December 2006
1727
ity previously.2) Thus, unlike the classical approach, we have
given a modern approach in every step of its synthesis to en-
hance the overall yield and stereoselectivity of the target
molecule.
filtrate was concentrated. The residue was subjected to column chromatogra-
phy over silica gel using 40% EtOAc in hexane to afford pure 1 (421 mg,
94%); 1H-NMR (CDCl3, 200 MHz): d: 7.68 (1H, s), 7.49 (2H, d, Jꢀ8.0 Hz),
6.90 (2H, d, Jꢀ8.0 Hz), 4.35 (1H, m), 4.06—3.92 (3H, m), 3.80—3.58 (3H,
m), 2.19 (3H, s), 1.90—1.76 (2H, m), 1.49—1.20 (22H, m), 0.92 (3H, t,
Jꢀ7.0 Hz); 13C-NMR (CDCl3, 50 MHz): d: 169.6, 159.8, 139.9, 131.9,
130.0, 128.1, 114.6, 70.7, 68.2, 65.7, 63.4, 32.0, 29.8, 29.6, 29.2, 27.3, 22.6,
Experimental
Synthesis of Baylis–Hillman Adduct 3i A solution of 4-(myristyloxy) 14.1; EI-MS: m/z 448 (Mꢂ·), 357, 279, 159; Anal. Calcd for C27H44O5: C,
benzaldehyde (6.36 g, 20 mmol) and methyl acrylate (5.36 ml, 60 mmol) in
50 ml of 1 : 1 dioxane–water (v/v) was stirred at room temperature in the
presence of 100 mol% DABCO (2.24 g, 20 mmol). The reaction progress
72.32; H, 9.82%. Found: C, 72.44; H, 9.76%.
Acknowledgement The authors thank CSIR and UGC, New Delhi for
was monitored by thin layer chromatography. Upon completion (7 d) the re- financial assistance.
action mixture was partitioned with tert-butylmethyl ether (500 ml) and
water (150 ml). The organic phase was washed with brine (2ꢁ80 ml), dried References and Notes
over anhydrous Na2SO4, filtered and concentrated under reduced pressure.
The resulting residue was purified by column chromatography (12% EtOAc
in hexane) to give the adduct 3i. Colorless powder, yield 5.9 g (73%).
1) Part 82 in the series, “Studies on Novel Synthetic Methodologies.”
2) Watanabe T., Hayashi K., Yoshimatsu S., Sakai K., Takeyama S.,
Takashima K., J. Med. Chem., 23, 50—59 (1980).
General Procedure for the One-Pot Synthesis of (E)-a-Methylcin-
namic Acids To a solution of Baylis–Hillman adduct 3 (5 mmol, 1 eq) in
anhydrous THF (10 ml) molecular I2 (10 mmol, 2 eq) was added and the
mixture was stirred for 5 min at room temperature under nitrogen atmo-
sphere. NaBH4 (10 mmol, 2 eq) was then added portion-wise to this mixture
and stirring was continued. Slow gas evaluation occurred with a little in-
crease in temperature and the brown solution was slowly turned colorless.
The reaction was monitored by TLC. After completion, THF was evaporated
and 60% KOH (3 g) in MeOH (5 ml) was added. The mixture was again
stirred for 2 h at room temperature. MeOH was removed under reduced pres-
sure. The residue was diluted with water (10 ml), acidified with dilute HCl
(1 N) and extracted with ether (3ꢁ20 ml). The extract was dried over Na2SO4
and concentrated. The crude product was crystallized from hexane–EtOAc
3) Senokuchi K., Nakai H., Nakayama Y., Odagaki Y., Sakaki K., Kato
M., Maruyama T., Miyazaki T., Ito H., Kamiyasu K., Kim S., Kawa-
mura M., Hamanaka N., J. Med. Chem., 38, 4508—4517 (1995).
4) Majetich G., Casares A., Chapman D., Behnke M., J. Org. Chem., 51,
1745—1753 (1986).
5) Teulade M. P., Savignac P., About-Jaudet E., Collignon N., Synth.
Commun., 19, 71—81 (1989) and references cited therein.
6) Rossi R., Carpita A., Cossi P., Tetrahedron, 48, 8801—8824 (1992).
7) Zargarian D., Alper H., Organometallics, 12, 712—724 (1993).
8) Das B., Banerjee J., Mahender G., Majhi A., Org. Lett., 6, 3349—3352
(2004).
9) Das B., Banerjee J., Ravindranath N., Venkataiah B., Tetrahedron Lett.,
45, 2425—2426 (2004).
(1 : 1) to afford pure (E)-a-methylcinnamic acid. The spectroscopic (1H-, 10) Das B., Banerjee J., Ravindranath N., Tetrahedron, 60, 8357—8361
13C-NMR and MS) and analytical data of some representative compounds
are given below.
(2004).
11) Das B., Mahender G., Chowdhury N., Banerjee J., Synlett, 2005,
5b: 1H-NMR (CDCl3, 200 MHz): d: 7.92 (1H, s), 7.50—7.21 (4H, m),
1000—1002 (2005).
2.02 (3H, s); 13C-NMR (CDCl3, 50 MHz): d: 174.1, 138.4, 134.2, 131.3, 12) Das B., Majhi A., Banerjee J., Chowdhury N., Venkateswarlu K.,
130.5, 130.0, 128.2, 126.8, 126.4, 13.8; EI-MS: m/z 198, 196 (Mꢂ·), 161,
115; Anal. Calcd for C10H9ClO2: C, 61.22; H, 4.59%. Found: C, 61.16; H, 13) Das B., Majhi A., Banerjee J., Chowdhury N., Venkateswarlu K.,
4.62%.
Tetrahedron Lett., 46, 7913—7915 (2005).
5d: 1H-NMR (CDCl3, 200 MHz): d: 7.78 (1H, s), 7.44 (2H, d, Jꢀ8.0 Hz), 14) Das B., Holla H., Venkateswarlu K., Majhi A., Tetrahedron Lett., 46,
6.90 (2H, d, Jꢀ8.0 Hz), 3.82 (3H, s) 2.10 (3H, s); EI-MS: m/z 192 (Mꢂ·),
8895—8897 (2005).
146, 121; Anal. Calcd for C11H12O3: C, 68.75; H, 6.25%. Found: C, 68.82; 15) Baylis A. B., Hillman M. E. D., German Patent 2155113 (1972)
H, 6.21%.
[Chem. Abstr., 77, 34174q (1972)].
2: H-NMR (CDCl3, 200 MHz): d: 7.69 (1H, s), 7.33 (2H, d, Jꢀ8.0 Hz), 16) Basavaiah D., Rao A. J., Satyanarayana T., Chem. Rev., 103, 811—892
6.81 (2H, d, Jꢀ8.0 Hz), 3.90 (2H, t, Jꢀ7.0 Hz), 2.10 (3H, s), 1.75—1.66
(2003) and references cited therein.
(2H, m), 1.48—1.32 (2H, m), 1.31—1.14 (20H, m), 0.82 (3H, t, Jꢀ7.0 Hz); 17) Hoffmann H. M. R., Rabe J., Angew. Chem. Int. Ed. Engl., 24, 94—
13C-NMR (CDCl3, 50 MHz): d: 174.5, 159.6, 141.0, 131.8, 126.2, 125.2,
110 (1985).
Chem. Lett., 34, 1492—1493 (2005).
1
114.6, 68.3, 32.0, 29.8, 29.5, 29.3, 26.1, 22.8, 14.2, 13.8; FAB-MS: m/z 375 18) Buchholz R., Hoffmann H. M. R., Helv. Chim. Acta, 74, 1213—1220
(Mꢂ·ꢂ1); Anal. Calcd for C24H38O3: C, 77.00; H, 10.16%. Found: C, 77.24;
H, 10.22%.
(1991).
19) Basavaiah D., Bakthadoss M., Pandiaraju S., J. Chem. Soc., Chem.
Commun., 1998, 1639—1640 (1998).
Esterification of 2 with Acetonide Protected Glycerol 6 A dried flask
was charged with 2 (748 mg, 2 mmol), acetonide protected glycerol 631) 20) Drewes S. E., Emslie N. D., J. Chem. Soc. Perkin Trans. 1, 1982,
(343 mg, 2.6 mmol), DMAP (12 mg, 0.1 mmol) and BOC2O (585 mg,
2079—2083 (1982).
2.6 mmol). Dry THF (5 ml) was added by syringe and the mixture was 21) Jenn T., Heissler D., Tetrahedron, 54, 97—106 (1998).
stirred at 50 °C. After completion of the reaction (monitored by TLC) 22) Grassi B., Lippuner V., Aebi M., Brunner J., Vasella A., J. Am. Chem.
EtOAc (10 ml) was added and the organic layer was washed consecutively
with HCl (2 N), NaHCO3 solution, water and brine and subsequently dried.
Soc., 119, 10992—10999 (1997).
23) Roush W. R., Brown B. B., J. Org. Chem., 58, 2151—2161 (1993).
The volatiles were removed in vacuo and the residue was subjected to col- 24) Mateus C. R., Feltrin M. P., Costa A. M., Cohelo F., Almedia W. P.,
umn chromatography over silica gel using 18% EtOAc in hexane as eluent to
obtain pure 7 (898 mg, 92%); H-NMR (CDCl3, 200 MHz): d: 7.63 (1H, s),
Tetrahedron, 57, 6901—6908 (2001).
25) Fernandes L., Bortoluzzi A. J., Sa’ M. M., Tetrahedron, 60, 9983—
9989 (2004).
26) Basavaiah D., Krishnamacharyulu M., Hyma R. S., Sarma P. K. S.,
Kumaragurabaran N., J. Org. Chem., 64, 1197—1200 (1999).
1
7.32 (2H, d, Jꢀ8.0 Hz), 6.84 (2H, d, Jꢀ8.0 Hz), 4.33 (1H, m), 4.21 (2H, d,
Jꢀ5.5 Hz), 4.09 (1H, dd, Jꢀ12.0, 2.0 Hz), 3.95 (2H, t, Jꢀ7.0 Hz), 3.78 (1H,
dd, Jꢀ12.0, 2.0 Hz), 2.12 (3H, s), 1.82—1.72 (2H, m), 1.41 (3H, s), 1.31
(3H, s), 1.30—1.18 (22H, m), 0.86 (3H, t, Jꢀ7.0 Hz); 13C-NMR (CDCl3, 27) Patra A., Batra S., Bhaduri A. P., Synlett, 2003, 1611—1614 (2003).
50 MHz): d: 168.9, 159.5, 139.6, 132.0, 129.8, 128.2, 114.6, 109.7, 68.1, 28) Larson G. L., de Kaifer C. F., Seda R., Torres L. E., Ramirez J. R., J.
67.2, 67.1, 64.9, 32.1, 29.8, 29.4, 27.5, 26.8, 25.2, 22.8, 14.0; EI-MS: m/z
Org. Chem., 49, 3385—3386 (1984).
488 (Mꢂ·), 433, 357, 250, 119; Anal. Calcd for C30H48O5: C, 73.77; H, 29) Basavaiah D., Sarma P. K. S., Bhavani A. K. D., J. Chem. Soc., Chem.
9.84%. Found: C, 73.64; H, 9.92%.
Acetonide Deprotection of 7 To a solution of 7 (488 mg, 1 mmol) in
MeOH (5 ml) Amberlyst-15 (100 mg) was added. The mixture was stirred at
Commun., 1994, 1091—1092 (1994).
30) Das B., Kashinatham A., Madhusudan P., Tetrahedron Lett., 39, 677—
678 (1998).
room temperature for 2 h. Amberlyst-15 was removed by filtration and the 31) GooBen L. J., Dohring A., Synlett, 2004, 263—266 (2004).