DBU-promoted condensation of acyldiazomethanes to aldehydes and imines under catalytic conditions

Article abstract of DOI:10.1016/S0040-4039(01)02375-9

The condensation of acyldiazomethanes to aldehydes and imines can be promoted with catalytic amount of DBU. The condensation gives β-hydroxy α-diazo carbonyl compounds or β-amino α-diazo carbonyl compounds in high yields.

Full text of DOI:10.1016/S0040-4039(01)02375-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1285–1287
DBU-promoted condensation of acyldiazomethanes to aldehydes
and imines under catalytic conditions
Nan Jiang and Jianbo Wang*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education,
Department of Chemical Biology, College of Chemistry, Peking University, Beijing 100871, China
Received 29 October 2001; revised 3 December 2001; accepted 14 December 2001
Abstract—The condensation of acyldiazomethanes to aldehydes and imines can be promoted with catalytic amount of DBU. The
condensation gives b-hydroxy a-diazo carbonyl compounds or b-amino a-diazo carbonyl compounds in high yields. © 2002
Elsevier Science Ltd. All rights reserved.
a-Diazo carbonyl compounds have attracted attention
because these compounds can undergo diverse syntheti-
cally useful transformations.1 For this purpose, the
synthesis of a-diazo compounds is of great interest.
a-Diazo carbonyl compounds are generally prepared by
diazo transfer reactions of carbonyl compounds. In
addition to these typical methods, they can also be
obtained by condensation reactions of acyldiazo-
methanes with aldehydes, ketones and imines through
nucleophilic addition (Scheme 1). This type of transfor-
mation is very useful because it can introduce a diazo
group as well as a hydroxyl or an amino group in a
single reaction step.
transformation to give b-dicarbonyl compounds.6 How-
ever, the deprotonation with LDA requires a low tem-
perature and absolutely anhydrous conditions, and
LDA is a very strong base, which may not be compat-
ible with functional groups in the substrates. Here we
report a milder deprotonation of acyldiazomethanes
with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Nucle-
ophilic condensation of acyldiazomethanes with alde-
hydes and imines can be promoted efficiently under
catalytic conditions.
Thus, ethyl diazoacetate (1a, R1=OEt) (EDA) was
dissolved and stirred with DBU (10 mol%) and various
aldehydes in anhydrous MeCN at room temperature
(Scheme 2).7
Nucleophilic addition of an acyldiazomethane to car-
bonyl compounds or imines requires deprotonation of
the acyldiazomethane. This is usually achieved by treat-
ment with a strong base, such as butyllithium,2 lithium
diisopropylamide (LDA),3 sodium hydride,4 potassium
hydroxide,5 etc. The most widely employed base by far
is LDA. The lithiated diazoesters and ketones can
convert aldehydes and ketones into a-diazo-b-hydroxy
carbonyl compounds, which can subsequently undergo
As shown by the data collected in Table 1, most
aromatic aldehydes react efficiently to give the corre-
sponding b-hydroxy a-diazo carbonyl compounds in
high yields. As anticipated, the nucleophilic addition to
an aromatic aldehyde with a strong electron-donating
substituent, such as a p-methoxy group, is very slow,
although the addition reaction did occur cleanly (entry
2). In addition to aromatic aldehydes, an a,b-unsatu-
rated aldehyde (entry 8) and aliphatic aldehydes (entries
O
O
O
XH
X
O
OH
R2
O
Base
O
H
H
R'
R"
DBU (10 % mol)
R
R
R
H
R1
R'
R"
R1
+
R2
N2
N2
H
N2
MeCN, N2
room temp.
8-24 h
N2
N2
(X = O, NTs, etc.)
3
2
1
4
1a R1 = OEt
1b R1 = Ph
1c R1 = Me
5
6
Scheme 1.
* Corresponding author.
Scheme 2.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02375-9

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N. Jiang, J. Wang / Tetrahedron Letters 43 (2002) 1285–1287
Table 1. DBU-promoted condensation of acyldiazomethanes to aldehydes
Entry
Acyldiazomethane
R1
Aldehyde
R2
Reaction time (h)
Yield (%)a
1
2
3
4
5
6
7
8
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
C6H5
C6H5
C6H5
CH3
CH3
CH3
C6H5-
p-MeOC6H4-
p-PhC6H4
8
24
8
8
8
8
8
8
8
8
8
8
24
24
24
24
24
24
78
27 (81)b
58
81
91
95
92
59
87
78
97
64
82
60
B10
77
65
B10
p-FC6H4-
m-CF3C6H4-
m-CNC6H4-
2,4-Cl2C6H3-
trans-PhCHꢀCH-
CH3(CH2)2-
CH3(CH2)3-
CH3(CH2)5-
9
10
11
12
13
14
15
16
17
18
CH3(CH2)10
-
m-CF3C6H4-
m-NC-C6H4-
C6H5-
m-CF3C6H4-
m-NC-C6H4-
C6H5-
a Yields after column chromatographic purification.
b The yield is based on the recovered starting.material.
9–12) can also react efficiently under the same condi-
tions. However, the reaction with ketones was found to
be too slow to be practically useful.
O
NHTs
R3
O
NTs
DBU (10 % mol)
H
R1
+
R1
R3
R2
R2
MeCN, N2
room temp.
8 h
N2
N2
For benzoyldiazomethane (1b, R=Ph) and acetyldiazo-
methane (1c, R=Me), the reactivity toward the alde-
hydes is lower compared to that of EDA (1a) under
identical condition (entries 15, 18). Nevertheless, for
these diazomethane derivatives, the reaction with the
aromatic aldehydes bearing electron-withdrawing sub-
stituents still works well (entries 13, 14, 16 and 17).
1a R1 = OEt
1b R1 = Ph
1c R1 = Me
7
8
Scheme 3.
greater than generally believed. It may be possible that
other types of acyldiazomethane anion reactions can
also be catalytically promoted by DBU. A closely
related reaction is the nucleophilic addition of an
acyldiazomethane anion to N-tosyl protected aromatic
imines. We found that this reaction can also be
efficiently promoted by catalytic amounts of DBU
(Scheme 3). The aromatic imines are found to be more
reactive toward the acyldiazomethane anion compared
To the best of our knowledge, there has been no report
on the deprotonation of acyldiazomethanes by DBU
and the subsequent nucleophilic addition under cata-
lytic conditions. Since DBU is a much weaker base
than LDA or NaH, the nucleophilic addition can be
efficiently performed with a catalytic amount of this
base suggesting that the acidity of the proton attached
to the diazo carbon of the acyldiazomethane is much
Table 2. DBU-promoted condensation of acyldiazomethanes to imines
Entry
Acyldiazomethane
R1
Imine
Reaction time (h)
Yield (%)a
R2
R3
1
2
3
4
5
6
7
8
OEt
OEt
OEt
OEt
o-MeC6H5-
m-BrC6H4-
trans-PhCHꢀCH-
C6H5-
p-Me2NC6H4-
m-CF3C6H4-
m-MeOC6H4-
C6H5
H
H
H
Me
H
H
H
H
H
H
H
8
8
8
8
8
8
8
8
8
8
8
77
64
53
B20
86
64
73
76
72
81
OEt
C6H5
C6H5
C6H5
CH3
CH3
CH3
9
10
11
m-CF3C6H4-
p-MeOC6H4-
C6H5-
57
a Yields after column chromatographic purification.

N. Jiang, J. Wang / Tetrahedron Letters 43 (2002) 1285–1287
1287
to the corresponding aldehydes (Table 2). For benzoyl-
diazomethane (1b, R=Ph) and acetyldiazomethane (1c,
R=Me), the reaction with N-tosyl benzaldimine gave
the expected products in moderate yields (entries 7 and
10). The condensation with imines gave a-amino-b-
diazo carbonyl compounds, which can subsequently be
transformed to a-aryl b-enamino esters by transition
metal-catalyzed or acid-catalyzed diazo decomposition.4
In conclusion, we have demonstrated that the conden-
sation of acyldiazomethanes with aldehydes and imines
can be promoted with catalytic quantities of DBU. The
reaction conditions are mild and should be compatible
with functional groups in the substrates.
Banhidai, B.; Frasnelli, H.; Meyer, R.; Beckhaus, H.
Liebigs Ann. Chem. 1974, 1767.
3. (a) Pellicciari, R.; Natalini, B. J. Chem. Soc., Perkin Trans.
1 1977, 1882; (b) Pellicciari, R.; Natalini, B.; Sadeghpour,
B. M.; Marinozzi, M.; Snyder, J. P.; Williamson, B. L.;
Kuethe, J. T.; Padwa, A. J. Am. Chem. Soc. 1996, 118, 1;
(c) Moody, C. J.; Taylor, R. J. Tetrahedron Lett. 1987, 28,
5351.
4. Jiang, N.; Qu, Z.; Wang, J. Org. Lett. 2001, 3, 2989.
5. (a) Wenkert, E.; McPherson, A. A. J. Am. Chem. Soc.
1972, 94, 8084; (b) Burkoth, T. L. Tetrahedron Lett. 1969,
57, 5049; (c) Woolsey, N. F.; Khalil, M. H. J. Org. Chem.
1972, 37, 2405.
6. For examples, see: (a) Pellicciari, R.; Fringuelli, R.; Cec-
cherelli, P.; Sisani, E. J. Chem. Soc., Chem. Commun.
1979, 959; (b) Ye, T.; McKervey, M. A. Tetrahedron 1992,
48, 8007.
Acknowledgements
7. A typical procedure. To a solution of ethyl diazoacetate
(1.2 mmol) in anhydrous CH3CN (5 mL), at room temper-
ature under N2, was added successively a solution of DBU
(0.1 mmol) in anhydrous CH3CN (1 mL) and aldehyde or
imine (1 mmol) in anhydrous CH3CN (4 mL) via syringe.
After stirring at room temperature for 8–24 h, the reaction
was quenched with saturated aqueous NaHCO3 and then
extracted with CH2Cl2 (20 mL). The solvent was removed
by evaporation under reduced pressure and the crude
product was purified by flash chromatography to give
b-hydroxy a-diazo carbonyl compounds or b-amino-a-
diazo carbonyl compounds. The structures of the products
The project is generously supported by Natural Science
Foundation of China (Grant No. 29972002). Ms.
Xiaoyu Xing performed part of the experimental work.
References
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Methods for Organic Synthesis with Diazo Compounds;
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2. (a) Schollkopf, U.; Frasnelli, H.; Hoppe, D. Angew.
Chem., Int. Ed. Engl. 1970, 9, 300; (b) Schollkopf, U.;
1
were confirmed by IR and H NMR (200 MHz) measure-
ments.