1.7 (1H, m, H-3) and 3.6 (1H, d, J2,3 5.5, H-2); dC (125.8 MHz,
C2H3O2H) 13.4 (CH3), 15.0 (CH3), 21.5 (ArCH3), 44.6 (C-2), 51.4
(C-3), 127.0, 130.0, 137.9 and 143.4 (Ar) and 178.9 (acid).
petroleum ether (1 : 2) as eluant gave methyl (2S,3S)-2-(para-
toluenesulfonylamino)-3-methylpent-4-ynoate 36 as a colourless
oil (10 mg, 37%); dH (360 MHz, C2HCl3) 1.3 (3H, d, JMe,3 6.6,
CH3), 2.1 (1H, d, J5,3 1.6, ≡CH), 2.4 (3H, s, ArCH3), 3.0 (1H, m,
H-3), 3.5 (3H, s, OCH3), 3.9 (1H, dd, J2,3 4.2, J2,NH 10.1, H-2), 5.3
(1H, d, JNH,2 10.1, NH), 7.3 (2H, d, J 8.1, ArH) and 7.8 (2H, d, J
8.1, ArH).
(2S,3S)-2-(para-Toluenesulfonylamino)-3-methyl-5-
trimethylsilylpent-4-ynoic acid (35)
n-Butyl lithium (1.6 M in hexanes, 2 ml, 3.2 mmol) was added to a
solution of trimethylsilylacetylene (0.5 ml, 3.54 mmol) in tetrahy-
drofuran (2 ml) at 0 ◦C under argon and the mixture was stirred
for 30 min. (2S,3S)-N-para-Toluenesulfonyl-3-methylaziridine-2-
carboxylate 30 (100 mg, 0.4 mmol) in tetrahydrofuran (2 ml)
was added, and the reaction was stirred at 0 ◦C for 1 h and
at room temperature for a further 2 h under argon. Saturated
aqueous ammonium chloride was added and the aqueous phase
was cooled on ice and acidified to pH 4 with 10% aqueous
citric acid. The aqueous phase was extracted with ethyl acetate
(3 × 30 ml) and the combined organic layers were dried
(Na2SO4). Removal of the solvent in vacuo yielded an amber
oil. Column chromatography on silica gel using (chloroform–
methanol–water–acetic acid 7 : 3 : 0.6 : 0.3)–ethyl acetate (1 : 2)
as eluant gave (2S,3S)-2-(para-toluenesulfonylamino)-3-methyl-5-
trimethylsilylpent-4-ynoic acid 35 as a pale yellow solid which was
recrystallised from dichloromethane and petroleum ether (96 mg,
Methyl (2S,3S)-N-para-toluenesulfonylisoleucine (37)
Palladium on calcium carbonate poisoned with lead (Lind-
lar’s catalyst) (6 mg, 20% m/m) and quinoline (1.2 mg,
4% m/m) were added to a solution of methyl (2S,3S)-2-
(para-toluenesulfonylamino)-3-methylpent-4-ynoate 36 (10 mg,
0.03 mmol) in ethyl acetate (30 ml). The mixture was flushed
three times with argon and a further three times with hydrogen,
and stirred under an atmosphere of hydrogen gas at rtp for 20 h.
The solvent was removed in vacuo to yield an oil. Column chro-
matography on silica gel using ethyl acetate–petroleum ether (1 :
2) as eluant gave methyl (2S,3S)-N-para-toluenesulfonylisoleucine
37 as a white solid which was recrystallised from dichloromethane
and petroleum ether (8 mg, 79%); mp 84–86 ◦C; [a]D +12.5
20
(c 0.3, CHCl3); m/z (EI) found 299.09798; C14H21O4NS re-
quires 299.11913; m/z [+ve FAB (3-nba)] 300 ([M + H]+); mmax
(KBr)/cm−1 1744 (ester); dH (360 MHz, C2HCl3) 0.9 (6H, m, 2 ×
CH3), 1.2 (1H, m, H-4A), 1.4 (1H, m, H-4B), 1.7 (1H, m, H-3), 2.4
(3H, s, ArCH3), 3.5 (3H, s, OCH3), 3.7 (1H, dd, J2,3 5.5, J2,NH 10.1,
H-2), 5.1 (1H, exch. d, JNH,2 10.1, NH), 7.3 (2H, d, J 8.2, ArH)
and 7.7 (2H, d, J 8.2, ArH).
70%); mp 111–114 ◦C; [a]D −25.7 (c 2, CHCl3); m/z (EI) found
34
353.11109; C16H23O4NSSi requires 353.11171; m/z [+ve FAB (3-
nba)] 354 ([M + H]+) and 308 ([M-CO2H]+); mmax (KBr)/cm−1
2173 (C C) and 1720 (acid); dH (360 MHz, C2HCl3) 0.2 (9H, s,
=
Si(CH3)3), 1.2 (3H, d, JMe,3 5.1, CH3), 2.4 (3H, s, ArCH3), 3.1 (1H,
m, H-3), 3.9 (1H, dd, J2,3 3.9, J2,NH 9.7, H-2), 5.4 (1H, exch. d, JNH,2
9.7, NH), 7.3 (2H, d, J 8.2, ArH) and 7.8 (2H, d, J 8.2, ArH); dC
(125.8 MHz, C2HCl3) 0.0 (Si(CH3)3), 17.9 (ArCH3), 21.5 (CH3),
Acknowledgements
We thank the EPSRC and BBSRC for financial support.
=
=
30.7 (C-3), 59.3 (C-2), 73.0 (C ), 104.0 ( CSi), 127.2, 136.7, 136.7
and 143.8 (Ar) and 174.5 (acid).
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1 N NaOH was added dropwise to a solution of (2S,3S)-2-(para-
toluenesulfonylamino)-3-methyl-5-trimethylsilylpent-4-ynoic acid
35 (100 mg, 0.3 mmol) in methanol (3 ml) until the pH reached
8. The mixture was heated at 50 ◦C for 18 h. The reaction was
cooled and acidified to pH 4 using 10% aqueous citric acid. The
aqueous mixture was extracted with ethyl acetate (3 × 20 ml) and
the combined organic layers were dried (Na2SO4). The solvent
was removed in vacuo to yield an oil. Column chromatography
on silica gel using (chloroform–methanol–water–acetic acid 7 :
3 : 0.6 : 0.3)–ethyl acetate (1 : 2) as eluant gave (2S,3S)-2-(para-
toluenesulfonylamino)-3-methylpent-4-ynoic acid as a colourless
oil (75 mg, 94%); dH (360 MHz, C2H3O2H) 1.3 (3H, d, JMe,3
5.3, CH3), 2.4 (3H, s, ArCH3), 3.1 (1H, m, H-3), 3.9 (1H, d,
J2,3 4.2, H-2), 7.3 (2H, d, J 8.2, ArH) and 7.8 (2H, d, J 8.2,
ArH). A solution of (2S,3S)-2-(para-toluenesulfonylamino)-3-
methylpent-4-ynoic acid (26 mg, 0.09 mmol) in methanol (3 ml)
was treated with BF3·Et2O (0.02 ml, 0.16 mmol) and heated
at reflux for 20 h. Water (5 ml) was added and the mixture
was extracted with ethyl acetate (3 × 20 ml). The combined
organic layers were dried (Na2SO4) and the solvent was removed
in vacuo. Column chromatography on silica gel using ethyl acetate–
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2896 | Org. Biomol. Chem., 2006, 4, 2888–2897
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