D. Zhuang, T. Gatera and R. Yan
Tetrahedron Letters 61 (2020) 152506
Table 2
efficient method for the C(3) formylation of indole and C(2)
formylation of pyrrole derivatives using TCT/DMF reagent [11c].
Moreover, Guo’s group has developed an efficient method for the
transamidation of DMF with weakly nucleophilic anilines [12].
However, The direct synthesis of formate esters with DMF which
acts not only as a solvent but also as the source of CHO has rarely
been exploited. Herein, we present a novel synthetic approach
toward formate esters through CuBr2-catalyzed ring opening and
formylation of cyclopropyl carbinols with DMF.
Scope of substituted cyclopropyl carbinols.a
Results and discussion
We started investigation from the reaction of cyclopropyl(phe-
nyl)methanol (1a) in DMF using FeCl3 as catalyst at 140 °C under
air for 12 h. To our surprise, (E)-4-phenylbut-3-en-1-yl formate
(2a) was obtained in 51% yield (Table 1, entry 1). The structure
of 2a was confirmed by spectroscopic analysis. Thus, the substrate
1a was chosen as the model substrate to optimize the reaction con-
ditions. Firstly, attempts to improve the yield using various metal
catalysts were evaluated, and copper catalysts exhibited the high-
est activity. The yield of 2a was increased to 60% when 10 mol% of
CuCl2 was added (Table 1, entries 1–7). Furthermore, a series of
copper catalysts were also screened and CuBr2 was the most effi-
cient for this transformation and the isolated 2a was obtained in
70% yield (Table 1, entries 8–9 and entry 11). The temperature
was also examined, and the result of changing the temperature
revealed that the yield was sharply decreased when the reaction
temperature was reduced. However, there was little effect on the
yield when the temperature reached 140 °C (Table 1, entries 10–
14). The reaction of cyclopropyl carbinol cannot work without
the catalyst CuBr2 (Table 1, entries 15). So the optimized conditions
were established as shown in Table 1, entry 11.
With the optimized reaction conditions in hand, the substrate
scope was then evaluated. As shown in Table 2, the optimized con-
ditions were compatible with various cyclopropyl carbinols with
electron-donating substituents on the aryl ring, such as Me, OMe,
Et, OEt, OPh, i-Pr, t-Bu, etc (2a-2o). Halogen-containing derivatives
of cyclopropyl carbinols could also tolerate this transformation,
and the corresponding products 2p, 2q, 2r were isolated in 57%,
56%, and 59% yields, respectively. Moreover, these reaction condi-
tions were also compatible with different heterocyclic substrates
(2s-2u). In addition, further investigation disclosed that the ter-
a
Reaction conditions: substrates 1 (0.3 mmol), CuBr2 (0.03 mmol), DMF (2 mL),
140 °C, 12 h.
tiary alcohol substrates also sustained well in this reaction and
the target products 2v-2y were isolated in good yields. The prod-
ucts were mixture of (E)- and (Z)-isomers, and the (E)-isomers
were obtained with excellent selectivity. Unfortunately, the sub-
strates 1-cyclopropyl-3-phenylpropan-1-ol (1z) and 1-cyclopropy-
lethanol (1aa) did not tolerate this reaction system and no desired
products were detected.
Table 1
Optimization of reaction conditions.a
To further highlight the versatility of this strategy, several
amide derivatives were tested (Scheme 2). To our delight, the
investigation showed that DMA and DMAA can also proceed
smoothly in this reaction, and the desired products were isolated
in 56% and 34% yields.
Entry
Catalyst
Temp (°C)
Yield (%)b
1
2
3
4
5
6
7
8
FeCl3
140
140
140
140
140
140
140
140
140
160
140
120
100
rt
51
34
46
28
37
42
60
52
47
63
70
53
36
Trace
n.d.
Ni(OAc)2
Pd(OAc)2
ZnCl2
MnCl2
CuCl
CuCl2
Cu(OAc)2
Cu(OTf)2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
–
9
10
11
12
13
14
15
140
a
Reaction conditions: 1a (0.3 mmol) and catalyst (10 mol%) in DMF (2 mL), 12 h.
Yields of isolated products.
b
Scheme 2. Scope of amide derivatives.
2
Zhuang, Daijiao
