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3989
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Nagao, Y. Tetrahedron Lett. 2002, 43, 281–284.
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Figure 1. Plausible transition state for diastereoselective
reduction of 3b with NaBH4.
proposed by Felkin and Anh.24–31 To minimize steric
interactions, the attack of hydride preferentially
involves the conformer A of the phosphonate, not B, as
indicated in the Newman projections in Figure 1.
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Med. Chem. 2003, 11, 207–215.
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273–277.
In conclusion, the tandem reduction–olefination of a-
acylphosphonates 3a–e was found to proceed efficiently
with excellent Z-selectivity. This one-pot reaction may
be expanded to provide wide application for convenient
syntheses of fluoroolefin peptide isosteres.
21. Typical procedure of tandem reduction–olefination: To
a solution of phosphonate 3a (100 mg, 0.273 mmol) in
EtOH (7 ml) was added a solution of NaBH4 (10.3 mg,
0.273 mmol) in EtOH (3 ml) at −78°C under argon.
After stirring at −78°C for 2 h, the reaction mixture
was allowed to warm to room temperature, then was
stirred for 1 h. The mixture was treated with aqueous
solution saturated with NH4Cl (5 ml) then extracted
with AcOEt (20 ml×3). The extract was washed with
brine, dried over anhydrous MgSO4, filtered, and con-
centrated in vacuo. The oily residue (E:Z=0:100) was
purified by silica gel column chromatography [n-hex-
ane–AcOEt (19:1)] to afford (Z)-4a (48 mg, 83%) as a
coloress oil.
Acknowledgements
This work was partially supported by Grants-in-Aid for
Scientific Research on Priority Areas (A) from the
Ministry of Education, Culture, Sports, Science, and
Technology, Japan and by a grant for Scientific
Research (B) from the Japan Society for the Promotion
of Science. A research grant from the Faculty of Phar-
maceutical Sciences at the University of Tokushima
was also greatly appreciated.
22. Alcohol 6: colorless prism (Et2O–n-hexane): mp 66.5–
67.5°C; 1H NMR (300 MHz CDCl3) l 1.24 (3H, t,
J=7.0 Hz), 1.32 (3H, t, J=7.0 Hz), 1.34 (3H, t, J=7.0
Hz), 1.54–1.71 (1H, m), 1.93–2.11 (1H, m), 2.60–2.79
(1H, m), 2.85–3.03 (1H, m), 3.40 (1H, brs), 4.09–4.42
(7H, m) 7.10–7.34 (5H, m); 13C NMR (75 MHz,
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