J.-C. Lee et al. / Tetrahedron Letters 42 (2001) 4519–4521
4521
Interscience Conference on Antimicrobial Agents and
Chemotherapy, New York, 4–7 October 1987; (b) Sato,
K.; Okachi, R.; Matsukuma, I.; Mochida, K.; Hirata, T. J.
Antibiot. 1989, 42, 1844.
at 0oC, the green solution became pale yellow and there
was no starting material present by TLC analysis. Satu-
rated aqueous sodium sulfite solution (7 mL) was added
and the solution was stirred for 30 min. Then, the two
layers were separated and the aqueous layer was extracted
with EtOAc (3×10 mL). The combined organic extracts
were washed with brine, dried over anhydrous MgSO4 and
evaporated under reduced pressure. The residue was
purified by flash chromatography on silica gel (25–33%
EtOAc–n-hexane gradient elution) to afford the desired
product (2S,3R)-6-benzyloxy-3-tert-butoxycarbonylamino-
2-hydroxy-hexanoic acid ethyl ester 4 (251 mg, 66% yield,
89% ee) as an oil and the regioisomer (2S,3R)-6-benzyl-
oxy-2-tert-butoxycarbonylamino-3-hydroxy-hexanoic acid
2. For a recent review of carbacephalosporins, see: Zhang, T.
Y.; Hatfield, L. D. In Comprehensive Heterocyclic Chem-
istry, 2nd ed.; Scriven, E. F. V.; Rees, C. W., Eds.;
Elsevier: London, 1996; Vol. 1, Chapter 20.
3. (a) Matsukuma, I.; Yoshiiye, S.; Mochida, K.; Hashimoto,
Y.; Sato, K.; Okachi, R.; Hirata, T. Chem. Pharm. Bull.
1989, 37, 1239; (b) Evans, D. A.; Sjogren, E. B. Tetra-
hedron Lett. 1985, 26, 3787; (c) Cooper, R. D. G.; Daugh-
erty, B. W.; Boyd, D. B. Pure Appl. Chem. 1987, 59, 485.
4. (a) Guzzo, P. R.; Miller, M. J. J. Org. Chem. 1994, 59,
4862; (b) Lotz, B. T.; Miller, M. J. J. Org. Chem. 1993, 58,
618; (c) Jackson, P. G.; Pedersen, S. W.; Fisher, J. W.;
Misner, J. W.; Gardner, J. P.; Staszak, M. A.; Doecke, C.;
Rizzo, J.; Aikins, J.; Farkas, E.; Trinkle, K. L.; Vicenzi, J.;
Reinhard, M.; Kroeff, E. P.; Higginbotham, C. A.; Gazak,
R. J.; Zhang, T. Y. Tetrahedron 2000, 56, 5667.
5. (a) Li, G.; Chang, H.; Sharpless, K. B. Angew. Chem., Int.
Ed. Engl. 1996, 35, 451; (b) O’Brien, P. Angew. Chem., Int.
Ed. Engl. 1999, 38, 326.
6. Deeter, J. B.; Hall, D. A.; Jordan, C. L.; Justice, R. M.;
Kinnick, M. D.; Morin, Jr., J. M.; Paschal, J. W.; Ternan-
sky, R. J. Tetrahedron Lett. 1993, 34, 3051.
7. Typical procedure for the synthesis of 4. A 50 mL round-
bottomed flask was charged with t-butyl carbamate (364
mg, 3.10 mmol) and n-propanol (4 mL). To this stirred
solution was added a freshly prepared aqueous solution of
NaOH (122 mg, 3.05 mmol in 8 mL water), followed by
t-butyl hypochlorite (0.35 mL, 3.05 mmol). After stirring
for 5 min, a solution of (DHQD)2PHAL (47 mg, 0.06
mmol) in n-propanol (4 mL) was added; the reaction
mixture should be homogeneous at this point. Then, a
solution of the conjugate ester 5 (248 mg, 1.00 mmol,
dissolved in 8 mL of n-propanol) was added, followed by
addition of K2OsO2(OH)4 (14.8 mg, 0.04 mmol). After 1 h
1
ethyl ester (19 mg, 5.0% yield) as an oil. Compound 4: H
NMR (400 MHz, CDCl3): l 7.22–7.31 (m, 5H), 4.79 (br s,
1H), 4.46 (s, 2H), 4.26 (q, J=6.9 Hz, 2H), 4.15 (d, J=2.6
Hz, 1H), 3.96–4.05 (m, 1H), 3.46–3.49 (m, 2H), 1.65–1.75
(m, 4H), 1.41 (s, 9H), 1.27 (t, J=6.9, 3H); 13C NMR (100
MHz, CDCl3) l 13.99, 26.31, 28.14, 28.20, 29.12, 52.60,
62.03, 69.82, 72.27, 72.84, 79.57, 127.45, 127.57, 128.29,
138.44, 155.31, 173.64; CIHRMS m/z calcd for
C20H32NO6(M+H+) 382.2229, found 382.2207; [h]2D7=+
33.7 (c=0.95, CHCl3). The enantiomeric excess of 4 indi-
cated 89% ee by chiral shift analysis with Eu(hfc)3 on the
corresponding MTPA ester and 4 was used as its present
optical purity without further purification.
(2S,3R) - 6 - Benzyloxy - 2 - tert - butoxycarbonyl - amino - 3-
hydroxy-hexanoic acid ethyl ester: 1H NMR (400 MHz,
CDCl3): l 7.22–7.28 (m, 5H), 5.34 (br s, 1H), 4.47 (s, 2H),
4.17 (q, J=6.9 Hz, 2H), 4.10 (d, J=2.6 Hz, 1H), 4.07–4.11
(m, 1H), 3.42–3.45 (m, 2H), 1.56–1.78 (m, 4H), 1.40 (s,
9H), 1.25 (t, J=6.9, 3H); 13C NMR (100 MHz, CDCl3): l
13.90, 26.01, 28.01, 28.11, 28.99, 58.80, 64.10, 69.62, 70.70,
73.37, 79.77, 126.55, 126.87, 127.89, 137.34, 156.30, 174.60;
[h]2D7=+30.2 (c=0.95, CHCl3).
8. Huang, H.; Iwasawa, N.; Mukaiyama, T. Chem. Lett.
1984, 1465.
.