Montmorillonite K10 clay catalyzed mild, clean, solvent free one-pot protection-isomerisation of the Baylis-Hillman adducts with alcohols

Article abstract of DOI:10.1246/cl.2002.1212

The montmorillonite K10 clay catalyzed mild, clean, and solvent free one-pot reactions of the Baylis-Hillman adducts with a number of alcohols undergo secondary alcohol protection followed by a facile 1,3-sigmatropic shift isomerised products in excellent yield. The isomerised products with propargyl alcohol are highly functionalized and useful for lignan natural product synthesis.

Full text of DOI:10.1246/cl.2002.1212

1212
Chemistry Letters 2002
Montmorillonite K10 Clay Catalyzed Mild, Clean, Solvent Free One-pot Protection-Isomerisation
of the Baylis–Hillman Adducts with Alcohols
Ponnusamy Shanmugamꢀ# and Paramasivan Rajasingh
Organic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum 695019, Kerala, India
(Received August 5, 2002; CL-020652)
The montmorillonite K10 clay catalyzed mild, clean, and
solvent free one-pot reactions of the Baylis–Hillman adducts with a
number of alcohols undergo secondary alcohol protection followed
by a facile 1,3-sigmatropic shift isomerised products in excellent
yield. The isomerised products with propargyl alcohol are highly
functionalized and useful for lignan natural product synthesis.
under similar condition although in low yield. Hence, we have
developed a high yield and clean green chemistry methodology to
effect the transformation. In this letter, we report the reaction of
alcohols with Baylis–Hillman adducts under solvent free and mild
conditions. The propargyl derivatives 2 and 3 obtained by this
methodology are extremely useful for the synthesis of core
structures of natural lignans4 4 and 5 through an n-Bu3SnH/AIBN
mediated vinyl radical cyclization5 protocol. Suitably substituted
propargyl derivatives would furnish the natural lignans4 such as
lariciresinol, olivil and hydroxysugiresinol (Scheme 1).
The isomerisation study with clay catalyst is represented in
Scheme 2. The Baylis–Hillman adduct 1 was prepared according to
the literature procedure.2d The isomerisation study was initiated by
heating a slurry (75 ꢁC, 1.5 h)made with the adduct 1, 2.5 equiv. of
propargyl alcohol and 60% w/w montmorillonite K10 without any
solvent in an oil bath furnished the ether 2 and its isomerised product
36 (99.9; E-selectivity)7 in 90% combined yield in 6 : 4 product
ratio.8 The reaction proceeded smoothly and furnished clean
products. The compounds were separated by a silica gel column
chromatography and characterized by spectral and analytical data.9
The usefulness of montmorillonite K10 clay in organic
synthesis and its application as a catalyst for a number of organic
reactions are well documented.1 Montmorillonite K10 and its
structurally modified clays are known to act as both Brꢀnsted and
Lewis acid catalysts for a variety of industrially important organic
reactions.1 The clay catalysts are known as eco-friendly acid
catalysts which have potential for replacing the conventional
mineral acids and are nonpollutant. The advantages of the clay-
catalyzed reactions are that they are generally mild and solvent free
and work-up is easy. The Baylis–Hillman reaction is one of the
important carbon–carbon bond forming reactions and has been used
in organic synthesis for the synthesis of a variety of compounds
having diverse functional groups and has been used as the starting
point for a variety of synthetic organic transformations.2 Stereo-
selective isomerisation of acetates of Baylis–Hillman adducts
catalyzed by TMSOTf,2d,e trifluoroacetic acid,2f and benzyltri-
methylammonium fluoride2g has appeared in the literature. In
continuation of our research work on clay catalysis,3 we have
recently reported the mont-K10-microwave assisted stereoselective
isomerisation of acetates of Baylis–Hillman adducts into its (E)-
trisubstituted alkenes and a one-pot protection-isomerisation of
Baylis–Hillman adduct with trimethyl orthoformate under similar
isomerisation conditions.3d
OH
H
O
CO2CH3
CO2CH3
a
+
Ph
90%
Ph
Ph
O
CO2CH3
1
3
(E:Z=99.9:0.1)
2
6:4
Reagents and Conditions: a. 60% w/w Mont. K10, 2.5 equvi. propargyl
alcohol, Neat, 75 °C, 1.5 h.
Scheme 2.
The reactivity of the Baylis–Hillman adduct 1, its OAc
protected adduct 6 and their isomerised compounds 7 and 8 with
propargyl alcohol under optimized condition described above was
compared and all of them furnished compounds 2 and 3 almost in the
same yield and product ratio. Interestingly, the simple Baylis–
Hillman adduct 1, without any protection, underwent protection-
isomerisation with propargyl alcohol and provided an excellent
yield (95%)of compounds 2 and 3 under clay catalytic condition.
Reaction of compounds 1 and 6 without propargyl alcohol furnished
the compounds 7 and 8 under clay catalytic condition in high yield
respectively. Reaction of compounds 7 and 8 with propargyl alcohol
under the optimized clay catalytic condition furnished compounds 2
and 3 in the ratio of 6 : 4 in excellent yield (>95%). Therefore, the
nucleophilic nature of the propargyl alcohol on the isomerised 7 and
8 and unisomerized 1 and 6 Baylis–Hillman adducts are the same,
since they afforded same products 2 and 3 in the same product ratio
(6 : 4). Hence, the experiment reveals that the reaction of alcohol
with simple unisomerized adduct 1 itself provides the required
products in excellent yield and no protection/isomerised starting
materials (6, 7 and 8)are necessary to effect this transformation. The
detail of the study is represented in scheme 3.
OH
CO CH
2
3
H
O
CO CH
2
3
a
+
Ph
Ph
Ph
O
CO CH
3
1
2
3
2
Radical cyclization
n-Bu SnH/AIBN, 80 °C,Neat
3
5-exo-trig
6-endo-trig
SnBu
3
CO Me
2
MeO C
Bu Sn
2
3
CO Me
2
CO Me
2
Bu Sn
3
SnBu
3
Ph
Ph
Ph
Ph
O
Ph
O
Ph
O
O
4
5
if phenyl propargyl alcohol used
Lignan Core Structures
Reagents and Conditions: a. Cat. H SO , CH Cl , propargyl alcohol, RT, 1 h, 70% ; 2:3 ratio varies
if phenyl propargyl alcohol used
2
4
2
2
Scheme 1.
Our attempt to the conventional acid catalyzed (concd H2SO4)
reaction of Baylis–Hillman adduct with propargyl alcohol furnished
the protected secondary alcohol 2 and its isomerised product 3. We
have observed that the ratio of the formation of the products (2 and
1
3)varies (as estimated by H NMR)when the reaction was repeated
The formation of the only isomerised product 3 over 2 under the
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
1213
OR
CO2CH3
Ph
CO2CH3
OR
H
The clay catalyst recovered from this reaction can be recycled
three times after activating the clay by heating at 100 ꢁC for 3 h. In
conclusion, we have demonstrated that mont. K10 clay is a useful,
speedy and efficient catalyst for the protection/isomerisation of the
Baylis–Hillman adducts with a variety of alcohols which provide
highly functionalized stereoselective (E)-alkenyl ethers. These
ethers are good candidates for the synthesis of lignan natural
products and useful substrates for RCM reactions. Further studies
involving the above catalyst system are underway.
a
Ph
95%
R=H, 1
R=H, 7
R=OAc, 8
R=OAc, 6
b
b
>95%
>95%, 99.9% E-selectivity
CO2CH3
O
H
+
Ph
Ph
O
CO2CH3
3 40%
60%
2
P.S. thanks Department of Science and Technology (DST),
New Delhi for the financial support as Fast Track Young Scientist
Project-2001. The authors thank Prof. Javed Iqbal, Director and Dr.
Mangalam S. Nair, Head, Organic Division for their encouragement
and infrastructure facilities provided. P.R. thanks CSIR (New
Delhi)for the award of Junior Research Fellowship.
Reagents and Conditions: a. 60% w/w Mont. K10, Neat, 2 h, 75 °C.
b. 60% w/w Mont. K10, propargyl alcohol, Neat, 6 h, 75 °C.
Scheme 3.
optimized condition described above can be achieved by increasing
the reaction time (Scheme 4). Complete conversion of 2 into
isomerised product 3 was observed at the reaction time 24 h and was
purified by passing through a silica gel column chromatography.
The distribution of products with respect to reaction time is
summarized in Table 1.
References and Notes
#
Present address: JSPS Fellow, Division of Chemistry, Graduate School of Science,
Hokkaido University, Sapporo 060-0810, Japan.
1
a)M. Balogh and P. Laszlo, ‘‘Organic Chemistry Using Clays,’’ Springer-Verlag,
New York (1993). b) G. W. Kabalka and R. M. Pagni, Tetrahedron, 53, 7999
(1997). c) A. Corma, Chem. Rev., 95, 559 (1995).
OH
As time increases
CO2CH3
O
CO2CH3
H
a
+
Ph
2
a)S. E. Derewes and G. H. P. Roos, Tetrahedron, 44, 4653 (1988). b) E. Cignek, in
‘‘Organic Reactions,’’ ed. by L. A. Paquette, Wiley & Sons, New York (1997),
Vol. 51, pp 201–350. c)H. M. R. Hofmann, U. Eggert, and W. Poly, Angew.
Chem., Int. Ed. Engl., 26, 1015 (1987). d) D. Basavaiah, K. Muthukumaran, and B.
Sreenivasulu, Synthesis, 2000, 545. e)D. Basavaiah, K. Padmaja, and T.
Satyanarayana, Synthesis, 2000, 1662, and references cited therein. f)H. S. Kim,
T. Y. Kim, K. Y. Ley, Y. M. Chung, H. J. Lee, and J. N. Kim, Tetrahedron Lett., 41,
2613 (2000). g) A. Foucaud and F. E. Guemmount, Bull. Soc. Chim. Fr., 1989,
403. h)D. Basavaiah, M. Krishnamacharyulu, R. S. Hyma., P. K. S. Sarma, and N.
Kumaragurubaran, J. Org. Chem., 64, 1197 (1999). i) J. N. Kim and K. Y. Lee,
Curr. Org. Chem., 6, 627 (2002).
Ph
Ph
O
CO2CH3
1
2
(E:Z=99.9:0.1)
3
Reagents and Conditions: a. 60% w/w Mont. K10, 2.5 equvi. propargyl alcohol, Neat, 75 °C, 2 h.
Scheme 4.
Table 1.
Time(h)
2(%)
3(%)
3
a)P. Shanmugam and V. Nair, Synth. Commun., 26, 3007 (1996). b) P.
Shanmugam, Synth. Commun., 29, 4409 (1999). c) P. Shanmugam and R. L.
Varma, Indian J. Chem., Sect. B, 40B, 1258 (2001). d) P. Shanmugam and P. R.
Singh, Synlett, 2001, 1314.
N. G. Lewis and L. B. Davin, in ‘‘Comprehensive Natural Products Chemistry,’’
ed. by D. Barton, K. Nakanishi, and O. Meth-Cohn, Pergamon Press, Oxford
(1999), Vol. 1, pp 639–712.
a)P. Shanmugam and P. Rajasingh, under preparation. b)B. Giese, ‘‘Radicals in
Organic Synthesis: Formation of Carbon–Carbon Bonds,’’ Pergamon Press,
Oxford (1986). c) J. Fossey, D. Lefort, and J. Sorba, ‘‘Free Radicals in Organic
Chemistry,’’ Wiley & Sons, Chichester (1995). d) C. P. Jasperse, D. P. Curran, and
T. L. Fevig, Chem. Rev., 91, 1237 (1991). e) S. Janardhanam, P. Shanmugam, and
K. Rajagopalan, J. Org. Chem., 58, 7782 (1993). f) P. Shanmugam, R. Srinivasan,
and K. Rajagopalan, Tetrahedron, 53, 6085 (1997). g) P. Shanmugam, R.
Srinivasan, and K. Rajagopalan, Tetrahedron, 53, 11685 (1997).
6
42
25
58
75
15
22
24
<5
trace
>95
>99
4
5
In order to exemplify the general nature of this reaction, we
have chosen a number of alcohols and found that the reactions are
clean and high yielding (11–17)under the optimized conditions
described above (Scheme 5). However, the reaction with phenols
and high boiling alcohols furnished a mixture of inseparable
compounds in poor yield. The results are summarized in Table 2.
6
7
D. Basavaiah, N. Kumaragurubaran, D. S. Sharada, and R. M. Reddy,
Tetrahedron, 57, 8167 (2001).
R
Z
OH
H
O
The 1H NMR spectra of the isomerised product 3 showed a peak at ꢀ 7.92 for the
presence of E-vinylic proton.
a
Z
+
Ph
Ph
90%
Ph
The product ratio was estimated by 1H NMR.
O
R
8
9
1
Z
9,10
11-17 (E:Z=99.9:0.1)
A Typical Procedure: A slurry of the adduct 1 (150 mg, 1.3 mmol), propargyl
alcohol (182 mg, 2.5 equiv., 3.25 mmole)and montmorillonite K10 clay (60% w/
w)was taken in a 50 mL RB flask which was tightly closed and kept in an oil bath
(75 ꢁC)for 24 h. Then the flask was cooled to room temperature and 20 mL of
CH2Cl2 was added and filtered through a celite pad. The solvent was removed
under vacuum. The crude mixture was purified through a column of silica gel
using 98 : 2 mixture of hexane: ethyl acetate afforded 95% isomerised compound
3 with 99.9% E-selectivity. By adjusting the reaction time (1.5 h), propargyl ether
derivative 2 can be isolated in 60% yield along with the isomerised product 3. 3-
aryl-2-methylene-3(prop-2-en-1-yloxy) propeonitrile 9: IR (neat) ꢁmax: 1728,
R=propargyl, allyl, isopropyl, n-octyl
Z= CO2Et, CO2Me, CN
Reagents and Conditions: a. 60% w/w Mont. K10, 2.5 equiv. R-OH, 75 °C, 24 h, Neat
Scheme 5.
Table 2. Isomerisation of Baylis–Hillman adducts with alcoholsa,b,c
Alcohol
Z
Product
Yield/%d
Propargyl
CO2Me
CO2Et
CN
11
12
13
14
15
16
17
95
96
96
95
95
98
97
1600, 1630, 1620 cmꢂ1 1H NMR (CDCl3/TMS, 300.1 MHz): ꢀ 3.93 (d, 2H,
;
00
00
J ¼ 5:67 Hz), 4.87 (s, 1H), 5.23 (s, 2H), 5.84 (m, 1H), 5.97 (s, 2H), 7.35 (m, 5H);
13C NMR (CDCl3/TMS, 75.3 MHz): ꢀ 69.75, 80.09, 107.23, 117.77, 127.03,
128.80, 128.83, 129.70, 130.01, 133.72, 137.65; MS m/z: 199 (Mþ); Anal. Calcd
for C13H13NO: Cacld. C, 78.36, H, 6.58, N, 7.03% Found: C, 78.30, H, 6.55, N,
7.00%; Methyl (2E)3-aryl-2(prop-2-yn-1-yloxymethyl) prop-2-enoate 11: IR
(neat) ꢁmax: 3285, 2112, 1714, 1633 cmꢂ1; 1H NMR (CDCl3/TMS, 300.1 MHz): ꢀ
2.42(t, 1H, J ¼ 2:34 Hz), 3.84 (s, 3H), 4.26 (d, 2H, J ¼ 2:34 Hz), 4.39 (s, 2H),
7.32 (m, 3H), 7.53 (m, 2H), 7.92 (s, 1H); 13C NMR (CDCl3/TMS, 75.3 MHz): ꢀ
52.26, 58.08, 64.25,74.70, 79.63, 128.51, 128.54, 129.55, 129.99, 134.51, 145.27,
167.98; MS m/z: 230 (Mþ); Anal. Calcd for C14H14O3: C, 73.03, H, 6.13% Found:
C, 73.00, H, 6.08%.
Allyl
Isopropyl
n-Octyl
00
CO2Me
CO2Me
CN
CO2Me
a60% w/w mont. K10 clay was used. bThe clay was dried at 100 ꢁC for
1 h. c60% mont-K10, 75 ꢁC, 24 h. dIsolated yield after column
purification.