Application of TMSOTf in the Baylis-Hillman Adducts

Article abstract of DOI:10.1081/SCC-100104835

A simple and convenient methodology for the stereoselective construction of 2-benzyl substituted trisubstituted olefins via TMSOTf catalyzed reaction of benzene with Baylis-Hillman adducts is described.

Full text of DOI:10.1081/SCC-100104835

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APPLICATION OF TMSOTf IN THE BAYLIS-HILLMAN
ADDUCTS
Subramanian Ravichandran a
a School of Chemistry, University of Hyderabad, Hyderabad, 500 046, India
Version of record first published: 09 Nov 2006.
To cite this article: Subramanian Ravichandran (2001): APPLICATION OF TMSOTf IN THE BAYLIS-HILLMAN ADDUCTS,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:15,
2345-2350
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SYNTHETIC COMMUNICATIONS, 31(15), 2345–2350 (2001)
APPLICATION OF TMSOTf IN THE
BAYLIS-HILLMAN ADDUCTS
Subramanian Ravichandran
School of Chemistry, University of Hyderabad,
Hyderabad-500 046, India
ABSTRACT
A simple and convenient methodology for the stereoselective
construction of 2-benzyl substituted trisubstituted olefins1,2
via TMSOTf catalyzed reaction of benzene with Baylis-
Hillman adducts is described.
As part of our research program in Baylis-Hillman reaction,3 I have
undertaken the investigation of the reactions of benzene with representative
3-hydroxy-2-methylenealkanenitriles and methyl 3-hydroxy-2-methylene-
alkanoates in the presence of trimethylsilyl trifluoromethanesulfonate4
(TMSOTf).
First I have examined the reaction of benzene (5 ml) with 3-hydroxy-2-
methylene-3-phenyl-propanenitrile (1a) (0.346 g, 2 mM) in the presence of
TMSOTf (0.222 g, 1 mM) was refluxed for about 30 minutes. (2Z)-2-benzyl-
3phenylprop-2-enenitrile (2a) was obtained in 86% yield (0.4371 g) after
usual workup followed by column chromatography (2% ethyl acetate in
hexane) in high stereoselectivity (97% (Z)-selectivity as evidenced by the
1H NMR spectral analysis).
Encouraged by this observation, a variety of the Baylis-Hillman
adducts (1b–1f) under the same conditions afforded the desired (2Z)-2-ben-
zylalk-2-enenitriles (2b–2f) in high stereoselectivity (Table 1) (eq. 1).
2345
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To generalize this observation, a variety of 3-hydroxy-2-methylene
alkanoates (3a–3f) on reaction with benzene in the presence of TMSOTf
under reflux temperature afforded the desired (2E)-2-benzyl-3-phenylalk-2-
enoates (4a–4f) in high (E)-stereoselectivity (eq. 2) (Table 2).
From these results, it is quite clear that nitriles (2a–2f) and esters
(4a–4f) provide 2-benzyl substituted functionalized alkenes with opposite
stereochemistry. This observation is consistent with our earlier results and
may be explained by considering the difference in steric demands between
the nitrile and ester groups.5–7
In conclusion, this methodology describes a simple stereoselective syn-
thesis of (Z)- and (E)-2-benzyl substituted functionalized alkenes thus
demonstrating the efficiency of trimethylsilyl trifluoromethane sulfonate.
Table 1. TMSOTf Catalyzed Reaction of Benzene with 3-Hydroxy-2-methylene-
alkanenitriles
Reaction
Time
(minutes)
Yield
(%)
Substrate
R
Product
Z:E
1a
1b
1c
1d
1e
1f
Phenyl
30
30
30
30
45
90
2a
2b
2c
2d
2e
2f
86
83
81
83
79
64
97:03
100:0
100:0
100:0
96:04
95:5
p-methylphenyl
p-chlorophenyl
p-isopropylphenyl
o-methylphenyl
n-pentyl

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Table 2. TMSOTf Catalyzed Reaction of Benzene with 3-Hydroxy-2-methylene-
alkanoates
Reaction
Time
(minutes)
Yield
(%)
Substrate
R
Product
Z:E
3a
3b
3c
3d
3e
3f
Phenyl
20
30
30
30
40
90
4a
4b
4c
4d
4e
4f
79
81
83
80
78
69
0:100
0:100
05:95
0:100
04:96
06:94
p-methylphenyl
p-chlorophenyl
p-isopropylphenyl
o-methylphenyl
n-pentyl
EXPERIMENTAL SECTION
Infrared spectra (IR) were recorded with a Perkin-Elmer 1310
spectrometer. 1H and 13C NMR spectra were recorded at 200 and
50 MHz, respectively. Elemental analyses were recorded on Perkin-Elmer
240C-CHN analyzer.
All the required starting materials were obtained as follows:
Molecules 1a–1f and 3a–3f were prepared by the reaction of the
corresponding aldehydes with acrylonitrile and methyl acrylate in presence
of a catalytic amount of DABCO according to the literature procedure.8–10
General Procedure for the Preparation of 2a–2f and 4a–4f
To a stirred solution of alcohol (1a–1f, 3a–3f) (2 mM) in dry benzene
(5 mL), was added TMSOTf (0.222 g, 1 mM) at room temperature and
heated under reflux for the time specified in the Table. Then the reaction
mixture was cooled and diluted with ether (20 mL), and washed successively
with water and aqueous K2CO3 solution. The organic layer was separated
and the aqueous layer was extracted with ether. The combined organic layer
was dried over anhydrous Na2SO4 and concentrated. The crude product
thus obtained was purified by column chromatography (silicagel, 2%
ethyl acetate in hexane) to afford the desired product (2a–2f, 4a–4f )
as colourless liquid. All compounds gave satisfactory spectral data (1R,
1H NMR and 13C NMR) and elemental analysis. Stereochemical assignment
and isomeric purities were based on difference in chemical shifts and
1
integration ratios of isomeric b-allylic protons in H NMR analysis.

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1
(2Z)-2-Benzyl-3-phenylprop-2-enenitrile(2a): H NMR: d 3.73 (s, 2H),
6.94 (s, 1H), 7.22–7.45 (m, 8H), 7.63–7.76 (m, 2H); 13C NMR: d 35.46, 42.08,
110.67, 118.63, 127.29, 128.64, 128.72, 128.83, 130.05, 133.52, 136.45, 143.98.
IR (neat): 2210, 1622 cmꢀ1; Elemental Analysis calculated for C16H13N: C,
87.63; H, 5.97; N, 6.38 and found C, 87.92; H, 5.95; N, 6.42.
(2Z)-2-Benzyl-3-(4-methylphenyl)prop-2-enenitrile(2b): 1H NMR (200 MHz)
(CDCl3): d 2.35 (s, 3H), 3.66 (s, 2H), 6.91 (s, 1H), 7.17–7.45 (m, 7H),
7.61 (d, 2H, J ¼ 8 Hz); 13C NMR (50 MHz, CDCl3): d 21.13, 41.82,
109.18, 118.68, 126.91, 128.57, 129.27, 130.61, 136.58, 140.21, 143.78; IR
(neat); 2210, 1610 cmꢀ1; Elemental Analysis calculated for C17H15N: C,
87.51; H, 6.48; N, 6.00 and found C, 87.48; H, 6.50; N, 5.97.
(2Z)-2-Benzyl-3-(4-chlorophenyl)prop-2-enenitrile(2c): 1H NMR: d 3.60
(s, 2H), 6.81 (s, 1H), 7.14–7.39 (m, 7H), 7.59 (d, 2H, J ¼ 8.0 Hz). 13C NMR:
d 41.91, 111.43, 118.33, 127.37, 128.85, 128.91, 129.87, 131.91, 135.87, 136.17,
142.49. IR (neat): 2212, 1624 cmꢀ1; Elemental Analysis calculated for
C16H12NCl: C, 75.74; H, 4.76; N, 5.52 and found C, 75.54; H, 4.76; N, 5.57.
(2Z)-2-Benzyl-3-(4-isopropylphenyl)prop-2-enenitrile(2d): 1H NMR:
d 1.32 (d, 6H, J ¼ 6.8 Hz), 2.92 (sept, 1H, J ¼ 6.8 Hz), 3.74 (s, 2H), 6.91
(s, 1H), 7.23–7.42 (m, 7H), 7.71 (d, 2H, J¼8.3 Hz); 13C NMR: d 23.67,
34.00, 42.15, 109.49, 118.89, 126.87, 127.27, 128.82, 131.23, 136.67, 144.01,
151.36; IR (neat): 2210, 1606 cmꢀ1; Elemental Analysis calculated for
C19H19N: C, 87.31; H, 7.33; N, 5.36 and found C, 87.56; H, 7.30; N, 5.37.
(2Z)-2-Benzyl-3-(2-methylphenyl)prop-2-enenitrile(2e):
1H
NMR
(200 MHz) (CDCl3): d 2.32 (s, 3H), 3.68 (s, 2H), 6.98 (s, 1H), 7.13–7.44
(m, 7H), 7.63 (d, 2H, J ¼ 8 Hz); 13C NMR (50 MHz, CDCl3): d 21.12,
41.80, 109.12, 118.69, 126.89, 128.54, 129.23, 130.64, 136.51, 140.22, 143.72;
IR (neat): 2214, 1613 cmꢀ1; Elemental Analysis calculated for C17H15N: C,
87.51; H, 6.48; N, 6.00 and found C, 87.46; H, 6.53; N, 6.02.
(2Z)-2-Benzyloct-2-enenitrile(2f):1HNMR:d0.91(dist.t,3H),1.14–1.58
(m, 6H), 2.32–2.53 (m, 2H), 3.52 (s, 2H), 6.22 (t, 1H, 7.6 Hz), 7.16–7.44
(m, 5H); 13C NMR: d 13.78, 22.24, 28.10, 31.12, 31.36, 40.23, 114.09, 117.38,
126.98, 128.62, 136.68, 148.64 IR (neat): 2212, 1624 cmꢀ1 Elemental
Analysis calculated for C15H19N: C, 84.45; H, 8.98; N, 6.56 and found C,
84.16; H, 6.92; N, 6.57.
1
Methyl(2E)-2-benzyl-3-phenylprop-2-enoate(4a): H NMR: d 3.74 (s,
3H), 3.93 (s, 2H), 7.92 (s, 1H), 7.12–7.49 (m, 10H). 13C NMR: d 33.15,
51.97, 126.09, 127.83, 128.54, 128.67, 129.17, 130.74, 134.96, 135.37, 139.41,
140.83, 168.52. IR (neat): 1714, 1631 cmꢀ1; Elemental Analysis calculated
for C17H16O2: C, 80.92; H, 6.39 and found C, 80.76; H, 6.42.
Methyl (2E)-2-benzyl-3-(4-methylphenyl)prop-2-enoate(4b): 1H NMR
(200 MHz, CDCl3): d 2.32 (s, 3H), 3.74 (s, 3H), 3.97 (s, 2H), 7.13–7.36
(m, 9H), 7.91 (s, 1H); 13C NMR (50 MHz, CDCl3): d 21.05, 33.07, 51.74,

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125.95, 127.71, 128.07, 128.35, 129.14, 19.68, 132.30, 138.73, 139.33, 140.77,
168.42; IR (neat): 1713, 1632 cmꢀ1; Elemental Analysis calculated for
C18H18O2: C, 81.17; H, 6.81 and found C, 81.08; H, 6.80.
1
Methyl(2E)-2-benzyl-3-(4-chlorophenyl)prop-2-enoate(4c): H NMR: d
3.76 (s, 3H), 3.93 (s, 2H), 7.86 (s, 1H), 7.12–7.41 (m, 9H); 13C NMR: d 33.13,
51.57, 52.16, 126.27, 127.84, 128.23, 128.65, 128.83, 129.57, 130.51, 131.38,
133.75, 134.71, 139.07, 139.52, 168.38. IR (neat): 1712, 1631 cmꢀ1
;
Elemental Analysis calculated for C17H15O2Cl: C, 71.20; H, 5.27 and
found C, 71.48; H, 5.28.
Methyl(2E)-2-benzyl-3-(4-isopropylphenyl)prop-2-enoate(4d): 1H NMR:
d 1.26 (d, 6H, J¼6.8 Hz), 2.93 (sept, 1H, J¼6.8 Hz), 3.73 (s, 1H), 4.21 (s,
2H), 7.09–7.43 (m, 9H), 7.89 (s, 1H); 13C NMR: d 23.79, 33.21, 33.97, 51.97,
126.04, 126.71, 127.91, 128.55, 129.49, 129.77, 132.87, 139.52, 141.06,
149.87, 168.77; IR (neat): 1712, 1630 cmꢀ1; Elemental Analysis calculated
for C20H22O2: C, 81.60; H, 7.53 and found C, 81.88; H, 7.52.
Methyl(2E)-2-benzyl-3-(2-methylphenyl)prop-2-enoate(4e): 1H NMR
(200 MHz, CDCl3): d 2.38 (s, 3H), 3.72 (s, 3H), 3.84 (s, 2H), 7.12–7.38
(m, 9H), 7.92 (s, 1H); 13C NMR (50 MHz), CDCl3): 21.08, 33.02, 51.76,
125.92, 127.74, 128.05, 128.38, 129.12, 19.66, 132.30, 138.71, 139.30, 140.72,
168.41; IR (neat): 1714, 1631 cmꢀ1; Elemental Analysis calculated for
C18H18O2; C, 81.17; H, 6.81 and found C, 81.04; H, 6.83.
2-Benzyloct-2-enoate(4f): 1H NMR: d 0.92 (dist.t, 3H), 1.121.56
(m, 6H), 2.48 (q, 2H), 3.52 (s, 2H), 6.22 (t, 1H, 7.6 Hz), 7.16–7.44 (m, 5H);
13C NMR: d 13.78, 22.24, 28.10, 31.12, 31.36, 40.23, 114.09, 117.38, 126.98,
128.62, 136.68, 148.64; IR (neat): 2212, 1624 cmꢀ1; Elemental Analysis
calculated for C16H22O2: C, 78.00; H, 9.00 and found C, 77.74; H, 8.93.
ACKNOWLEDGMENT
SR thanks his brothers SS and Dr. SP for financial support and
constant encouragement in research. SR also thanks COSIST program in
School of Chemistry, University of Hyderabad.
REFERENCES
1. Basavaiah, D.; Gowriswari, V.V.L.; Sarma, P.K.S. Tetrahedron Lett.
1994, 35, 4227.
2. Basavaiah, D.; Pandiaraju, S.; Sarma, P.K.S. Tetrahedron Lett. 1994,
35, 4227.
3. Baylis, A.B.; Hillman, M.E.D. German Patent. 1972, 2155113.

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4. Oishi, M.; Aratake, S.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120,
8271.
5. Basavaiah, D.; Sarma, P.K.S. J. Chem. Soc. Chem. Commun.
1992, 955.
6. Basavaiah, D.; Pandiaraju, S. Tetrahedron 1996, 52, 2261.
7. Basavaiah, D.; Sarma, P.K.S.; Bhavani, A.K.D. J. Chem. Soc. Chem.
Commun. 1994, 1015.
8. Basavaiah, D.; Gowriswari, V.V.L. Synth. Commun. 1987, 17, 1893
and references cited therein.
9. Hoffmann, H.M.R.; Rabe, J. Angew. Chem. 1983, 22, 795.
10. Amri, H.; Villieras, J. Tetrahedron Lett. 1986, 27, 4307.
Received in the Netherlands November 1, 2000

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