Effects of substituents in the β-position of 1,3-dicarbonyl compounds in bromodimethylsulfonium bromide-catalyzed multicomponent reactions: A facile access to functionalized piperidines

Article abstract of DOI:10.1021/jo8014962

(Chemical Equation Presented) 1,3-Dicarbonyl compounds can be converted to Mannich-type products A or highly functionalized piperidines B in the presence of a catalytic amount of bromodimethylsulfonium bromide (BDMS). The combination of aromatic aldehyde, amine, and 1,3-dicarbonyl compounds in the presence of a catalytic amount of BDMS leads to the formation of Mannich-type product A when R is a non-enolizable carbon or an alkoxy group, whereas in cases when R = CH₃, the same combination yielded highly functionalized piperidines B. A synthetic study and mechanistic proposal are presented.

Full text of DOI:10.1021/jo8014962

Effects of Substituents in the ꢀ-Position of 1,3-Dicarbonyl
Compounds in Bromodimethylsulfonium Bromide-Catalyzed
Multicomponent Reactions: A Facile Access to Functionalized
Piperidines
Abu T. Khan,*,† Tasneem Parvin,† and Lokman H. Choudhury‡
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India, and
Department of Basic Sciences & Social Sciences, North-Eastern Hill UniVersity, Shillong 793 022, India
atk@iitg.ernet.in
ReceiVed July 11, 2008
1,3-Dicarbonyl compounds can be converted to Mannich-type products A or highly functionalized
piperidines B in the presence of a catalytic amount of bromodimethylsulfonium bromide (BDMS). The
combination of aromatic aldehyde, amine, and 1,3-dicarbonyl compounds in the presence of a catalytic
amount of BDMS leads to the formation of Mannich-type product A when R is a non-enolizable carbon
or an alkoxy group, whereas in cases when R ) CH3, the same combination yielded highly functionalized
piperidines B. A synthetic study and mechanistic proposal are presented.
Introduction
nomic as they avoid time-consuming and costly purification
processes, as well as protection-deprotection steps.3 The
synthesis of heterocycles with use of multicomponent reactions
often involves classical carbonyl condensation chemistry.
Among carbonyl compounds, 1,3-dicarbonyl derivatives con-
stitute important synthetic intermediates, incorporating multiple
functionalities that can be involved either as nucleophilic or
electrophilic species in a variety of synthetic transformations.4
The high synthetic potential of these easily accessible reagents
has found numerous applications, especially for the synthesis
of complex heterocyclic structures.5
Multicomponent reactions (MCRs) involving domino pro-
cesses, with at least three different substrates reacting in a well-
defined manner to form a single compound, have emerged as a
powerful tool in organic synthesis.1 In recent years MCRs have
received considerable attention from the organic community due
to their advantages over conventional multistep synthesis.2 These
reactions constitute an especially attractive synthetic strategy
since they provide easy and rapid access to large libraries of
organic compounds with diverse substitution patterns. In addi-
tion, MCRs are more environmentally benign and atom eco-
† Indian Institute of Technology Guwahati.
(3) (a) Trost, B. M. Angew. Chem., Int. Ed. 1995, 34, 259–281. (b) Wender,
P. A.; Handy, S. T.; Wright, D. L. Chem. Ind. 1997, 765–769.
(4) For some representative reviews, see:(a) Benetti, S.; Romagnoli, R.; De
Risi, C.; Spalluto, G.; Zanirato, V. Chem. ReV. 1995, 95, 1065–1114. (b) Langer,
P. Chem. Eur. J. 2001, 7, 3858–3866. (c) Langer, P. Synthesis 2002, 441–459.
(d) Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J. Org. Chem. 2004, 4957–
4980.
(5) (a) Lie´by-Muller, F.; Simon, C.; Constantieux, T.; Rodriguez, J. QSAR
Comb. Sci. 2006, 25, 432–438. (b) Sharma, G. V. M.; Reddy, K. L.; Lakshmi,
P. S.; Krishna, P. R. Synthesis 2006, 55–58. (c) Wang, L.-M.; Sheng, J.; Zhang,
L.; Han, J.-W.; Fan, Z.-Y.; Tian, H.; Qian, C.-T. Tetrahedron 2005, 61, 1539–
1543.
‡ North-Eastern Hill University.
(1) (a) Zhu, J.; Bienayme´, H. Multicomponent Reactions, 1st ed.; Wiley-
VCH: Weinheim, Germany, 2005. (b) Tempest, P. A. Curr. Opin. Drug
DiscoVery 2005, 8, 776–788. (c) Fujioka, H.; Murai, K.; Kubo, O.; Ohba, Y.;
Kita, Y. Org. Lett. 2007, 9, 1687–1690. (d) Evdokimov, N. M.; Kireev, A. S.;
Yakovenko, A. A.; Antipin, M. Y.; Magedov, I. V.; Kornienko, A. J. Org. Chem.
2007, 72, 3443–3453.
(2) For recent reviews see:(a) Do¨mling, A. Chem. ReV. 2006, 106, 17–89.
(b) Ramo´n, D. J.; Yus, M. Angew Chem., Int. Ed. 2005, 117, 1628–1661. (c)
Zhu, J. Eur. J. Org. Chem. 2003, 1133–1144. (d) Do¨mling, A.; Ugi, I. Angew.
Chem., Int. Ed. 2000, 39, 3168–3210.
8398 J. Org. Chem. 2008, 73, 8398–8402
10.1021/jo8014962 CCC: $40.75 2008 American Chemical Society
Published on Web 10/08/2008

A Facile Access to Functionalized Piperidines
SCHEME 1. Preferential Formation of Functionalized Piperidines 1b over the Mannich-Type Product 2b
TABLE 1. Results for the Reaction of Benzaldehyde, Aniline, and
Different 1,3-Dicarbonyl Compounds in the Presence of a Catalytic
Amount of BDMSa
Bromodimethylsulfonium bromide (BDMS) has proven to be
a very useful reagent in organic synthesis.6 Due to its versatile
activity both as a brominating agent6b,7 and as a catalyst, it has
recently been used in a wide variety of synthetic transforma-
tions.8 As part of our ongoing research program to develop new
methodologies, we have been engaged in an exploration of the
virtues of BDMS for organic synthesis,9 and envisaged that
BDMS might act as an efficient catalyst for a diverse range of
multicomponent reactions. Herein we report interesting MCRs
of 1,3-dicarbonyl compounds that lead to different products,
depending upon the substituent in the ꢀ-position.
Results and Discussion
Bromodimethylsulfonium bromide was prepared from di-
methyl sulfide and molecular bromine by using the reported
procedure.6e In our initial study to assess the utility of
bromodimethylsulfonium bromide in multicomponent reactions,
a mixture of 4-methylbenzaldehyde (2 mmol), aniline (2 mmol),
and methyl acetoacetate (2 mmol) in acetonitrile (5 mL) was
stirred in the presence of 10 mol % of BDMS. At the outset we
were expecting a Mannich-type reaction leading to product 2b.
Interestingly, instead we isolated a highly functionalized pip-
eridine 1b in a moderate yield of 39% (Scheme 1).
It is noteworthy that we have recently reported a three-
component reaction involving aromatic aldehyde, aniline, and
enolizable carbonyl compounds for the synthesis of correspond-
ing Mannich-type product using bromodimethylsulfonium
bromide.9e We therefore sought to use the same strategy for
the synthesis of ꢀ-amino acid derivative 2b. Generally, ꢀ-keto
esters react with electrophiles at the R-position.10 Only a few
cases of R-alkylated ꢀ-keto esters/amides reacting with aldehyde
electrophiles at the γ-position have appeared in the literature.11
Fujioka and Kita et al. have reported a multicomponent reaction
a Reactions were performed in
a ratio of 1:1:1 (benzaldehyde:
aniline:1,3-dicarbonyl compounds) in the presence of 10 mol % BDMS
at room temperature. b Yield of pure product after crystallization. c For
optimized yield see Table 2. d Optimized yield was 35%. e Starting
material dibenzoyl acetone was recovered along with aldimine.
employing the γ-position of ꢀ-keto esters to form seven-
membered-ring products from the combination of aromatic
aldehydes, ethylenediamine, and ꢀ-keto esters.1c Interestingly,
the formation of 1b is an example in which both the R- and
γ-positions of a ꢀ-keto ester are involved in C-C bond
formation.
This unexpected result encouraged us to investigate the scope
of this multicomponent reaction through a systematic study. A
variety of 1,3-dicarbonyl compounds were treated with benzal-
dehyde and aniline in the presence of a catalytic amount of
bromodimethylsulfonium bromide and the results are sum-
marized in Table 1. As with methyl acetoacetate, ethyl acetoac-
etate provides the corresponding piperidine derivative in
(6) (a) Choudhury, L. H. Synlett 2006, 1619–1620. (b) Khan, A. T.; Ali, A.;
Goswami, P.; Choudhury, L. H. J. Org. Chem. 2006, 71, 8961–8963. (c) Jiang,
B.; Dou, Y.; Xu, X.; Xu, M. Org. Lett. 2008, 10, 593–596. (d) Meerwein, H.;
Zenner, K. F.; Gipp, R. Justus Liebigs Ann. Chem. 1965, 688, 67–77. (e) Olah,
G. A.; Arvanaghi, M.; Vankar, Y. D. Synthesis 1979, 721.
(7) (a) Furukawa, N.; Inoue, T.; Aida, T.; Oae, S. J. Chem. Soc., Chem.
Commun. 1973, 212. (b) Das, B.; Venkateswarlu, K.; Krishnaiah, M.; Holla,
H.; Majhi, A. HelV. Chim. Acta 2006, 89, 1417–1421.
(8) (a) Khan, A. T.; Mondal, E.; Borah, B. M.; Ghosh, S. Eur. J. Org. Chem.
2003, 4113–4117. (b) Kudrimoti, S.; Bommena, V. R. Tetrahedron Lett. 2005,
46, 1209–1210. (c) Das, B.; Ravikanth, B.; Thirupathi, P.; Rao, B. V. Tetrahedron
Lett. 2006, 47, 5041–5044. (d) Das, B.; Ramu, R.; Ravikanth, B.; Reddy, K. R.
Synthesis 2006, 1419–1422. (e) Das, B.; Holla, H.; Srinivas, Y. Tetrahedron
Lett. 2007, 48, 61–64. (f) Rani, S.; Babu, J. L.; Vankar, Y. D. Synth. Commun.
2003, 33, 4043–4052.
(9) (a) Khan, A. T.; Mondal, E.; Ghosh, S.; Islam, S. Eur. J. Org. Chem.
2004, 2002–2009. (b) Khan, A. T.; Sahu, P. R.; Majee, A. J. Mol. Catal. A:
Chem. 2005, 226, 207–212. (c) Khan, A. T.; Islam, S.; Majee, A.; Chattopadhyay,
T.; Ghosh, S. J. Mol. Catal. A: Chem. 2005, 239, 158–165. (d) Khan, A. T.;
Parvin, T.; Gazi, S.; Choudhury, L. H. Tetrahedron Lett. 2007, 48, 3805–3808.
(e) Khan, A. T.; Parvin, T.; Choudhury, L. H Eur. J. Org. Chem. 2008, 834–
839.
(11) (a) Habib-Zahmani, H.; Hacini, S.; Charonnet, E.; Rodoriguez, J. Synlett
2002, 1827–1830. (b) Charonnet, E.; Filippini, M. H.; Rodoriguez, J. Synthesis
2001, 788–804. (c) Habib-Zahmani, H.; Viala, J.; Hacini, S.; Rodriguez, J. Synlett
2007, 1037–1042. (d) Sotoca, E.; Constantieux, T.; Rodriguez, J. Synlett 2008,
1313–1316.
(10) For review see:Benetti, S.; Romagnoli, R.; Risi, C. D.; Spalluto, G.;
Zanirato, V. Chem. ReV. 1995, 95, 1065–1114.
J. Org. Chem. Vol. 73, No. 21, 2008 8399

Khan et al.
TABLE 2. Results for the Reaction of Aldehydes, Anilines, and
ꢀ-Keto Esters in the Presence of Bromodimethylsulfonium Bromide
in Acetonitrilea
moderate yield (Table 1, entry 1). This suggests that the alkoxy
moiety of these ꢀ-keto esters does not have any significant role
in determining the course of the reaction. However, in the case
of diethyl malonate (Table 1, entry 2), the corresponding
Mannich-type product 2a was obtained in good yield, as there
is no other option due to the lack of an enolizable position.
Likewise, ethyl benzoylacetate (Table 1, entry 3) gave Mannich-
type product 2c as a mixture of diastereomers, with the trans
isomer predominating. However, in the case of benzoyl acetone
(Table 1, entry 4) the corresponding piperidine was obtained
in moderate yield.
In the case of dibenzoyl acetone (Table 1, entry 5) only the
imine formed between benzaldehyde and aniline was obtained
in addition to unreacted dibenzoyl acetone. From these results
it is clear that diethyl malonate is acting as a better nucleophile
in this Mannich-type reaction than the other 1,3-dicarbonyl
compounds in the presence of bromodimethylsulfonium bromide
(Table 1). We believe that the bulkiness of the phenyl group
may have an effect on the nucleophilicity of ethyl benzoyl
acetate and dibenzoyl acetone. From these studies it is apparent
that substituents on the 1,3-dicarbonyl component play a vital
role in determining the reactivity of substrates and the course
of reactions.
A γ-substituted ꢀ-keto ester ethyl butyrylacetate was next
treated with aniline and benzaldehyde under similar experimental
conditions. Piperidine 1t was not observed in the crude 1H NMR
after 24 h (Scheme 2). This suggests that the presence of methyl
group in the ꢀ-position of ꢀ-keto esters is necessary for the
successful formation of highly functionalized piperidines using
these multicomponent reactions.
Functionalized piperidine rings are present in many natural
products12 and are important building blocks in pharmaceuticals.
Recently, considerable attention has been paid to the synthesis
of functionalized piperidines,13,14 while, in general, the develop-
ment of new synthetic methods for the efficient preparation of
nitrogen heterocycles is an interesting challenge.16 Thus we
turned our attention to the optimization of this multicomponent
approach to piperidines.
The influences of the catalyst, solvent, and the ratio of the
components were investigated by using the combination of
p-methylbenzaldehyde, aniline, and methylacetoacetate as a
model reaction. The stoichiometric ratio 2:2:1 (aldehyde:aniline:
methyl acetoacetate) in the presence of 10 mol % of bromodim-
ethylsulfonium bromide at room temperature was found to be
the most suitable condition for obtaining functionalized pip-
eridines. Under these standard reaction conditions, the product
1b was synthesized in good yield (80%) after a short time (3
h). A range of solvents were screened to find out the best solvent
for this transformation. Among dichloromethane, acetonitrile,
(12) (a) Viegas, C.; Bolzani, J. V. S.; Furlan, M.; Barreiro, E. J.; Young,
M. C. M.; Tomazela, D.; Eberlin, M. N. J. Nat. Prod. 2004, 67, 908–910. (b)
Dewick, P. M., Medicinal Natural Products: A Biosynthetic Approach, 2nd ed.;
Wiley: New York, 2002; pp 307-316.
(13) (a) Esquivias, J.; Arrayas, R. G.; Carretero, J. C. J. Am. Chem. Soc.
2007, 129, 1480–1481. (b) Zhu, X. -F.; Lan, J.; Kwon, O. J. Am. Chem. Soc.
2003, 125, 4716–4717. (c) Takemiya, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006,
128, 6042–6043. (d) Amat, M.; Bassas, O.; Perica’s, M. A.; Pasto, M.; Bosch,
J. Chem. Commun. 2005, 1327–1329. (e) Mart´ın, R.; Murruzzu, C.; Perica`s,
M. A.; Riera, A J. Org. Chem. 2005, 70, 2325–2328.
(14) Clarke, P. A.; Zaytzev, A. V.; Whitwood, A. C. Tetrahedron. Lett. 2007,
48, 5209–5212.
(15) Yang, Y.-Y.; Shou, W.-G.; Wang, Y.-G. Tetrahedron 2006, 62, 10079–
10086.
(16) (a) Sridharan, V.; Perumal, P. T.; Avendano, C.; Menendez, J. C.
Tetrahedron 2007, 63, 4407–4413. (b) Jiang, J.; Yu, J.; Sun, X.-X.; Rao, Q.-Q.;
Gong, L.-Z. Angew. Chem., Int. Ed. 2008, 2458–2462.
a Aldehyde, amine, and ꢀ-keto esters were taken in (2:2:1) ratio in
presence of 10 mol
%
of BDMS. b Yield of pure product after
crystallization from the reaction mixture.
8400 J. Org. Chem. Vol. 73, No. 21, 2008

A Facile Access to Functionalized Piperidines
SCHEME 2. Reaction of Ethyl Butyrylacetate with Aniline and Benzaldehyde
SCHEME 3. Possible Mechanistic Illustration Showing the
Role of the R Group and the Formation of Functionalized
Piperidines via Intermediates Z
ethanol, and water, the use of acetonitrile was found to give
superior yields. However, ethanol can also be used for this
transformation. The neat reaction, without any solvent, resulted
in a moderate yield (40%) that may be due to the lack of
effective interaction of the reactants under solvent-free reaction
conditions. In the absence of BDMS, the same combination of
reactants failed to provide 1b under identical reaction conditions
even after 24 h of stirring. This illustrates the efficacy of BDMS
as a catalyst. Using a catalytic amount of aqueous 48% HBr
instead of BDMS gave lower yields (45%). This result indicates
that the generation of the protic acid HBr may not be the only
factor responsible for the catalytic activity of BDMS. It is
possible that the positive sulfonium moiety also has some role
in facilitating the process.
To explore the generality and scope of this multicomponent
reaction a variety of aldehydes, ꢀ-keto esters, and aniline
derivatives were tested and the results are summarized in
Table 2. Aromatic aldehydes bearing substituents such as Cl,
Me, and OMe as well as NO2 were treated with aniline and
methyl acetoacetate under the standard reaction conditions
and the corresponding products (1a-h) were obtained in good
to moderate yields. In the case of nitro aldehydes (Table 2,
entries 6-8) the yields were low, which may be due to steric
factors as well as the electron-withdrawing effect of the nitro
group.
Aniline derivatives such as 4-methoxyaniline and 4-bromoa-
niline were also tested in the multicomponent reaction, smoothly
provding the corresponding piperidine derivatives in good yields
(Table 2, entries 9 and 10). To further explore the generality
and scope of this MCR, benzylamine and butylamine were also
treated under the same reaction conditions. The corresponding
piperidines were obtained in low to moderate yields. Other
ꢀ-keto esters such as ethyl acetoacetate, tert-butyl acetoacetate,
and allyl acetoacetate also took part in this multicomponent
reaction to provide the corresponding piperidine derivatives
(Table 2, entries 13-18) with good yields under the optimized
conditions. Unfortunately, in the case of the aliphatic aldehyde,
heptanal, the present method failed to produce the corresponding
functionalized piperidines.
In the case when R ) alkoxy group, e.g., OEt, the combina-
tion of an aromatic amine, such as aniline, and an aromatic
aldehyde, with the diester, leads to the Mannich-type products
following path A via the formation of an imine followed by
nucleophilic attack by the 1,3-diesters. As the carbonyl group
of ester substrates is less electrophilic than that of the ketone
substrates, there is no reaction with the aromatic amines at room
temperature, and straightforward formation of ꢀ-amino acid
derivatives (Mannich-type product) is observed. However, when
R is an alkyl or aryl group then the scenario becomes different.
This can be attributed to the more reactive keto functionality
and the emergence of other reaction pathways. In the case of
ꢀ-keto esters, where R is a methyl group, enamine X (path B)
is formed by reaction with the amine. This enamine X may then
react with the aromatic aldehyde to produce the Knoevenagel-
type product Y (path C).
Next, there will be a spontaneous tendency under acidic
conditions for tautomerization to give the intramolecular
hydrogen bonded enamine Z. Presumably, this hydrogen bond-
ing along with high conjugation is the driving force for this
tautomerism. The X-ray structure of compounds 1c and 1m
shows that the carboxyl and amino goups are on the same face
of the products and show intramolecular hydrogen bonding
(Figure 1) thus indirectly supporting our hypothesis. Another
equivalent of amine and aldehyde react in the presence of BDMS
To confirm the structure as well as the relative stereochemistry
of these highly functionalized piperidines, X-ray crystallographic
analysis of 1c and 1m was carried out. In both cases, the relative
stereochemistry at the 2- and 6-positions of the piperidines was
shown to be anti (see the Supporting Information, Figure 1). In
addition, amino groups at the 4-position and carboxyl groups
at the 3-position show intramolecular hydrogen bonding.
Next, we turned our attention to gaining mechanistic insights
into this transformation. From our study we have revealed that
the R group of the ꢀ-keto esters plays a crucial role in this
multicomponent reaction (see Table 1). A possible mechanism
is illustrated in Scheme 3.
J. Org. Chem. Vol. 73, No. 21, 2008 8401

Khan et al.
and recrystallized to provide the pure product. The pure product
was characterized by conventional spectroscopic methods.
General Procedure for the Synthesis of Highly Func-
tionalized Piperidines. To a solution of aniline (2 mmol) and
methyl acetoacetate (1 mmol) in 5 mL of acetonitrile was added
bromodimethylsulfonium bromide (0.1 mmol). Subsequently 4-me-
thylbenzaldehyde (2 mmol) was added to the mixture. The resulting
mixture was stirred at room temperature. After completion of the
reaction as checked by TLC, the solvent was evaporated in a
rotatory evaporator and the crude product was washed with ethanol
and filtered off. The pure product was characterized by conventional
spectroscopic methods.
Representative data for compound 1a: light yellow solid (0.345
g, 75%); mp 169-171 °C; IR (KBr) 3241, 3058, 2948, 1655, 1594,
1500, 1257, 1072 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.75 (1H,
dd, J ) 2.4 Hz, J ) 15.2 Hz), 2.86 (1H, dd, J ) 5.6 Hz, J ) 15.2
Hz), 3.93 (3H, s), 5.13-5.14 (1H, m), 6.26-6.28 (2H, m), 6.44
(1H, s), 6.51 (2H, d, J ) 8.8 Hz), 6.59 (1H, t, J ) 7.2 Hz),
7.03-7.10 (5H, m), 7.16 (2H, d, J ) 8.0 Hz), 7.20-7.22 (1H, m),
7.24-7.32 (7H, m), 10.24 (1H, br s); 13C NMR (100 MHz, CDCl3)
δ 33.8, 51.2, 55.2, 58.3, 98.0, 113.0, 116.3, 125.9, 126.0, 126.5,
126.8, 127.3, 128.4, 128.8, 128.9, 129.0, 137.9, 142.9, 144.0, 147.1,
156.4, 168.7. Anal. Calcd for C31H28N2O2 (460.58): C, 80.84; H,
6.13; N, 6.08. Found: C, 80.71; H, 6.07; N, 6.19.
to provide the corresponding imine. We believe BDMS facili-
tates the formation of imine as well as enamine X in this
multicomponent reaction. This imine and the intermediate Z
undergo [4+2] aza-Diels-Alder reaction to provide the func-
tionalized piperidine. In an attempt to prove this mechanism,
we synthesized the enamine from methyl acetoacetate and
aniline and the resulting enamine was treated with another
equivalent of 4-methylbenzaldehyde. However, we could not
isolate the intermediate Z, instead we found a trace amount of
the corresponding piperidine 1b. It is possible that the inter-
mediate is highly reactive and not possible to trap. However,
the exact explanation is not yet clear.
Conclusions
In summary, we have demonstrated that bromodimethylsul-
fonium bromide mediates a new multicomponent reaction for
the synthesis of highly functionalized piperidines. In addition,
we have shown that substituents on the 1,3-dicarbonyl compo-
nents determine the course of the reaction. This strategy is
interesting as both the R- and γ-positions of ꢀ-keto esters are
involved in C-C bond formation under the mild conditions.
The resultant heterocyclic systems have both secondary amine
and enamino esters, which enable further modifications leading
to molecular diversity. Studies toward the further generalization
of this approach and the application of this method to access
other heterocyclic scaffolds are underway.
Acknowledgement. T.P. is thankful to IIT Guwahati for her
research fellowship. A.T.K is grateful to the Director, IIT
Guwahati for providing the general facilities to carry out the
works. We are thankful to DST for XRD facility under the FIST
programme. The authors are also grateful to Dr. David J. Procter,
School of Chemistry, the University of Manchester, for doing
necessary English corrections to the manuscript.
Experimental Section
General Procedure for Mannich-Type Reaction.9e To a
solution of benzaldehyde (2 mmol), aniline (2 mmol), and 1,
3-dicarbonyl compound (2 mmol) in 5 mL of acetonitrile was added
bromodimethylsulfonium bromide (0.2 mmol) then the solution was
stirred at room temperature. After completion of the reaction, the
crude solid was just filtered off and washed with a hexane/ethanol
(80:20) mixture. The solid residue was then dissolved in hot ethanol
Supporting Information Available: The general experi-
mental methods, full characterization data for 1b-s, 2a, and
1
2c, H NMR,13C NMR spectra of new compounds, and X-ray
structure, data, and CIFs of 1c and 1m. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO8014962
8402 J. Org. Chem. Vol. 73, No. 21, 2008