In conclusion, we accomplished highly enantioselective
CBS-catalyzed asymmetric BH3 reduction of 2 by electronic
tuning of the catalyst. The enantioselectivity of reaction
product (S)-3 is influenced by the coordination capability of
4. We are now able to predict roughly the enantioselectivities
of the products of reduction of 6 from calculated DE values,
although at present these predictions can be applied exclusively
to trifluoroacetophenone analogues. Such electronic control of
CBS catalysis should be effective for other highly reactive
substrates if the relationship between catalyst and substrate is
well designed.
Fig. 6 DE values 6–4h for prediction of % ee of BH3 reduction.
Notes and references
high correlation indicated that the enantioselectivity of the
product formed by reduction of 2 was mainly influenced by
coordination between 2 and catalyst. When the substituent
was B-Me (4a), coordination between 2 and 4a was very weak
due to the high p*B orbital energy of 4a (that is, large DE),
indicating that noncatalytic reduction of 2 with BH3 occurred
dominantly (Table 1, entry 1). When the substituent was
changed to B-Ar, coordination between 2 and 4 drastically
improved (Table 1, entries 2–9), owing to the lower p*B orbital
energy (that is, smaller DE) of 4 relative to that of 4a.
Although large numbers of fluoro-functional groups tended
to decrease DE, the order turned back in the case of 4e, 4f, 4g
and 4h. This disorder is because of the mesomeric effect of
fluorine’s lone pair to the boron atom, particularly at the 2, 4,
and 6 positions. The enantioselectivity of product 3 increased
with decreasing DE values for 4 until 4h (OAB 1h) (Fig. 5).
However, further decrease in DE resulted in a loss of enantio-
selectivity for 3, suggesting the generation of an inhibition
process. Although one likely reason for the inhibition is
dimerization of OAB,4b dimer suspect signals could not be
observed in 19F NMR analyses of the catalysts 1e, 1f, and 1h in
THF at 30 1C. Therefore, we hypothesized that sluggish
elimination of the product owing to the strong Lewis acidity
of the catalyst inhibited catalyst reproduction (Fig. 3, reaction
step D) in the cases of 1e, 1f, 1g, and 1i. Although the reasons
for this phenomenon are not clear, a subtle inhibition process
would decrease the enantioselectivity of (S)-3 considerably
because of the ease of noncatalytic reduction of 2.
1 Review: S. P. Flanagan and P. J. Guiry, J. Organomet. Chem.,
2006, 691, 2125.
2 Recent example: (a) W. Kashikura, J. Itoh, K. Mori and
T. Akiyama, Chem.–Asian J., 2010, 5, 470; (b) L. Yang, Q. Zhu,
S. Guo, B. Qian, C. Xia and H. Huang, Chem.–Eur. J., 2010, 16,
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Synlett, 2009, 2312.
3 Reviews: (a)
G. Paul, in Name Reactions for Functional
Group Transformations, ed. J. J. Li and E. J. Corey, Wiley, 2007,
pp. 2–21; (b) B. T. Cho, Tetrahedron, 2006, 62, 7621; (c) E. J. Corey
and C. J. Helal, Angew. Chem., Int. Ed., 1998, 37, 1986;
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4 (a) W. Xu, H. Guo, J. Zhang, Q. Zhu and X. Hu, J. Mol. Catal. A:
Chem., 2009, 300, 25; (b) J. Du, Z. Li, D.-M. Du and J. Xu, J. Mol.
Catal. A: Chem., 2008, 284, 40; (c) H. Liu and J. Xu, J. Mol. Catal. A:
Chem., 2006, 244, 68.
5 (a) E. J. Corey and C. J. Helal, Tetrahedron Lett., 1995, 36, 9153;
(b) J. Xu, T. Wei and Q. Zhang, J. Org. Chem., 2004, 69, 6860;
(c) E. Fuglseth, E. Sundby, P. Bruheim and B. H. Hoff,
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6 (a) S. Goushi, K. Funabiki, M. Ohta, K. Hatano and M. Matsui,
Tetrahedron, 2007, 63, 4061; (b) M. Zhao and F. Xiao, Huaxue
Yanjiu Yu Yingyong, 1999, 11, 282.
7 When catecholborane was used instead of BH3 as a reducing agent,
(R)-3 was obtained with 90% ee in the presence of B-nBu-(S)-CBS
at À78 1C: E. J. Corey, J. O. Link and R. K. Bakshi, Tetrahedron
Lett., 1992, 33, 7107.
8 (a) N. Asao, T. Asano and Y. Yamamoto, Angew. Chem., Int. Ed.,
2001, 40, 3206; (b) A. Vargas, T. Burgi, M. von Arx, R. Hess and
¨
A. Baiker, J. Catal., 2002, 209, 489.
9 All calculations were performed at the B3LYP/6-311G(2d,p)//
B3LYP/6-311G(2d,p) by using Gaussian 03 (see ESIw).
10 In ref. 4b, for example, the asymmetric reduction of
p-nitroacetophenone by using OAB bearing several B-Ar groups
gave similar enantioselectivity at 110 1C in toluene.
We obtained the DE values between each of the other
trifluoroacetophenone analogues 6a–6c and 4h by DFT
calculations. Each DE value between 6a and 4h and between
6b and 4h was similar to that between 2 and 4h within the
difference of Æ0.1 eV; however, the difference of those from
the value between 6c and 4h was 0.33 eV (Fig. 6). These values
indicated that, compared to the product of reduction of 2, the
products of reduction of 6a and 6b should have similar
enantioselectivity and the product of reduction of 6c should
have lower enantioselectivity.16 In fact, the products of BH3
reduction of 6a and 6b had similar enantioselectivities (86%
and 90% ee, respectively) to the product of reduction of 2
(90% ee) when the catalyst (S)-1h was used under the same
condition, and the product of reduction of 6c had low
enantioselectivity (54% ee) owing to weak coordination
between 6c and 4h, as indicated by the DE value (Fig. 6).
11 T. Korenaga, F. Kobayashi, K. Nomura, S. Nagao and T. Sakai,
J. Fluorine Chem., 2007, 128, 1153.
12 J. Xu, T. Wei and Q. Zhang, J. Org. Chem., 2003, 68, 10146 and
references therein.
13 T. Korenaga, K. Kadowaki, T. Ema and T. Sakai, J. Org. Chem.,
2004, 69, 7340.
14 One likely reason for the different results between our catalytic
system and CBS with catecholborane is due to asymmetric
reduction with another catecholborane in the presence of
CBS–catecholborane adduct: Y.-Y. Yeung, R.-J. Chein and
E. J. Corey, J. Am. Chem. Soc., 2007, 129, 10346.
15 Definition of two layers was shown in ESIw (Fig. S2). Harmonic
vibrational frequencies were computed for all stationary points in
order to characterize them as saddlepoints. The energies were
corrected using the zero-point energy. IRC calculations were
performed to confirm the formation of product.
16 The correlations in Fig. 5 are not applied to the results of reduction
of 6 as it is, because EWG in phenyl group accelerates
non-catalytic BH3 reduction, particularly, in 6c. See ref. 8b.
c
8626 Chem. Commun., 2010, 46, 8624–8626
This journal is The Royal Society of Chemistry 2010