Synthesis of Cyclic Organic Carbonates Using Atmospheric Pressure CO2 and Charge-Containing Thiourea Catalysts

Article abstract of DOI:10.1021/acs.joc.8b01374

Cycloadditions of epoxides with CO₂ to synthesize cyclic five-membered ring organic carbonates are of broad interest from a synthetic, environmental, and green chemistry perspective, and the development of effective catalysts for these transformations is an ongoing challenge. A series of eight charge-containing thiourea salts that catalyze these reactions under mild conditions (i.e., 60 °C and atmospheric CO₂ pressure) are reported. Substrate scope and mechanistic studies were also carried out, isotope effects were measured, and a reactive intermediate was isolated revealing a surprising pathway in which a thiourea catalyst serves as a nucleophile in the cleavage of the epoxide ring.

Full text of DOI:10.1021/acs.joc.8b01374

Subscriber access provided by UNIV OF CAMBRIDGE
Article
Synthesis of Cyclic Organic Carbonates Using Atmospheric
Pressure CO2 and Charge-Containing Thiourea Catalysts
Yang Fan, Maximilian Tiffner, Johannes Schörgenhumer,
Raphaël Robiette, Mario Waser, and Steven Robert Kass
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01374 • Publication Date (Web): 18 Jul 2018
Downloaded from http://pubs.acs.org on July 19, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Synthesis of Cyclic Organic Carbonates Using Atmospheric
Pressure CO2 and Charge-Containing Thiourea Catalysts
9
Yang Fana, Maximilian Tiffnerb, Johannes Schörgenhumer,b Raphaël Robiette,c
Mario Waserb* and Steven R. Kassa*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aDepartment of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis,
Minnesota 55455, United States
bInstitute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstraße 69, 4040
Linz, Austria
cInstitute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis
Pasteur 1, box L4.01.02, 1348 Louvain-la-Neuve, Belgium
E-mail: Mario.waser@jku.at, kass@umn.edu
Table of Content Graphic
S
N
I–
O
N
N
CH3
H
H
O
(1 mol%)
Ar
O
O
+ CO2
Ar
TBAI (2 mol%), 60 o
C
90-99% yield
11 examples
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 35
1
2
3
4
ABSTRACT
5
6
7
8
9
Cycloadditions of epoxides with CO2 to synthesize cyclic five-membered ring organic
carbonates are of broad interest from a synthetic, environmental and green chemistry perspective,
and the development of effective catalysts for these transformations is an ongoing challenge. A
series of eight charge-containing thiourea salts that catalyze these reactions under mild
conditions (i.e., 60 ˚C and atmospheric CO2 pressure) are reported. Substrate scope and
mechanistic studies were also carried out, isotope effects were measured, and a reactive
intermediate was isolated revealing a surprising pathway in which a thiourea catalyst serves as a
nucleophile in the cleavage of the epoxide ring.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
ACS Paragon Plus Environment

Page 3 of 35
The Journal of Organic Chemistry
1
2
3
4
INTRODUCTION
5
6
7
8
9
Carbon dioxide (CO2) is a problematic greenhouse gas of great concern in the Earth's
atmosphere. Its atmospheric concentration has been rapidly rising over the past fifty years in
large part due to human activities such as fuel combustion, and this is a major cause of global
warming.1 Reduction of unwanted CO2 emissions and atmospheric levels, consequently is a
subject of the utmost importance in the development of a modern sustainable society.2 Carbon
dioxide is also a non-toxic and renewable potential C1 feedstock in organic synthesis that could
be of enormous utility in industrial and pharmaceutical applications.3 Sustainable and efficient
methods of chemical fixation of CO2 are urgently needed, and are the focus of current research in
the management strategy of this greenhouse gas.4 One alternative approach is the incorporation
of CO2 into epoxides to afford cyclic five-membered ring organic carbonates because this
chemical transformation is 100% atom economical and the resulting compounds are of broad
utility. For example, they are used as aprotic polar solvents in the development of batteries and
ionic liquids, and as precursors and intermediates in organic and polymer syntheses.5,6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Despite the global desire to readily and sustainably make use of CO2 in chemical reactions,
this has proven to be difficult due to its kinetic and thermodynamic stability. Elevated temper-
atures and pressures are typically required to overcome energy barriers and make use of this
abundant potential C1 feedstock. The development of catalysts to exploit this reagent under
milder conditions has received considerable attention in recent years. A wide range of species
have been studied for carrying out cycloadditions of epoxides with CO2 to afford cyclic
carbonates with a focus on metal complexes,7 ionic liquids8 and combinations of the two. Halide
salt additives have proven useful in these systems but the resulting processes suffer from air
and/or water sensitivity, poor reactivity necessitating harsh reaction conditions, and the need for
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 35
1
2
3
4
5
organic solvents.9 In this context, the development of organocatalysts has emerged as an
attractive new research direction.
6
7
8
9
Hydrogen bond catalysts such as alcohols,10 polyphenols,11 carboxylic acids,12 silanediols13
and squaramides14 have been reported recently and show promising results for the preparation of
cyclic carbonates. Electrophilic activation of the epoxide via a hydrogen bonded complex is
generally considered to facilitate its ring-opening in the presence of a halide anion in the rate
determining step.15 When compared to metal-based catalysts and ionic liquids, organic hydrogen
bond donors are considered to be advantageous with respect to toxicity, sustainability, and the
use of milder conditions.16
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Thioureas are the most extensively studied hydrogen bond catalysts and of these, Schreiner's
thiourea (1, (3,5-(CF3)2C6H3NH)2CS) is commonly viewed as the most active species. We
recently reported on a series of novel charge-enhanced derivatives bearing one or two N-
alkylpyridinium ion centers and a weakly coordinating counteranion.17 These solid salts proved
to be more active than Schreiner’s thiourea by orders of magnitude in several organic
transformations carried out in non-polar media. Inspired by these results, we decided to examine
their ability to catalyze the cycloadditions of epoxides with CO2. The catalytic performance of
eight such derivatives (T1-T8, Figure 1) is reported herein.
RESULTS AND DISCUSSION
To initiate our study upon the chemical fixation of CO2 into epoxides using charged thiourea
salts as catalysts, we first examined the reaction of 2-phenyloxirane (2) with CO2 to afford the
phenyl-substituted carbonate 3 (eq. 1). Under mild solvent free conditions at 60 ˚C with an
4
ACS Paragon Plus Environment

Page 5 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
S
S
N
N
N
Octyl
N
H
N
H
Octyl
N
H
N
H
Octyl
–OTf
–OTf
–OTf
7
T1
T2
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
S
S
N
N
N
N
H
N
H
N
H
N
H
X–
X–
X–
X = BArF4 (T4)
= I (T6)
X = BArF4 (T3)
= I (T5)
CF3
S
NMe2R
I–
F3C
N
N
H
H
R = CH3 (T7)
R = CH2Ph (T8)
Figure 1. Charge-containing thiourea salts examined in this work.
O
O
O
cat. (1 mol%)
salt additive
O
(1)
+ CO2
60 ˚C, 6 h
2
3
atmospheric pressure of CO2, 1 mol% of T1 and a halide salt, the cyclic carbonate was formed
with moderate conversions after 6 h (Table 1). When tetrabutylammonium iodide (TBAI) was
employed, 57% of the 2-phenyloxirane was converted to 3 (entry 1) whereas progressively
smaller amounts were obtained in going to the bromide and chloride salts (entries 2-3). This
order is the reverse of the gas-phase proton affinities of these halide anions and their
nucleophilicities in aprotic media. Use of bis(triphenylphosphine)iminium chloride (PPNCl) had
little, if any, impact (entry 4) even though this salt is known to dissociate to a larger extent than
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 35
1
2
3
4
5
Table 1. Catalytic Performance of T1 with Various Halide Salt Co-catalysts in the Fixation
of CO2 into 2-Phenyloxirane.a
6
7
8
9
entry additive
(mol%) conversion (%)b
1
(Bu)4NI
1
1
1
57
41
20
19
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
3
(Bu)4NBr
(Bu)4NCl
4
5
6c
7c
8
(Ph3P)2NCl 1
none
(Bu)4NI
(Bu)4NI
(Bu)4NI
(Bu)4NI
(Bu)4NI
(Bu)4NI
(Bu)4NI
1
2
2
3
5
10
2
29
56
74
65
66
53
16
9
10
11
12d
aUnless otherwise indicated, this reaction was carried out at 60 ˚C with 1 mol% of catalyst T1 and the indicated
additive under an atmospheric pressure (0.1 MPa) of CO2. Reaction conversions were obtained after 6 h by H
NMR. cNo thiourea catalyst was used. dThe reaction was carried out under 4.0 MPa of CO2 and analyzed after 1.5 h.
b
1
TBACl in nonpolar media.18 Omission of the halide salt led to no observed product (entry 5)
whereas when the catalyst (T1) was excluded but 1 mol% of TBAI was employed about half the
amount of product was formed (entry 6). These results indicate that a nucleophilic anion is
required for product formation and the presence of thiourea T1 improves the efficiency of this
process.
Further optimization of this transformation was carried out by varying the amount of the
TBAI additive. When 2 mol% of this salt was used, a higher conversion of 74% was achieved
(entry 8) and this exceeds the 56% that is obtained when T1 was omitted from the reaction (entry
7). Further increases of TBAI were explored (3-10 mol%), but this led to smaller amounts of
product (entries 9-11). We speculate that this is due to aggregation and/or a medium effect
resulting in a decrease in the nucleophilicty of I–. A reaction was also carried out at an elevated
6
ACS Paragon Plus Environment

Page 7 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
pressure of CO2 (4.0 MPa) with 1 mol% T1 and 2 mol% TBAI, but this did not appear to
accelerate the transformation.19 These results suggest that CO2 is not involved in the rate-
determining step, but that both the nucleophile and the hydrogen bond catalyst play an important
role in this process.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Based upon these preliminary results with catalyst T1, a variety of catalyst structures (T2-T8)
were examined with varying amounts of TBAI (Table 2). Incorporation of a second positively
charged center into the thiourea (T2) leads to a less efficient catalyst than T1 (entries 1-2). The
Table 2. Catalyst and Additive Screening for the Reaction of 2-Phenyloxirane with CO2.a
entry catalyst
TBAI (mol%) conversion (%)b
1
2
3
4
5
6
7
8
T1
T2
T3
T3
T3
T4
T4
T5
T5
T5
T5
T5
T5
T5
T5
T6
2
2
0
1
2
0
2
0
1
2
3
2c
2
2
2
0
2
0
0
2
2
74
53
0
20
52
0
87
48
61
88
88
79
83
71
82
17
54
28
34
48
40
9
10
11
12
13d
14e
15f
16
17
18
19
20
21
T6
T7
T8
(PhNH)2CS
1
aThese transformations were carried out for 6 h with 1 mol% of the catalyst and atmospheric pressure (0.1 MPa)
b
1
c
CO2 at 60 ˚C. Product conversions were obtained by H NMR. Tetra-n-heptylammonium iodide was used instead
of TBAI. d4-Dimethylaminopyridine (DMAP, 2 mol%) was added. eAcetic acid (1 mol%) was added.
fTrifluoroacetic acid (1 mol%) was added.
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 35
1
2
3
4
triflate counteranion is weakly basic but previously was shown to have a deleterious effect on the
5
6
rate of a Friedel-Crafts alkylation.20 Consequently, mono- and bis-charged thioureas T3 and T4
7
8
9
with weakly coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anions (BArF –) were
4
explored.17 In the absence of a nucleophile no carbonate was produced (entries 3 and 6) and the
mono-charged catalyst T3 is not as effective as T1 (entries 4-5), but the bis-charged derivative
T4 gave an improved result (entry 7). Bifunctional thiourea salts T5-T8 with iodide
counteranions were also examined. Unlike T1-T4, these species led to product formation without
the need for an external iodide source and the conversions followed the order: T6 < T7 < T8 <
T5 (entries 8, 16 and 18-19). Further optimization of T5 led to our best result and an 88%
conversion to product in a 6 h time period at 60 ˚C (entries 9-11); this was achieved with 2 or 3
mol% TBAI. A larger quaternary ammonium salt, tetra-n-heptylammonium iodide was tested too
(entry 12), but it led to slightly poorer results.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Previous studies have found that organic bases can facilitate the cycloaddition of epoxides
with CO2 by activating the latter reagent.21 When we added 2 mol% of 4-dimethylamino-
pyridine (DMAP) along with T5 and TBAI, no improvement was observed (entry 13). This is
consistent with our observation that an increase in the CO2 pressure did not accelerate the
reaction. Alternatively, thioureas can be activated by BrØnsted acids22 so 1 mol% of acetic acid
and trifluoroacetic acid were tested (entries 14-15). Both of these additives, however, had a small
deleterious effect. Finally, reactions were carried out with diphenylthiourea and (3,5-
(CF3)2C6H3NH)2CS (1), and as suspected the conversions (48 and 40%, respectively) were
reduced with respect to our charged analogs (entries 20-21). In fact under the employed
conditions both compounds actually function slightly as inhibitors since a 56% conversion was
obtained when they were omitted.
8
ACS Paragon Plus Environment

Page 9 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Given the excellent performance of the binary T5/TBAI catalyst system,23 the scope of this
transformation was explored (eq. 2, Table 3). A series of 11 monosubstituted aromatic and
aliphatic epoxides were examined at 60 ˚C with 1 atmosphere pressure of CO2, 1 mol% T5 and 2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
T5 (1 mol%)
TBAI (2 mol%)
O
O
R
R
O
(2)
+ CO2
60 ˚C, 8 h
R"
R'
R"
R'
Table 3. Reaction scope with the use of the T5/TBAI binary catalyst system.
entry epoxide (and carbonate 3)
yield (%)
95
95
1
2
3
4
5
6
7
8
R = Ph, R', R" = H (2a)
R = p-ClC6H4, R', R" = H (2b)
R = p-FC6H4, R', R" = H (2c)
R = p-MeOC6H4, R', R" = H (2d)
R = p-O2NC6H4, R', R" = H (2e)
R = PhOCH2, R', R" = H (2f)
R = ClCH2, R', R" = H (2g)
93
98a
98b
99
98
R = CH2=CHCH2CH2, R', R" = H (2h) 90
9
R = CH2=CH, R', R" = H (2i)
R = PhCH2, R', R" = H (2j)
R = BnOCH2, R', R" = H (2k)
R,R" = (CH2)4, R' = H (2l)
R = Ph, R' = CH3, R" = H (2m)
97
97
95
trace
trace
10
11
12
13
at = 3 h. bt = 4 h and T = 90 ˚C.
mol% TBAI, and isolated yields of ≥ 90% were obtained after 8 h in all cases (entries 1-11); see
the supporting information for the application scope of T7 and T8. Disubstituted epoxides (1,1-
and 1,2-), however, are not suitable substrates under the employed reaction conditions (entries
12-13). From a mechanistic standpoint, these results suggest that sterics are important.
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 35
1
2
3
4
5
6
7
8
9
To address the mechanism of this transformation further, (R)-2-phenyloxirane (2a, ≥ 99% ee)
and (R)-2-(benzyloxymethyl)oxirane (2k, ≥ 99% ee) were reacted with T5 as illustrated in eq. 2
and the isolated products were both obtained in 95% yields with 86% ee for 3a and ≥ 99% ee for
3k. The absolute configuration of the major enantiomer in both cases corresponded to retention
of configuration (R) by comparison to previously reported chiral HPLC data.24 In accord with
these findings, when enantiopure samples of 2a were heated to 60 ˚C in the absence of CO2 but
in the presence of T1 and TBAI (1 and 2 mol%, respectively) or T7 (1 and 3 mol%),
racemization was observed to slowly occur (eq. 3). In the former case, the epoxide had
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
T1, TBAI
O
O
O
or
T7
+
(3)
60 °C
(R)-2a
(R)-2a
(S)-2a
T1 (1 mol%), TBAI (2 mol%): 86% ee (R) (1 h), racemic (18 h)
T7: 86% ee (R) (1 mol%, 15 h), 55% ee (R) (3 mol%, 15 h)
an 86% ee after 1 h and was completely racemized within 18 h. In the latter instance with 1 or 3
mol% of T7, 86% and 55% ee samples were obtained respectively after 15 h. These results
reveal that a slow epimerization takes place when a stabilized benzylic cation can form when
starting with 2a, but not when a secondary alkyl carbenium ion would be produced using epoxide
2k. These acid-catalyzed processes presumably are catalytically off-cycle events (i.e., they are
unrelated to the mechanism for formation of the cyclic carbonate) given that alkyl substituted
epoxides are good substrates, 1,1-disubstituted derivative 2l is unreactive, and a competition
study showed that the reaction of 2-(p-nitrophenyl)oxirane (2e) takes place more rapidly than the
parent compound, 2-phenyloxirane (2a). That is, a 1:1 mixture of 2e and 2a at 60 ˚C with 1 mol%
T5 and 2 mol% TBAI led to 54% and 32% conversions to their respective carbonates after 2 h.
10
ACS Paragon Plus Environment

Page 11 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Electrophilic activation of the monosubstituted epoxide by coordination to the thiourea
catalyst via hydrogen bond formation might be expected to preferentially activate the internal
position due to a larger build-up of positive charge at this site.17 To probe this latter mechanistic
detail, kinetic isotope effects were measured using 2-deuterio-2-phenyloxirane (2a-d1, >99% D)
and 3,3-dideuterio-2-phenyloxirane (2a-d2, 85% D2) at 45 ˚C with 1 mol% T5 and 2 mol% TBAI
(eq. 4). Surprisingly, kH/kD = 1.0 for the monodeuterio compound and 1.6 for the dideuterio
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
T5 (1 mol%)
O
TBAI (2 mol%)
O
O
Ph
(4a)
Ph
CO2, 45 ˚C
D
D
kH/kD = 1.0
2a-d
O
O
D
D
Ph
O
O
(4b)
D
Ph
kH/kD = 1.6
D
2a-d2
species were observed (see Table S4 in the supporting information for additional details). The
latter secondary kinetic isotope effect is large, and taken together these results indicate that
nucleophilic attack occurs at the terminal methylene carbon of 2-phenyloxirane. Additionally,
when the reaction of 2a with T7 was monitored by 1H NMR, a small amount of an intermediate
was observed. This species (4) was subsequently isolated and characterized, and is the product
resulting from nucleophilic attack of the epoxide by the sulfur atom of the thiourea; a similar
observation with 2-methyloxirane to afford 4' was found. Submission of this compound to the
reaction conditions led to the formation of the cyclic carbonate product in a kinetically
competent fashion and led us to propose the novel mechanism illustrated in Scheme 1.
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 35
1
2
3
4
5
Thiourea-catalyed pathways:
O
CF3
6
7
8
9
O
O
O
S
Ph
+
2a
NMe3
Ph
F3C
N
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H
H
(b)
I
T7
(a)
CF3
CF3
Ph
S
S
+
2a
O
NMe3
O
F3C
N
N
H
F3C
N
H
N
HO
H
I
O
NMe3
+
5
I
Ph
CF3
6
Ph
OH
S
I
F3C
N
H
N
CO2
NMe3
+
4
TBAI-catalyed route in the absence of T7:
O
O
O
O
TBAI
Ph
Ph
O
+
O
TBA
+
TBA
O
O
I
Ph
I
Ph
CO2
Scheme 1. Proposed mechanism for the cycloaddition of 2-phenyloxirane with CO2 in the
presence of a charge-containing thiourea/TBAI binary catalyst system (top), and an alternative
route in the absence of the thiourea (bottom).
12
ACS Paragon Plus Environment

Page 13 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In our proposed mechanism, the charge-containing thiourea catalyst acts as a nucleophile in
an SN2 ring opening of the epoxide at the less hindered methylene carbon to yield 4 via pathway
a. Alternatively, iodide may serve as the initial nucleophile to afford 6 as shown in route b. An
ensuing displacement of I– by the sulfur atom of the thiourea would lead to 4 by a two step
process. Both pathways account for the formation of this intermediate and the observed
secondary kinetic isotope effect, and are consistent with 1,1- and 1,2-disubstituted epoxides
being poor reaction partners due to increased steric effects. Subsequent trapping of CO2 to give 5
followed by cyclization via an intramolecular substitution reaction affords the carbonate product
and regenerates the thiourea catalyst. Putative intermediate 6 also could react with CO2 (pathway
c, not shown) in a similar manner to the TBAI-catalyzed process that takes place in the absence
of a thiourea. If this is the case, then the conversion of 6 to 4 would need to be reversible.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To address these mechanistic alternatives further, B3LYP calculations were carried out on
different structural arrangements of hydrogen bonded complexes between T7 and 2a (see
supporting information for additional details). Low energy structures that are well positioned to
use the sulfur or iodine atom as the nucleophile were located (Figure 2, 7 and 8, respectively).
b
1.949
2.045
1.960
a
3.202
2.727
a = 2.781
a
b
a = 2.783
b = 2.831
b = 2.783
3.118
7
8
Figure 2. Fully optimized B3LYP/aug-cc-pVDZ/6-311G(d) structures, where the second all
electron basis set was used for iodine. Distances are given in Å and most of the hydrogen atoms
attached to carbon are omitted for clarity sake.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 35
1
2
3
4
5
6
7
8
9
The covalently bound complex between the thiourea catalyst and 2-phenyloxirane (i.e., 4) is
more stable than 6 by 13.3 kcal mol–1, but the reaction barrier for formation of the latter is much
more favorable than the one for direct formation of 4. That is, nucleophilic attack of the epoxide
by I– has a computed barrier of 25.5 kcal mol–1 whereas that for the sulfur atom of the catalyst is
46.8 kcal mol–1 (Figure 3).25 These results suggest that pathway b is the favored process,26 but
given the computational complexity of this system, additional experimental data would be useful
for further differentiating the various reaction pathways.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
TSS
46.8
TSI
25.5
6
7.8
7
5.5
8
0.0
4
-5.5
Figure 3. Computed B3LYP/aug-cc-pVDZ/6-311+G(d) single point free energy reaction
diagrams for the T7 catalyzed ring opening of 2-phenyloxirane. Relative free energies are given
in kcal mol–1 at 298 K.
CONCLUSION
A series of metal-free electrostatically enhanced thiourea catalysts T1-T8 were explored and
found to induce CO2 fixation at atmospheric pressure into monosubstituted epoxides with low
loadings (1 mol%) and the addition of a small amount (2 mol%) of tetrabutylammonium iodide.
High yields of ≥ 90% were obtained at modest temperatures for 11 different substrates in 8 h or
14
ACS Paragon Plus Environment

Page 15 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
less. These species are more active than the only other thiourea catalyst previously reported, an
ionic liquid containing a remote imidizolium ion,7g in that lower temperatures (60 vs 130 ˚C) and
pressures (1 vs 15 atm.) were employed in this work. Mechanistic studies suggest that this
cycloaddition reaction occurs via a novel pathway in which the thiourea acts as a nucleophile to
either open the epoxide directly at the less hindered position or to replace the iodine in 2-iodo-1-
phenylethanol. In either case, the resulting covalently bound thiourea 4 was spectroscopically
observed, isolated, and found to react with CO2 in a kinetically competent manner to afford the
cyclic carbonate product and regenerate the thiourea catalyst.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Experimental
General. All chemicals and reagents were obtained from Sigma Aldrich and Alfa Aesar except
for deuterated solvents which came from Cambridge Isotope Laboratories. Reactions were
carried out in oven-dried glassware (i.e., flasks, vials and NMR tubes) under an argon or CO2
atmosphere. NMR spectra were recorded on 300, 500 and 700 MHz instruments. The 1H and 13C
chemical shifts are given in ppm and were referenced respectively as follows: 7.26 and 77.2
(CDCl3); 2.05 and 29.8 (acetone-d6). IR spectra were obtained with a FT-IR and an ATR source.
High resolution mass spectra were recorded by ESI with a TOF mass analyzer using methanolic
solutions containing polyethylene glycol as an internal standard. Enantiomeric ratios were
measured with HPLC systems using 25 cm x 4.6 mm (5 µm) RegisPackTM and Chiracel OD-H
chiral columns. Synthesis and characterization data for T1-T6 have been reported in previous
work.17,20
General Procedure for the Cycloaddition Reactions of 2-Phenyloxirane (2) with CO2. A 3-
dram vial was purged with gaseous CO2 for 5 min and then charged with 2-phenyloxirane (57 µL,
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 35
1
2
3
4
5
6
7
8
9
0.5 mmol), TBAI (3.7 mg, 10 µmol) and T5 (1.9 mg, 5 µmol). The vial was then sealed with a
septum which was connected to a balloon filled with CO2 and heated at 60 ˚C for 6 h. Reaction
conversions were obtained by 1H NMR in CDCl3 using integrations for the signals of 2 at δ 3.84
and 3 at δ 4.32 ppm.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,3-Dideuterio-2-phenyloxirane (2a-d2). A solution of 2-bromoacetophenone (1999 mg,
10 mmol) in 5 mL CDCl3 was cooled to 0 ˚C. Carefully, t-BuOK (842 mg, 7.5 mmol) was added
in small portions while the reaction mixture was strongly stirred (Warning: chloroform is
incompatible with strong caustics). After 1 h of stirring at 0 ˚C, 3 mL of D2O was slowly added.
1
A H NMR sample of the CDCl3 phase was recorded which showed a degree of deuteration of
only 33%. Additional t-BuOK (562 mg, 5.0 mmol) was then carefully added to the strongly
stirred biphasic mixture, which was stirred for 2 h while allowing it to warm to room temperature.
The two phases were separated and the aqueous solution was extracted with CDCl3 (2 x 2 mL).
The combined organic material was dried with Na2SO4 and the solvent was removed by rotatory
evaporation. Purification of the crude product was carried out by column chromatography on
silica gel with heptanes/EtOAc (50:1 → 30:1) to afford 1.42 g (62%) of 2-bromoacetophenone-
2,2-d2 as a white orange solid with 90% deuterium incorporation at the acidic α-position.
Analytical data are in accord with those reported in the literature.27 1H NMR (300 MHz, CDCl3)
δ 8.02 – 7.95 (m, 2H), 7.65 – 7.56 (m, 1H), 7.54 – 7.45 (m, 2H), 4.47 – 4.42 (m, 0.21 H).
13C NMR (75 MHz, CDCl3) δ 191.3, 133.9, 133.8, 128.8, 128.7, 30.3 (quintet, J = 22.5 Hz).
2-Bromoacetophenone-2,2-d2 (1400 mg, 7 mmol) was put into a Schlenk flask which was then
evacuated and refilled three times with argon before adding 15 mL of MeOH. This suspension
was cooled to 0 ˚C using an ice-salt water bath and sodium borohydride (294 mg, 7.7 mmol) was
added portionwise. The resulting reaction mixture was stirred for 3 h while letting it slowly
16
ACS Paragon Plus Environment

Page 17 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
warm to room temperature. Subsequently, K2CO3 (968 mg, 7 mmol) was added in one portion
and stirring was continued for 15 h. Methanol was then removed by rotatory evaporation, 50 mL
of H2O was added and the aqueous phase was extracted with CH2Cl2 (3 x 50 mL). The combined
organic material was washed with brine (50 mL), dried over Na2SO4 and the solvent was
removed under reduced pressure to afford 720 mg (84%) of 2a-d2 as a colorless liquid. Its
analytical data are in accord with those reported in the literature.28 1H NMR (300 MHz, CDCl3) δ
7.40 – 7.25 (m, 5H), 3.86 (s, 1H), 3.18 – 3.12 (m, 0.15H), 2.83 – 2.78 (m, 0.15H).
13C NMR (75 MHz, CDCl3) δ 137, 128.4, 128.1, 125.4, 52.1, 51.5 (quintet, J = 26 Hz).
2-Deuterio-2-phenyloxirane (2a-d). 2-Bromoacetophenone (1000 mg, 5 mmol) was put into a
Schlenk flask and then evacuated and refilled with argon (3x) before adding 12 mL of MeOH.
The resulting suspension was cooled to 0 ˚C with an ice-salt water bath and sodium
borodeuteride (210 mg, 5.5 mmol) was added portionwise with stirring. Over the course of 3 h
the reaction mixture was allowed to warm up to room temperature. Potassium carbonate (691 mg,
5 mmol) was then added in one portion and stirring was continued for 20 h. The reaction mixture
was then filtered through a plug of Na2SO4 and the solvent was removed by rotatory evaporation.
Purification of the crude product by column chromatography on silica gel with heptanes/EtOAc
(100:1 → 50:1) afforded 545 mg (91%) of 2a-d as a colourless liquid. Its analytical data are in
accord with those reported in the literature.29 1H NMR (300 MHz, CDCl3) δ 7.41 – 7.26 (m, 5H),
3.17 (d, J = 5.5 Hz, 1H), 2.84 (d, J = 5.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 137.4, 128.4,
128.1, 125.4, 51.9 (t, 27 Hz), 51.0.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Catalyst T7. To a suspension of 2-(aminoethyl)trimethylammonium iodide (1 g, 2.81 mmol)30 in
10 mL of dry CH2Cl2 was added triethylamine (392 µL, 2.81 mmol) at room temperature. This
mixture turned clear and subsequently 3,5-bis(trifluoromethylphenyl)isothiocyanate (517 µl,
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 35
1
2
3
4
5
6
7
8
9
3.09 mmol) was added. Stirring was continued for 15 h before filtering the reaction mixture
through a plug of Na2SO4. Removal of the solvent by rotatory evaporation afforded the crude
product which was purified by column chromatography on silica gel with CH2Cl2/MeOH (50:1
→ 10:1) to afford 1.35 g (96%) of T7 as a white solid; analytical data are in accord with the
previously reported chloride salt.31 1H NMR (300 MHz, CDCl3) δ 9.79 (s, 1H) ppm, 8.49 (t,
J = 5.8 Hz, 1H), 8.24 (s, 2H), 7.60 (s, 1H), 4.38 – 4.28 (m, 2H), 3.98 – 3.91 (m, 2H), 3.45 (s, 9H).
13C NMR (75 MHz, CDCl3) δ 181.7, 140.3, 131.4 (q, J = 34 Hz), 123.1 (q, J = 274 Hz), 123.0,
118.0, 64.9, 54.8, 38.3. 19F NMR (282 MHz, D2O) δ -64.5. HRMS-ESI: calcd for C14H18F6N3S+
(M)+ 374.1120, found: 374.1125.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Catalyst T8. To a solution of 3,5-bis(trifluoromethyl)phenyl isothiocyanate (0.336 mL, 1.84
mmol) in toluene (2 mL) was added N,N-dimethylethylenediamine (0.201 mL, 1.84 mmol). After
stirring for 14 h at room temperature the reaction mixture was directly subjected to column
chromatography on silica gel with CH2Cl2/MeOH (20:1) to afford 625 mg (95%) of the known
thiourea intermediate.32 A mixture of this compound (100 mg, 0.278 mmol) and benzyl bromide
(95 mg, 0.556 mmol) was stirred in 2 mL of CH3CN for 15 h at room temperature. The reaction
mixture was directly subjected to column chromatography on silica gel with CH2Cl2/MeOH
(10:1) to yield 148 mg (92%) of T8 as a white solid. 1H NMR (300 MHz, CDCl3) δ 9.83 (s, 1H),
8.74 (t, J = 5.7 Hz, 1H), 8.24 (s, 2H), 7.42 – 7.60 (m, 6H), 4.83 (s, 2H), 4.37 – 4.48 (m, 2H), 3.99
(t, J = 5.8 Hz, 2H), 3.29 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 181.8, 140.4, 133.0, 131.4 (q, J =
34 Hz), 131.4, 129.6, 126.0, 123.1 (q, J = 274 Hz), 123.0, 118.0, 68.9, 63.6, 50.7, 38.3. HRMS-
ESI: calcd for C20H22F6N3S+ (M)+ 450.1433, found 450.1439.
Isolation of 4. This compound can be obtained by heating 0.04 mmol (20 mg) of the ammonium
salt T7 with 48 mg (10 equivalents) of 2-phenyloxirane in a pressure Schlenk vessel until the
18
ACS Paragon Plus Environment

Page 19 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
ammonium salt is dissolved, allowing the organic material to cool to room temperature and then
performing a purification by silica gel column chromatography with CH2Cl2/MeOH (20:1) as the
7
8
9
1
eluent. This afforded 9 mg (36%) of 4 as a colorless oil. H NMR (700 MHz, MeOD) δ 7.51 (s,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1H), 7.39 (s, 2H), 7.37 – 7.34 (m, 2H), 7.34 – 7.30 (m, 2H), 7.28 – 7.25 (m, 1H), 4.83 (dd,
J = 8.4 and 3.7 Hz, 1H), 3.88 (t, J = 6.4 Hz, 2H), 3.66 (t, J = 6.6 Hz, 2H), 3.26 (s, 9H), 3.24 –
13
3.21 (m, 2H), 3.14 (dd, J = 14.4 and 3.4 Hz, 1H). C NMR (175 MHz, MeOD) δ 155.6, 152.0,
143.0, 131.7 (q, J = 33 Hz), 128.2, 127.7, 125.8, 123.8 (q, J = 273 Hz), 123.0, 115.2, 73.5, 64.2,
52.9, 39.6, 36.6. HRMS-ESI: calcd for C22H26F6N3OS+ (M)+ 494.1695, found: 494.1699.
Isolation of 4'. This compound was obtained when heating 0.04 mmol (20 mg) of the
ammonium salt T7 with 23 mg (10 equivalents) of methyloxirane in a pressure Schlenk vessel
until the ammonium salt is dissolved, allowing the organic material to cool to room temperature
and then performing a purification by silica gel column chromatography with CH2Cl2/MeOH
1
(20:1) as the eluent. This afforded 7 mg (31%) of 4' as a colorless oil H NMR (300 MHz,
MeOD) δ 7.53 (s, 1H), 7.45 (s, 2H), 3.96 – 3.89 (m, 3H), 3.72 (t, J = 6.5 Hz, 2H), 3.30 (s, 9H),
3.15 – 2.93 (m, 2H), 1.26 (d, J = 6.2 Hz, 3H). 13C NMR (75 MHz, MeOD) δ 155.7, 151.9,
131.6 (q, J = 33 Hz), 123.5 (q, J = 273 Hz), 122.9, 115.0, 66.9, 64.1, 52.9, 39.2, 36.5, 21.3.33
HRMS-ESI calcd for C17H24F6N3OS+ (M)+ 432.1539, found 432.1539.
Analytical Data for Carbonates 3. 4-Phenyl-1,3-dioxolan-2-one (3a). This material (311 mg)
was formed in a 95% yield and the analytical data are in accord with those reported in the
literature.34 1H NMR (300 MHz, CDCl3) δ 7.48 – 7.39 (m, 3H), 7.38 – 7.33 (m, 2H), 5.67 (t, J =
8 Hz, 1H), 4.79 (t, J = 8.4 Hz, 1H), 4.34 (dd, J = 8.6 and 7.9 Hz, 1H). 13C NMR (75 MHz, CDCl3)
δ 154.7, 135.7, 129.5, 129.0, 125.7, 77.8, 71.0. HRMS-ESI: calcd for C9H8NaO3 (M + Na)+
187.0371, found 187.0367. Enantiomer separation was accomplished with a Chiracel OD-H
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 35
1
2
3
4
5
6
7
8
9
column using hexanes/i-PrOH = 70:30) and a flow rate of 1 mL min–1 to give retention times of
8.8 (R) and 10.0 (S) min.24 When (R)-2a was used, (R)-3a was observed as the major enantiomer.
4-(4-Chlorophenyl)-1,3-dioxolan-2-one (3b). This material (378 mg) was formed in a 95% yield
and the analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz,
CDCl3) δ 7.42 – 7.34 (d, 2H, 8.5 Hz), 7.33 – 7.26 (d, 2H, 8.5 Hz), 5.65 (t, J = 8 Hz, 1H), 4.79 (t,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
J = 8.5 Hz, 1H), 4.28 (dd, J = 8.6 Hz and 7.8 Hz, 1H). C NMR (75 MHz, CDCl3) δ 154.5,
135.4, 134.2, 129.2, 127.2, 77.1, 71.8. HRMS-ESI: calcd for C9H7ClNaO3 (M + Na)+ 220.9981,
found 220.9978.
4-(4-Fluorophenyl)-1,3-dioxolan-2-one (3c). This material (341 mg) was formed in a 93% yield
and the analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz,
CDCl3) δ 7.41 – 7.30 (m, 2H), 7.17 – 7.06 (m, 2H), 5.66 (t, J = 8 Hz, 1H), 4.79 (t, J = 8.5 Hz,
13
1H), 4.31 (dd, J = 8.6 and 7.8 Hz, 1H). C NMR (75 MHz, CDCl3) δ 163.2 (d, J = 249 Hz),
154.6, 131.5 (d, J = 3.3 Hz), 127.9 (d, J = 8.5 Hz), 116.2 (d, J = 22.1 Hz), 77.4, 71.0. 19F NMR
(282 MHz, CDCl3) δ -111.1. HRMS-ESI: calcd for C9H7FNaO3 (M + Na)+ 205.0277, found:
205.0271.
4-(4-Methoxyphenyl)-1,3-dioxolan-2-one (3d). This material (380 mg) was formed in a 98%
yield and the analytical data are in accord with those reported in the literature.35 The product
1
decomposed upon column chromatography. H NMR (300 MHz, CDCl3) δ 7.30 (d, J = 8.7 Hz,
2H), 6.96 (d, J = 8.7 Hz, 2H), 5.62 (t, J = 8.0 Hz, 1H), 4.75, (t, J = 8.4 Hz), 4.34 (t, J = 8.4 Hz,
1H), 3.83 (s, 3H).
4-(4-Nitrophenyl)-1,3-dioxolan-2-one (3e). This material (409 mg) was formed in a 98% yield
and the analytical data are in accord with those reported in the literature.36 1H NMR (300 MHz,
CDCl3) δ 8.28 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 5.83 (t, J = 7.9 Hz, 1H), 4.91, (t,
20
ACS Paragon Plus Environment

Page 21 of 35
The Journal of Organic Chemistry
1
2
3
4
13
J = 8.5 Hz), 4.32 (t, J = 8.2 Hz, 1H). C NMR (75 MHz, CDCl3) δ 154.1, 148.4, 142.7, 126.5,
5
6
124.3, 76.3, 70.6.
7
8
9
4-(Phenoxymethyl)-1,3-dioxolan-2-one (3f). This material (384 mg) was formed in a 99% yield
and the analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz,
CDCl3) δ 7.31 (t, J = 7.8 Hz, 2H), 7.02 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 8.1 Hz), 5.09 – 4.96 (m,
1H), 4.60 (t, J = 8.5 Hz, 1H), 4.51 (dd, J = 6.0 and 8.4 Hz, 1H), 4.24 (dd, J = 10.5 and 3.8 Hz,
1H), 4.12 (dd, J = 10.5 and 3.8 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 157.7, 154.7, 129.5,
121.8, 114.5, 74.1, 66.7, 66.1. HRMS-ESI: calcd for C10H10NaO4 (M+Na)+ 217.0477, found
217.0475.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-(Chloromethyl)-1,3-dioxolan-2-one (3g). This material (267 mg) was formed in a 98% yield
and the analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz,
CDCl3) δ 5.04 – 4.91 (m, 1H), 4.59 (t, J = 8.2 Hz, 1H), 4.41 (dd, J = 5.5 and 8.0 Hz, 1H), 3.83 –
3.68 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 154.3, 74.3, 66.7, 44.1. HRMS-ESI: calcd for
C4H5ClNaO3 (M+Na)+ 158.9825, found: 158.9821.
4-(But-3-en-1-yl)-1,3-dioxolan-2-one (3h). This material (256 mg) was formed in a 90% yield
and the analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz,
CDCl3) δ 5.84 – 5.66 (m, 1H), 5.10 – 4.96 (m, 2H), 4.77 – 4.63 (m, 1H), 4.50 (t, J = 8.1 Hz, 1H),
4.05 (t, J = 7.8 Hz, 1H), 2.32 – 2.05 (m, 2H), 1.98 – 1.81 (m, 1H), 1.81 – 1.65 (m, 1H). 13C NMR
(75 MHz, CDCl3) δ 154.9, 136.0, 116.1, 76.2, 69.2, 32.8, 28.4. HRMS-ESI: calcd for C7H10NaO3
(M+Na)+ 165.0528, found 165.0526.
4-Vinyl-1,3-dioxolan-2-one (3i). This material (222 mg) was formed in a 97% yield and the
analytical data are in accord with those reported in the literature.34 1H NMR (300 MHz, CDCl3) δ
4.92 – 4.78 (m, 1H), 5.50 – 5.33 (m, 2H), 5.09 (q, J = 7.4 Hz, 1H), 4.56 (t, J = 8.3 Hz, 1H), 4.10
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 35
1
2
3
4
13
(t, J = 8 Hz, 1H). C NMR (75 MHz, CDCl3) δ 154.7, 132.0, 120.9, 77.2, 68.9. HRMS-ESI:
5
6
calcd for C5H6NaO3 (M + Na)+ 137.0215, found: 137.0211.
7
8
9
4-Benzyl-1,3-dioxolan-2-one (3j). This material (345 mg) was formed in a 97% yield and the
analytical data are in accord with those reported in the literature.37 1H NMR (300 MHz, CDCl3) δ
7.40 – 7.28 (m, 3H), 7.26 – 7.21 (m, 2H), 5.01 – 4.91 (m, 1H), 4.46 (t, J = 8.2 Hz, 1H), 4.18 (dd,
J = 8.6 and 6.9 Hz, 1H), 3.16 (dd, J = 14.2 and 6.3 Hz, 1H), 3.01 (dd, J = 14.1 and 6.1 Hz, 1H).
13C NMR (75 MHz, CDCl3) δ 154.7, 133.8, 129.2, 128.8, 127.4, 76.7, 68.4, 39.4. MS-ESI: calcd
for C10H14NO3 (M + NH4)+ 196.1, found 196.1.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-((Benzyloxy)methyl)-1,3-dioxolan-2-one (3k). This material (396 mg) was formed in a 95%
yield and the analytical data are in accord with those reported in the literature.38
1H NMR (300 MHz, CDCl3) δ 7.40 – 7.27 (m, 5H), 4.85 – 4.75 (m, 1H), 4.58 (dd, J = 17.5 and
12.0 Hz, 2H), 4.45 (t, J = 8.4 Hz, 1H), 4.35 (dd, J = 8.4 and 6.0 Hz, 1H), 3.70 (dd, J = 11.0 and
3.7 Hz, 1H) 3.59 (dd, J = 11.1 and 3.7 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 154.9, 137.0,
128.3, 127.8, 127.5, 74.9, 73.4, 68.7, 66.1. MS-ESI: calcd for C11H12NaO4 (M + Na)+ 231.1,
found: 231.1. Enantiomer separation was achieved on a Chiracel OD-H column using hexanes/i-
PrOH = 80 : 20 and a flow rate of 1.0 mL/min to give retention times of 22.0 and 32.4 min.
When the (R)-enantiomer of 2k was used only the stereoisomer of 3k eluting at 22.0 min was
observed.
1
4-Phenyl-1,3-dioxolan-2-one-4-d (3a-d). H NMR (300 MHz, CDCl3) δ 7.46 – 7.25 (m, 5H),
13
4.79 (d, J = 8.6 Hz, 1H), 4.33 (d, J = 8.6 Hz, 1H). C NMR (75 MHz, CDCl3) δ 154.9, 135.7,
129.6, 129.4, 125.9, 77.5 (t, J = 24 Hz), 71.1. MS-ESI: calc for C9H7DNaO3 (M + Na)+ 188.0,
found 188.0.
22
ACS Paragon Plus Environment

Page 23 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4-Phenyl-1,3-dioxolan-2-one-5,5-d2 (3a-d2). 1H NMR (300 MHz, CDCl3) δ 7.48 – 7.40 (m, 3H),
7.38 – 7.30 (m, 2H), 5.70 (s, 1H), 4.80 (m, 0.14H), 4.35 (m, 0.14H). 13C NMR (75 MHz, CDCl3)
δ 154.8, 135.8, 129.8, 129.3, 125.9, 77.8, 70.8 (quintet, J = 24 Hz). MS-ESI: calc for
C9H6D2NaO3 (M + Na)+ 189.1, found 189.1.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Computations. Different orientations of hydrogen bonded complexes between T7 and 2a were
fully optimized with Spartan 1439 using B3LYP40 and the 6-31G(d,p) basis set except for iodine,
which was treated with the LANL2DZ pseudopotential.41 Subsequent structures for 4, 6, and
transition states leading to their formation were also located. Single point energies,
reoptimizations and vibrational frequencies for select species were computed with Gaussian 0942
using the aug-cc-pVDZ43 and 6-311G(d) all electron basis set for iodine.44 Thereafter,
B3LYP/aug-cc-pVDZ/6-311+G(d) single point energies were computed.
Supporting Information Available: Additive, racemization and application scope data, NMR
spectra, HPLC chromatograms, computed structures and energies, and the complete citation to
ref. 42. This material is available free of charge via the internet at http://pubs.acs.org.
Competing financial interests: The authors declare no competing financial interests.
ACKNOWLEDGMENT
We wish to thank Mr. Curtis Payne for his assistance in determining the absolute chirality of 3a
when (R)-2a was used as the starting material. Generous support from the National Science
Foundation (CHE-1665392), the Petroleum Research Fund (55631-ND4) as administered by the
American Chemical Society, and the Minnesota Supercomputer Institute for Advanced
Computational Research are gratefully acknowledged. The work carried out in Linz was
supported by the Austrian Science Funds (FWF): Project No. P26387-N28. Computational
resources were provided by the super-computing facilities of the Université catholique de
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 35
1
2
3
4
5
6
7
8
9
Louvain (CISM/UCL) and the Consortium des Équipements de Calcul Intensif en Fédération
Wallonie Bruxelles (CÉCI) funded by the Fond de la Recherche Scientifique–FNRS de Belgique
(F.R.S.-FNRS) under convention 2.5020.11. The NMR spectrometers used were acquired in
collaboration with the University of South Bohemia (CZ) with financial support from the
European Union through the EFRE INTERREG IV ETC-AT-CZ program (project M00146,
„RERI-uasb"). Raphaël Robiette is a Maître de recherche of the F.R.S.-FNRS.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
24
ACS Paragon Plus Environment

Page 25 of 35
The Journal of Organic Chemistry
1
2
3
4
References
5
6
7
8
9
1. Tans, P., NOAA/ESRL (www.esrl.noaa.gov/gmd/ccgg/trends/) and Keeling, R., Scripps
Institution of Oceanography (scrippsco2.ucsd.edu/).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2. (a) Trogler, W. C. The Environmental Chemistry of Trace Atmospheric Gases. J. Chem. Educ.
1995, 72, 973-976. (b) Quadrelli, E. A.; Centi, G.; Duplan, J.-L.; Perathoner, S. Carbon Dioxide
Recycling: Emerging Large-Scale Technologies with Industrial Potential. ChemSusChem 2011, 4,
1194-1215. (c) Martín, R.; Kleij, A. W. Myth or Reality? Fixation of Carbon Dioxide into
Complex Organic Matter under Mild Conditions. ChemSusChem 2011, 4, 1259-1263. (d) Centi,
G.; Iaquaniello, G.; Perathoner, S. Can We Afford to Waste Carbon Dioxide? Carbon Dioxide as
a Valuable Source of Carbon for the Production of Light Olefins. ChemSusChem 2011, 4, 1265-
1273. (e) Aresta, M.; Dibenedetto, A.; Angelini, A. Catalysis for the Valorization of Exhaust
Carbon: from CO2 to Chemicals, Materials, and Fuels. Technological Use of CO2. Chem. Rev.
2014, 114, 1709-1742.
3. (a) Leitner, W. Supercritical Carbon Dioxide as a Green Reaction Medium for Catalysis. Acc.
Chem. Res. 2002, 35, 746-756. (b) Omae, I. Aspects Of Carbon Dioxide Utilization. Catal.
Today 2006, 115, 33-52. (c) Aresta, M.; Dibenedetto, A. Utilisation Of CO2 As A Chemical
Feedstock: Opportunities And Challenges. Dalton Trans. 2007, 2975-2992. (d) D’Alessandro, D.
M.; Smit, B.; Long, J. R. Carbon Dioxide Capture: Prospects for New Materials. Angew. Chem.,
Int. Ed. 2010, 49, 6058-6082. (e) Riduan, S.N.; Zhang, Y. Recent Developments In Carbon
Dioxide Utilization Under Mild Conditions. Dalton Trans. 2010, 39, 3347-3357. (f) Cokoja, M.;
Bruckmeier, C.; Rieger, B.; Herrmann, W. A.; Kühn, F. E. Transformation of Carbon Dioxide
with Homogeneous Transition-Metal Catalysts: A Molecular Solution to a Global Challenge?
Angew. Chem. Int. Ed. 2011, 50, 8510-8537.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 35
1
2
3
4
5
6
7
8
9
4. (a) Jessop, P. G.; Ikariya, T.; Noyori, R. Homogeneous Hydrogenation of Carbon Dioxide.
Chem. Rev. 1995, 95, 259-272. (b) Gibson, D. H. The Organometallic Chemistry of Carbon
Dioxide. Chem. Rev. 1996, 96, 2063-2096. (c) Tundo, P.; Selva, M. The Chemistry of Dimethyl
Carbonate. Acc. Chem. Res. 2002, 35, 706-716. (d) Sakakura, T.; Choi, J. C.; Yasuda, H.
Transformation of Carbon Dioxide. Chem. Rev. 2007, 107, 2365-2387. (e) North, M.; Pasquale,
R.; Young, C. Synthesis Of Cyclic Carbonates From Epoxides And CO2. Green Chem. 2010, 12,
1514-1539.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5. (a) Shaikh, A.-A. G.; Sivaram, S. Organic Carbonates. Chem. Rev. 1996, 96, 951-976. (b)
Fukuoka, S.; Kawamura, M.; Komiya, K.; Tojo, M.; Hachiya, H.; Hasegawa, K.; Aminaka, M.;
Okamoto, H.; Fukawa, I.; Konno, S. A Novel Non-Phosgene Polycarbonate Production Process
Using By-Product CO2 As Starting Material. Green Chem. 2003, 5, 497-507. (c) Ochiai, B.;
Endo, T. Carbon Dioxide And Carbon Disulfide As Resources For Functional Polymers. Prog.
Polym. Sci. 2005, 30, 183-215. (d) Schäffner, B.; Schäffner, F.; Verevkin, S. P.; Börner, A.
Organic Carbonates as Solvents in Synthesis and Catalysis. Chem. Rev. 2010, 110, 4554-4581. (e)
Balaraman, E.; Gunanathan, C.; Zhang, J.; Shimon, L. J. W.; Milstein, D. Efficient
Hydrogenation Of Organic Carbonates, Carbamates And Formates Indicates Alternative Routes
To Methanol Based On CO2 And CO. Nat. Chem. 2011, 3, 609-614.
6. (a) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet, P. G.; Guy, R. K.; Claiborne, C.
F.; Renaud, J.; Couladouros, E. A.; Paulvannan, K.; Sorensen, E. J. Total Synthesis Of
Taxol .Nature 1994, 367, 630-634. (b) Chang, H. T.; Sharpless, K. B. A Practical Route To
Enantiopure 1,2-Aminoalcohols. Tetrahedron Lett. 1996, 37, 3219-3222. (c) Takata, T.; Furusho,
Y.; Murakawa, K.; Endo, T.; Matsuoka, H.; Hirasa, T.; Matsuo, J.; Sisido, M. Optically Active
Poly(aryl carbonates) Consisting of Axially Chiral Units. Chiral Binaphthyl Group Induced
26
ACS Paragon Plus Environment

Page 27 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Helical Polymer. J. Am. Chem. Soc. 1998, 120, 4530-4531. (d) Bayardon, J.; Holz, J.; Schäffner,
B.; Andrushko, V.; Verevkin, S.; Preetz, A.; Börner, A. Propylene Carbonate As A Solvent For
Asymmetric Hydrogenations. Angew. Chem. Int. Ed. 2007, 46, 5971-5974. (e) Yu, K. M. K.;
Curcic, I.; Gabriel, J.; Tsang, S. C. E. Recent Advances in CO2 Capture and Utilization.
ChemSusChem 2008, 1, 893-899. (f) Sakakura, T.; Kohno, K. The Synthesis Of Organic
Carbonates From Carbon Dioxide. Chem. Commun. 2009, 1312-1330.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7. (a) Lu, X.; Liang, B.; Zhang, Y.; Tian, Y.; Wang, Y.; Bai, C.; Wang, H.; Zhang, R.
Asymmetric Catalysis with CO2:ꢀ Direct Synthesis of Optically Active Propylene Carbonate from
Racemic Epoxides. J. Am. Chem. Soc. 2004, 126, 3732-3733. (b) Jing, H.; Nguyen, S. T. SnCl4-
Organic Base: Highly Efficient Catalyst System For Coupling Reaction Of CO2 And Epoxides. J.
Mol. Catal. A 2007, 261, 12-15. (c) Zhang, X.; Jia, Y.; Lu, X.; Li, B.; Wang, H.; Sun, L.
Intramolecularly Two-Centered Cooperation Catalysis For The Synthesis Of Cyclic Carbonates
From CO2 And Epoxides. Tetrahedron Lett. 2008, 49, 6589-6592. (d) Ren, Y.; Shi, Y.; Chen, J.;
Yang, S.; Qi, C.; Jiang, H. Ni(Salphen)-Based Metal–Organic Framework For The Synthesis Of
Cyclic Carbonates By Cycloaddition Of CO2 To Epoxides. RSC Adv. 2013, 3, 2167-2170. (e)
Whiteoak, C. J.; Kielland, N.; Laserna, V.; Adán, E. C. E.; Martin, E.; Kleij, A. W. A Powerful
Aluminum Catalyst for the Synthesis of Highly Functional Organic Carbonates. J. Am. Chem.
Soc. 2013, 135, 1228-1231. (f) Maeda, C.; Taniguchi, T.; Ogawa, K.; Ema, T. Bifunctional
Catalysts Based on m-Phenylene-Bridged Porphyrin Dimer and Trimer Platforms: Synthesis of
Cyclic Carbonates from Carbon Dioxide and Epoxides. Angew. Chem. Int. Ed. 2015, 54, 134-138.
(g) Xu, F.; Cheng, W.; Yao, X.; Sun, J.; Sun, W.; Zhang, S. Thiourea-Based Bifunctional Ionic
Liquids As Highly Efficient Catalysts For The CycloAddition Of CO2 To Epoxides. Catal. Lett.
2017, 147, 1654-1664.
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 35
1
2
3
4
5
6
7
8
9
8. (a) Peng, J.; Deng, Y. Cycloaddition Of Carbon Dioxide To Propylene Oxide Catalyzed By
Ionic Liquids. New. J. Chem. 2001, 25, 639-641. (b) Kawanami, H.; Sasaki, A.; Matsui, K.
Ikushima, Y. A Rapid And Effective Synthesis Of Propylene Carbonate Using A Supercritical
CO2–Ionic Liquid System. Chem. Commun. 2003, 39, 896-897. (c) He, L.; Yasuda, H.; Sakakura,
T. New Procedure For Recycling Homogeneous Catalyst: Propylene Carbonate Synthesis Under
Supercritical CO2 Conditions. Green Chem. 2003, 5, 92-94. (d) Xie, H.; Li, S.; Zhang, S. Highly
Active, Hexabutylguanidinium Salt/Zinc Bromide Binary Catalyst For The Coupling Reaction
Of Carbon Dioxide And Epoxides. J. Mol. Catal. A: Chem. 2006, 250, 30-34. (e) Sun, J.; Wang,
L.; Zhang, S.; Li, Z.; Zhang, X.; Dai, W.; Mori, R. ZnCl2/Phosphonium Halide: An Efficient
Lewis Acid/Base Catalyst For The Synthesis Of Cyclic Carbonate. J. Mol. Catal. A: Chem. 2006,
256, 295-300. (f) Lee, J. K.; Kim, Y. J.; Choi, Y. S.; Lee, H.; Lee, J. S.; Hong, J.; Jeong, E.-K.;
Kim, H. S.; Cheong, M. Zn-Containing Ionic Liquids Bearing Dialkylphosphate Ligands For The
Coupling Reactions Of Epoxides And CO2. Appl. Catal., B 2012, 111-112, 621-627. (g) Song, Y.;
Cheng, C.; Jing, H. Aza-Crown Ether Complex Cation Ionic Liquids: Preparation And
Applications In Organic Reactions. Chem. Eur. J. 2014, 20, 12894-12900. (h) Jiang, X.; Gou, F.;
Fu, X.; Jing, H. Ionic Liquids-Functionalized Porphyrins As Bifunctional Catalysts For
Cycloaddition Of Carbon Dioxide To Epoxides. J. CO2 Util. 2016, 16, 264-271.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
9. Sun, J.; Han, L.; Cheng, W.; Wang, J.; Zhang, X.; Zhang, S. Efficient Acid-Base Bifunctional
Catalysts for the Fixation of CO2 with Epoxides under Metal- and Solvent-Free Conditions.
ChemSusChem 2011, 4, 502-507.
10. (a) Shen, Y.; Duan, W.; Shi, M. Chemical Fixation of Carbon Dioxide Co-Catalyzed by a
Combination of Schiff Bases or Phenols and Organic Bases. Eur. J. Org. Chem. 2004, 3080-
3089. (b) Whiteoak, C. J.; Nova, A.; Maseras, F.; Kleij, A. W. Merging Sustainability with
28
ACS Paragon Plus Environment

Page 29 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Organocatalysis in the Formation of Organic Carbonates by Using CO2 as a Feedstock.
ChemSusChem, 2012, 5, 2032-2038. (c) Whiteoak, C. J.; Henseler, A. H.; Ayats, C.; Kleij, A. W.;
Pericàs, M. A. Conversion Of Oxiranes And CO2 To Organic Cyclic Carbonates Using A
Recyclable, Bifunctional Polystyrene-Supported Organocatalyst. Green Chem. 2014, 16, 1552-
1559. (d) Sopeña, S.; Fiorani, G.; Martín, C.; Kleij, A. W. Highly Efficient Organocatalyzed
Conversion of Oxiranes and CO2 into Organic Carbonates. ChemSusChem 2015, 8, 3248-3254.
(e) Okada, M.; Nishiyori, R.; Kaneko, S.; Igawa, K.; Shirakawa, S. KI–Tetraethylene Glycol
Complex as an Effective Catalyst for the Synthesis of Cyclic Thiocarbonates from Epoxides and
CS2. Eur. J. Org. Chem. 2018, 2022-2027.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11. (a) Xiao, B.; Sun, J.; Wang, J.; Liu, C.; Cheng, W. Triethanolamine/KI: A Multifunctional
Catalyst for CO2 Activation and Conversion with Epoxides into Cyclic Carbonates. Synth.
Commun. 2013, 43, 2985-2997. (b) Werner, T.; Büttner, H. Phosphorus-Based Bifunctional
Organocatalysts for the Addition of Carbon Dioxide and Epoxides. ChemSusChem 2014, 7,
3268-3271. (c) Wilhelm, M. E.; Anthofer, M. H.; Cokoja, M.; Markovits, I. I. E.; Herrmann, W.
A.; Kühn, F. E. Cycloaddition of Carbon Dioxide and Epoxides using Pentaerythritol and
Halides as Dual Catalyst System. ChemSusChem, 2014, 7, 1357-1360. (d) Büttner, H.;
Steinbauer, J.; Werner, T. Synthesis of Cyclic Carbonates from Epoxides and Carbon Dioxide by
Using Bifunctional One-Component Phosphorus-Based Organocatalysts. ChemSusChem 2015, 8,
2655-2669. (e) Alves, M.; Grignard, B.; Gennen, S.; Méreau, R.; Detrembleur, C.; Jerome, C.;
Tassaing, T. Organocatalytic Promoted Coupling Of Carbon Dioxide With Epoxides: A Rational
Investigation Of The Cocatalytic Activity Of Various Hydrogen Bond Donors. Catal. Sci.
Technol. 2015, 5, 4636-4643.
29
ACS Paragon Plus Environment