on silica gel, eluting with chloroform–methanol (1:0 to 10:1,
eluant gradient) to give the alcohol 17 (34 mg, 84%) as a
white solid; mp 89–90 ЊC (ethyl acetate–toluene–hexane); RF
0.35 (chloroform–methanol 10:1); [α]D20 Ϫ147.6 (c 1.31,
CHCl3); νmax(CHCl3)/cmϪ1 3490br m (OH), 3376m (NH),
2107s (N3), 1673s (amide CO); δH(400 MHz; CDCl3) 1.88–
2.00 (1H, m, CHH), 2.03–2.22 (2H, m, CH2), 2.57–2.71 (1H,
auxiliary), 4.44 (1H, m, CHN), 4.69 (1H, m, CHN auxiliary),
4.80 (1H, br m, NH), 4.98 (1H, dd, J 8.7, 4.1, CHN3), 5.48–5.55
(2H, m, CH᎐CH), 7.19–7.45 (11H, m, Ph) and 7.64–7.67 (4H,
᎐
m, Ph); δC(100 MHz; CDCl3) 19.3 (SiCMe3), 24.1 (CH2), 26.8
(SiCMe3), 28.3 (OCMe3), 31.0 (CH2), 37.5 (PhCH2), 55.4 (CHN
auxiliary), 59.9 (CHNH), 63.4 (CHN3), 66.2 (CH2OSi), 66.6
(OCH2), 79.1 (OCMe3), 127.3, 127.5, 127.7, 129.0, 129.4, 129.7,
m, ᎐CHCHH), 3.24 (1H, br s, OH), 3.66 (1H, dd, J 11.6, 7.0,
130.2, 133.2, 134.8 and 135.6 (CH᎐CH and Ph), 152.8 and
᎐
᎐
CHHOH), 3.81 (1H, dd, J 11.6, 3.5, CHHOH), 4.03 (1H, dd,
J 11.3, 5.9, CHN3), 4.21 (1H, m, J 1.6, CHN), 5.38 (1H,
155.2 (NCOO carbamate and OCON auxiliary) and 170.8
(CON); m/z (CI) 684 [(M Ϫ N2 ϩ H)ϩ, 10%], 274 (7), 195 (100),
178 (26) and 44 (8) [Found: (M Ϫ N2 ϩ H)ϩ 684.347. C39H50-
N5O6Si requires M, 684.3469].
br dd, J 11.9, 1.6, ᎐CHCHN), 5.83 (1H, ddt, J 11.9, 8.9, 2.1,
᎐
᎐CHCH ) and 7.56 (1H, br s, NH); δ (100 MHz; CDCl )
᎐
2
C
3
22.2 and 30.5 (2 × CH2), 56.4 (CHN), 57.7 (CHN3), 64.2
(CH OH), 129.0 and 129.7 (CH᎐CH) and 174.7 (CON); m/z
(5Z,2R,7R)-2-Azido-8-(tert-butyldiphenylsilyloxy)-7-(tert-
butyloxycarbonylamino)oct-5-enoic acid 24. Carboximide 23
(E:Z ratio 1:13, 975 mg, 1.38 mmol) was applied to the pro-
cedure described for acid 15 and the acid 24 was isolated (708
mg, 94%, E:Z ratio 1:13) as a very pale yellow oil; RF 0.33
(hexane–ethyl acetate–acetic acid 100:100:1); [α]D23 Ϫ7.4 (c 0.60,
᎐
2
(CI) 197 [(M ϩ H)ϩ, 51%], 169 [(M Ϫ N2 ϩ H)ϩ, 100], 152 (8)
and 137 (9) [Found: (M ϩ H)ϩ 197.1039. C8H13N4O2 requires
M, 197.1038).
(4R)-3-[(5Z,2R,7R)-2-Azido-7-(tert-butyloxycarbonylamino)-
8-hydroxy-1-oxooct-5-enyl]-4-phenylmethyl-1,3-oxazolidin-2-
one 22. A solution of acetonide (E:Z ratio 1:13, 1.22 g, 1.9
mmol) in acetic acid–water (4:1, 25 cm3) was warmed to 40–
50 ЊC and stirred for 4 h. TLC showed the reaction to be com-
plete. The solvents were removed in vacuo and residual traces of
acetic acid and water removed azeotropically with toluene
(2 × 25 cm3). The crude residue was purified by flash chrom-
atography on silica gel, eluting with hexane–ethyl acetate (2:1
to 1:2, eluant gradient) to give the alcohol 22 (807 mg, 90%) as
a colourless oil; RF 0.15 (hexane–ethyl acetate 1:1); [α]D22 Ϫ36.6
(c 0.94, CHCl3); νmax(CHCl3)/cmϪ1 3442br m (NH, OH), 3052w
(HPh), 2109s (N3), 1782s (carboximide CO), 1705s (carbamate
CO); δH(400 MHz; CDCl3) 1.43 (9H, s, CMe3), 1.83–2.02 (2H,
CHCl3); νmax(CHCl3)/cmϪ1 3444w (NH), 3100–2500br
w
(COOH), 3072w (HPh), 2109s (N3), 1714s (acid CO); δH(500
MHz; CDCl3) 1.07 (9H, s, SiCMe3), 1.45 (9H, s, OCMe3), 1.74–
1.95 (2H, m, CH CHN ), 2.06–2.29 (2H, m, ᎐CHCH ), 3.59
᎐
2
3
2
(1H, dd, J 10, 5.3, OCHH), 3.68 (1H, br m, OCHH), 3.88 (1H,
m, NH), 4.44 (1H, br m, CHN), 4.96 (1H, br m, CHN3), 5.45
(2H, br m, CH᎐CH), 7.37–7.46 (6H, m, Ph) and 7.64–7.67
᎐
(4H, m, Ph); δC(100 MHz; CDCl3) 19.2 (SiCMe3), 23.9 (CH2),
26.8 (SiCMe3), 28.4 (OCMe3), 31.1 (CH2), 49.7 (CHNH), 61.3
(CHN3), 66.2 (CH2OSi), 79.9 (OCMe3), 127.7, 129.0, 129.8,
130.6, 133.1 and 137.8 (CH᎐CH and Ph), 155.8 (NCOO
᎐
carbamate) and 173.9 (COOH); m/z (CI) 553 [(M ϩ H)ϩ, 2%],
525 [(M Ϫ N2 ϩ H)ϩ, 6], 481 (12), 274 (30), 208 (26), 135
(59) and 79 (100) [Found: (M ϩ H)ϩ 553.285. C29H41N4O5Si
requires M, 553.2846].
m, CH CHN ), 2.28–2.44 (2H, m, ᎐CHCH ), 2.66 (1H, br s,
᎐
2
3
2
OH), 2.81 (1H, dd, J 13.4, 9.5, CHHPh), 3.32 (1H, dd, J 13.4,
3.1, CHHPh), 3.52–3.62 (2H, m, OCH2 auxiliary), 4.22 (1H, dd,
J 9.1, 2.8, OCHH), 4.28 (1H, br t, J 9.1, OCHH), 4.42 (1H, m,
CHN), 4.68 (1H, m, CHN auxiliary), 4.75 (1H, br m, NH), 4.96
(3R,8R)-3-Azido-8-(tert-butyldiphenylsilyloxymethyl)-1,2,3,
4,5,8-hexahydroazocin-2-one 26. A solution of Boc-amino
acid 24 (E:Z ratio 1:13, 426 mg, 0.77 mmol) in DCM (10
cm3) was cooled to 0 ЊC, treated with TFA (5 cm3) and stirred
at 0 ЊC for 35 minutes. The solvents were removed in vacuo
and the residual pale brown resin was dried at high vacuum
(0.05 mmHg) for 1.5 h. The amino acid TFA salt 25 was
dissolved in THF (200 cm3) and cooled to 0 ЊC. Then tri-
ethylamine (0.38 cm3, 2.70 mmol) was added, the mixture
stirred for 15 minutes and diphenoxyphosphoryl azide (0.42
cm3, 1.93 mmol) added. The stirred mixture was allowed to
warm to rt. After 20 h, TLC showed only little product and
more triethylamine (0.25 cm3, 1.93 mmol) and diphenyl-
phosphoryl azide (0.42 cm3, 1.93 mmol) were added. Stirring
was continued at 30–35 ЊC for a further 24 h. The resulting pale
brown reaction mixture was concentrated in vacuo and the
crude material purified by flash chromatography on silica gel,
eluting with hexane–ether (1:0 to 3:1, eluant gradient) to
give the lactam 26 (245 mg, 73%) as a very pale yellow oil;
RF 0.20 (hexane–ether 2:1); [α]D23 Ϫ21.3 (c 0.76, CHCl3);
νmax(CHCl3)/cmϪ1 3378m (NH), 3073w (HPh), 3054w (HPh),
2107s (N3), 1676s (amide CO); δH(400 MHz; CDCl3) 1.06
(1H, dd, J 9.2, 4.2, CHN ), 5.38 (1H, dd, J 10.6, 2, ᎐CHCHN),
᎐
3
5.51 (1H, dt, J 10.6, 7.6, ᎐CHCH ) and 7.19–7.36 (5H, m, Ph);
᎐
2
δC(100 MHz; CDCl3) 24.2 (CH2), 28.3 (CMe3), 30.8 (CH2), 37.5
(PhCH2), 50.5 (CHNH), 55.5 (CHN auxiliary), 59.8 (CHN3),
66.2 (CH2OH), 66.7 (OCH2), 79.9 (OCMe3), 127.5, 129.0,
129.4, 131.5 and 134.7 (CH᎐CH and Ph), 152.9 and 156.2
᎐
(NCOO carbamate and OCON auxiliary) and 170.8 (CON);
m/z (CI) 474 [(M ϩ H)ϩ, 1%], 446 [(M Ϫ N2 ϩ H)ϩ, 3%], 195
(100), 178 (39) and 44 (41) [Found: (M Ϫ N2 ϩ H)ϩ 446.2291.
C23H32N3O6 requires M, 446.2291].
(4R)-3-[(5Z,2R,7R)-2-Azido-8-(tert-butyldiphenylsilyloxy)-7-
(tert-butyloxycarbonylamino)-1-oxooct-5-enyl]-4-phenylmethyl-
1,3-oxazolidin-2-one 23. A solution of alcohol 22 (E:Z-ratio
1:13, 780 mg, 1.65 mmol) in DMF (2.5 cm3) was treated with
tert-butyldiphenylchlorosilane (0.65 cm3, 2.52 mmol) and imid-
azole (290 mg, 4.2 mmol) and the pale yellow mixture stirred
at rt for 16 h. TLC showed the reaction to be complete. The
mixture was poured into water (50 cm3), extracted with ethyl
acetate (3 × 50 cm3), the combined organic layers dried
(MgSO4) and the solvent removed under reduced pressure to
give a pale yellow oil. The crude material was purified by flash
chromatography on silica gel, eluting with hexane–ethyl acetate
(5:1 to 3:1, eluant gradient) to give the silyl ether 23 (1.01 g,
86%, E:Z ratio 1:13) as a white foam; RF 0.57 (hexane–ethyl
acetate 1:1); [α]D23 Ϫ40.2 (c 1.41, CHCl3); νmax(CHCl3)/cmϪ1
3445m (NH), 3071w (HPh), 2108m (N3), 1783s (carboximide
CO), 1705s (carbamate CO); δH(500 MHz; CDCl3) 1.07 (9H, s,
SiCMe3), 1.44 (9H, s, OCMe3), 1.75–1.99 (2H, m, CH2CHN3),
(9H, s, CMe ), 1.78–2.16 (3H, m, ᎐CHCHHCH ), 2.55–2.68
᎐
3
2
(1H, m, ᎐CHCHH), 3.56 (1H, dd, J 10.5, 7.1, OCHH), 3.76
᎐
(1H, dd, J 10.5, 3.5, OCHH), 3.96 (1H, dd, J 11.2, 5.6,
CHN3), 4.09 (1H, br m, CHNH), 5.27 (1H, dd, J 11, 5,
CHNCH᎐), 5.76 (1H, dt, J 11, 7, CH CH᎐), 6.13 (1H, br m,
᎐
᎐
2
NH), 7.37–7.47 (6H, m, Ph) and 7.57–7.65 (4H, m, Ph);
δC(100 MHz; CDCl3) 19.2 (SiCMe3), 22.3 (CH2), 26.8
(CMe3), 30.1 (CH2), 55.1 and 58.0 (CHN and CHN3), 65.1
(OCH2), 127.9, 129.1, 129.4, 129.8, 130.1, 132.4, 132.5, 135.4
2.16–2.37 (2H, m, ᎐CHCH ), 2.84 (1H, dd, J 13.5, 9.7,
and 135.5 (CH᎐CH and Ph) and 173.1 (CON); m/z (CI) 435
᎐
᎐
2
CHHPh), 3.34 (1H, dd, J 13.5, 3.0, CHHPh), 3.61 (1H, dd,
J 10.1, 5, OCHH), 3.70 (1H, dd, J 10.1, 4.5, OCHH), 4.21 (1H,
dd, J 9.0, 2.8, OCHH auxiliary), 4.26 (1H, br t, J 9.0, OCHH
[(M ϩ H)ϩ, 57%], 407 [(M Ϫ N2 ϩ H)ϩ, 48], 344 (100), 327
(45), 274 (18), 153 (19), 137 (33) and 88 (55) [Found:
(M ϩ H)ϩ 435.2216. C24H31N4O2Si requires M, 435.2216].
2954
J. Chem. Soc., Perkin Trans. 1, 2000, 2943–2956