1208
J. Zhu et al. / Tetrahedron Letters 53 (2012) 1207–1209
Table 2
could lead to 3-aryl acroleins (6). Successful realization of the pro-
posal would afford a new alternative strategy for the preparation of
valuable 3-aryl acroleins. In this Letter, we reported the results of
the investigation.
Scope of oxidative conversion of aldehydes to enalsa
O
N
The effects of reaction media, time, and temperature on the
reaction were firstly investigated employing 3-phenyl propional-
dehyde as the model compound aimed at obtaining the optimal
reaction parameter with 2.0 equiv of CAN (Table 1). We initially
screened five solvents in the presence of 20 mol % imidazolidinone
catalyst 1 at 25 °C (entries 1–5). The results showed that indeed
the processes took place, but were highly solvent-dependent.
Among them examined, ethylene glycol dimethyl ether (DME)
was the best (72% yield) with exclusive trans-configuration due
to the good solubility of CAN in it (entry 4). Addition of water
was detrimental to the reaction efficiency (entry 5). Further opti-
mization of reaction conditions unveiled that raising reaction tem-
perature led to lower yields and more side reactions were observed
(entries 6–7). The use of 1.5 equiv of CAN as an oxidant was suffi-
cient (75% yield, entries 8–9). Finally, as expected, the oxidative
conversion cannot proceed without amine catalyst 1 (entry 10).
With the established optimal reaction conditions in hand, we
next have probed the effectiveness of this new methodology for
the conversion of propionaldehydes to acroleins. As summarized
in Table 2. This process takes place efficiently (60–90%) for the
transformation of 3-aryl-propionaldehydes to the corresponding
3-aryl-acroleins with excellent E selectivity (entries 1–13). Signifi-
cant structural variation in phenyl ring of the 3-phenyl-propional-
dehydes is tolerated in this process, which occurs efficiently,
independent of the nature of the substituents on the phenyl ring,
where neutral groups (entry 1), electron-donating groups (entries
2–5), or electron-withdrawing groups (entries 6–11) are included.
It is noteworthy that the process can be applied to the preparation
of 3-phenyl-acroleins bearing para acetyl substituent (entry 11), a
dual carbonyl compound, that cannot be prepared by using cross
aldol condensation9 or Wittig reactions.10 Furthermore, under the
reaction conditions, the sensitive functionalities are not affected
by CAN. It was observed that the methyl group was not oxidized
by CAN, while seen in other reactions (entry 4).18 It is noteworthy
that heteroaromatic substrates could effectively engage in the oxi-
dative process as well (entries 12–13). Finally, as it might be ex-
pected on the basis of a presumed carbanion (3 and 4, Scheme
20 mol%
R2
Ph
N
H
R2
R1
O
CAN, 1.5 equiv.
R1
O
25 oC, DME
6
Entry
R1/R2
Phenyl/H (6a)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1.5
3.5
1
8
3
4
4
1
3
2
4
1
2
1.5
24
24
75
60
84
73
68
61
74
90
87
88
88
70
85
ndc
ndc
ndc
4-MeOC6H4/H (6b)
2-MeOC6H4/H (6c)
2-MeC6H4/H (6d)
4-AcNHC6H4/H (6e)
4-CNC6H4/H (6f)
4-NO2C6H4/H (6g)
2-ClC6H4/H (6h)
4-ClC6H4/H (6i)
2,4-DiClC6H3/H (6j)
4-CH3COC6H4/H (6k)
2-Furanyl/H (6l)
3-Py/H (6m)
C6H5CH2/H (6n)
CH3(CH2)6/H (6o)
Phenyl/CH3 (6p)
a
Reactions were conducted in a mixture of 0.37 mmol of an aldehyde, 1.5 equiv
of oxidant CAN, 20 mol % imidazolidinone catalyst 1 in 1 mL of DME. The detailed
reaction conditions, see Reference 17.
b
Isolated yield
c
Not determined.
1), their formation might be problematic with aliphatic systems
owning to deactivation and complicated formed dienamine. In-
deed, 4-phenylbutanal (entry 14) and decanal (entry 15) failed to
produce the corresponding
a,b-unsaturated aldehydes under the
reaction conditions. No reaction occurred with ketone (entry 16)
because presumably the ketone carbonyl group was less reactive.
In conclusion, inspired by the SOMO-hypothesis, we have devel-
oped a new alterative strategy for the preparation of synthetically
significant enals. The reaction is efficiently carried out in an amine-
catalyzed CAN-mediated single electron transfer oxidation process,
which is different from our oxidative enamine catalysis with 2
electron transfer. The mild reaction conditions allow for a broad
spectrum of functionality compatibility, an attractive feature for
complex molecule construction.
Table 1
Optimization of reaction conditionsa
Acknowledgments
O
N
We are grateful for the financial supports from the National
Natural Science Foundation of China (Grant 21002028, J.Z.), Na-
tional S&T Major Project, China (Grant 2011ZX09102-005-02,
J.L.), the 111 Project (Grant B07023, J.L. and W.W.) and East China
University of Science & Technology (W.W.).
20 mol%
Ph
N
H
cat. 1
O
O
CAN
solvent, temperature
Entry
Solvent
T (°C)
t (h)
CAN
Yieldb (%)
References and notes
1
2
3
4
5
6
7
8
Toluene
THF
CH3CN
DME
DME/H2O (8/2)
DME
DME
DME
DME
DME
25
25
25
25
25
40
40
25
25
25
24
2
2
1.5
1.5
0.5
1
1.5
1.5
1.5
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
2 equiv
1.2 equiv
1.5 equiv
1.5 equiv
5
23
49
72
60
48
69
49
75
0
1. For recent relevant examples, see: (a) DiRocco, D. A.; Rovis, T. J. Am. Chem. Soc.
2011, 133, 10402; (b) Cohen, D. T.; Cardinal-David, B.; Scheidt, K. A. Angew.
Chem., Int. Ed. 2011, 50, 1678; (c) Doyle, L.; Heaney, F. Tetrahedron 2011, 67,
2132; (d) Maiti, S.; Sridharan, V.; Mene´ndez, J. C. J. Comb. Chem. 2010, 12, 71.
2. For recent relevant examples, see: (a) Sun, Q.; Wu, R.; Cai, S.; Lin, Y.; Sellers, L.;
Sakamoto, K.; He, B.; Peterson, B. R. J. Med. Chem. 2011, 54, 1126; (b) Wang, P.;
Naduthambi, D.; Mosley, R. T.; Niu, C.; Furman, P. A.; Otto, M. J.; Sofia, M. J.
Bioorg. Med. Chem. Lett. 2011, 21, 4642; (c) Kumar, A.; Maurya, R. A.; Sharma, S.;
Kumar, M.; Bhatia, G. Eur. J. Med. Chem. 2010, 45, 501; (d) Rocha-Pereira, J.;
Cunha, R.; Pinto, D. C. G. A.; Silva, A. M. S.; Nascimento, M. S. J. Bioorg. Med.
Chem. 2010, 18, 4195.
9
10c
a
Unless specified, the reaction was conducted with 0.37 mmol of 3-phenyl-
propionaldehyde, CAN, and 20 mol % imidazolidinone catalyst 1 in 1 mL of solvents.
3. For reviews, see: (a) Lelais, G.; MacMillan, D. W. C. M. Aldrichimica Acta 2006,
39, 79; (b) Erkkilä, A.; Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416; (c)
Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 2007, 1701; (d) Almaßsi, D.; Alonso, D. A.;
b
Isolated yields.
The reaction was carried without 1.
c