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to perform efficiently the substitution reaction on the iron-
activated urea, a factor that can be modulated by the introduc-
tion of electron-donor groups. Benzyl derivatives provided the
desired products in excellent yields, allowing even the intro-
duction of electron-withdrawing groups without lack of effec-
tiveness (3g–h, 92 and 87% yield, respectively). Gratifyingly,
the reaction of urea with the more stericly hindered 1-phenyle-
thanol (2i) gave place to the product 3i in a bit lower 78%
yield. However, the introduction of a second phenyl group at
the nucleophile led to a drastic decrease of the conversion,
and the reaction with diphenylmethanol (2j) only afforded the
corresponding primary carbamate in 44% isolated yield. Relat-
edly, the product expected from the reaction of urea with the
tertiary alcohol 2k was not detected.
Alternatively, this transformation takes place with allyl alco-
hols. Thus, cinnamyl alcohol (2l) gave rise to allyl carbamate 3l
in a good yield (73%). Then, we tested alcohols presenting
heteroatoms in their structure. In this way, ethyl glycolate (2m)
was effectively converted into the desired product 3m in 80%
yield. Besides to the ester group, this reaction also tolerates
functional groups, such as tertiary amines, halides, or silanes.
Hence, the iron-catalyzed treatment of urea with alcohols 2n–
p afforded the respective carbamates in good yields and selec-
tivities (3n–p, 76-83%). Unfortunately, corresponding thiols
showed no conversion under the same reaction conditions. In
general, all these reactions showed to be highly selective to-
wards the synthesis of primary carbamates producing only one
equivalent of ammonia as stoichiometric residue. This selectivi-
ty and the possibility of using differently substituted alcohols
provide an added value to this methodology.
Table 2. Iron-catalyzed reaction of 1-undecenol (2a) with different substi-
tuted ureas and carbamates (4–6).[a]
Entry
Electrophile
structure
Product
label structure
R
label yield[b] [%]
1
2
3
tBu 4a
7a
7b
7c
49[c]
31[d]
80[e]
Bn
Ph
4b
4c
4
–
5
8
n.d.[f]
5
6
7
Me
Bn
Ph
6a
6b
6c
3a
3a
3a
84
83
97
[a] Unless otherwise specified, all reactions were carried out with FeBr2
(0.01 mmol), urea or carbamate (4–6, 0.5 mmol), and 1-undecenol (2a,
0.75 mmol) in 1,4-dioxane (1 mL) at 1508C for 6 h. [b] Isolated yields.
[c] 3a was isolated in 40% yield. [d] 3a was isolated in 27% yield. [e] 3a
was isolated in 15% yield. [f] n.d.: not detected.
place, but 1-undecenol was shown to be more reactive in all
examples. Since aromatic alcohols are not active in this trans-
formation as discussed above, the use of phenyl carbamate
(6c) afforded 3a in quantitative yield.
For practical applications the use of diols as nucleophiles on
our process is highly interesting, since the resulting bifunction-
al products are valuable building blocks for polymers/oligo-
mers (Scheme 3). Notably, these substrates might promote also
an intramolecular reaction to afford the cyclic carbonate. In
fact, the reaction of urea (1, 0.5 mmol) with 2-phenyl-1,3-pro-
panediol (9a, 0.75 mmol) under FeBr2 catalysis (0.01 mmol)
gave a mixture of the respective mono- and dicarbamates.
Owing to the biological relevance of 10a, an anticonvulsant
drug used for the treatment of epilepsy (Felbamate),[20] we op-
timized this reaction to favor its synthesis. In this way, the use
of 2.0 mmol of urea and 0.5 mmol of 9a in the presence of
To increase the versatility of this protocol, we tested differ-
ent electrophiles in the iron-catalyzed reaction with 1-undece-
nol (2a). Initially, we proposed the use of N-monosubstituted
ureas to study the potential formation of N-substituted carba-
mates. Unfortunately, the reaction of 2a (0.75 mmol) with N-
tert-butylurea (4a, 0.5 mmol) under FeBr2 catalysis (0.01 mmol)
in 1,4-dioxane at 1508C, led to a mixture of products. The cor-
responding N-tert-butylcarbamate 7a was obtained in 49%
yield, whereas the formation of the corresponding product 3a
was observed in 40% yield (Table 2, entry 1). The use of benzy-
lurea (4b) afforded a similar result (Table 2, entry 2). However,
when phenlyurea (4c) was used as electrophile, the N-phenyl
substituted carbamate 7c was obtained in a good yield (80%;
Table 2, entry 3). Here, 3a was isolated in only 15% yield,
which demonstrates the lower reactivity of aniline to act as
leaving group. At that point, we investigated the synthesis of
thiocarbamates, but the reaction of 1-undecenol (2a) with thi-
ourea (5) showed no conversion (Table 2, entry 4). Apparently,
in this case the iron(II) bromide is unable to activate the elec-
trophile by coordination to the sulfur atom, disfavoring the nu-
cleophilic substitution. On the other hand, the iron-catalyzed
transcarbamoylation reaction using different substituted carba-
mates (6a–c) works well.[19] As shown in Table 2 (entries 5–7),
this latter transformation provided the primary carbamate 3a
in excellent yields using either O-methyl, -benzyl, and -phenyl
carbamates. In this case a competitive substitution reaction be-
tween the starting alcohol and the leaving group can take
Scheme 3. Iron-catalyzed reaction of urea (1) with diols (9). [a] Reactions per-
formed with FeBr2 (0.02 mmol), urea (1, 2.0 mmol), and diol (9a–d,
0.5 mmol) in 1,4-dioxane (1 mL) at 1508C for 6 h. [b] Isolated yields.
ChemSusChem 2016, 9, 1 – 7
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