Copper-catalyzed coupling of arylboronic acids with potassium cyanate: A new approach to the synthesis of aryl carbamates

Article abstract of DOI:10.1002/adsc.201100153

The copper-catalyzed coupling of aromatic boronic acids with potassium cyanate in the presence of an alcohol has been employed for the synthesis of arylcarbamates. This simple and highly efficient approach can be carried out in air at room temperature and, importantly, no base, ligand, or additive is required. Copyright

Full text of DOI:10.1002/adsc.201100153

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DOI: 10.1002/adsc.201100153
Copper-Catalyzed Coupling of Arylboronic Acids with Potassium
Cyanate: A New Approach to the Synthesis of Aryl Carbamates
Ebrahim Kianmehra,* and Mohammad Hadi Baghersada
a
School of Chemistry, College of Science, University of Tehran, Tehran 1417614411, Iran
Fax : (+98)-21-66495291; phone: (+98)-21-61113301; e-mail: kianmehr@khayam.ut.ac.ir
Received: March 3, 2011; Revised: May 14, 2011; Published online: August 25, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100153.
Abstract: The copper-catalyzed coupling of aromat-
ic boronic acids with potassium cyanate in the pres-
ence of an alcohol has been employed for the syn-
thesis of arylcarbamates. This simple and highly ef-
ficient approach can be carried out in air at room
temperature and, importantly, no base, ligand, or
additive is required.
Cs2CO3-induced reaction of amines with alkyl halides
and CO2,[9] reaction of azides and chloroformates in
the presence of trimethylphosphine,[10] 1,1-carbonyl-
diimidazole-promoted reaction between alcohols and
amines[11] and reaction of tetraethylammonium hydro-
gen carbonate with amines.[12] The other methods em-
ployed to prepare carbamates are carbonylation of
amines[13] and alcoholysis of urea.[14] Transition metal-
catalyzed cross-coupling reactions are now recognized
as extremely powerful strategies for the formation of
carbon-heteroatom bonds. The pioneering studies of
Buchwald and Hartwig established palladium com-
plexes as efficient catalysts for these reactions.[15]
These studies provided the impetus to evaluate other
Keywords: arylboronic acids; carbamates; cross-
coupling; homogeneous catalysis
Carbamates show remarkable biological activities. transition metal catalysts and have led to a renais-
They are known to have pesticide, insecticide, antibi- sance in copper-based couplings.[16] Copper catalysis
otic, fungicide, herbicide and other pharmacological enables the use of a wide scope of reagents as aryl
properties.[1] They are also of considerable importance sources such as aryl halogenides, arylsiloxanes, aryl-
because of their application as intermediates for the trialkylstannes, diaryliodonium salts, triarylbismuth-
synthesis of polyurethane-based polymers and as pro-
anes, or aryllead triacetates.[17] Independently report-
ACHTUNGTRENNUNG
tecting groups[2] of amines in peptide synthesis. Be- ed by the groups of Chan, Evans, and Lam in 1998,
cause of their importance, the synthesis of carbamates this cross-coupling procedure resolved the long-stand-
has become a focus of synthetic organic chemistry ing problem of the simple and mild formation of C-
and several efforts have been made for the prepara- heteroatom bonds using an arylboronic acid as the
tion of the title compounds. Initially carbamates were aryl donor. The method has proven to have a wide
almost exclusively synthesized by the reaction of range of nucleophilic reaction partners including phe-
amines with phosgene or its derivatives such as chlor- nols, amines, N-hydroxyphthalimides and N-heterocy-
oformate,[2a,3] dialkyl carbonates[4] or reaction of alco- cles to give the corresponding N- or O-arylated prod-
hols with isocyanates.[5] These procedures had several ucts.[18] Arylboronic acids have also been widely used
drawbacks, notably the extreme toxicity of reagents as precursors in other synthetic organic transforma-
and generation of by-products. Numerous methods tions such as cyanation, trifluoromethylation, halogen-
have been described to avoid such drawbacks, such as ations, alkynylation and carboxylation.[19] To the best
reductive carbonylation of aromatic nitro com- of our knowledge there is no example for the conver-
pounds[6] and oxidative carbonylation of amines cata- sion of arylboronic acids to carbamates. Herein we
lyzed by various transition metal complexes.[7] Howev- report this methodology by which carbamates were
er, the former route suffers from a lack of economical prepared by a copper-catalyzed reaction of arylboron-
viability while the latter suffers from hazards in the ic acids with potassium cyanate in the presence of an
handling of carbon monoxide and oxygen under high alcohol.
pressures. Carbamate synthesis has been accom-
Initially, 4-chlorobenzeneboronic acid was chosen
plished by Hofmann rearrangement from amides,[8] as the model substrate. To optimize the reaction con-
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Ebrahim Kianmehr and Mohammad Hadi Baghersad
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Table 1. Optimization of the reaction conditions.
under the optimized reaction conditions. (Table 2, en-
tries 14 and 18)
Therefore our optimal reaction conditions for most
of the conversions of 4-chlorobenzeneboronic acid to
the titled product are as follows: 10 mol% of CuBr2
as the catalyst, alcohol as the solvent and alkoxy
source of products, and the reaction is carried out in
air at 608C.
Entry Catalyst
Solvent T [8C] t [h] 2a [%]
1
Cu
N
24
24
24
20
20
20
25
22
25
25
48
20
20
24
43
49
38
69
75
63
47
72
40
44
57
76
–
Next we investigated the scope of the copper-cata-
lyzed reaction with respect to the arylboronic acid
and alcohol. As shown in Table 2, most of the arylbor-
onic acids examined under the standard reaction con-
ditions provided moderate to good yields of the prod-
ucts. The aromatic boronic acids substituted with hal-
ogen and electron-deficient CF3 groups gave the cor-
responding carbamates in good yields. Arylboronic
acids with electron-donating alkyl, alkoxy and phen-
oxy groups led to relatively lower yields of aryl carba-
mates under the optimized reaction conditions. 2,5-
Dimethoxybenzeneboronic acid, with high steric hin-
drance, led to the protolytic deboronation under the
reaction conditions. (Table 2, entry 13) Ethanol, prop-
anol, 2-propanol and allyl alcohol led to the forma-
tion of the corresponding products. (Table 2, en-
tries 14–19)
2
CuBr2
MeOH r.t.
MeOH r.t.
3
CuSO4·5H2O
4
CuACHTUNGTRENNUNG(OAc)2·H2O MeOH 60
5
CuBr2
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
MeOH 60
6
7
CuSO4·5H2O
CuCO3
8
9
CuCl2·2H2O
Cu2O
10
11
12
13
14
CuI
[a]
CuBr2[b]
CuBr2[c]
CuBr2
–
–
[a]
[b]
[c]
CuBr2 (5 mol%).
CuBr2 (20 mol%).
The reaction was carried out under a nitrogen atmos-
phere.
To broaden the scope of substrate used, we carried
out the reaction of 4-chlorobenzeneboronic acid ester
ditions, catalysts, solvents and temperatures of the re- with potassium cyanate and methanol under the stan-
action were investigated. As shown in Table 1, the dard conditions and the corresponding product was
best activity was shown at 608C. The reaction provid- afforded in moderate yield. (Table 2, entry 12)
ed a lower conversion at room temperature. (Table 1,
Although the mechanism for the coupling of orga-
entries 1–3) Different Cu sources were tested using noboranes with the cyanate ion is not clear at this
potassium cyanate in methanol. We observed that, in moment, a possible catalytic cycle is shown in
open air (without bubbling air), all tested Cu(I) salts Scheme 1.
and CuCO3 showed relatively lower catalytic activity.
The proposed mechanism involves rapid coordina-
(Table 1, entries 7, 9, 10). All the other tested Cu(II) tion/ligand exchange of the Cu(II) salt by a cyanate
salts gave better results and the best conversion was ion to form the intermediate OCNCu(II)Br. The
observed with CuBr2. (Table 1, entry 5) No desired second step involves transmetallation of the arylbor-
product was observed in the absence of air (in a nitro- onic acid with OCNCu(II)Br to give the intermediate
gen atmosphere, Table 1, entry 13) which indicated ArCu(II)NCO complex. ArCu(II)NCO may undergo
that an oxidative process was involved in the forma- reductive elimination to give the product ArNCO. Al-
tion of the products. The reaction was also monitored ternatively, ArCu(II)NCO may undergo air oxidation
with different catalyst loadings and the results showed to yield the corresponding higher oxidation-state
that 10 mol% of CuBr2 (relative to the aromatic bor- copperACTHNUTRGENN(UG III) complex ArCuACHTUNGTERN(NUGN III)NCO, which can more
onic acid) was the best choice for completing the re- efficiently reductively eliminate to afford the product
action. At a lower catalyst loading the reaction took ArNCO. The copper(I) formed can then be easily oxi-
longer and was not complete even after stirring for dized by oxygen to copper(II) to complete the catalyt-
several days. (compare Table 1, entry 5 with Table 1, ic cycle. Subsequent reaction of the aryl isocyanate
entries 11 and 12). No reaction occurred in the ab- with the alcohol affords the corresponding carbamate.
sence of a copper catalyst. (Table 1, entry 14) Since
In summary, a simple and efficient copper-catalyzed
the reaction is catalyzed by Cu(II), the effect of dif- method for the synthesis of carbamates by coupling of
ferent ligands such as 1,10-phenanthroline, 2,2’-bipyri- aromatic boronic acids with potassium cyanate has
dine, PPh3 and S-proline was investigated under the been developed. The coupling reactions were per-
reaction conditions and no improvement was ob- formed in air, without the need for sealed reaction
served in reaction efficiency.
vessels and neither a base, ligand nor additive was
When ethanol and allyl alcohol were used as the necessary.
solvent the corresponding carbamates were obtained
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Adv. Synth. Catal. 2011, 353, 2599 – 2603

Copper-Catalyzed Coupling of Arylboronic Acids with Potassium Cyanate
Table 2. Copper-catalyzed reaction of arylboronic acids with ptassium cyanate in the presence of an alcohol at 608C.
[a]
The corresponding carbamoylcarbamate was obtained as the by-product.
Isolated yield.
[b]
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Ebrahim Kianmehr and Mohammad Hadi Baghersad
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To a solution of arylboronic acid (1.0 equiv.) or arylboronic
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(1.5 equiv.) and CuBr2 (10 mol%) were added and the mix-
ture was stirred at 608C for 24 h. The reaction progress was
monitored by TLC. Work-up of the reaction involved evapo-
rating the solvent under reduced pressure, then extraction
with dichloromethane. The solvent was removed under
vacuum and the product was purified by column chromatog-
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We gratefully acknowledge the financial support from the Re-
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Karol Gajewski, Canadian Intellectual Property Office, for
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