C O M M U N I C A T I O N S
Table 3. Organocatalytic Asymmetric Michael Reaction Using
Next, the reaction of trans-ꢀ-nitrostyrene and n-pentanal was chosen
as the model to examine the recyclability of the catalytic system (5
mol % of catalyst 2 was used). After the reaction was completed, the
reaction mixture was extracted two times by adding a mixture solvent
of Et2O-hexane (1:8). The product was obtained by simple evaporation
of the organic phase and further purification by flash silica gel
chromatography. The recovered aqueous phase was used again for the
next cycle directly by addition of the new reagent benzoic acid and
new reactants n-pentanal and trans-ꢀ-nitrostyrene. As shown in Table
2, the catalytic activity of catalyst 2 dropped gradually after four cycles,
but the yield of cycle 8 dropped dramatically to 15% even with
prolonged reaction time to 24 h. However, the enantioselectivity was
not affected and remains above 99% throughout all catalytic cycles.
These results demonstrate that catalyst 2 is the best recyclable
organocatalyst developed so far for the asymmetric Michael reactions
between aldehydes and nitroolefins on water with excellent stereose-
lectivities as well as a very simple, practical, and green procedure for
catalytic system recovery.
Aldehydes and Nitroalkenesa
entry
R1
R2
product t (h) yield (%)b syn/antic ee (%)d
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
n-Pr
5a
5b
5c
5d
5e
5f
5g
5h
5i
5
5
8
97
94
99
99
84
86
74
78
96
83
93
76
97/3
97/3
98/2
97/3
97/3
96/4
97/3
96/4
95/5
95/5
97/3
98/2
>99
99
99
n-Bu
n-C5H11
n-C7H15
i-Pr
n-Pr
n-Pr
22
21
24
24
72
12
22
5
99
>99
>99
98
>99
99
98
>99
99
p-BrC6H4
o-ClC6H4
o-CF3C6H4
n-Pr
m-MeOC6H4 n-Pr
10 p-MeOC6H4 n-Pr
11 2-furyl
12 n-Bu
5j
5k
5l
n-Pr
Bn
5
a Reactions performed on 0.5 mmol scale using catalyst 2, benzoic
acid, aldehydes (2 equiv), and water (0.5 mL). b Yields of isolated
Table 2. Recycling Studies of Water-Soluble 2-Catalyzed Michael
Addition of n-Pentanal to trans-ꢀ-Nitrostyrenea
c
product. Determined by H NMR. d Determined by chiral HPLC.
1
cycle t (h) yield (%) syn/anti ee (%) cycle t (h) yield (%) syn/anti ee (%)
Acknowledgment. We are grateful to the Robert A. Welch
Foundation (T-0014), NSF-REU (Grant No. 0851966), and Office
of Graduate Studies & Research at Texas A&M University-
Commerce for financial support of this research.
1
2
3
4
5
5
5
5
97
96
97
97
97/3
97/3
96/4
97/3
99
99
99
99
5
6
7
8
6
8
12
24
93
95
68
15
96/4
97/3
97/3
96/4
99
99
99
99
a Reactions performed on 0.6 mmol scale using catalyst 2, benzoic
acid, n-pentanal (2 equiv), and water (0.8 mL).
Supporting Information Available: Experimental details and
characterization data. This material is available free of charge via the
The scope of the Michael reactions using catalyst 2 on water
was examined with a variety of aldehydes and nitroolefins (Table
3). As demonstrated in Table 3, not only linear aldehydes (entries
1-4) but also a branched aldehyde (entry 5) can be all employed
successfully as the Michael donors to afford the products 5a-e in
high yields (84f99%) and excellent enantioselectivities (ee: up to
>99%). Nitroolefins bearing electron-deficient and electron-rich
aromatic substituents and heteroaromatic group were excellent
Michael acceptors for n-pentanal (entries 6-11). Furthermore,
catalyst 2 is also highly effective for Michael addition of aldehyde
to aliphatic nitroolefin at room temperature for 5 h providing product
5l in good yield and excellent stereoselectivities (syn/anti: 98/2,
ee: 99%) (entry 12). However, the R,R′-disubstituted aldehyde
isobutyraldehyde was found to be a poor Michael donor with low
yield of the Michael adduct formed.2b
The large-scale (10 mmol) preparation of the Michael product of
n-pentanal to trans-ꢀ-nitrostyrene under standard reaction conditions
was also investigated to give product 5a in 96% yield with excellent
stereoselectivities (98% ee; syn/anti: 97/3).5 Notably, after the reaction
was completed, the product was isolated by simple phase separation
and no organic solvent is required for the workup step.
We have developed a novel strategy for the catalytic asymmetric
Michael addition of aldehydes to nitroolefins on water providing
the Michael adducts with excellent diastereo- and enantioselectivi-
ties. There are several advantages in the present reaction: (a) the
diarylprolinol silyl ether 2 catalyst is readily available; (b) a broad
range of nitroolefins, including aromatic and aliphatic introolefins,
are accessible; (c) the reaction can be conducted under mild
conditions using only 3 mol % of catalyst and a slight excess
amount of aldehydes (2 equiv); (d) the catalytic system can be easily
recovered and reused for at least six times without significant loss
of catalytic activity and stereoselectivities; (e) no organic solvent
is required except in the purification step. These remarkable
advantages will make this approach suitable not only for laboratory-
scale research but also for industrial applications.
References
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(5) For the details, see the Supporting Information.
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with a large hydrophobic group, which accurately served as a “concentrated
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