CaI2-Catalyzed direct transformation of: N -Alloc-, N -Troc-, and N -Cbz-protected amines to asymmetrical ureas

Article abstract of DOI:10.1039/c9nj03111a

A novel and facile CaI₂-catalyzed direct synthesis of asymmetrical ureas from N-Alloc-, N-Troc-, and N-Cbz-protected amines is developed. In this study, the efficient reaction of Alloc-, Troc-, and Cbz-carbamates with amines in the presence of catalytic CaI₂ successfully generated various asymmetrical ureas. This catalytic synthetic procedure provided the desired ureas via reactions of these protected aromatic and aliphatic amines with various amines in high yields without side products. This suggests that novel direct synthesis of ureas from Alloc-, Troc-, and Cbz-carbamates can be a promising approach for the synthesis of useful ureas.

Full text of DOI:10.1039/c9nj03111a

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CaI2-Catalyzed Direct Transformation of N-Alloc-, N-Troc-,
and N-Cbz-Protected Amines to Asymmetrical Ureas
Van Hieu Tran ab and Hee-Kwon Kim*ab
a Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center,
Chonbuk National University Medical School and Hospital, Jeonju, 54907, Republic of Korea
b Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research
Institute of Chonbuk National University Hospital, Jeonju, 54907, Republic of Korea
* Corresponding author.
Hee-Kwon Kim
Tel: +82 63 250 2768 Fax: +82 63 255 1172.
E-mail address: hkkim717@jbnu.ac.kr (H-K Kim).

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Abstract
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A novel and facile CaI2-catalyzed direct synthesis of asymmetrical ureas from N-Alloc-, N-Troc-,
and N-Cbz-protected amines is developed. In this study, efficient reaction of Alloc-, Troc-, and
Cbz-carbamate with amines in the presence of catalytic CaI2 successfully generated various
asymmetrical ureas. This catalytic synthetic procedure provided the desired ureas via reactions of
these protected aromatic and aliphatic amines with various amines in high yields without side
products. This suggests that novel direct synthesis of ureas from Alloc-, Troc-, and Cbz-
carbamates can provide a promising approach for the synthesis of useful ureas.
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Introduction
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Urea is an important structure in bioactive natural products, and pharmaceuticals. For examples,
many biologically active compounds including antitumor agents, antagonists of natural receptors,
allosteric modulators, enzyme inhibitors, anti-Parkinson’s agents, and anti-mycobacterial agents,
contain urea unit in their chemical structures.1-9 Various materials have used urea units a large
number of organic materials exhibit the urea motif due to its unique properties, including
hydrogen bonding and polarity of the urea structure.10,11 Several types of prepared molecular gels
and self-assembled structures, including macrocycles, contain some kind of urea structure.12-16
Due to their importance in various fields, several synthetic procedures have been reported for
the formation of urea structures.17,18 Treatment of amines with isocyanate (which are produced
from the reaction of phosgene) or carbamoyl chlorides are widely employed protocols in organic
synthesis used to produce target ureas.19 Although many urea structures have been prepared via
these methods, they have their weaknesses. Phosgene, for example, is toxic and carbamoyl
chloride intermediates are unstable, which limits their use for organic synthesis. Other
approaches have employed 1,1’-carbonyldiimidazole (CDI) and p-nitrophenyl carbamates to
synthesize ureas.20-23 However, the desired ureas were sometimes prepared with low conversion
yield during the treatment of those reagents. In additions, urea derivatives have been prepared
from the reaction of amines with CO2 without utilization of phosgene.24-27
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Amine is a widely used functional group in organic chemistry. In many multi-step synthetic
procedures, amines have been protected by a carbamate protecting group to undergo organic
reactions without the production of unwanted side products. In particular, allyl-carbamate
(Alloc-carbamate), 2,2,2-Trichloroethyl carbamate (Troc-carbamate), and benzyl-carbamate
(Cbz-carbamate) are commonly used as amine protecting groups in many total synthesis works

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and medicinal chemistry28-34 because easy and simple synthetic methods for the preparation of
Alloc-carbamate, Troc-carbamate, and Cbz-carbamate have been developed from primary or
secondary amines. However, these protected amines require two separate reactions for urea
synthesis: deprotection of amines and the formation of urea via treatment of nucleophilic free
amines. Thus, discovery of a new direct conversion of these protected amines to ureas is
desirable for efficient multi-step synthesis. Particularly, the catalyst-mediated direct synthetic
methods for asymmetrical ureas from N-Alloc-, N-Troc- and N-Cbz-protected amines are not
extensively studied. In our previous study, we reported that conversion of Alloc- and Cbz-
carbamate compounds to ureas was achieved through the treatment of DABAL-Me3.35 However,
the previous protocol used 1.2 equiv. of DABAL-Me3. With an interest in developing efficient
transformation, we propose novel catalyst-mediated direct synthesis of ureas. To the best of our
knowledge, simple and efficient direct preparation of ureas from protected carbamates using an
effective catalyst has not yet been reported. Herein, we report the novel catalytic reagent
mediated direct synthesis of various ureas from N-Alloc-, N-Troc-, and N-Cbz-protected amines,
which can be readily used to perform multi-step organic syntheses.
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Results and Discussion
In the initial study, N-Alloc-protected aniline and benzylamine were used as a model substrate
and a nucleophilic amine to discover optimal conditions in the preparation of asymmetrical ureas.
Urea formation reactions were performed in the presence of 1.0 equiv. of N-Alloc-protected
aniline, 1.5 equiv. of benzylamine, and 0.15 equiv. of various catalytic reagents at 80 °C for 12 h,
and the conversion yields from Alloc-protected aniline to the corresponding urea were examined.

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Alkali metals and alkaline earth metals have been widely employed in many useful organic
syntheses such as the halogenation of imidazo-fused heterocycles, sulfenylation of 4-
anilinocoumarins, synthesis of isatins and isoindigoes, and synthesis of 1,2-dihydroquinolines.36-
41 Therefore, in this study, we tried to employ alkali metals and alkaline earth metals for a highly
effective catalytic method for the synthesis of ureas. First, a series of commercially available
alkali metal salts such as NaI, KI, RbCl, and CsBr were investigated, as shown in Table 1.
However, the catalytic reaction between N-Alloc-protected aniline and benzylamine provided the
desired product with low yield or did not produce the urea product: the synthetic yield of
reactions using alkali metal salts to yield the urea is less than 15%. Some alkaline earth metal
salts showed better catalytic ability to prepare the urea structure than alkali metal salts. The
reaction experiment with CaBr2 and BaI2 afforded the target urea with increased yield (77% for
CaBr2, and 74% for BaI2). Using CaI2 for the catalyst-mediated reaction yielded the desired urea
in 93% yield under the same conditions (Figures S1). The screening of catalytic reagents
therefore suggested CaI2 as a highly effective catalyst for the direct conversion of N-Alloc-
protected amine to urea .
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Catalyst activity of alkaline earth metal salts on the synthesis of urea can be affected by several
factors.42 The first factor is Lewis acidity of the alkaline earth metal due to the interaction of the
metal with oxygen of carbamate. The Lewis acidity increases from Rb2+ to Be2+, Therefore,
MgBr2 can be better choice. Another factor is the basicity of the catalyst. BaI2 has the higher
basicity than MgBr2. Based on the consideration of two factors, neither Mg salts or Ba salts are
not the best choice. Calcium is the alkaline earth metal in the middle of periodic table, and has
both the factors. In additions, the basic character of halides follows the order I<Br<Cl<F. In this
study, iodide ion, which is known as a weak base, exhibited efficient catalytic properties for the

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urea formation. Iodide ion has larger size, and do not strongly attract electron density from Ca2+
like chlorine ion. It means that the negative charge on the iodide ion can be properly dispersed to
provide right interaction of Ca2+ with amine, not strong interaction with amine. Therefore, our
result suggested that CaI2 is the suitable catalyst to yield the desired urea. Interaction of amine
with catalyst can be influenced by counter-anions. Counter-anions can keep and abstract proton
from amine. In this reaction, -C(=O)-O- of carbamate can be acting as counter-anions to
accelerate the reaction.
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Next, the solvent effect was investigated to find the optimized reaction conditions. As shown in
Table 2, reactions in 1,4-dioxane and 1,2-dichloroethane (DCE) produced the target urea with
low yield. Utilization of tetrahydrofuran (THF) as a reaction solvent allowed us to prepare urea
with moderate synthetic yield (75%). When acetonitrile (CH3CN) and toluene were used for the
reaction, desired urea was obtained with highly increased yield (89% for reaction in CH3CN, and
93% for reaction in toluene), indicating that toluene was a more suitable solvent for CaI2-
catalyzed direct conversion from N-Alloc-protected amine to urea than the other solvents. It was
interesting note that the reaction using CaI2 was homogeneous: CaI2 was completely soluble
under reaction conditions, and there was no solid in the reaction mixture. Besides toluene does
not contain oxygen and nitrogen which can reduce interaction of Ca2+ with carbamate and amine.
Several temperatures for the reaction were also examined. As shown in Table 2, reactions at
higher temperature usually resulted in enhanced synthetic yields for the synthesis of target urea
(93% for reaction at 80oC and 90oC, and 37% for reaction at 60oC). Thus, a reaction temperature
at 80oC was selected for the further study of urea synthesis.

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Table 1. Screening of reagents for the preparation of urea structure a
NH2
O
O
catayst
+
toluene, 80 oC
N
N
N
O
H
H
H
9
2a
3a
1a
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Entry
Catalyst
time
Temp. Yieldb
(%)
11
5
1
2
NaI
KI
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
3
RbCl
CsBr
MgBr2
CaCl2
CaBr2
CaI2
NR
NR
9
4
5
6
5
7
77
93
74
NR
8
9
BaI2
10
None
a Reaction conditions: 1a Alloc-protected amine (1.0 mmol), amine (1.5 mmol), catalyst (0.15
mmol), toluene (2 mL), 12 h.
b Isolated yield after column purification.
c No reaction
In addition, different amounts of CaI2 (0.05 equiv., 0.1 equiv., 0.15 equiv., 0.3 equiv., and 1.0
equiv.) were added into the catalyzed reaction and evaluated. The results suggested that the
synthetic yield was influenced by the amount of CaI2. Enhanced amounts of CaI2 in the reaction
resulted in increased conversion yield to give the corresponding urea: The reaction with 0.3
equiv. of CaI2 for 8 h produced the corresponding urea with 94% yield, and the reaction with 1.0
equiv. of CaI2 for 6 h afforded the desired urea with 94% yield (Figures S2). A reduced amount
of CaI2 was also tested for the catalyzed reaction, and 0.05 equiv. of CaI2 were found to yield the
target urea product with 61% yield. Besides, different molar ratio (1:1.2 and 1:1) between N-

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Alloc-protected aniline and benzylamine for CaI2-catalyzed urea formation reaction were tested.
The 1:1.2 ratio reaction and the 1:1 ratio reaction produced the corresponding urea with reduced
yield (87% for 1:1.2 ratio reaction, and 80% for 1:1 ratio reaction, respectively). From these
primary optimization studies, reaction conditions including 15 mol% CaI2, toluene solvent, and
80 oC were selected for the next studies.
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Table 2. Screening of reaction conditions for the preparation of urea structure a
NH2
O
O
CaI2
+
N
N
solvent, 12 h
N
O
H
H
H
2a
1a
3a
Entry CaI2 (equiv)
Solvent Temp.
Yieldb
(%)
3
1
0.15
1,4-
dioxane
DCE
80 oC
2
3
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0.15
0.15
0.15
0.15
1
80 oC
reflux
10
75
89
93
93
37
14
94
94
87
61
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5
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toluene
toluene
toluene
toluene
toluene
toluene
toluene
80 oC
90 oC
60 oC
40 oC
80 oC
80 oC
80 oC
80 oC
6
7
8
9c
10d
11
12
0.3
0.1
0.05
a Reaction conditions: 1a Alloc-protected amine (1.0 mmol), amine (1.5 mmol), CaI2 (0.15
mmol), solvent (2 mL), 12 h.
b Isolated yield after column purification.
c Reaction for 6 h.
d Reaction for 8 h.

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Considering the optimized reaction conditions, the scope of the CaI2-catalyzed direct synthesis
of ureas was investigated (Table 3). First, N-Alloc-protected aniline, which comes from an
aromatic compound, was tested to prepare asymmetrical ureas. N-Alloc-protected aniline
successfully reacted with benzylamine and butylamine, primary amines, to produce the
corresponding asymmetrical ureas (3a-3b) in high yield. In the same conditions, reactions of N-
Alloc-protected anilines with secondary amines such as piperidine 2c, dipropylamine 2d and
pyrrolidine 2e readily afforded the desired trisubstituted ureas (3c-3e) with 92%, 94% and 90%
yield, respectively (Table 3, entries 3-5).
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Syntheses of ureas from N-Alloc-protected 4-methylaniline containing the electron-donating
group and 4-chloroaniline containing the electron-withdrawing group were also examined. The
directional synthesis of ureas proceeded well. The reaction of N-Alloc-protected 4-methylaniline
with benzylamine, cyclohexylamine and piperidine provided the target ureas in high yield (Table
3, entries 6-8), and the reaction of N-Alloc-protected 4-chloroaniline with benzylamine,
cyclohexylamine and piperidine yielded the corresponding urea in 80%-85% yield (Table 3,
entries 9-11).
N-Alloc-protected benzyl amine, which comes from an aliphatic amine, was used to produce an
asymmetric urea to assess this reaction procedure, and the desired asymmetrical benzylureas
were successfully obtained in the range of 62%-85% yield via the CaI2-catalyzed reaction with
benzylamine, butylamine, aniline, piperidine and dipropylamine (Table 3, entries 12-16). The
reactions of N-Alloc-protected N-methylaniline with benzylamine and piperidine were also
carried out, which produced the corresponding ureas (3q-3r).

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Table 3. Scope of urea formation from N-Alloc-protected amines a
O
O
R3
15 mol% CaI2
R1
R1
NH
R3
N
R2
+
N
R4
O
1
N
R2
toluene, 80 oC, 12 h
R4
2
3
Productb
Entry Alloc-carbamate Amine
Productb
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Entry Alloc-carbamate Amine
Cl
Cl
O
O
O
O
NH2
1
10
NH2
N
H
O
O
O
N
N
N
N
N
O
H
H
H
H
H
1a
2a
2b
1c
2f
3a, 93%
3j, 84%
Cl
Cl
O
O
O
O
NH
11
2
NH2
N
H
N
N
N
H
N
N
H
1c
O
H
H
1a
3b, 91%
3k, 85%
2c
O
O
O
O
NH
3
4
NH2
N
N
N
O
12
13
N
H
N
N
H
H
H
H
2c
1d
1a
3c, 92%
2a
3l, 81%
O
O
O
O
NH
N
O
N
N
N
N
NH2
NH2
H
N
O
O
H
H
H
H
1a
2d
3d, 94%
1d
2b
2g
3m, 85%
O
O
O
O
NH
5
N
O
14
N
N
N
N
N
H
H
H
H
H
2e
2a
2f
3e, 90%
1a
1d
3n, 62%
O
O
O
O
NH2
NH
N
H
N
N
O
6
7
N
O
15c
N
N
H
H
H
H
3o, 67%
1b
3f, 74%
1d
2c
O
O
O
O
N
O
N
N
16
NH2
NH
H
H
N
O
N
H
N
H
H
1d
1b
2d
3g, 80%
3p, 75%
O
O
O
O
NH
8
9
NH2
17
N
N
N
O
N
O
N
H
N
H
H
CH3
CH3
1b
2c
1e
2a
3q, 80%
3h, 81%
O
Cl
Cl
O
O
O
18c
NH
NH2
N
N
N
O
N
H
N
N
O
CH3
CH3
H
H
3r, 52%
1e
2a
2c
1b
3i, 80%
a
Reaction conditions: Alloc-carbamate (1.0 mmol), amine (1.5 mmol), CaI2 (0.15 mmol),
toluene (2 mL), 80 oC for 12 h,
b Isolated yields after column purification.
c Reaction at 110 oC for 24 h.
Troc protection groups have been commonly used to protect amines in various organic syntheses.
CaI2-catalyzed urea formation was also applied for the direct transformation of N-Troc-protected

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amines to asymmetrical ureas. The reaction of N-Troc-protected aniline with primary amines and
secondary amines in the presence of catalytic CaI2 led to the successful production of
corresponding ureas in high yields (Table 4, entries 1-3). In addition, N-Troc-protected amines
from benzylamine and piperidine readily reacted with several amines to yield the desired ureas
(Table 4, entries 4-9).
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Next, the scope of CaI2-catalyzed reaction was extended to the synthesis of ureas from N-Cbz-
protected amines because many multi-step syntheses have employed N-Cbz-protected amines.
The CaI2-catalyzed reaction of N-Cbz-protected aniline or N-Cbz-protected benzylamine
proceeds effectively with primary and secondary amines. CaI2-catalyzed reactions with
benzylamine, butylamine, piperidine, pyrrolidine, and morpholine yielded the corresponding
ureas in the range of 62–91% (Table 4, entries 10-18). These results confirmed that catalytic
CaI2-mediated reactions of protected amines with several free amines as an efficient synthesis
technique of ureas with high conversion yields.

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Table 4. Scope of urea formation from N-Troc-/ N-Cbz-protected amines a
O
O
R4
15 mol% CaI2
R1
R4
R1
R3
NH
N
R2
+
N
R5
O
N
R2
toluene, 80 oC, 12 h
R5
5
4
6
10
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12
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Entry Troc-carbamate Amine
Productb
Entry Cbz-carbamate
Amine
Productb
O
O
O
O
NH2
NH2
N
N
N
O
1
2
10
11
N
N
N
H
O
CCl3
CCl3
H
H
H
H
H
6a, 82%
4d
5a
4a
5a
6a, 96%
O
O
O
O
NH2
NH2
N
N
N
O
N
N
N
H
O
H
H
H
H
H
5d
6j, 91%
4d
4a
6b, 96%
5b
O
O
O
O
NH
NH
3
4
12
13
14
15
16
17
N
N
N
H
N
N
H
O
N
H
O
CCl3
CCl3
H
6c, 93%
6c, 91%
4a
4d
5c
5c
5a
O
O
O
O
NH2
NH
N
N
N
O
N
N
H
H
H
N
O
O
H
H
4b
6d, 95%
4d
5e
5f
6k, 90%
O
O
O
O
NH
N
O
CCl3
NH2
N
N
5
6
N
N
N
H
O
H
H
H
H
O
4b
5b
6e, 94%
4d
6l, 85%
O
O
O
O
NH
N
H
N
NH2
N
H
O
CCl3
N
N
N
O
O
H
H
H
4b
5c
6f, 91%
6d, 72%
4e
5a
5d
O
O
O
O
NH2
N
N
O
CCl3
N
N
H
7c
N
N
N
H
NH2
H
H
6m, 81%
6g, 65%
4e
4c
5a
O
O
O
O
O
CCl3
NH
N
O
N
N
H
N
H
N
8
NH2
H
4c
5d
6h, 72%
4e
5c
6f, 62%
O
O
O
O
NH
N
N
9c
N
H
N
N
O
NH
N
O
CCl3
18
H
4c
5e
6i, 53%
4e
5c
6n, 71%
a Reaction conditions: Troc-/Cbz-carbamate (1.0 mmol), amine (1.5 mmol), CaI2 (0.15 mmol),
toluene (2 mL), 80 oC for 12 h
b Isolated yields after column purification.
c Reaction at 110 oC for 24 h.
Next, a scaled-up CaI2-catalyzed conversion of N-Alloc-protected amines to ureas was
performed (Scheme 1). The gram-scale reaction using 0.15 equiv. of CaI2 successfully gave the

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target product. The reaction of N-Alloc-protected aniline 1a (5.00 g, 28.2 mmol) with
benzylamine 2a in toluene (100 mL) within 250 mL round-bottom flask afforded the
corresponding product 3a in 90% yield under the optimized reaction conditions. It showed that
the CaI2-catalyzed reaction procedure was scalable and practical.
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NH2
O
O
15 mol% CaI2
+
N
N
N
O
toluene
80 oC, 12 h
H
H
H
1a
28.2 mmol, 5.00 g
2a
3a
5.74 g, 90%
Scheme 1. The gram-scale reaction of N-Alloc-protected aniline with benzylamine
A proposed reaction mechanism for CaI2-catalyzed direct synthesis of ureas is shown in Scheme
2. Carbamate is coordinated with CaI2 to generate a stable CaI2-carbamate complex intermediate.
Then nucleophilic attacking by amine affords urea unit and releases alcohol. After urea product
was produced, CaI2 was regenerated and given back to the synthetic reaction of urea.

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O
O
1
R
N
H
N
H
CaI2
N
H
O
3
7
8
9
I
I
Ca2+
10
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I
I
Ca2+
O
O
N
O
N
N
H
R
H
7
H
11
HO
H2N R
2
I
I
2+
Ca
I
I
O
Ca2+
O
H
N
H
N
O
R
H
H
N
N
H
H
R
8
10
O
I
I
Ca2+
H
O
N
N
O
H
R
H
9
Scheme 2. Proposed etherification mechanism for the preparation of ureas using Cal2.
Conclusions
Novel and practical CaI2-catalyzed direct preparation of asymmetrical ureas from N-Alloc-, N-
Troc-, and N-Cbz-protected amines has been described. Several reagents such as alkali metals
and alkaline earth metals were examined to discover an efficient catalyst to yield ureas, and CaI2
was demonstrated as an effective catalyst for the direct reaction of N-Alloc-, N-Troc-, and N-
Cbz-protected amines to produce target asymmetrical ureas in high yields. Our results show that
the novel CaI2-catalyzed direct conversion of N-Alloc-, N-Troc- and N-Cbz-protected amines
into asymmetrical ureas is efficient and applicable for the preparation of many useful ureas.

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Experimental
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General information
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All chemicals were purchased from Sigma-Aldrich and used without further purification.
Reaction progress was monitored by thin-layer chromatography (TLC) analysis. TLC analysis
was performed using an aluminum plate with silica gel 60 F254, and TLC spots were visualized
by UV light (254nm) exposure. Flash chromatography was performed using 230–400 mesh silica
gel and analytical grade solvent. Melting points were recorded using a Stuart SMP10 Melting
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1
Point Apparatus. H and 13C NMR spectra were recorded on a 600 MHz & 150 MHz
respectively JEOL JNM-ECA600 spectrometer or a 400 MHz & 100 MHz respectively Bruker
Avance 400 spectrometer. The chemical shifts were reported in δ units (ppm) relative to the
residual protonated solvent resonance, and the coupling constants (J) quoted in Hz.
General procedure for the preparation of allyl phenylcarbamate compounds (1a-1f)
To a solution of aniline (2.0 g, 21.47 mmol) and NaHCO3 (2.16 g, 25.76 mmol) in
tetrahydrofuran, ally chloroformate (3.104 g, 25.76 mmol) was added. The reaction mixture was
stirred for 2 h at room temperature. The reaction mixture was quenched by the addition of H2O
(5 mL) and extracted with EtOAc (3 x 20 mL). The organic layer was dried over sodium sulfate
and concentrated under reduced pressure. The resulting residue was then purified by flash
column chromatography on silica gel with hexane-EtOAc 20/1 as eluent to afford the desired
product 1a (3.6 g, 95%).
Allyl phenylcarbamate (1a). Yield 95%; white solid. m.p 65-66°C; 1H NMR (400 MHz, CDCl3)
δ 5.98 – 5.89 (m, 1H), 5.32 -5.26 (dq, J = 17.2 Hz, J = 1.6 Hz, 1H), 5.21 -5.17 (dq, J = 10.4 Hz, J
= 1.2 Hz, 1H), 4.59 – 4.57 (dt, J = 5.6 Hz, J = 1.2 Hz, 2H), 3.43 (t, J = 5.6 Hz, 4H), 1.62 – 1.52

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(m, 6H); 13C NMR (100 MHz, CDCl3) δ 155.14, 133.31, 116.98, 65.75, 44.78 (2C), 25.66, 24.36
5
6
(2C); HRMS (ESI) m/z (M+H)+ calcd for C10H12NO2 = 178.0868; found 178.0863.
7
8
9
1
Allyl p-tolylcarbamate (1b). Yield 96%; m.p 48-50°C; H NMR (400 MHz, CDCl3) δ 7.13 –
10
11
12
13
14
15
16
17
18
19
20
21
22
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7.28 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.81 (s, 1H), 6.03 – 5.95 (m, 1H), 5.14 -5.35 (dq, J = 17.2
Hz, J = 1.6 Hz, 1H), 5.29 -5.26 (dq, J = 10.4 Hz, J = 1.2 Hz, 1H), 4.69 (d, J = 5.6 Hz, 2H), 2.33
13
(s, 3H); C NMR (100 MHz, CDCl3) δ 153.45, 135.24, 133.05, 132.56, 129.53 (2C), 118.87,
118.13 (2C), 65.78, 20.77; HRMS (ESI) m/z (M+H)+ calcd for C11H14NO2 = 192.1025; found
192.1022.
1
Allyl 4-chlorophenylcarbamate (1c). Yield 96%; white solid. m.p 68-70°C; H NMR (400
MHz, CDCl3) δ 7.37 – 7.35 (m, 2H), 7.29 – 7.26 (m, 2H), 6.73 (s, 1H), 6.03 – 5.93 (m, 1H), 5.15
-5.36 (dq, J = 17.2 Hz, J = 1.6 Hz, 1H), 5.31 -5.28 (dq, J = 10.4 Hz, J = 1.2 Hz, 1H), 4.69 (d, J =
5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 153.08, 136.39, 132.23, 129.06 (2C), 128.52,
119.89, 118.46 (2C), 66.04; HRMS (ESI) m/z (M+H)+ calcd for C10H11ClNO2 = 212.0478; found
212.0473.
1
Allyl benzylcarbamate (1d). Yield 95%; colorless; H NMR (400 MHz, CDCl3) δ 7.38 – 7.28
(m, 5H), 6.00 – 5.91 (m, 1H), 5.35 (d, J = 17.2 Hz, 1H), 5.25 -5.22 (dd, J = 10.8 Hz, J = 1.2 Hz,
1H), 5.15 (s, 1H), 4.62 (d, J = 5.6 Hz, 2H), 4.41 (d, J = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ 156.31, 138.47, 132.87, 128.66 (2C), 127.49 (2C), 117.71, 65.69, 45.10; HRMS (ESI) m/z
(M+H)+ calcd for C11H14NO2 = 192.1025; found 192.1020.
1
Allyl methyl(phenyl)carbamate (1e). Yield 94%; white solid. m.p 42-44°C; H NMR (400
MHz, CDCl3) δ 7.40 – 7.22 (m, 5H), 5.96 - 5.89 (m, 1H), 5.31 - 5.18 (m, 2H), 4.64 (d, J = 5.2 Hz,
13
2H), 3.34 (s, 1H); C NMR (100 MHz, CDCl3) δ 155.36, 143.22, 132.77, 128.86 (2C), 126.13,

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125.79, 117.25 (2C), 66.24, 37.77; HRMS (ESI) m/z (M+H)+ calcd for C11H14NO2 = 192.1025;
found 192.1020.
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General procedure for the preparation of urea compounds (3a-3t)
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To a solution of 1a (0.177 g, 1.00 mmol) in toluene (2 mL), benzylamine (0.160 g, 1.5 mmol)
and CaI2 (0.044 g, 0.15 mmol) was added. The mixture was stirred for 12 h at 80 °C. The
reaction mixture was extracted with CH2Cl2 (2 x 20 mL). The organic layer was dried over
sodium sulfate and concentrated under reduced pressure. The resulting residue was then purified
by flash column chromatography on silica gel with hexane-EtOAc as eluent to afford the desired
product 3a (0.21 g, 93%).
1
1-Benzyl-3-phenylurea (3a). Yield 93%; white solid; m.p. 210 - 212°C; H NMR (400 MHz,
DMSO-d6) δ 8.56 (s,1H), 7.42 – 7.22 (m, 9H), 6.89 (t, J = 7.2 Hz, 1H), 6.61 (t, J = 5.6 Hz, 1H),
4.31 (d, J = 6.0 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 155.67, 140.91, 140.81, 129.11 (2C),
128.76 (2C), 127.56 (2C), 127.17, 121.53, 118.12 (2C), 43.18; HRMS (ESI) m/z (M+H)+ calcd
for C14H15N2O = 227.1184; found 227.1179.
1
1-Butyl-3-phenylurea (3b). Yield 91%; white solid; m.p. 129 - 130°C; H NMR (400 MHz,
DMSO-d6) δ 8.35 (s,1H), 7.39 – 7.36 (m, 2H), 7.22 – 7.18 (m, 2H), 6.89 (t, J = 7.2 Hz, 1H), 6.08
(t, J = 5.2 Hz, 1H), 3.08 (q, J = 6.0 Hz, 2H), 1.45 – 1.38 (m, 2H), 1.34 – 1.24 (m, 2H), 0.89 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 155.64, 141.06, 129.05 (2C), 112.31, 111.7 (2C),
39.13, 32.35, 19.99, 14.16; HRMS (ESI) m/z (M+H)+ calcd for C11H17N2O = 193.1341; found
193.1336.
1
N-Phenylpiperidine-1-carboxamide (3c). Yield 92%; white solid; m.p. 131 - 132°C; H NMR
(400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.46 (d, J = 7.6 Hz, 2H), 7.21 (t, J = 8.4 Hz, 2H), 6.91 (t, J

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= 7.2 Hz, 1H), 3.41 (t, J = 5.6 Hz, 4H), 1.61 -1.55 (m, 2H), 1.51 – 1.46 (m, 4H); 13C NMR (100
MHz, DMSO-d6) δ 155.33, 141.23, 128.66 (2C), 121.91, 120.00 (2C), 45.13 (2C), 25.98 (2C),
24.58; HRMS (ESI) m/z (M+H)+ calcd for C12H17N2O = 205.1341; found 205.1356.
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3-Phenyl-1,1-dipropylurea (3d). Yield 94%; white solid; m.p. 68 - 70°C; 1H NMR (400 MHz,
CDCl3) δ 7.40 - 7.36 (m, 2H), 7.30 - 7.25 (m, 2H), 7.03 – 6.99 (m, 1H), 6.32 (s, 1H), 3.27 (t, J =
7.6 Hz, 4H), 1.71- 1.61 (m, 4H), 0.96 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 145.98,
139.29, 128.81 (2C), 122.74, 119.75 (2C), 49.46 (2C), 21.88(2C), 11.44 (2C); HRMS (ESI) m/z
(M+H)+ calcd for C13H21N2O = 211.1654; found 211.1677.
N-Phenylpyrrolidine-1-carboxamide (3e). Yield 90%; white solid; m.p. 132 - 134°C; 1H NMR
(400 MHz, CDCl3) δ 7.43 – 7.40 (m, 2H), 7.30 – 7.25 (m, 2H), 7.04 – 6.99 (m, 1H), 6.23 (s, 1H),
3.48 -3.45 (m, 4H), 2.01 – 1.93 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 153.91, 139.16, 128.85
(2C), 122.75, 119.47 (2C), 45.86 (2C), 25.62 (2C); HRMS (ESI) m/z (M+H)+ calcd for
C11H15N2O = 191.1184; found 191.1196.
1
1-Benzyl-3-p-tolylurea (3f). Yield 74%; white solid; m.p. 182 - 184°C; H NMR (400 MHz,
DMSO-d6) δ 8.43 (s, 1H), 7.34 – 7.24 (m, 7H), 7.03 (d, J = 8.4 Hz, 2H), 6.55 (t, J = 6.0 Hz, 1H),
4.29 (d, J = 6.0 Hz, 2H), 2.22 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 155.73, 140.87, 138.35,
130.23, 129.52 (2C) 128.80 (2C), 127.56 (2C), 127.14, 118.30 (2C), 43.19, 20.76; HRMS (ESI)
m/z (M+H)+ calcd for C15H17N2O = 241.1341; found 241.1337.
1
1-Cyclohexyl-3-p-tolylurea (3g). Yield 80%; white solid; m.p. 199 - 201°C; H NMR (400
MHz, DMSO-d6) δ 8.16 (d, J = 5.2 Hz, 1H), 7.25 – 7.22 (m, 2H), 7.02 – 7.98 (m, 2H), 6.02 (d, J
= 7.2 Hz, 1H), 3.48 – 3.43 (m, 1H), 2.21 (s, 3H), 1.81 – 1.76 (m, 2H), 1.67 -1.65 (m, 2H), 1.53-
1.52 (m, 1H), 1.35 – 1.26 (m, 2H), 1.22 – 1.09 (m, 3H); 13C NMR (100 MHz, DMSO-d6) δ

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154.92, 138.46, 129.97, 129.96 (2C), 117.99 (2C), 47.98, 33.48 (2C), 24.83 (2C), 20.75; HRMS
(ESI) m/z (M+H)+ calcd for C14H21N2O = 233.1654; found 233.1660.
7
8
9
N-p-Tolylpiperidine-1-carboxamide (3h). Yield 81%; white solid. m.p. 155 – 157°C; 1H NMR
(400 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.34 (d, J = 9.2 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 3.39 (t,
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13
J = 4.8 Hz, 4H), 2.22 (s, 3H), 1.57- 1.54 (m, 2H), 1.49 – 1.45 (m, 4H); C NMR (100 MHz,
DMSO-d6) δ 155.43, 138.62, 130.66 (), 128.58 (2C), 120.19 (2C), 45.09 (2C), 25.98 (2C), 24.60,
20.79; HRMS (ESI) m/z (M+H)+ calcd for C13H19N2O = 219.1497; found 219.1495.
1-Benzyl-3-(4-chlorophenyl)urea (3i). Yield 80%%; white solid. m.p 206 – 208°C; 1H NMR
(400 MHz, DMSO-d6) δ 8.72 (s, 1H), 7.45 – 7.42 (dt, J = 8.8 Hz, J = 1.6 Hz, 2H), 7.36 – 7.23
(m, 7H), 6.67 (t, J = 6.0 Hz, 1H), 4.31 (t, J = 6.0 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ
155.52, 140.67, 139.94, 128.91 (2C), 128.76 (2C), 127.57 (2C), 127.19, 124.98, 119.63 (2C),
43.21; HRMS (ESI) m/z (M+H)+ calcd for C14H14ClN2O = 261.0795; found 261.0798.
1-(4-Chlorophenyl)-3-cyclohexylurea (3j). Yield 84%; white solid; m.p. 239 - 240°C; 1H NMR
(400 MHz, DMSO-d6) δ 8.43 (s, 1H), 7.40 – 7.37 (m, 2H), 7.26 – 7.22 (m, 2H), 6.11 (d, J = 8.0
Hz, 1H), 3.49 – 3.42 (m, 1H), 1.81 – 1.78 (m, 2H), 1.68 -1.63 (m, 2H), 1.56-1.52 (m, 1H), 1.35 –
13
1.25 (m, 2H), 1.19 – 1.11 (m, 3H); C NMR (100 MHz, DMSO-d6) δ 154.66, 140.01, 128.96
(2C), 124.73, 119.45 (2C), 48.07, 33.37 (2C), 25.68, 24.80 (2C); HRMS (ESI) m/z (M+H)+ calcd
for C13H18ClN2O = 253.1108; found 253.1104.
N-(4-Chlorophenyl)piperidine-1-carboxamide (3k). Yield 85%; white solid; m.p. 143 - 145°C;
1H NMR (400 MHz, CDCl3) δ 7.33 – 7.30 (m, 2H), 7.23 – 7.21 (m, 2H), 6.54 (s, 1H), 3.44 (t, J
= 4.4 Hz, 4H), 1.68 -1.61 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 154.70, 137.95, 128.74 (2C),

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127.72, 121.07 (2C), 45.27 (2C), 25.67 (2C), 24.32; HRMS (ESI) m/z (M+H)+ calcd for
C12H16ClN2O = 239.0951; found 239.0956.
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8
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1,3-Dibenzylurea (3l). Yield 81%; white solid; m.p. 167 – 169°C; 1H NMR (400 MHz, CDCl3)
δ 7.30 – 7.20 (m,10H), 4.27 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 158.34, 139.16 (2C), 128.56
(4C), 127.34 (4C), 127.22 (2C), 44.42 (2C); HRMS (ESI) m/z (M+H)+ calcd for C15H17N2O =
241.1341; found 241.1338.
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1-Benzyl-3-butylurea (3m). Yield 85%; white solid; m.p. 99 - 101°C; H NMR (400 MHz,
CDCl3) δ 7.34 – 7.24 (m, 5H), 4.33 (s, 2H), 3,13 (t, J = 7.2 Hz, 2H), 1.46 – 1.42 (m, 2H), 1.34 –
13
1.30 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) δ 158.44, 139.32, 128.58
(2C), 127.38 (2C), 127.23, 44.46, 40.29, 32.26, 20.00, 13.78; HRMS (ESI) m/z (M+H)+ calcd for
C12H19N2O = 207.1497; found 207.1492.
1
N-Benzylpiperidine-1-carboxamide (3o). Yield 70%; white solid; m.p. 103 - 105°C; H NMR
(400 MHz, CDCl3) δ 7.37 – 7.27 (m, 5H), 4.74 (s, 1H), 4.46 (d, J = 5.2 Hz, 2H), 3.36 (t, J = 4.8
Hz, 4H), 1.66 – 1.5 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 157.51, 139.64, 128.60 (2C), 127.80
(2C), 127.24, 45.06 (2C), 25.62 (2C), 24.41, 43.35, 29.11, 20.49(2C); HRMS (ESI) m/z (M+H)+
calcd for C13H19N2O = 219.1497; found 219.1520.
3-Benzyl-1,1-dipropylurea (3p). Yield 75%; white solid; m.p. 42 - 45 °C; 1H NMR (400 MHz,
CDCl3) δ 7.36 - 7.25 (m, 5H), 4.64 (s,1H), 4.46 (d, J = 4.8 Hz, 2H), 3.19 (t, J = 8.0 Hz, 4H),
1.64- 1.55 (m, 4H), 0.91 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 157.57, 139.93,
128.81 (2C), 127.58 (2C), 127.13, 49.19 (2C), 44.92, 21.80 (2C), 11.38 (2C); HRMS (ESI) m/z
(M+H)+ calcd for C14H23N2O = 235.1810; found 235.1843.

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3-Benzyl-1-methyl-1-phenylurea (3q). Yield 80%; white solid; m.p. 92 - 95°C; H NMR (400
5
6
MHz, CDCl3) δ 7.45 – 7.40 (m, 2H), 7.32 – 7.23 (m, 8H), 4.68 (s, 1H), 4.42 (t, J = 5.2 Hz, 2H),
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8
13
3.33 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.19, 143.29, 139.55, 130.09 (2C), 128.51 (2C),
9
127.42 (3C), 127.31 (2C), 127.08, 44.74, 37.37; HRMS (ESI) m/z (M+H)+ calcd for C15H17N2O
= 241.1341; found 241.1352.
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N-Methyl-N-phenylpiperidine-1-carboxamide (3r). Yield 52%; colorless liquid; 1H NMR
(400 MHz, DMSO-d6) δ 7.36 – 7.31 (m, 2H), 7.10 – 7.06 (m, 3H), 3.09 (t, J = 5.2 Hz, 4H), 3.07
(s, 3H), 1.46- 1.40 (m, 2H), 1.31 – 1.25 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ 160.58,
147.24, 129.71 (2C), 124.03, 123.02 (2C), 46.46 (2C), 39.28, 25.41 (2C), 24,41; HRMS (ESI)
m/z (M+H)+ calcd for C13H19N2O = 219.1497; found 219.1494.
General procedure for the preparation of 2,2,2-trichloroethyl phenylcarbamate compounds
(4a-4c)
To a solution of aniline (1.4 g, 15.0 mmol) and pyridine (4,74 g, 60.0 mmol) in dichloromethane,
2,2,2-chloroethyl chloroformate (3.8 g, 18.0 mmol) was added. The reaction mixture was stirred
for 10 h at room temperature. The reaction mixture was quenched by the addition of H2O (20
mL) and extracted with EtOAc (3 x 20 mL). The organic layer was dried over sodium sulfate and
concentrated under reduced pressure. The resulting residue was then purified by flash column
chromatography on silica gel with hexane-EtOAc 20/1 as eluent to afford the desired product 4a
(3.75 g, 94%).
General procedure for the preparation of benzyl phenylcarbamate compound (4d-4e)
To a solution of aniline (2.04 g, 21.9 mmol) and NaHCO3 (2.02 g, 24.0 mmol) in
tetrahydrofuran, benzyl chloroformate (3.4 ml, 25.76 mmol) was added. The reaction mixture
was stirred for 2 h at room temperature. The reaction mixture was quenched by the addition of

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H2O (15 mL) and extracted with EtOAc (3 x 20 mL). The organic layer was dried over sodium
sulfate and concentrated under reduced pressure. The resulting residue was then purified by flash
column chromatography on silica gel with hexane-EtOAc 20/1 as eluent to afford the desired
product 4d (4.72 g, 95%).
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2,2,2-Trichloroethyl phenylcarbamate (4a). Yield 96%; White solid. m.p 72-74°C; H NMR
(400 MHz, CDCl3) δ 7.43 – 7.32 (m, 4H), 7.12 (t, J = 7.6 Hz, 1H), 6.86 (s, 1H), 4.83 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 151.47, 137.00, 129.09 (2C), 124.20, 118.87 (2C), 95.25, 74.52;
HRMS (ESI) m/z (M+H)+ calcd for C9H9Cl3NO2 = 267.9699; found 267.9695.
1
2,2,2-Trichloroethyl benzylcarbamate (4b). Yield 95%; white solid. m.p 66-68°C; H NMR
(400 MHz, CDCl3) δ 7.39 – 7.28 (m, 5H), 5.33 (s, 1H), 4.79 (s, 2H), 4.46 (d, J = 6.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 154.62, 137.72, 128.78 (2C), 127.77, 127.57 (2C), 95.56, 74.62,
45.35; HRMS (ESI) m/z (M+H)+ calcd for C10H11Cl3NO2 = 281.9855; found 281.9858.
1
2,2,2-Trichloroethyl piperidine-1-carboxylate (4c). Yield 94%; white solid. m.p 48-50°C; H
NMR (400 MHz, CDCl3) δ 4.74 (m, 2H), 3.52 (d, J = 20.4 Hz, 2H), 3.37 – 3.32 (q, J = 7.2 Hz,
13
2H), 1.66 – 1.57 (m, 3H), 1.21 – 1.15 (m, 3H); C NMR (100 MHz, CDCl3) δ 153.94, 95.87,
74.97, 45.25, 45.17, 42.36, 24.27; HRMS (ESI) m/z (M+H)+ calcd for C8H13Cl3NO2 = 260.0012;
found 260.0005.
1
Benzyl phenylcarbamate (4d). Yield 95%; white solid. m.p 77-78 °C; H NMR (400 MHz,
CDCl3) δ 7.43 – 7.29 (m, 9H), 7.07 (t, J = 7.6 Hz, 1H), 6.76 (s, 1H), 5.21 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 153.36, 137.78, 136.06, 129.08 (2C), 128.64 (2C), 128.37 (2C), 128.34 (2C),
123.54, 118.72, 67.04; HRMS (ESI) m/z (M+H)+ calcd for C14H14NO2 = 228.1025; found
228.1020.

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Benzyl benzylcarbamate (4e). Yield 96%; white solid. m.p 63-65°C; H NMR (400 MHz,
5
6
13
CDCl3) δ 7.39 – 7.28 (m, 10H), 5.17 (s, 2H), 5.10 (s, 1H), 4.42 (d, J = 6.0 Hz, 2H); C NMR
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(100 MHz, CDCl3) δ 156.39, 138.38 (2C), 136.48 (2C), 128.68 (2C), 128.53 (2C), 128.15 (2C)
127.53 (2C), 66.89, 45.18; HRMS (ESI) m/z (M+H)+ calcd for C15H16NO2 = 242.1181; found
242.1177.
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General procedure for the preparation of urea compounds (6a-6n)
To a solution of 4a (0.268 g, 1.00 mmol) in toluene (2 mL), benzylamine (0.160 g, 1.50 mmol)
and CaI2 (0.044 g. 0.15 mmol) was added. The mixture was stirred for 12 h at 80 °C. The
reaction mixture was extracted with CH2Cl2 (2 x 20 mL). The organic layer was dried over
magnesium sulfate and concentrated under reduced pressure. The resulting residue was then
purified by flash column chromatography on silica gel with hexane-EtOAc as eluent to afford the
desired product 6a (0.216 g, 96%).
1
1-Isobutyl-3-phenylurea (6b). Yield 96%; white solid; m.p. 156 - 158°C; H NMR (400 MHz,
DMSO-d6) δ 8.37 (s,1H), 7.38 – 7.36 (m, 2H), 7.23 – 7.21 (m, 2H), 6.89 (t, J = 7.6 Hz, 1H), 6.16
13
(t, J = 5. Hz, 1H), 2.92 (d, J = 0.4 Hz, 2H), 1.70 -1.65 (m,1H), 0.88 (d, J = 6.8 Hz, 6H); C
NMR (100 MHz, DMSO-d6) δ 155.69, 141.05, 129.07 (2C), 112.07, 117.94 (2C), 46.95, 28.94,
20.47(2C); HRMS (ESI) m/z (M+H)+ calcd for C11H17N2O = 193.1341; found 193.1346.
1
1-Benzyl-3-isobutylurea (6e). Yield 94%; white solid; m.p. 143 - 145°C; H NMR (400 MHz,
DMSO-d6) δ 7.33 – 7.21 (m, 5H), 6.25 (t, J = 6.0 Hz, 1H), 5.95 (t, J = 6.0 Hz, 1H), 4.21 (d, J =
13
6.0 Hz, 2H), 2.85 (d, J = 6.4 Hz, 2H), 1.66 – 1.59 (m,1H), 0.84 (d, J = 6.8 Hz, 6H); C NMR
(100 MHz, DMSO-d6) δ 158.59, 141.49, 128.65 (2C), 127.39 (2C), 126.94, 47.35, 43.35, 29.11,
20.49(2C); HRMS (ESI) m/z (M+H)+ calcd for C12H19N2O = 207.1497; found 207.1505.

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N-Butylpiperidine-1-carboxamide (6h). Yield 72%; white solid; m.p. 43 - 45°C; 1H NMR (400
MHz, CDCl3) δ 4.81 (s, 1H), 3.29 (d, J = 4.8 Hz, 4H), 3.25- 3.15 (m, 2H), 1.60 -1.42 (m, 8H),
6
7
8
13
1.38 – 1.23 (m, 2H), 0.91 – 0.88 (t, J = 6.0 Hz, 3H); C NMR (100 MHz, CDCl3) δ 157.79,
9
44.90 (2C), 40.66, 32.43, 25.58 (2C), 24.42, 20.12, 13.84; HRMS (ESI) m/z (M+H)+ calcd for
C10H21N2O = 185.1654; found 185.1674.
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Dipiperidin-1-ylmethanone (6i). Yield 53%; colorless liquid; 1H NMR (400 MHz, CDCl3) δ
3.18 – 3.13 (m, 8H), 1.59 – 1.49 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.82, 47.91 (4C),
25.78 (4C), 24.78 (2C); HRMS (ESI) m/z (M+H)+ calcd for C11H21N2O = 197.1654; found
197.1675.
N-Phenylmorpholine-4-carboxamide (6l). Yield 85%; white solid; m.p. 260 - 262°C; 1H NMR
(400 MHz, CDCl3) δ 7.38 – 7.28 (m, 4H), 7.09 – 7.05 (m, 1H), 6.45 (s, 1H), 3.75 (t, J = 5.2 Hz,
4H), 3.49 (t, J = 5.2 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 155.09, 138.65, 128.95 (2C),
123.39, 120.06 (2C), 66.49 (2C), 44.31 (2C); HRMS (ESI) m/z (M+H)+ calcd for C11H15N2O2 =
207.1134; found 207.1129.
N-Benzylpyrrolidine-1-carboxamide (6n). Yield 71%; light yellow solid; m.p. 120 - 123°C; 1H
NMR (400 MHz, CDCl3) δ 7.36 – 7.26 (m, 5H), 4.55 (s, 1H), 4.46 (s, 2H), 3.41 -3.35 (m, 4H),
13
1.96 – 1.88 (m, 4H); C NMR (100 MHz, CDCl3) δ 156.68, 139.83, 128.52 (2C), 127.72 (2C),
127.17, 45.61 (2C), 45.54, 25.63 (2C); HRMS (ESI) m/z (M+H)+ calcd for C12H17N2O =
205,1341; found 205.1336.
Electronic supplementary material
Electronic Supplementary Material (ESI) available: 1H and 13C NMR spectra of all compounds.
See DOI:

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Conflicts of interest
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There are no conflicts to declare.
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Acknowledgments
This research was supported by Basic Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07047572).
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A practical CaI2-catalyzed direct synthesis of asymmetrical ureas from N-Alloc-, N-Troc-, and N-
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Cbz-carbamate compounds has been developed.