 1 H, C = CH). 13C NMR (100 MHz,
CDCl3/TMS): d = 47.3, 52.4, 55.1, 113.8, 127.5, 128.3,
129.1, 129.9, 130.6, 133.1, 134.1, 137.9, 165.9, 167.6,
192.2. MS (EI): m/z = 344 [M+]. Anal. Calcd for
,
7.38–7.28 (m, 2 Harom, 4-MeOPh), 7.86–7.82 (m, 2 Harom
4-MeOPh), 7.98 (s, 1 H, C = CH). 13C NMR (100 MHz,
CDCl3/TMS): d = 40.3, 52.8, 55.1, 114.2, 126.5, 127.5,
128.1, 129.1, 129.8, 130.7, 134.9, 137.6, 165.8, 167.3,
,
C19H17ClO4: C, 66.19; H, 4.97. Found: C, 66.50; H, 4.79.
Synlett 2010, No. 17, 2649–2653 © Thieme Stuttgart · New York

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