11
DBU
CH2Cl2
12
9
We thus started to explore the practicability of the proposed
conjugated strong base-promoted method in Scheme 1. Initially,
a reaction of propylene glycol 1a, propargylic alcohol 2a, and
CO2 in CH3CN under the given conditions was investigated
(Table 1). To our delight, when 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) was employed as the catalyst, the corresponding
products, i.e. propylene carbonate (PC, 3a) and α-hydroxy
ketone 4a were obtained in 61% and 58% yields, respectively
(entry 1). At the same time, several typical guanidine bases were
also examined as catalyst. As seen from the results (entries 2‒4),
they also showed catalytic activity for the transformation. 1,5-
Diazabicyclo[4.3.0]non-5-ene (DBN) possessing the similar
structure with DBU gave the equivalent level result (entry 2).
The other strong base such as 1,5,7-triazabicyclo[4.4.0]dec-5-
ene (TBD) and 1,1,3,3-tetramethylguanidine (TMG) gave lower
yields (entries 3 and 4). As we all know, the basicity strength of
the catalyst plays a key role in the coupling reaction of CO2 and
propargylic alcohol, which is the rate-determining step in the
three-component reaction [32, 39]. Generally, the weak basicity
of catalysts resulted in low activity, while the strong base
exhibited a higher conversion and a lower yield because of some
side reactions [38]. The basicity of the guanidine bases (entries
1‒4) followed the order: TBD > DBN > DBU > TMG [39‒41].
However, their catalytic activity showed as DBU, DBN > TBD >
TMG, an action from both basicity and nucleophilicity
indicating a good agreement with the previous works [38, 42].
Additionally, both K2CO3 and Cs2CO3 led to the lower yields
(entries 5 and 6). The unconjugated base, i.e. Et3N exhibited
significantly a lower catalytic activity than that of guanidine
bases (entries 7 vs. 1‒4). Clearly, the guanidine bases displayed
better performance than that of the other basic catalysts.
a Reaction conditions: 1a (76.1 mg, 1 mmol), 2a (84.1 mg, 1 mmol),
catalyst (0.5 mmol), solvent (2 mL), CO2 1 MPa, 120 oC, 10 h.
b Determined by GC using biphenyl as the internal standard. 3a yield
is based on 1a, and 4a yield is based on 2a.
Next, the effect of CO2 pressure on the reaction was tested,
and the results were shown in Fig. 1a. No target product was
detected under the atmospheric pressure. However, the yield of
product obviously increased when CO2 pressure was from 2 to 5
MPa. Especially, the best result was obtained under 3 MPa, and
the yields of 3a and 4a were 79% and 85%, respectively.
Notably, due to the formation of carbonic acid from high
pressure CO2 and trace water in the reaction system, the activity
of the strong base DBU might be weakened [43, 44]. As a result,
a slightly lower product yield was obtained in 4 and 5 MPa CO2.
As shown in Fig. 1b, reaction temperature had a great influence
on the process. 4a yield was continually increased from 43% to
98% with the increase of temperature. Nevertheless, a decline of
3a yield occurred when the temperature was higher than 120 oC.
Clearly, 120 oC was the optimized reaction temperature.
According to the reported works [31, 34], this three-
component reaction proceeded with a sequential carboxylation
and cyclization of propargylic alcohol and CO2 (R1, Scheme 2),
and interesterification between intermediate α-alkylidene cyclic
carbonate (α-ACC) and 1,2-diol (R2) with the generation of
cyclic carbonate and α-hydroxyl ketone. In addition, α-ACC was
easily hydrolyzed to α-hydroxyl ketone in a basic condition (R3).
Therefore, there was a competitive relationship between R2 and
o
R3. As seen from Fig. 1b, increase temperature from 80 C to
120 oC narrowed the gap in yield between 4a and 3a.
Presumably, although the reaction rates of R2 and R3 were both
accelerated with increasing temperature, R2 was signally
promoted in the presence of the strong base DBU. In contrast,
further increase in temperature led to a weaker catalytic activity,
and the reaction rate of R3 was faster than that of R2.
Accordingly, the yield of 4a was getting higher than that of 3a
Furthermore, the reactions in different solvents were explored
in the presence of DBU, and the results revealed the obvious
influence of the medium. The use of DMF as the solvent gave a
higher yield than that of CH3CN, dimethyl sulfoxide (DMSO) or
CH2Cl2 (entries 9 vs. 1, 10 and 11). In addition, the reaction
worked with less efficiency under the solvent-free conditions
(entry 8).
o
from 120 to 160 C. Additionally, an increased CO2 pressure
might inhibit R3, leading to the decreased yield of 4a (Fig. 1a).
100
80
60
40
20
0
100
80
60
40
20
0
(a)
3a
4a
(b)
Table 1
The effect of different basic catalysts and solvents on the synthesis
of 3a and 4a.a
3a
4a
Entry Catalyst
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
neat
3a Yield (%)b
4a Yield (%)b
1
2
3
DBU
DBN
TBD
61
57
38
35
7
9
2
20
73
69
58
61
41
36
11
14
5
44
71
63
0
1
2
3
4
5
80
100
120
140
160
Reaction temperature (oC)
CO2 pressure (MPa)
Fig. 1. Effect of (a) CO2 pressure and (b) reaction temperature on
the product yields. Reaction conditions: 1a (76.1 mg, 1 mmol), 2a
(84.1 mg, 1 mmol), DBU (76.0 mg, 0.5 mmol), DMF (2 mL), 10 h.
(a) 120 oC; (b) CO2 (3 MPa). The yield was determined by GC using
biphenyl as the internal standard. 3a yield was based on 1a, and 4a
yield was based on 2a.
4
5
6
7
TMG
K2CO3
Cs2CO3
Et3N
8
9
10
DBU
DBU
DBU
DMF
DMSO