8600
D. R. Williams et al. / Tetrahedron Letters 42 (2001) 8597–8601
argon was added ZrCl4 (1.5 mmol), NaBH4 (6.0 mmol)
and diethyl ether (12 mL). After 10 min, CH2Cl2 (15
mL) was added dropwise until the mixture became an
evenly dispersed, fine suspension. The mixture was
allowed to stir overnight under argon at room tempera-
ture. Upon cooling to −10°C, a solution of oximino
ether (1.5 mmol) in Et2O (3 mL) was slowly added.
After 30 min, the reaction was allowed to warm to 0°C,
and was maintained at 0°C with continuous stirring for
24 h. The reaction was then quenched by the dropwise
addition of water. This mixture was first acidified with
10% aqueous HCl followed by stirring for 40 min. The
subsequent addition of 25% aqueous NH4OH was fol-
lowed by the separation of the aqueous phase and
extraction with Et2O (3×20 mL) permitted recovery of
the amino alcohol products. The combined organic
extracts were dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. The crude product was
generally purified by flash chromatography or by
preparative TLC techniques (0.50 mm×20 cm×20 cm
plates: EtOAc/hex). Yields of diastereomers and recov-
ered starting oxime accurately accounted for the quan-
tity of starting reactant. Ratios of diastereomers were
Weber, T.; Piotrowski, D. W. J. Am. Chem. Soc. 1987,
109, 2224; (c) Yamamoto, Y.; Komatsu, T.; Maruyama,
K. J. Chem. Soc., Chem. Commun. 1985, 814.
4. (a) Narasaka, K.; Uraji, Y. Chem. Lett. 1984, 147; (b)
Narasaka, K.; Yamazaki, S.; Uraki, Y. Chem. Lett. 1984,
2065; (c) Narasaka, K.; Uraki, Y.; Yamazaki, S. Bull.
Chem. Soc. Jpn. 1986, 59, 525.
5. Iida, H.; Yamazaki, N.; Kibayashi, C. J. Chem. Soc.,
Chem. Commun. 1987, 746.
6. Harada, K.; Shion, S. Bull. Chem. Soc. Jpn. 1984, 57,
1040.
7. Williams, D. R.; Osterhout, M. H. J. Am. Chem. Soc.
1992, 114, 8750.
8. Williams, D. R.; Osterhout, M. H.; Reddy, J. P. Tetra-
hedron Lett. 1993, 34, 3271.
9. Williams, D. R.; Osterhout, M. H.; McGill, J. M. Tetra-
hedron Lett. 1989, 30, 1327.
10. Benbow, J. W. Ph. D. Thesis, Indiana University, 1990,
pages 21–31. The starting ester 1 was prepared via the
alkylation of the monoanion of tert-butyl pyruvate
oximino ether followed by Sharpless asymmetric epoxida-
tion of the Z-allylic alcohol (Williams, D. R.; Benbow, J.
W. Tetrahedron Lett. 1990, 31, 5881).
1
evaluated by integration of selected H NMR signals,
and subsequently by analytical HPLC separations.
11. Generally it is difficult to avoid concomitant reduction of
the NꢁO bond, and substantial amounts of cyclized and
uncyclized (NꢁH) amine side products are produced.
12. The 3-oxa-8-azabicyclo[3.2.1]octane skeleton of 4 was
characterized as follows: Rf=0.55 in 50% EtOAc/hex-
anes; IR (neat) w 2959, 2930, 2860, 1461, 1150–1073 (br)
In summary, the partial (CꢀN) reduction of oximino
ethers can be accomplished without NꢁO bond cleav-
age, providing novel N-alkoxyamine derivatives. Stud-
ies suggest that the in situ generation of zirconium
borohydride facilitates formation of an activated chela-
tion complex due to the presence of a neighboring
hydroxyl group. Modest diastereofacial selectivity is
observed based upon the configuration of the resident
secondary alcohol.
cm−1 1H NMR (400 MHz) l 4.79 (AB, JAB=7.8 Hz,
;
Dw=19.9 Hz, 2H), 3.89 (d, J=10.9 Hz, 1H), 3.85 (AB of
ABX, JAB=10.2 Hz, JAX=6.3 Hz, JBX=5.5 Hz, Dw=
45.0 Hz, 2H), 3.51 (m, 1H), 3.45 (dd, J=10.9, 3.1 Hz,
1H), 3.39 (s, 3H), 2.16–1.92 (m, 2H), 1.90–1.86 (m, 2H),
0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H); MS (CI, NH3),
m/e (relative intensity) 317 (1), 260 (51), 256 (69), 230
(77), 172 (37), 89 (92), 82 (100); HRMS m/e calcd. For
C15H31NO4Si (M+) 317.2023, found 317.2033.
Acknowledgements
13. (a) Itsuno, S.; Sakurai, Y.; Shimizu, K.; Ito, K. J. Chem.
Soc., Perkin Trans. 1 1989, 1548; (b) Itsuno, S.; Sakurai,
Y.; Shimizu, K.; Ito, K. J. Chem. Soc., Perkin Trans. 1
1990, 1859.
We gratefully acknowledge financial assistance pro-
vided by the National Institutes of Health (GM-41560).
14. Karabatsos, G. J.; His, N. Tetrahedron 1967, 23, 1079.
See also: Ref. 5.
References
15. Reductions in THF with Red-Al®, lithium pyrrolidi-
noborohydride, and lithium diethylaminoborohydride
gave only phenylethylene diol and primary amines. See:
Singaram, B.; Fisher, G. B.; Harrison, J.; Fuller, J. C.;
Goralski, C. T. Tetrahedron Lett. 1992, 33, 4533 and
Singaram, B.; Fuller, J. C.; Belisle, C. M.; Goralski, C. T.
Tetrahedron Lett. 1994, 35, 5389. Use of lithium triethyl-
borohydride and zinc borohydride resulted in no reac-
tion, and reduction with tetra-n-butylammonium
triacetoxyborohydride (AcOH/CH3CN) proceeded at
very slow rates for these substrates.
1. (a) Seyden-Penne, J. Chiral Auxiliaries and Ligands in
Asymmetric Synthesis; John Wiley & Sons: New York,
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and use of 1,2-amino alcohols: Ager, D. J.; Prakash, I.;
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Chem. 1989, 54, 3750. Previous studies include: (b)
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Bull. Chem. Soc. Jpn. 1987, 60, 395; (c) Landor, S. R.;
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3. Several noteworthy studies have examined the nucle-
ophilic addition of Grignard reagents, allylboranes and
organolithium species to chiral imines and hydrazones:
(a) Claremon, D. A.; Lumma, P. K.; Phillips, B. T. J.
Am. Chem. Soc. 1986, 108, 8265; (b) Denmark, S. E.;
16. The appearance of sodium chloride precipitate occurs
upon stirring ZrCl4 and NaBH4. Crystalline zirconium
borohydride is essentially tetrahedral as the Zr(h3-BH4)4
complex. For crystallography, see: Bird, P. H.; Churchill,
M. R. Chem. Commun. 1967, 403.
17. Recovered oximino ethers did not undergo CꢀN isomer-
ization under these conditions.