Chemistry Letters Vol.36, No.6 (2007)
and Na atoms in the TS. The distances in the TS are 2.82 A in
739
˚
lectivity. Whereas, the Co–carbene complexes prepared by the
treatment with diazoacetates catalyzed the enantioselective
borohydride reduction to afford the corresponding alcohol with
good-to-high enantioselectivity. As shown in Table 2, methyl
diazoacetate was found to work as the best activator of the
CoII complex among the methyl, ethyl, t-butyl, and benzyl
diazoacetates. Under the optimized conditions, the correspond-
ing reduced product with a 97% ee was obtained in 76% yield.
The Co–carbene complex derived from methyl diazoacetate
was then successfully applied to the catalytic enantioselective
reduction of aryl alkyl ketones. For examples, the cyclopropyl-
phenyl ketone and isopropylphenylketone were reduced to the
corresponding alcohols with 85 and 96% ee, respectively. These
results suggested that the Co–carbene complexes derived from
the diazoacetates would work as efficient catalysts for the enan-
tioselective borohydride reduction in a halogen-free solvent.
It is noted that the rational reaction simulation based on the
theoretical analysis could provide a promising method for the
ligand design of catalytic enantioselective reactions. Further
studies on the design of the axial ligands, the optimization
of the reaction conditions, and the scope and limitation of the
present catalytic system are ongoing.
˚
˚
CH2Cl (Entry 4), 2.99 A in CHCl2 (Entry 5), and 3.12 A in CCl3
(Entry 6). The shortest Cl–Na bond was observed in CH2Cl
and the activation energy was the lowest. It was considered
that the complex with the shorter hetero atom–Na bond should
give the better results. Therefore, other alkyl groups containing
the coordination site, such as methoxycarbonylmethyl, pyridyl
methoxycarbonylmethyl carbene (oxygen atom), and 2-group
(nitrogen atom) were examined. TSs were obtained, though the
activation energies of the methoxycarbonylmethyl and 2-pyridyl
groups were unexpectedly higher than that of the dichloromethyl
group (Entries 7 and 8). On the contrary, the activation energy of
the carbene complex was lower than those of the methoxy-
carbonylmethyl and 2-pyridyl groups and similar to that of the
dichloromethyl group. (Entry 9 in Table 1 and Figure 2). The
transition state’s structure of the Co–carbene complex was sim-
ilar to that of the dichloromethyl group; the Naþ was efficiently
coordinated by the oxygen atoms of the aminato-ligand and ester
part in the carbene part.
H
2.5
H
O
H
1.6
References and Notes
1
N
2.3
O
2.2
2.2
Na+
Mukaiyama, Chem. Lett. 1996, 737. c) T. Nagata, K. D. Sugi, T.
Yamada, T. Mukaiyama, Synlett 1996, 1076.
Co
N
O
2.3
HC
O
2
3
K. D. Sugi, T. Nagata, T. Yamada, T. Mukaiyama, Chem. Lett. 1997, 493.
a) T. Yamada, Y. Ohtsuka, T. Ikeno, Chem. Lett. 1998, 1129. b) Y.
Other examples: c) U. Leutenegger, A. Madin, A. Pfaltz, Angew. Chem.,
CH3
distance Å
O
Figure 2. TS structure of the cobalt–carbene complex.
Table 2. Enantioselective borohydride reduction catalyzed by
cobalt–carbene complexes
4
a) T. Yamada, T. Nagata, T. Ikeno, Y. Ohtsuka, A. Sagara, T.
Nagata, K. D. Sugi, K. Yorozu, T. Ikeno, Y. Ohtsuka, D. Miyazaki, T.
5 mol %
5
6
I. Iwakura, M. Hatanaka, A. Kokura, H. Teraoka, T. Ikeno, T. Yamada,
7.5 mol % N2CHCO2R
N
N
O
N
N
O
Co
Co
1966, 6, 181. b) Q. Chen, L. G. Marzilli, N. B. Pahor, L. Randaccio,
Y. Maeyama, T. Kaieda, T. Matsuo, E. Matsui, Y. Naruta, Y. Hisaeda,
O
O
O
O
O
O
Complex A
OR
HC
O
OH
R'
O
R'
NaBH4, EtOH,
7
8
A. Kokura, S. Tanaka, H. Teraoka, A. Shibahara, T. Ikeno, T. Nagata,
HO
O
THF, 0 °C
The calculations were performed at the B3LYP/6-31Gꢀ level using a
suite of the Gaussian program. The method was suitable for the present
calculation according to a previous study. See Refs. 5 and 9. a) Gaussian
98, Revision A.6 and A.11, Gaussian, Inc., Pittsburgh (USA), 1998
Entry
Substrate
O
Catalyst
Complex A
Yield/%
ee/%
1
2
3
4
5
74
76
74
quant.
93
41
97
69
75
48
Co–carbene R = Me
R = Et
R = t-Bu
R = Bn
9
It is generally known that the B3LYP method overestimates the stability
of the higher spin states. However, in our case, the B3LYP methods
produced sufficiently reliable results based on our previous analysis
of the Co-complex-catalyzed reaction, see Ref. 5: a) M. Reiher, O.
Salomon, B. A. Hess, Theor. Chem. Acc. 2001, 107, 48. b) T. Ikeno,
O
O
6
7
Co–carbene R = Me
98
90
85
96
Based on the prediction from these theoretical calculations,
the enantioselective borohydride reduction was examined using
the Co–carbene complex prepared from the original Co complex
and alkyl diazoacetate. Various alkyl diazoacetates were first
screened using the reduction of valerophenone as the model
reaction. When the original CoII complex was employed as the
catalyst in THF solvent, valerophenone was converted into the
corresponding alcohol in good yield, but with a low enantiose-
10 Theoretically, it was considered that the solvent effect might make an
influence on the results, because the reaction was performed in the polar
solvents. However, the previous study showed that the results were
little effected by the solvent,5 accordingly, the present calculations were
performed without considering the solvent effect.
11 Supporting Information is available electronically on the CSJ-Journal web