Silica sulfuric acid as a reusable heterogeneous catalyst for the diastereoselective Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan: Facile synthesis of γ-butenolides

Article abstract of DOI:10.1007/s00706-010-0388-z

Silica sulfuric acid was found to be an efficient catalyst for the vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aldehydes with good diastereoselection. The reaction proceeds rapidly in THF, affording the corresponding 5-(arylhydroxymethyl)furan-2(5H)-ones in good yields. This method offers significant advantages such as experimental simplicity, and recoverability and reusability of the catalyst.

Full text of DOI:10.1007/s00706-010-0388-z

Monatsh Chem (2010) 141:1245–1248
DOI 10.1007/s00706-010-0388-z
ORIGINAL PAPER
Silica sulfuric acid as a reusable heterogeneous catalyst
for the diastereoselective Mukaiyama aldol reaction of
2-(trimethylsilyloxy)furan: facile synthesis of c-butenolides
•
Gowravaram Sabitha M. Nagendra Prasad
•
•
M. Ramesh J. S. Yadav
Received: 28 July 2009 / Accepted: 10 August 2010 / Published online: 8 September 2010
Ó Springer-Verlag 2010
Abstract Silica sulfuric acid was found to be an efficient
catalyst for the vinylogous Mukaiyama aldol reaction of
2-(trimethylsilyloxy)furan with various aldehydes with
good diastereoselection. The reaction proceeds rapidly in
THF, affording the corresponding 5-(arylhydroxymethyl)
furan-2(5H)-ones in good yields. This method offers sig-
nificant advantages such as experimental simplicity, and
recoverability and reusability of the catalyst.
the cost of the triflates restricts their use [8–11]. Enantio-
selective versions of these reactions have been known by
use of chiral mediators. Racemic examples of the vinylo-
gous Mukaiyama aldol reaction are known employing
Lewis acids such as SnCl4, ZnCl2, TiCl4, BF3ÁOEt2, SiCl4
or silyl triflates [12–20]. Recently, Bi(OTf)3Á4H2O [22] has
been used for the vinylogous Mukaiyama aldol reaction of
2-(trimethylsilyloxy)furan. In view of the versatility of this
reaction, there is still a need to develop a new catalytic
system that can be recyclable.
Keywords 2-(trimethylsilyloxy)furan Á Aldehydes Á
Diastereoselectivity Á c-Butenolides Á
Heterogeneous reagent systems have many advantages
such as simple experimental procedures, mild reaction
conditions, and minimization of chemical waste as com-
pared with their liquid-phase counterparts. The use of solid
acids such as silica sulfuric acid (SSA) [23–26] for syn-
thesizing organic intermediates and fine chemicals is
attracting increasing attention, also making a field of
intense research activity [27].
Vinylogous Mukaiyama aldol reaction
Introduction
The Mukaiyama aldol reaction is one of the most important
carbon–carbon bond-forming processes in organic synthesis
[1, 2]. The catalytic coupling of 2-(trimethylsilyloxy)furan
(TMSOF, 2) with aldehydes 1 by means of a vinylogous
Mukaiyama aldol reaction has emerged as an important
method to provide 5-(arylhydroxymethyl)furan-2(5H)-ones
(c-butenolides) 3 [3]. The butenolide moiety substituted at
the c-position by a chain bearing hydroxyl groups is an
important structural subunit in many natural products and
biologically active compounds [4–7] such as muricatacin,
L-factor, sapinofuranone, isocalpalide B, cardiobutanolide,
etc. (Fig. 1). Various lanthanide triflates have been repor-
ted for the vinylogous Mukaiyama aldol reaction; however,
Results and discussion
Initially, the reaction of benzaldehyde with 2-(trimethyl-
silyloxy)furan was studied in the presence of a catalytic
amount of silica sulfuric acid in THF at -78 °C and found
to give 5-(hydroxyphenylmethyl)furan-2(5H)-one (c-bute-
1
nolide) in 93% yield (Scheme 1). Preliminary H nuclear
magnetic resonance (NMR) studies of the crude product
revealed that the reaction provided syn diastereoselectivity
(the syn/anti ratio was determined to be 91:9). Encouraged
by this result, the scope of the reaction was explored with
various aldehydes, as indicated in Table 1. A variety of
aromatic aldehydes were used as coupling partners with
TMSOF. Aldehydes containing electron-donating as well
as electron-withdrawing substituents cleanly underwent
G. Sabitha (&) Á M. Nagendra Prasad Á M. Ramesh Á
J. S. Yadav
Organic Chemistry Division-I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India
e-mail: gowravaramsr@yahoo.com
123

1246
G. Sabitha et al.
Fig. 1 Naturally occurring
5-(1-hydroxyalkyl)-c-
butyrolactones
O
O
O
7
O
O
O
OH
OH
OH
Muricatacin
OH
L-factor
Sapinofuranone B
OH OH
OH
HO
H
O
OH
Ph
O
O
O
Isocalpalide B
(+)-Cardiobutanolide
Conclusions
OH
O
O
OTMS
Silica sulfuric acid
THF, -78 °C
O
O
R
+
R
H
Silica sulfuric acid proved to be an efficient heterogeneous
catalyst for addition of TMSOF to aldehydes. The reaction
is applied to synthesis of natural products such as muri-
catacin and L-factor in racemic form.
rac-3a-3c
rac-3f-3j
1a-1c
1f-1j
2
Scheme 1
reaction in isolated yields ranging from 86% to 93% and
with good diastereoselectivities. This clearly indicates that
variation in the electronic nature of the substituent on the
aromatic ring has apparently no influence on the efficiency
and diastereoselectivity of the reaction. The syn/anti
relative stereodisposition of products was assigned based
on known compounds [14, 19]. The present reaction con-
ditions also work for a,b-unsaturated aldehydes (Table 1,
entry 9) as well as heteroaromatic aldehydes such as fur-
fural. Aliphatic aldehydes can also serve as substrates in
this reaction, giving the corresponding butenolides in lower
yields with moderate diastereoselectivity when compared
with aromatic aldehydes. Thus, the reaction of tridecanal
and hexanal with TMSOF produced the corresponding
butenolides 3d and 3e in 85% yield (Scheme 2).
Experimental
Starting materials were purchased from Aldrich Chemical
Company, USA, and used as received. Evaporation of
solvents was performed at reduced pressure using a Buchi
rotary evaporator. H and 13C NMR spectra of samples in
1
CDCl3 were recorded on a Bruker UXNMR FT-300 MHz
(Avance) spectrometer. Mass spectra were recorded on a
LC-MSD (Agilent technologies) spectrometer at 70 eV.
Thin-layer chromatography (TLC) was performed on
Merck 60 F-254 silica gel plates.
Preparation of silica sulfuric acid
Silica sulfuric acid was prepared according to a previously
reported procedure [27].
Hydrogenation of these precursors using Pd/C led to the
naturally occurring molecules muricatacin (4) and L-factor
(5) in racemic form. Literature precedents for enantiose-
lective versions of the reaction exist [27, 28].
General experimental procedure for the silica sulfuric
acid-catalyzed Mukaiyama aldol reaction of TMSOF
with aldehydes
The catalyst works under heterogeneous conditions and
can easily be prepared from readily available ClSO3H and
silica gel [27]. It can be conveniently handled and removed
from the reaction mixture. The catalyst was recycled three
times without loss of activity. The salient features of the
present method are mild reaction conditions, simple
experimental procedure, high yields, good diastereoselec-
tivities, and reusability of the catalyst. To our knowledge,
this is the first report on synthesis of butenolides from
aldehydes and TMSOF using a heterogeneous solid acid
catalyst.
To a solution of the aldehyde 1 (1 mmol) in THF, silica
sulfuric acid catalyst (20 mol%) was added and stirred for
10 min. Then the reaction mixture was brought to -78 °C,
and a solution of 2-(trimethylsilyloxy)furan (2, 1 mmol) in
THF was added dropwise. The reaction mixture was stirred
at -78 °C until the reaction was completed as indicated by
TLC. The mixture was filtered, and the catalyst was
washed with a small amount of THF. The recovered cat-
alyst can be used for further reactions. The filtrate was
123

Silica sulfuric acid as a reusable heterogeneous catalyst
1247
Table 1 Silica sulfuric acid-
Entry
1
RCHO 1
Product 3a
3a [21]
Time (h)
1.5
dr (syn:anti)
Yield (%)c
catalyzed reactions of
various aldehydes with
2-(trimethylsilyloxy)furan
CHO
91:9
93
92
CHO
2
3
3b [21]
2.0
1.0
90:10
Me
CHO
3c [20]
93:7
90
O2N
CHO
4
5
3d [27]
3e [28]
3.0
3.0
80:20
78:22
85
85
10
3
CHO
CHO
6
3f [21]
1.6
90:10
90
Cl
Br
CHO
7
8
3g [20]
3h [21]
1.8
1.4
89:11
85:15
91
89
CHO
CHO
9
3i [21]
3j [21]
1.6
0.8
89:11
86:14
88
86
aAll products were characterized
by 1H NMR, infrared (IR), and
mass spectral data
bThe diastereomeric ratio was
determined based on 1H NMR
studies of crude products
cYields refer to isolated yields of
the mixture of syn/anti
diastereomers
MeO
O
CHO
10
123

1248
G. Sabitha et al.
OH
OH
O
Catalyst
10% Pd/C
O
OTMS
O
CHO
O
+
O
8
8
8
THF,-78 °C
EtOAc
r.t, 10 h
rac-Muricatacin4
rac-3d
Tridecanal
2
OH
OH
O
10% Pd/C
Catalyst
O
OTMS
O
CHO
O
+
O
3
3
3
THF,-78 °C
EtOAc
r.t, 10 h
Hexanal
2
rac-3e
-L-factor 5
rac
Scheme 2
7. Dalpiaz A, Pavan B, Scaglianti M, Vitali F, Bortolotti F, Biondi
C, Scatturin A, Manfredini S (2005) Indian J Pharmacy 291:171
8. Kobayashi S, Sugiura M, Kitagawa H, Lam WWL (2002) Chem
Rev 102:2227
concentrated under reduced pressure and purified by silica
gel column chromatography to obtain the pure product 3.
General procedure for the preparation of compounds 4
and 5
9. Kobayashi S, Hamada T, Nagayama S, Kanabe K (2001) Org Lett
3:165
10. Kobayashi S, Hachiya I, Takahori T (1993) Synthesis 371
11. Kobayashi S, Hachiya I (1992) Tetrahedron Lett 33:1625
12. Rassu G, Zanardi F, Battistini L, Casiraghi G (1999) Synlett 1333
13. Casiraghi G, Rassu G (1995) Synthesis 607
14. Jefford CW, Jaggi D, Boukouvalas J (1987) Tetrahedron Lett
28:4037
15. Acocella MR, De Rosa M, Massa A, Palombi L, Villano R,
Scettri A (2005) Tetrahedron 61:4091
16. Kong K, Romo D (2006) Org Lett 8:2909
17. Yoshii E, Koizumi T, Kitatsuji E, Kawazoe T, Kaneko T (1976)
Heterocycles 4:1663
To a stirred solution of 3e (0.2 g, 1.08 mmol) in 10 cm3
EtOAc, 10% Pd/C (50 mg) was added, and the reaction
mixture was stirred under H2 atmosphere for 10 h at room
temperature and then filtered through Celite. The filtrate
was concentrated under reduced pressure to yield com-
pound 5 (0.18 g, 89%) as a colorless liquid. A similar
procedure was used for the preparation of compound 4.
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Org Chem 70:3654
Acknowledgments M.N.P. thanks CSIR, New Delhi, for the award
of a fellowship. M.R. thanks IICT, Hyderabad for providing facilities.
20. For a recent organocatalytic approach, see: De Rosa M, Citro L,
Soriente A (2006) Tetrahedron Lett 47:8507
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