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S. Bazin et al. / Tetrahedron 61 (2005) 4261–4274
an enriched chromatographic fraction: d 1.10 (s, 9H), 2.80
(br s, 1H, OH), 5.6 (br, s, 1H, C]CH).
(d, 3H, JZ6.8 Hz), 0.78 (d, 3H, JZ6.8 Hz), 1.04 (d, 3H,
JZ7.0 Hz), 1.07 (d, 3H, JZ7.0 Hz), 2.14 (dsept, 1H, JZ
4.2, 7.0 Hz), 2.33 (oct, 1H, JZ6.8 Hz), 3.47–3.56 (m, 2H),
3.57–3.63 (m, 1H), 3.96 (dd, 1H, JZ1.7, 8.5 Hz), 4.95 (dd,
1H, JZ6.8, 9.4 Hz), 5.78 (d, 1H, JZ9.4 Hz), 7.17–7.25 (m,
2H), 7.31–7.38 (m, 3H). 13C NMR (75 MHz): d 14.7 (CH3),
17.7 (CH3), 18.9 (CH3), 20.2 (CH3), 28.5 (CH), 28.8 (CH),
47.3 (CH), 47.5 (CH), 58.8 (CH), 63.5 (CH2), 79.3 (CH),
127.4 (CH), 128.4 (CH), 129.1 (CH), 135.9 (C), 153.8 (C),
169.5 (C), 177.1 (C). [a]2D5ZC4 (c 1.02, CHCl3).
4.2.16. 2-tert-Butyl-1,4-bis-((S)-4-i-propyl-2-oxo-oxazoli-
din-3-yl)-butane-1,4-dione (13a,b). To a solution contain-
ing 1 (50 mg, 0.148 mmol) and ZnCl2 (40 mg, 0.3 mmol) in
a 4:1 mixture of CH2Cl2 (3 mL) and THF (740 mL), were
added t-BuI (0.74 mmol, 89 mL) and Bu3SnH (0.3 mmol,
80 mL, 2 equiv) at K78 8C. Et3B (1 M in hexane, 0.3 mmol,
300 mL) was then added via syringe, and then air (7.4 mL)
was added with a syringe pump over 15 min. The reaction
was stirred for 1 h at K78 8C, then the reaction mixture was
diluted with Et2O (22 mL), washed with 1 M HCl (2!
3 mL) and concentrated. The residue dissolved in CH2Cl2
was washed with saturated Na2S2O3, the organic phase was
dried over MgSO4 and concentrated. After dilution with
Et2O, the solution was stirred with KF (5 equiv) overnight,
filtered, concentrated and the residue was purified by flash
chromatography (0–50%, EtOAc–pentane) to give 13a and
13b in a 60:40 ratio (37 mg, 0.093 mmol, 63%).
1
Compound 17. H NMR (300 MHz): d 0.74 (d, 3H, JZ
6.8 Hz), 0.88 (d, 3H, JZ6.8 Hz), 1.04 (d, 3H, JZ6.8 Hz),
1.14 (d, 3H, JZ6.8 Hz), 2.02 (oct, 1H, JZ6.8 Hz), 2.38
(dsept, 1H, JZ4.1, 6.9 Hz), 2.97 (dd, 1H, JZ5.9, 8.7 Hz),
4.24 (dd, 1H, JZ9.3, 3.4 Hz), 4.34 (dd, 1H, JZ9.3, 8.3 Hz),
4.35–4.40 (superimposed m, 1H), 4.56 (dd, 1H, JZ8.5,
7.0 Hz), 5.82 (d, 1H, JZ7.0 Hz), 7.29–7.46 (m, 5H). 13C
NMR (75 MHz): d 14.4 (CH3), 17.8 (CH3), 19.7 (CH3), 21.9
(CH3), 27.7 (CH), 28.0 (CH), 48.2 (CH), 52.7 (CH), 58.6
(CH), 63.6 (CH2), 80.1 (CH), 125.4 (CH), 128.8 (CH), 128.6
(CH), 138.0 (C), 153.5 (C]O), 169.5 (C]O), 175.4
(C]O). [a]2D5ZK16 (c 1.04, CHCl3).
4.2.17. 2-[2-((S)-4-i-Propyl-2-oxo-oxazolidin-3-yl)-2-oxo-
ethyl]-3,3-dimethyl-butyric acid ethyl ester (14). Treating
2 (50 mg, 0.196 mmol) with Et2Zn (0.35 mmol, 353 mL)
and t-BuI (8.82 mmol, 1.1 mL) according to the procedure
already described for the preparation of 13, led after
purification by FC (5–30%, EtOAc–pentane) to 14 (46 mg,
0.147 mmol, 75%) as a nearly 1:1 mixture of diastereomers.
1
Compound 16. H NMR (300 MHz): d 0.74 (d, 3H, JZ
6.8 Hz), 0.78 (d, 3H, JZ6.8 Hz), 0.89 (d, 3H, JZ6.8 Hz),
1.31 (d, 3H, JZ6.8 Hz), 2.11 (dsept, 1H, JZ4.3, 6.8 Hz),
2.24 (dsept, 1H, JZ10.2, 6.8 Hz), 2.61 (dd, 1H, JZ6.6,
10.2 Hz), 3.20 (dd, 1H, JZ8.1, 8.9 Hz), 3.64 (ddd, 1H, JZ
2.1, 4.3, 8.1 Hz), 3.84 (dd, 1H, JZ2.1, 8.9 Hz), 5.36 (dd,
1H, JZ5.7, 6.6 Hz), 5.56 (d, 1H, JZ5.7 Hz), 7.31–7.40 (m,
5H). 13C NMR (75 MHz): d 15.0 (CH3), 17.7 (CH3), 21.3
(CH3), 21.7 (CH3), 25.4 (CH), 29.0 (CH), 48.2 (CH), 51.4
(CH), 58.6 (CH), 63.6 (CH2), 79.0 (CH), 125.6 (CH), 128.3
(CH), 128.4 (CH), 134.9 (C), 153.4 (C]O), 169.0 (C]O),
175.7 (C]O). [a]D25ZC109.4 (c 1.02, CHCl3).
1H NMR (300 MHz): d 0.87 (d, 6H, JZ6.8 Hz), 0.88 (d, 3H,
JZ6.8 Hz), 0.90 (d, 3H, JZ6.8 Hz), 1.00 (s, 9H), 1.01 (s,
9H), 1.26 (t, 3H, JZ7.0 Hz), 1.28 (t, 3H, JZ7.2 Hz), 2.22–
2.42 (m, 2H), 2.65 (dd, 1H, JZ12.1, 2.9 Hz), 2.68 (dd, 1H,
JZ12.1, 2.9 Hz), 3.10 (dd, 1H, JZ18.5, 2.9 Hz), 3.14 (dd,
1H, JZ18.3, 2.9 Hz), 3.35 (dd, 1H, JZ18.9, 12.1 Hz), 3.42
(dd, 1H, JZ18.5, 12.1 Hz), 4.04–4.30 (m, 8H), 4.35–4.45
(m, 2H). 13C NMR (75 MHz): d 14.2 (CH3), 14.3 (CH3),
14.6 (CH3), 14.7 (CH3), 17.8 (CH3), 17.9 (CH3), 28.0 (2!
CH3), 28.3 (CH), 28.4 (CH), 32.5 (C), 32.6 (C), 34.7 (2!
CH2), 50.6 (CH), 50.8 (CH), 58.3 (CH), 58.4 (CH), 60.1
(CH2), 60.2 (CH2), 63.4 (CH2), 63.5 (CH2), 154.1 (2!
C]O), 172.3 (C]O), 172.5 (C]O), 174 (C]O), 174.4
(C]O). HRMS calcd for C16H28NO5 [MHC]: 314.1967;
found: 314.1968.
1
Compound 18. Mp 181 8C. H NMR (300 MHz): d K0.01
(d, 3H, JZ7.0 Hz) (the shielding indicates that the protons
are held above the aromatic ring as confirmed by X-ray
spectroscopy28), 0.67 (d, 3H, JZ7.0 Hz), 0.84 (d, 3H, JZ
6.6 Hz), 1.30 (d, 3H, JZ6.6 Hz), 1.64 (dsept, 1H, JZ2.7,
7.0 Hz), 2.06 (dsept, 1H, JZ10.6, 6.6 Hz), 2.64 (dd, 1H, JZ
6.6, 10.6 Hz), 4.03 (dd, 1H, JZ2.7, 9.3 Hz), 4.10 (t, 1H, JZ
9.3 Hz), 4.25 (dt, 1H, JZ9.3, 2.7 Hz), 5.39 (dd, 1H, JZ5.6,
6.6 Hz), 5.63 (d, 1H, JZ5.6 Hz), 7.24–7.37 (m, 3H), 7.38–
7.45 (m, 2H). 13C NMR (75 MHz): d 13.6 (CH3), 18.0
(CH3), 21.2 (CH3), 21.9 (CH3), 25.8 (CH), 28.3 (CH), 47.3
(CH), 52.4 (CH), 58.5 (CH), 63.0 (CH2), 79.3 (CH), 126.0
(CH), 128.4 (CH), 128.5 (CH), 134.4 (C), 153.5 (C]O),
169.1 (C]O), 175.4 (C]O). [a]2D5ZC54 (c 1.01, CHCl3).
4.2.18. 3-(4-i-Propyl-5-oxo-2-phenyl-tetrahydro-furan-
3-carbonyl)-4-i-propyl-oxazolidin-2-one (15–20). Treat-
ing 1 (100 mg, 0.29 mmol) according to method B led to a
mixture of isomeric lactones 15–20 (76 mg, 0.215 mmol,
73%) isolated after purification by FC (5–20%, EtOAc–
pentane). The diastereomeric ratio (34:9.5:27:16.5:6:7),
given by order of elution, was determined on the isolated
products after having achieved a complete separation of the
mixture by chiral HPLC (CHIRALCEL OD (250!10 mm),
hexane–ethanol (80:20), 4.5 mL/min, UV detection at
220 nm). This led by order of elution to 15 (4.90 min,
26.2 mg, 34%), 17 (5.90 min, 7.3 mg, 9.5%), 16 (6.79 min,
20.6 mg, 27%), 18 (9.06 min, 12.7 mg, 16.5%), 19
(10.10 min, 4.6 mg, 6%), 20 (11.45 min, 5.1 mg, 7%).
Anal. Calcd for C20H25NO5 (mixture of isomers): C, 66.84;
H, 7.01; N, 3.90. Found: C, 66.90; H, 6.95; N, 3.81.
1
Compound 19. H NMR (300 MHz): d 0.25 (d, 3H, JZ
7.0 Hz), 0.66 (d, 3H, JZ7.0 Hz), 1.01 (d, 3H, JZ7.0 Hz),
1.05 (d, 3H, JZ7.0 Hz), 1.51–1.62 (m, 1H), 2.28 (dsept, 1H,
JZ5.1, 7.0 Hz), 3.56 (dd, 1H, JZ5.1, 8.3 Hz), 4.08–4.25
(m, 3H), 4.67 (dd, 1H, JZ8.3, 9.3 Hz), 5.96 (d, 1H, JZ
9.3 Hz), 7.23–7.34 (m, 5H). 13C NMR (75 MHz): d 14.3
(CH3), 18.1 (CH3), 19.0 (CH3), 20.0 (CH3), 28.3 (CH), 28.7
(CH), 47.3 (CH), 47.9 (CH), 59.0 (CH), 63.7 (CH2), 79.6
(CH), 127.2 (CH), 128.6 (CH), 129.2 (CH), 135.8 (C), 153.8
(C]O), 169.0 (C]O), 176.8 (C]O). [a]2D5ZC156 (c
0.98, CHCl3).
Compound 15. Mp 125–126 8C. 1H NMR (300 MHz): d 0.76