[ϩve FAB (3-nba)] 354 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 1730
(CO2H); δH(360 MHz, C2HCl3) 1.3 (6H, s, 2 × CH3), 1.9 (2H, t,
J 6.8, CH2), 2.1 (3H, s, CH3), 2.5 (1H, d, J3S,2 3.9, H-3S), 2.6
[2 × 3H, 2 × s, C-(CH3)2], 2.7 (2H, t, J 6.8, CH2), 2.8 (1H, d,
J3R,2 7.1, H-3R), 3.3 (1H, dd, J2,3S 3.9, J2,3R 7.1, H-2) and 7.1
10% aqueous citric acid and extracted with ethyl acetate (3 × 15
ml). The combined organic phases were dried (Na2SO4), and
the solvent was removed in vacuo to yield an amber oil. The
crude product was purified by chromatography on silica gel
using (chloroform–methanol–water–acetic acid 7:3:0.6:0.3)–
ethyl acetate (1:2) as eluent to yield (2S)-N-(2,2,5,7,8-
pentamethylchroman-6-ylsulfonyl)-2-(3-trimethylsilylprop-2-
ynyl)glycine ent-23 as a pale yellow solid which was recrystal-
lised from ethyl acetate and light petroleum (15 mg, 33%); mp
140–145 ЊC; [α]D34 ϩ30.8 (c 0.2, CHCl3); m/z [ϩve FAB (3-nba)]
474 ([M ϩ Na]ϩ) 452 ([M ϩ H]ϩ) (m/z found 451.18446;
2
(1H, s, CO2H, exchangeable in H2O); δC(125.8 MHz, C2HCl3)
12.2 (CH3), 17.6 and 18.6 (2 × CH3), 21.4 (C-3Ј), 26.7
[C-(CH3)2], 32.0 (C-3), 32.5 (C-4Ј), 34.7 (C-2), 74.3 [C-(CH3)2],
118.7, 125.0, 126.3, 137.8, 137.8 and 155.7 (quaternary Ar-C)
and 171.9 (CO2H).
C22H33O5NSSi requires 451.18488); νmax(KBr)/cmϪ1 2180 (C᎐C)
᎐
(2R)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)aziridine-2-
carboxylate 22
᎐
and 1720 (CO2H); δH(360 MHz, C2HCl3) 0.1 [9H, s, (CH3)3Si],
This was prepared as described above using (2R)-methyl N-
(2,2,5,7,8-pentamethylchroman-6-ylsulfonyl)aziridine-2-
carboxylate 21 (0.8 g, 2.2 mmol) and was a solid (0.77 g, 100%);
mp 121–124 ЊC; [α]D22 ϩ38.3 (c 0.4, CHCl3) (Found C, 57.8; H,
6.7; N, 3.9%. C17H23O5NS requires C, 57.8; H, 6.5; N, 4.0%);
m/z [ϩve FAB (3-nba)] 354 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 1714
(CO2H); δH(360 MHz, C2HCl3) 1.3 (6H, s, 2 × CH3), 1.9 (2H,
t, J 6.8, CH2), 2.1 (3H, s, CH3), 2.5 (1H, d, J3R2 3.9, H-3R),
2.6 [2 × 3H, 2 × s, C-(CH3)2], 2.7 (2H, t, J 6.8, CH2), 2.9
(1H, d, J3S,2 7.1, H-3S) and 3.4 (1H, dd, J2,3R 3.9, J2,3S 7.1,
H-2); δC(125.8 MHz, C2HCl3) 12.2 (CH3), 17.6 and 18.6 (2 ×
CH3), 21.4 (C-3Ј), 26.7 [C-(CH3)2], 32.0 (C-3), 32.5 (C-4Ј), 34.7
(C-2), 74.3 [C-(CH3)2], 118.7, 125.0, 126.3, 137.8, 137.9 and
155.8 (quaternary Ar-C) and 171.9 (CO2H).
1.3 (6H, s, 2 × CH3), 1.9 (2H, t, J 6.8, CH2), 2.1 (3H, s, CH3),
2.5 (1H, obscured m, H-3S), 2.6 [2 × 3H, 2 × s, C-(CH3)2], 2.7
(2H, t, J 6.8, CH2), 2.7–2.8 (1H, dd, J3R,2 4.0, J3R,3S 17.1, H-3R),
4.1 (1H, m, H-2) and 5.4 (1H, d, JNH,2 8.5, NH).
(2R)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)-2-(3-tri-
methylsilylprop-2-ynyl)glycine 23
This was prepared as described above using (2R)-N-(2,2,5,7,8-
pentamethylchroman-6-ylsulfonyl)aziridine-2-carboxylate 22
(0.7 g, 1.8 mmol), and was a solid (0.3 g, 36%); mp 112–115 ЊC;
[α]D23 Ϫ29.2 (c 1.5, CHCl3) (Found C, 58.2; H, 7.5; N, 3.1%.
C22H33O5NSSi requires C, 58.5; H, 7.3; N, 3.1%); m/z [ϩve FAB
(glycerol)] 452 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 2182 (C᎐C), 1718
᎐
᎐
(CO2H); δH(360 MHz, C2H3O2H) 0.0 [9H, s, Si(CH3)3], 1.3 (6H,
s, 2 × CH3), 1.8 (2H, t, J 6.8, CH2), 2.1 (3H, s, CH3), 2.5–2.6
(1H, obscured m, H-3R), 2.6 [2 × 3H, 2 × s, C-(CH3)2], 2.6–2.7
(1H, dd, J3S,2 6.0, J3S,3R 17.0, H-3S), 2.7 (2H, t, J 6.7, CH2) and
3.8 (1H, dd, J2,3R 6.2, J2,3S 6.0, H-2); δC(125.8 MHz, C2H3O2H)
0.2 [Si(CH3)3], 12.2 (CH3), 17.3 and 18.3 (2 × CH3), 21.4
(C-3Ј), 24.6 (C-3), 26.6 [C-(CH3)2], 32.6 (C-4Ј), 53.9 (C-2), 74.1
(2R,3R)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl[3-2H1]-
aziridine-2-carboxylate 22 HB ؍
2H
This was prepared as described above using (2R,3R)-methyl N-
(2,2,5,7,8-pentamethylchroman-6-ylsulfonyl)[3-2H1]aziridine-2-
carboxylate 21, HB = 2H (0.5 g, 1.4 mmol) and was a solid (0.5 g,
100%); mp 124–127 ЊC; [α]D25 ϩ29.3 (c 0.3, CHCl3); m/z [ϩve
FAB (3-nba)] 355 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 1733 (CO2H);
δH(360 MHz, C2HCl3) 1.3 (6H, s, 2 × CH3), 1.9 (2H, t, J 6.8,
CH2), 2.1 (3H, s, CH3); 2.6 [2 × 3H, 2 × s, C-(CH3)2], 2.7 (2H,
t, J 6.8, CH2), 2.9 (1H, d, J3S,2 7.1, H-3S) and 3.4 (1H, d,
J2,3S 7.1, H-2); δC(125.8 MHz, C2HCl3) 12.2 (CH3), 17.6 and
18.6 (2 × CH3), 21.4 (C-3Ј), 26.7 [C-(CH3)2], 31.5 (t, C-3), 32.5
(C-4Ј), 34.7 (C-2), 74.2 [C-(CH3)2], 118.6, 124.8, 126.7, 137.7,
137.8 and 155.6 (quaternary Ar-C) and 167.8 (CO2H).
᎐
᎐
[C-(CH ) ], 89.0 (C᎐CSiMe ), 100.1 (C᎐CSiMe ), 118.4, 124.7,
᎐
᎐
3
2
3
3
128.5, 136.5, 136.7 and 154.8 (quaternary Ar-C) and 174.9
(CO2H).
(2R)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)-2-{(1R)-
[1-2H1]-3-trimethylsilylprop-2-ynyl}glycine 23, HB ؍
2H
This was prepared as described above using (2R,3R)-N-
2,2,5,7,8-pentamethylchroman-6-ylsulfonyl)[3-2H1]aziridine-2-
carboxylate 22, HB = 2H (0.5 g, 1.4 mmol) and was a solid (0.2 g,
30%); mp 99–102 ЊC; [α]D25 Ϫ28.0 (c 0.7, CHCl3); m/z [ϩve FAB
(3-nba)] 475 ([M ϩ Na]ϩ) and 453 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1
(2R,3S)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)[2,3-
2H2]aziridine-2-carboxylate 22 HA ؍
2H
2
2
᎐
2176 (C᎐C) and 1721 (CO H); δ (360 MHz, C H O H) 0.1 [9H,
᎐
2
H
3
This was prepared as described above using (2R,3S)-methyl N-
(2,2,5,7,8-pentamethylchroman-6-ylsulfonyl)[2,3-2H2]aziridine-
2-carboxylate 21, HA = 2H (0.3 g, 0.8 mmol), and was a solid
(0.3 g, 100%); mp 116–120 ЊC; [α]D27 ϩ33.1 (c 0.4, CHCl3); m/z
[ϩve FAB (3-nba)] 356 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 1726
(CO2H); δH(360 MHz, C2HCl3) 1.3 (6H, s, 2 × CH3), 1.9 (2H, t,
J 6.7, CH2), 2.1 (3H, s, CH3), 2.5 (1H, s, H-3R), 2.6 [2 × 3H,
2 × s, C-(CH3)2] and 2.7 (2H, t, J 6.7, CH2); δC(125.8 MHz,
C2HCl3) 12.2 (CH3), 17.6 and 18.6 (2 × CH3), 21.4 (C-3Ј),
26.7 [C-(CH3)2], 31.7 (t, C-3), 32.5 (C-4Ј), 34.3 (t, C-2), 74.3
[C-(CH3)2], 118.7, 125.0, 126.3, 137.8, 137.9 and 155.7 (quater-
nary Ar-C) and 172.5 (CO2H).
s, Si(CH3)3], 1.4 (6H, s, 2 × CH3), 1.9 (2H, t, J 6.8, CH2), 2.2
(3H, s, CH3), 2.5 (1H, obscured, H-3S), 2.6 [2 × 3H, 2 × s,
C-(CH3)2], 2.7 (2H, t, J 6.8, CH2) and 3.8 (1H, d, J2,3S 5.9, H-2);
δC(125.8 MHz, C2H3O2H) 0.2 [Si(CH3)3], 12.2 (CH3), 17.3 and
18.3 (2 × CH3), 21.4 (C-3Ј), 24.4 (t, C-3), 26.6 [C-(CH3)2],
᎐
32.6 (C-4Ј), 53.7 (C-2), 74.1 [C-(CH ) ], 87.1 (C᎐CSiMe ),
᎐
3
2
3
᎐
105.8 (C᎐CSiMe ), 118.4, 124.7, 128.5, 136.5, 136.7 and 154.5
᎐
3
(quaternary Ar-C) and 174.9 (CO2H).
(2R)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)-2-{(1S)-
[1-2H1]-3-trimethylsilylprop-2-ynyl}[2-2H1]glycine 23, HA ؍
2H
This was prepared as outlined above from (2R,3S)-N-(2,2,5,7,8-
pentamethylchroman-6-ylsulfonyl)[2,3-2H2]aziridine-2-
(2S)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)-2-(3-tri-
methylsilylprop-2-ynyl)glycine ent-23
carboxylate 22, HA = 2H (0.3 g, 0.8 mmol) and was a solid (0.1
g, 28%); mp 99–102 ЊC; [α]D28 Ϫ34.3 (c 0.4, CHCl3); m/z [ϩve
FAB (3-nba)] 454 ([M ϩ H]ϩ); νmax(KBr)/cmϪ1 2178 (C᎐C)
᎐
n-Butyllithium (1.6 in hexane, 0.6 ml, 0.9 mmol) was added to
a cold (0 ЊC) solution of trimethylsilylacetylene (0.2 ml, 1.4
mmol) in THF (2 ml) and the mixture was stirred under
argon for 30 min. (2S)-N-(2,2,5,7,8-Pentamethylchroman-6-
ylsulfonyl)aziridine-2-carboxylate ent-22 (39 mg, 0.1 mmol) in
THF (10 ml) was added, and the mixture was stirred at 0 ЊC for
2.5 hours under argon, and then allowed to warm slowly to
room temperature over 1 hour. The reaction was quenched by
addition of saturated aqueous ammonium chloride (20 ml), and
the aqueous phase was cooled on ice, acidified to pH 4 with
᎐
and 1718 (CO2); δH(360 MHz, C2HCl3) 0.1 [9H, s, Si(CH3)3],
1.4 (6H, s, 2 × CH3), 1.8 (2H, t, J 6.8, CH2), 2.2 (3H, s,
CH3), 2.6 (1H, s, H-3R), 2.6 [2 × 3H, 2 × s, C-(CH3)2] and
2.7 (2H, t, J 6.7, CH2); δC(125.8 MHz, C2HCl3) 0.1 [Si(CH3)3],
12.2 (CH3), 17.3 and 18.3 (2 × CH3), 21.5 (C-3Ј), 24.3 (t,
C-3), 26.6 [C-(CH3)2], 32.6 (C-4Ј), 53.3 (t, C-2), 74.1 [C-
᎐
᎐
(CH ) ], 87.1 [C᎐CSi(CH ) ], 105.8 [C᎐CSi(CH ) ], 118.5, 124.8,
᎐
᎐
3
2
3
3
3 3
128.5, 136.5, 136.7 and 154.9 (quaternary Ar-C) and 174.0
(CO2H).
1480
J. Chem. Soc., Perkin Trans. 1, 1998