COMMUNICATION
Table 2. Asymmetric Michael addition of nitromethane to chalcones 1a–
u.[a]
Entry R2
R3
Product Yield [%][b] ee [%][c]
1[d]
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3 f
3g
3h
99
99
99
97
98
92
99
99
94
98
95
99(S)[e]
99
4-FC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-BrC6H4
4-MeC6H4
3-MeC6H4
4-MeOC6H4 3i
3-MeOC6H4 3j
2-MeOC6H4 3k
99(S)[e]
99
99
99
99
99
98
99
99
were investigated. These revealed that utilizing DMAP as
an additive provides a slight increase in the yield (Table 1,
entry 10). If the nitromethane reagent was used as the sol-
vent, both an excellent yield and enantioselectivity were ob-
tained within half the original reaction time (24 h, Table 1,
entry 11). Furthermore, even if the catalyst loading was re-
duced to 2 mol%, the yield and enantioselectivity were
maintained after the same reaction time (24 h, Table 1,
entry 12). The reaction was also tested under 1 mol% cata-
lyst loading and the corresponding product was obtained
without any loss of yield or enantiomeric excess, but a
longer reaction time was required (72 h, Table 1, entry 13).
Under the optimized conditions (Table 1, entry 12), a
series of functionalized chalcones were examined, giving the
corresponding products in excellent yields with 98 to
>99% ee (Table 2). It is notable that this catalyst system ex-
hibited a remarkably broad substrate scope, in which neither
the electronic properties, nor the steric hindrance of the sub-
stituent on benzene had an evident effect on the enantiose-
lectivity (Table 2, entries 1–12, 16–19). Chalcone derivatives
containing a naphthalene moiety reacted smoothly with ni-
tromethane to give the expected products in excellent enan-
tioselectivities (Table 2, entries 13 and 20). Furthermore, the
excellent enantioselectivities were also achieved for hetero-
aromatic chalcone derivatives (99 to >99% ee; Table 2, en-
tries 14 and 21). Moreover, the reaction was applicable to
(2E,4E)-1,5-diphenylpenta-2,4-dien-1-one, giving an excel-
lent result for the corresponding 1,4-addition product
(Table 2, entry 15).
10
11
12
Ph
3l
99
99
13
14
15
Ph
Ph
Ph
3m
3n
3o
81
86
95
99
99
99
16
17
18
19
4-FC6H4
Ph
Ph
Ph
Ph
3p
3q
3r
3s
99
99
99
99
>99
>99
99
4-ClC6H4
4-MeC6H4
3-MeC6H4
99
20
Ph
3t
99
99
21
Ph
Ph
3u
3v
87
>99
22[f]
Ph
56/44[g]
98/>99
[a] Unless otherwise stated, reactions were performed with chalcones 1
(0.4 mmol) and M/L/A (1:1:1, 2 mol%) in nitromethane (0.43 mL) at
308C for 48 h (M=Metal, L=Ligand, A=Additive). [b] Yield of isolated
product. [c] Determined by HPLC analysis. [d] Reaction was finished
after 24 h. [e] The absolute configurations were determined by compari-
son with the literature.[5c,9] [f] Reaction was carried out with chalcone 1a
(0.25 mmol) and M/L/A (1:1:1, 5 mol%) in nitroethane (0.36 mL) at
308C for 4 d. [g] Diastereomers.
rivative containing a naphthyl group was also promoted
under the same conditions and provided the desired product
in an excellent yield and enantiomeric excess (Table 3,
entry 9). An a,b-unsaturated aliphatic ketone was also ex-
amined and gave a good yield and enantiomeric excess
(Table 3, entry 10).
Nitroethane was also investigated as a reagent in this
asymmetric conjugate addition reaction. Each diastereomer
of the desired product could be obtained separately by using
silica gel column chromatography and both were formed in
excellent enantioselectivities (Table 2, entry 22).
Interestingly, this L5–Sc
(OTf)3 catalyst can also promote
To further investigate the synthetic potential of this strat-
egy, chalcone (10 mmol, 2.08 g) was reacted under the opti-
mal conditions for functionalized “cinnamones” and the cor-
responding product was obtained without any loss of yield
(2.67 g, 99% yield) or enantiomeric excess (99% ee,
Scheme 1).
In summary, we have developed a simple to handle,
highly efficient N,N’-dioxide–scandiumACTHNUTRGNEUNG(III) catalyst for the
asymmetric conjugate addition of nitromethane to chalcone,
as well as “cinnamone”, derivatives, under mild conditions.
the conjugate addition of nitromethane with a wide range of
“cinnamone” derivatives. The reactions of “cinnamone” de-
rivatives, compared with those of chalcone derivatives, gen-
erally needed a longer reaction time and 5 mol% catalyst
loading due to their lower reactivity. As summarized in
Table 3, “cinnamones” bearing not only electron-donating,
but also electron-withdrawing groups on benzene proceeded
in high to excellent yields with excellent enantioselectivities
(Table 3, entries 1–8). The reaction of the “cinnamone” de-
Chem. Eur. J. 2010, 16, 7696 – 7699
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7697