Direct α-Alkylation of Aldehydes by Brønsted-Acid Catalysis
Table 2 Substrates scope of aldehydes and diarylmethanolsa
could participate in this reaction and afford the desired
products with middle to good yields, but the diastereo-
selectivities were very poor (Table 2, Entries 12—17).
The diarylmethanols containing heterocyclic aryl, which
has not been tested in the previous literatures, were also
good reaction partners in this reaction (Table 2, Entries
15—16). The triarylmethanol 2h could not react with
aldehyde and afford the desired product, probably due
to the steric influence or the low electrophilic ability of
the corresponding carbocation intermediate.
OH
Ar
O
R2
20 mol% 3a
THF, T oC
H
H3C
R1
N
1
CH3
2
O
Ar
H
R2
R1
CH3
N
Conclusions
4
CH3
In conclusion, we disclosed an efficient Brønsted
acid catalyzed direct alkylation reaction of aldehydes.
The 3,5-dinitrobenzoic acid 3a could promote this
transformation with middle to high yields. This reaction
has a broad substrates scope for aliphatic aldehydes.
OH
Ar
HO Ph
H3C
N
N
N
CH3
2h
Acknowledgement
2b Ar = 4-MeOC6H4
2c Ar = 2-MeOC6H4
2d Ar = 3-MeOC6H4
2e Ar = 4-MeC6H4
2f Ar = 2-thiophenyl
2g Ar = 2-furanyl
We are grateful for financial support from NSFC
(20902074) and the financial support from Southwest
University (SWUB2008056).
References
Entry
1
4
R1, R2
2
t/h T/℃
drb Yieldc/%
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4a Me, H
4b Me, Me
4c Et, H
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2a 96
50
50
50
50
50
50
50
50
50
50
50
80
80
80
50
80
80
—
—
91
52
90
88
68
90
81
91
86
91
50
71
73
76
83
77
2
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3
2a 24
2a 48
2a 96
2a 42
2a 42
2a 42
—
4
4d n-Pr, H
4e i-Pr, H
4f n-Bu
—
5
—
6
—
7
4g n-C5H11, H
4h n-C8H17, H
—
8
—
9
4i n-C10H21, H 2a 42
—
10
11
12
4j PhCH2, H
4k c-C6H11
4l Me, H
2a 24
2a 96
2b 18
2c 14
2e 11
2f 44
2g 19
—
—
1∶0.89
1∶0.99
1∶0.62
1∶0.62
1∶0.95
13 4m Me, H
14
15
16
17
4n Me, H
4o PhCH2, H
4p PhCH2, H
4q PhCH2, H
d
2h 44
—
—
c
a
b
1
See the experimental section; determined by H NMR; iso-
lated yield; d no desired reaction occurred.
and cyclohexanecarbaldehyde, could react with the di-
arylmethanol 2a and afford the desired products with
middle yields (Table 2, Entries 2, 5, 11). Next, several
diarylmethanols were introduced in this alkylation reac-
tion. We found not only the diarylmethanol 2a, which
could generate stable carbocation under acid conditions,
could react with various aldehydes smoothly and afford
the desired products with good yields, but also the di-
arylmethanols that led to less-stabllized carbocations
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
17