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G. Enierga et al. / Tetrahedron: Asymmetry 12 (2001) 597–604
NMR (300 MHz, CDCl3): d 1.37 (s, 3H, CH3), 1.40 (s,
3H, CH3), 1.52–1.60 (m, 2H, 2×H-2), 2.12–2.38 (m, 2H,
2×H-3), 2.49–2.68 (bs, 2H, NH2), 2.75 (t, 2H, J=7.3
Hz, 2×H-1), 3.54 (t, 1H, J=8.3 Hz, H-5%), 4.08 (m, 1H,
H-5%), 4.84–4.92 (m, 1H, H-4%), 5.44 (m, 1H, H-4),
5.62–5.70 (m, 1H, H-5). 13C NMR (75 MHz, CDCl3): d
24.9 (C-3), 25.8 (CH3), 26.6 (CH3), 33.2 (C-2), 41.3
(C-1), 69.1 (C-5%), 71.5 (C-4%), 108.6 (CMe2), 128.2
(C-4), 131.7 (C-5).
(CH2Ph), 76.5 (C-4%), 109.2 (CMe2), 127.2, 127.3, 128.6,
136.1 (Ph), 156.2 (CO). HRMS calcd for (M+Na+)
C18H24ClHgNNaO4: 578.0997. Found: 578.0998. Anal.
calcd for C18H24ClHgNO4: C, 38.99; H, 4.36; N, 2.53.
Found: C, 39.06; H, 4.23; N, 2.57%.
4.12. N-Benzyloxycarbonyl-(5R)-[((4S)-2,2-dimethyl-
1,3-dioxolan-4-yl)methyl]pyrrolidine 20
Tributylstannane (0.63 g, 2.16 mmol) was added drop-
wise to a stirred solution of 19 (0.3 g, 0.54 mmol) and
AIBN (0.03 g, 0.18 mmol) in toluene (3 mL) under a
nitrogen atmosphere. Metallic mercury immediately
began to precipitate. The reaction was stirred at rt for
1 h and then at 70°C for 2 h. The mixture was allowed
to cool to rt. Carbon tetrachloride (2 mL) was added
and the mixture stirred for an additional 1 h. The
solution was decanted from the precipitated mercury,
diluted with ether (100 mL) and washed with a 5%
aqueous potassium fluoride solution (2×45 mL). The
organic layer was dried (MgSO4), filtered and concen-
trated in vacuo. Purification of the residue by column
chromatography (ethyl acetate–dichloromethane 1:4,
Rf=0.5) gave 20 as a yellow oil (0.13 g, 73%). [a]D
4.10. N-Benzyloxycarbonyl-(4Z)-5-[(4S)-2,2-dimethyl-
1,3-dioxolan-4-yl]-4-pentenamine 18
Benzyl chloroformate (2.4 mL, 1.62 mmol) was added
dropwise to an ice-cooled solution of the amine 17 (252
mg, 1.35 mmol) and triethylamine (3 mL, 2.16 mmol) in
THF (5 mL) under nitrogen. The reaction mixture was
stirred overnight at rt, filtered and the solid washed
with ether. The filtrate was washed with saturated
aqueous sodium chloride, separated and dried
(Na2SO4). The solvent was removed under reduced
pressure and the crude product was purified by flash
chromatography (ethyl acetate–hexane 1:3, Rf=0.7).
Carbamate 18 was obtained as a yellow oil (0.29 g,
66%). [a]D −10.0 (c 1.0, CH2Cl2). IR nmax (cm−1): 3364
1
+35.1 (c 1.0, CH2Cl2). IR nmax (cm−1): 1699 (CO). H
1
(NH), 1706 (CO). H NMR (300 MHz, CDCl3): d 1.37
NMR (300 MHz, CDCl3): d 1.32 (s, 3H, CH3), 1.37 (s,
3H, CH3), 1.53–1.68 (bm, 2H, 2×H-3), 1.81–1.93 (bm,
4H, 2×H-4 and 2×H), 3.38 (m, 2H, 2×H-2), 3.52 (m,
1H, H-5%a), 3.86 (m, 1H, H-5%b), 4.04 (m, 1H, H-5),
4.16 (m, 1H, H-4%), 5.10 (m, 2H, CH2Ph), 7.32 (m, 5H,
Ph). 13C NMR (75 MHz, CDCl3): d 24.1 (C-3), 26.1
(CH3), 27.3 (CH3), 31.1 (C-4), 38.7 (CH2), 46.4 (C-2),
54.4 (C-5), 66.8 (CH2Ph), 67.3 (C-5%), 68.5 (C-4%), 108.2
(CMe2), 127.6, 127.7, 128.3, 137.8 (Ph), 154.9 (CO).
HRMS calcd for (M+Na+) C18H25NaO4: 342.1681.
Found: 342.1681. Anal. calcd for C18H25NO4: C, 67.69;
H, 7.89; N, 4.39. Found: C, 67.39; H, 7.76; N, 4.46%.
(s, 3H, CH3), 1.41 (s, 3H, CH3), 1.65 (m, 2H, 2×H-2),
2.25 (m, 2H, 2×H-3), 3.21 (m, 2H, 2×H-1), 3.53 (t, 1H,
J=7.8 Hz, H-5%), 4.10 (m, 1H, H-5%), 4.81 (m, 1H,
H-4%), 5.10 (bs, 3H, CH2Ph and NH), 5.41–5.50 (m, 1H,
H-4), 5.56–5.66 (m, 1H, H-5), 7.30–7.39 (m, 5H, Ph).
13C NMR (75 MHz, CDCl3): d 24.9 (C-3), 25.9 (CH3),
26.7 (CH3), 27.4 (C-2), 39.9 (C-1), 66.4 (CH2Ph), 69.4
(C-5%), 71.6 (C-4%), 109.1 (CMe2), 127.7, 127.9, 128.3
(Ph), 134.2 (C-4), 136.5 (C-5), 156.2 (CO). HRMS calcd
for (M+Na+) C18H25NNaO4: 342.1681. Found:
342.1911.
4.11. N-Benzyloxycarbonyl-(5R)-5-[(S)-chloromercu-
rio((4S)-2,2-dimethyl-1,3-dioxolan-4-
yl)methyl]pyrrolidine 19
4.13. N-Benzyloxycarbonyl-(5R)-5-[(2S)-2,3-dihydroxy-
prop-1-yl]pyrrolidine 21
A solution of mercuric acetate (1.99 g, 6.26 mmol) in
dry dichloromethane (34 mL) was added slowly to a
stirred solution of carbamate 18 (1 g, 3.13 mmol). The
mixture was allowed to stir for 24 h at rt, aqueous
saturated NaCl was added and the mixture was stirred
for an additional 15 min. The organic phase was dried
(Na2SO4), filtered and concentrated in vacuo. Purifica-
tion by column chromatography (ethyl acetate–
dichloromethane 1:4, Rf=0.75) of the crude residue
afforded pyrrolidine 19 as a white solid (1.4 g, 82%).
[a]D +59.6 (c 1.0, CH2Cl2). IR nmax (cm−1): 1664 (CO).
1H NMR (300 MHz, CDCl3): d 1.26 (s, 3H, CH3), 1.39
(s, 3H, CH3), 1.78–1.98 (m, 4H, 2×H-3 and 2×H-4),
2.62 (dd, 1H, J=11.6, 5.8 Hz, CHHgCl), 3.31 (m, 2H,
2×H-2), 3.58 (t, 1H, J=7.6 Hz, H-5%a), 3.84–3.94 (m,
1H, H-5), 4.08 (bt, J=5.9 Hz, 1H, H-5%b), 4.36 (m, 1H,
H-4%), 5.05 and 5.08 (ABq, 2H, J=11.4 Hz, CH2Ph),
7.30–7.39 (m, 5H, Ph). 13C NMR (75 MHz, CDCl3): d
23.9 (C-3), 25.7 (CH3), 27.4 (CH3), 32.1 (C-4), 46.5
(C-2), 59.8 (C-HgCl), 60.1 (C-5), 67.5 (C-5%), 70.9
A 50% aqueous acetic acid solution (1 mL) was added
to 20 (50 mg, 0.16 mmol) and the resulting solution was
stirred at rt for 24 h. The solvent was removed under
reduced pressure without heating. Toluene (0.5 mL)
was added and the solvent was concentrated in vacuo.
Purification of the crude mixture by flash chromatogra-
phy (ethyl acetate, Rf=0.5) afforded the diol 21 as a
yellow oil (45 mg, 77%). [a]D −2.4 (c 1.0, CH2Cl2). IR
nmax (cm−1): 3404 (OH), 1676 (CO). 1H NMR (300
MHz, CDCl3): d 1.44 (m, 2H, H-1%), 1.63 (m, 2H,
2×H-4), 1.94 (m, 3H, 2×H-3 and OH), 3.43 (bt, J=6.6
Hz, 2H, 2×H-2), 3.46–3.61 (bm, 2H, 2×H-3%), 3.68 (m,
1H, H-5), 4.26 (m, 1H, H-2%), 5.15 (s, 2H, CH2Ph), 7.36
(m, 5H, Ph). 13C NMR (75 MHz, CDCl3): d 23.6 (C-1%),
31.3 (C-3), 39.3 (C-4), 46.5 (C-2), 54.5 (C-5), 66.5
(CH2Ph), 67.4 (C-3%), 68.7 (C-2%), 127.9, 128.2, 128.6,
136.6 (Ph), 157.1 (CO). HRMS calcd for (M+Na+)
C15H21NaO4: 302.1368. Found: 302.1365. Anal. calcd
for C15H21NO4: C, 64.5; H, 7.58; N, 5.01. Found: C,
64.34; H, 7.48; N, 4.86%.