4748
C. Suttibut et al. / Tetrahedron Letters 52 (2011) 4745–4748
Figure 2. (a) B3LYP/6-311++g(d,p) 0.002 au isodensity surface with superimposed electrostatic potential using the optimized structure at the B3LYP/6-311++g(d,p) level of
theory. (b) Frontier orbitals calculated at the B3LYP/6-311++g(d,p) level of theory for the iminium ion (left) and 7 (right).
The origin of the enantioselectivity in our catalytic system
would be affected by the structural and electronic features of the
amino alcohol catalysts. As shown in Scheme 5, for the highly
enantioselective DA reaction of (7S)-9a (96% ee), 7 approaches
from the sterically less hindered bottom face of the iminium ion
intermediate to generate a hydrogen bond between the N–H
hydrogen atom of the iminium and the carbonyl oxygen atom of
7, as well as an electrostatic interaction between those two mole-
cules. Thus the electrostatic potential analysis shows that there ex-
ists an effective intermolecular interaction between the iminium
and 7 [Fig. 2 (a)]. Simultaneously, si-face of the olefin moiety on
the iminium was attacked by the diene 7, which would enable a
more favorable frontier orbital overlap [Fig. 2 (b)] and thus en-
hance the enantioselectivity.
We next evaluated the effectiveness of superior catalyst 6a in
the DA reaction using acrolein derivative 14 (Scheme 6). The reac-
tions of dienes, 7 or 11 with dienophile 14 were carried out at 0 °C
in the presence of 10 mol % of superior catalyst 6a to give the DA
adducts 15 or 16 and the chemical and optical yields were deter-
mined by converting to the alcohols 17 or 18, respectively. Both
reactions showed satisfactory asymmetric catalytic activity and
the desired DA adducts 17 or 18 were obtained in excellent chem-
ical yields and excellent enantioselectivities (17: 96% yield, 98% ee,
18: 93% yield, 98% ee).
In conclusion, new chiral b-amino alcohol organocatalysts 6a–j
were prepared easily in two steps, and they showed dramatic reac-
tivity, excellent chemical yield, and excellent enantioselectivity
(up to 98% yield, up to 98% ee) in the Diels–Alder reactions of
1,2-dihydropyridines 7 or 11 with acroleins 10 or 14. In particular,
6a bearing 2-tert-butyl moiety gave the chiral isoquinuclidines 9a
in almost complete chemical yields and excellent enantioselectiv-
ities when the catalyst was used in the DA reactions of 7 or 11 with
10 or 14, respectively. One advantage is that the developed cata-
lysts are very stable in air and might be superior for practical use
compared with the results of the same reactions of oxazolidine
(9a: 82%, 99% ee) and MacMillan catalysts (9a: 26% yield, 99%
ee). Further studies to examine the scope and limitations of this
b-amino alcohol organocatalyst for the catalytic asymmetric ver-
sion of the DA reactions of 1,2-dihydropyridines with acroleins
are now in progress.
Acknowledgment
This work was partially supported by an Adaptable and Seam-
less Technology transfer Program grant from the Japan Science
and Technology Agency (JST).
Supplementary data
Supplementary data associated with this article can be found, in
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