222
B. Branstetter, M. M. Hossain / Tetrahedron Letters 47 (2006) 221–223
yield the highly versatile 3-hydroxy-2-arylacrylate (Eq.
2).7 Due to the success of this reaction, we shifted our
attention to the highly reactive unsaturated aldehydes
(mainly acrolein and some of its derivatives). Herein,
we report the first formation of ethyl 2-formyl-1-cyclo-
propanecarboxylate in very high yield from acrolein
and EDA.
gel and the resulting product was ethyl 2-formyl-1-cyclo-
propanecarboxylate in 100% yield, containing both cis-
and trans-isomers (a ratio of 40:60).8 This is the first
report of a cyclopropane directly from acrolein and
EDA (Table 1, entry 2).
After these exciting results, we wanted to see whether or
not the solvent had any effect on formation of cyclopro-
pane or selectivity between cis- and trans-isomers (Table
1, entries 3 and 4). When a polar coordinating solvent
(such as ether) was used, the formation of ethyl 2-for-
myl-1-cyclopropanecarboxylate was again in 100% total
isolated yield. Interestingly, under these conditions, the
reaction favored the trans-isomer (entry 3). In the case
of a non-polar solvent (such as pentane) the formation
of cyclopropane decreased significantly (entry 4).
H
OH
CHO
10 mol % Cat.
CH2Cl2
+
N2CHCOOEt
COOEt
ð2Þ
With this surprising result, we decided to try other a,b-
unsaturated aldehydes. We chose mainly those substi-
tuted in the b position because the resulting cyclopro-
pane would be substituted on all three carbons.
Crotonaldehyde was the first b-substituted aldehyde
subjected to our current reaction conditions and again
we discovered the formation of ethyl 2-formyl-3-methyl-
cyclopropane-1-carboxylate, in 60% yield (Table 1, entry
5). In 2000, Aggarwal and co-workers reported the for-
mation of ethyl 2-formyl-3-methylcyclopropane-1-car-
boxylate in only 28% yield from crotonaldehyde and
(ethoxycarbonylmethyl)sulfonium ylide, which was a
mixture of two diastereomers.5,6 Interestingly, only one
of the two previously reported diastereomers was
formed under our reaction conditions (1RS,2RS,3SR).
The first major difference in our reaction conditions,
compared to the other cyclopropanation reactions
discussed earlier, is the use of the Brønsted acid
HBF4ÆOEt2. In the past, reactions between acrolein
and EDA were run at 0 °C in order to observe the
formation of the 2-pyrazoline. Our first step was to
run an acid catalyzed reaction between acrolein and
EDA at 0 °C to compare results (Table 1, entry 1).
The observed product did not match that of the 2-pyraz-
oline reported in the past. Instead, the observed product
appeared to be polymeric in nature by 1H and 13C
NMR. To investigate further, we decided to slow the
reaction down by running at even colder temperatures
(i.e., ꢀ78 °C). We have found in the past with aromatic
aldehydes, EDA and HBF4ÆOEt2 as catalyst, that better
conversion to product was observed at ꢀ78 °C.7
1
This was confirmed by comparing H and 13C NMR
values to previously reported values. In an attempt to
increase the yield, the reaction was run at ꢀ100 °C; how-
ever, a decrease in yield was observed (Table 1, entry 6).
Only one diastereomer was formed. Then, we ran the
reaction in a polar solvent and non-polar solvent and
the same phenomenon was observed as in the case with
acrolein (Table 1, entries 7 and 8). When 3-methyl-2-
butenal was reacted under the same conditions as acro-
lein, no cyclopropane was observed and the product
When 1.0 equiv of acrolein and 10 mol % HBF4ÆOEt2
were added to CH2Cl2 at ꢀ78 °C, and a solution of
1.2 equiv of EDA diluted in CH2Cl2 was added drop-
wise over 30 min, the result was quite surprising. After
the reaction mixture was allowed to stir for 24 h at
ꢀ78 °C, the mixture was pushed through a plug of silica
Table 1. Acid-catalyzed reactions of a,b-aldehyde in the presence of EDAa
R
2
R
2
O
R
1
10 mol % HBF4
solvent
+
N2CHCOOEt
COOEt
H
R
1
R = R = H
1
2
OHC
R = CH , R = H
1
3
2
Entry
Substrate
Solvent
T (°C)
% Yield (cis vs trans)b
1
2
3
4
5
6
7
8
Acrolein
Acrolein
Acrolein
Acrolein
Crotonaldehyde
Crotonaldehyde
Crotonaldehyde
Crotonaldehyde
CH2Cl2
CH2Cl2
Ether
Pentane
CH2Cl2
CH2Cl2
Pentane
Ether
0
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ100
ꢀ78
ꢀ78
0c
100 (40:60)
100 (30:70)
61 (45:55)
60
42
15
60
a EDA (1.2 equiv) was added dropwise over 30 min.
b Ratio determined by 1H NMR.
c Unidentified polymeric substance was isolated.