J. Kim, B. Singaram / Tetrahedron Letters 47 (2006) 3901–3903
3903
Table 2. Comparison of CBS catalyst, DIP-Clꢀ, and TarB–NO2 for
the enantioselective reduction of aliphatic ketones
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Entry Ketone
% ee
CBS Catalyst DIP-Clꢀ TarB–NO2
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1
2
3
98a
95b
98b
32b
94
95
80
92a
91a
84a
4
5
26c
7b
82
60
16. Gribble, G. W. Chem. Soc. Rev. 1998, 27, 395–404.
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a See Ref. 2.
b See Ref. 4.
c See Ref. 23.
method is inexpensive and mild, as TarB–NO2 is easily
prepared from 3-nitrophenylboronic acid and tartaric
acid, and NaBH4 is used as the hydride source. Asym-
metric reduction of aliphatic ketones produced the cor-
responding alcohols in enantiomeric excesses of 56–94%.
The utility of this reagent for the reduction of a wide
range of substrates, as well as the low cost and ease with
which it is prepared, make it attractive for both aca-
demic and industrial applications.
21. Salunkhe, A. M.; Burkhardt, E. R. Tetrahedron Lett.
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Acknowledgements
22. General procedure for the reduction of aliphatic ketones.
The reduction of pinacolone is representative. An oven
dried 50 mL round bottom flask was cooled under argon
and charged with 3,3-dimethyl-2-butanone (0.62 mL,
5 mmol) and TarB–NO2 (10 mL of a 0.5 M solution in
THF, 5 mmol) and allowed to stir for 10 min. NaBH4
(0.377 g, 10 mmol) was added in a single portion to the
ketone/TarB–NO2 solution, causing rapid evolution of H2
gas. The reaction was allowed to stir for 30 min. Water
was added dropwise to quench the reaction until gas
evolution ceased. The mixture was brought to pH 12 with
solid NaOH and stirred. The solution was extracted with
pentane (10 mL) and the organic layer washed with 3 M
NaOH (10 mL), brine (10 mL), and dried over MgSO4.
Evaporation under reduced pressure gave (R)-(ꢀ)-3,3-
The authors thank Soya Gamsey and Lacie Hirayama,
for their helpful discussions.
References and notes
1. Asymmetric Synthesis; Morrison, J. D., Ed.; Academic
Press: New York, 1983; Vol. 2, Chapters 2 and 3.
2. For a detailed review, see: Corey, E. J.; Helal, C. J. Angew.
Chem., Int. Ed. 1998, 37, 1986–2012.
3. For a detailed review, see: Brown, H. C.; Ramachandran,
P. V. Acc. Chem. Res. 1992, 25, 16–24.
4. Brown, H. C.; Chandresekharan, J.; Ramachandran, P. V.
J. Am. Chem. Soc. 1988, 110, 1539–1546.
5. Enantiomeric excess was determined by chiroptical com-
parison. Chandrasekhar, S.; Hota, R. Tetrahedron: Asym-
metry 2005, 16, 751–754.
20
dimethyl-2-butanol (0.403 g, 80% yield), ½aꢁD ꢀ6.3 (c 4.3,
MeOH). The alcohol was then acetylated using acetyl
chloride in CH2Cl2 and pyridine. Enantiomeric excess of
the acetylated alcohol was determined to be 94% by chiral
GC analysis using a Supelco b-cyclodextrin 120 column
(30 m · 0.25 mm).
6. Umino, N.; Iwakuma, T.; Itoh, N. Chem. Pharm. Bull.
1979, 27, 1479–1481.
7. Yamada, K.; Takeda, M.; Iwakuma, T. J. Chem. Soc.,
Perkin Trans. 1 1983, 265–270.
23. Brown, H. C.; Ramachandran, P. V. J. Org. Chem. 1989,
54, 4504–4511.