F. A. Jaipuri et al. / Tetrahedron Letters 45 (2004) 4149–4152
4151
Scheme 5. Microwave-assisted basic hydrolysis of the Weinreb amide.
tert-butoxide (6 equiv) and water (2 equiv) in THF,11 but
these reactions can be difficult. Since aqueous KOH in
methanol/water at room temperature has been used to
remove the Evans et al. chiral auxiliary,6 we decided to
investigate these conditions to remove the Weinreb
amide. The reaction was successful, but took 4 days to go
to completion. Recent advances in microwave synthesis14
inspired us to attempt this hydrolysis under microwave
irradiation. Amide 9 was dissolved in MeOH–H2O (1:1)
and subjected to microwave irradiation (130 °C, 90 psi)
in the presence of KOH (2 N) (Scheme 3). After 20 min
the desired final product 1 was obtained in 87% yield. No
product was observed upon conventional heating of the
reaction mixture for 1 h. This method delineates a new
mild and efficient method to hydrolyze Weinreb amides,
thereby rendering this group more practical for the
protection of carboxylic acids. This hydrolysis step
completed the synthesis (R)-3-hydroxydecanoic acid
from (S)-3-hydroxy-c-butyrolactone 3.15–21
References and notes
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J. Appl. Microbiol. Biotechnol. 1999, 51, 553–563.
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M. A.; Thaisrivongs, S.; Zimmerman, J. Liebigs Ann.
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Lett. 1985, 651–654; (c) Seebach, D.; Zueger, M. Helv.
Chim. Acta 1982, 65, 495–498.
3. (a) Seebach, D.; Chow, H.-F.; Jackson, R. F. W.; Sutter,
M. A.; Thaisrivongs, S.; Zimmerman, J. Liebigs Ann.
Chem. 1986, 1281–1308; (b) Chiba, T.; Nakai, T. Chem.
Lett. 1985, 651–654; (c) Steinbuchel, A.; Valentin, H. E.
FEMS Microbiol. Lett. 1995, 128, 219–228.
4. Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.;
Sayo, N.; Kumobayashi, H.; Akutagawa, S. J. Am. Chem.
Soc. 1987, 109, 5856–5858.
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1998, 9, 4113–4115.
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1981, 103, 2127–2129.
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2000, 531, 173–181.
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89, 5505–5507; (b) Smith, A.; Barbosa, J.; Wong, W.;
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10. (a) Basha, A.; Lipton, M.; Weinreb, S. Tetrahedron Lett.
1977, 48, 4171–4174; (b) Lipton, M.; Basha, A.; Weinreb,
S. Org. Synth. 1980, 59, 49–53.
11. Rodriques, K. E. Tetrahedron Lett. 1991, 32, 1275–1278.
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Chem. 1998, 63, 2058–2059.
13. (a) Ranu, B. C.; Sarkar, A.; Guchhait, S. K.; Ghosh, K. J.
Indian Chem. Soc. 1988, 75, 690–694; (b) Banik, B. K.;
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567–579; (b) Majetich, G.; Hicks, R. J. Microwave Power
3. Conclusion
Previous syntheses of chiral b-hydroxy acids have relied
on either Grignard reagents for chain elongation and
were thereby limited in the functional groups that were
tolerated in the side chain or on Evan’s chiral auxiliary,
which provided mixtures in the absence of an alpha
substituent. The use of the versatile Wittig reaction for
chain elongation allows the introduction of alkyl groups
with varying carbon chain length and different func-
tionalities such as halogen, carboxylic acid, and ester
group. These functionalized chiral b-hydroxy acids can
be used for the synthesis of a wide variety of complex
compounds as well as for the study of the enzyme sys-
tems involved in the biosynthesis of poly(hydroxyalk-
anoates). The dramatic decrease in the observed reaction
times for our hydrogenation and Weinreb amide
hydrolysis steps further demonstrates the utility of
microwave irradiation in synthetic applications.
€
Electromagn. Energy 1995, 30, 27–45; (c) Lidstrom, P.;
Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57,
9225–9283; (d) Perreux, L.; Loupy, A. Tetrahedron 2001,
57, 9199–9223; (e) Hayes, B. L. Microwave Synthesis:
Chemistry at the Speed of Light; CEM: Matthews, NC,
2002.
15. Analytical data for compound 7: (S)-3-Benzyloxy-N,O-
dimethyl-4-hydroxybutyramide: 1H NMR (300 MHz,
CDCl3): d (ppm) 2.51 (t, 1H, J ¼ 6:3 Hz), 2.61–2.69 (dd,
1H, J ¼ 6:3 Hz), 2.83–2.92 (dd, 1H, J ¼ 5:7 Hz), 3.18 (s,
3H), 3.58–3.66 (m, 4H), 3.73-3.76 (m, 1H), 4.03–4.07 (m,
1H), 4.57–4.66 (dd, 2H, J ¼ 11:7, J ¼ 3:9 Hz), 7.23–7.34
(m, 5H); 13C NMR (75 MHz, CDCl3): d (ppm) 34.4, 41.8,
Acknowledgements
61.5, 64.2, 72.3, 76.6, 127.9, 128.0, 128.6, 138.6, 172.3; Mþ
25
D
16. Analytical data for compound 2: (S)-3-Benzyloxy-N,O-
We thank Prof. R. Hollingsworth and Synthon Chira-
genics for a generous donation of lactone 3 and the
Department of Chemistry and the Plant Sciences Insti-
tute for their support of this research. N.L.P. is a
Cottrell Scholar of Research Corporation.
(EI, 70 eV): 253; ½aꢁ (c 1.0, CHCl3): þ23.1.
1
dimethyl-4-oxobutyramide: H NMR (300 MHz, CDCl3):
d (ppm) 2.92–2.93 (d, 2H, J ¼ 4:5 Hz), 3.19 (s, 3H), 3.67
(s, 3H), 4.27–4.31 (m, 1H),4.67–4.72 (m, 2H), 7.19–7.37