Ligand-free cross-coupling of boronic acids with Cu(NO3) 2 complexes of amines in aqueous media

Article abstract of DOI:10.3184/174751912X13364681530823

The efficient conversion of boronic acids, both arylboronic acids and alkylboronic acids, to the corresponding amines in water was accomplished in moderate to good yields using Cu(NO₃)₂ complexes of amines as the nitrogen source. The

Full text of DOI:10.3184/174751912X13364681530823

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 381
JULY, 381–382
Ligand-free cross-coupling of boronic acids with Cu(NO3)2 complexes of
amines in aqueous media
Juan Xu and Jia Rong Li*
School of Chemical Engineering and Environment, Beijing Institute ofTechnology, Beijing 100081, P. R. China
The efficient conversion of boronic acids, both arylboronic acids and alkylboronic acids, to the corresponding amines
in water was accomplished in moderate to good yields using Cu(NO3)2 complexes of amines as the nitrogen source.
The coupling reactions were performed in water at 30 °C for 2 hours.
Keywords: boronic acid, Cu(NO3)2 complexes of amines, amination in water
Amines are important compounds found throughout the
pharmaceutical, bioactive natural products and agrochemical
industries.1,2 Establishing efficient methods for the construc-
tion of C–N bond is currently an active area in organic synthe-
sis. Transition-metal-catalysed transformations of aromatic
halides and tosylates have been used in the synthesis of
arylamines,3−5 and nitroarenes.6 However, this methodology
has been hampered by some shortcomings which included the
use of expensive, toxic catalysts and ligands for palladium
catalysis or harsh reaction conditions and limited substrate
scope for copper catalysis.
Aryl boron compounds are common chemicals and they are
easily prepared from readily available aryl halides and tosyl-
ates. The aryl boron compounds have been used as the starting
materials to make aromatic compounds containing various
functional groups (including arylamines7 and nitroarenes8,9)
through an aerobic oxidative strategy. For example, Chan and
Lam have described a Cu(OAc)2-promoted N-arylation of
commercially available arylboronic acids with imidazoles at
room temperature.10−13 Many extensions and applications of
this new methodology have been reported.14−19 And various
efficient catalysts have been developed that allow amines to be
effective coupled with aryl boronic acids.20−29 Even so, Lam’s
method12 requires more than a stoichiometric amount of oxi-
dant such as pyridine N-oxide, TEMPO [(2,2,6,6-tetramethyl-
piperidin-1-yl)oxyl] or NMO (N-methylmorpholine-N-oxide)
as well as Et3N or pyridine and elevated temperature, whereas
the system described by Buchwald14 requires the addition of a
stoichiometric amount of 2,6-lutidine as well as myristic acid
and gives a low yield (32%).
In modern organic synthesis, the ideal reaction conditions
include the use of cheap, highly efficient catalyst systems,
environment friendly water as the solvent, room temperature
reactions under air (without using air) and easy workup proce-
dures after reactions. Here, we report a convenient and effec-
tive amination of boronic acid using Cu(NO3) complexes of
amines as nitrogen source without ligand in water at 30 °C for
2 hours with moderate to good yield.30−32
Using the reaction of phenylboronic acid as a template,
various metal complexes of piperidine were screened in water
(Table 1). Metal complexes of piperidine such as ZnCl2–
2NH(CH2)5–2HCl, CuCl2–2NH(CH2)5–2HCl and Cu(NO3)2–
(CH2)5NH were investigated and it was found that only
Cu(NO3)2–(CH2)5NH gave the desired product (entries 1–4).
Bases such as Et3N, NaHCO3, Na2CO3, K2CO3 and NaOH were
found to facilitate this coupling reaction and among them Et3N
is the best (entries 4-9). It needs to be emphasised is that the
Cu(NO3)2 complexes combine several advantageous features
such as solid, stable in air, no smell and excellent water-
solubility.
and provide the corresponding arylamines in moderate yields.
Various amines, such as primary alkylamine (entry 1), dialkyl-
amine (entry 2), cyclic alkylamine (entry 3) and aromatic
amine (entry 4), were all suitable amines for the amination
of phenylboronic acid. As for arylboronic acids with an elec-
tron-withdrawing group (e.g. p-CF3, p-Cl) and Naphthalen-2-
ylboronic acid could be substituted by ring alkylamine (entries
5–7). Arylboronic acids with an electron-donating group (eg.
p-CH3) generated expected products bearing n-propyl (entry
8), morpholinyl (entry 9) and phenyl (entry 10). Meanwhile,
we were pleased to observe that when trans-beta- styrene-
boronic acid (sp2) treated with Cu(NO3)2 complexes of n-propyl-
amine, the corresponding product were obtained (entry 11).
Phenethylboronic acid (sp3) had no reaction with all
Cu(NO3)2 complexes of amines. Electron-deficient pyridin-4-
ylboronic acid was converted into pyridin-4-ol when reacted
with Cu(NO3)2 complexes of amines.
Although comprehensive studies are required to elucidate
the mechanistic details of the present reaction, a possible
intermediate is presented in Scheme 1. Comparing entry 4 with
entry 5 in Table 1, the product was phenol if there was no Et3N
in system. So we consider that33 Cu(NO3)2 complex of amine
could become Cu(NR1R2)2 under the conditions of Et3N. Then
Cu(NR1R2)2 reacted with boronic acid to give the amination
product.
In conclusion, the construction of C–N bond was achieved
effectively by Cu(NO3)2 complexes of amines as nitrogen
source under mild condition. It is environmentally friendly
because it uses water as a reaction medium for organic
synthesis.
Experimental
ESI-MS were recorded with a ZAB-HS mass spectrometer in the
positive ion mode.
Synthesis of Cu(NO3)2 complex of amine; general procedure
A complex of copper nitrate (10 mmol) and amine (10 mmol) was
refluxed in ethanol (25 mL) for 10 hours. After the reaction was
completed, ethanol was evaporated under vacuum conditions.
Table 1 Effect of metal complex and basea
Entry Metal complexes of
piperidine
Base
Product
Yield/%
1
2
ZnCl2–2NH(CH2)5–2HCl
ZnCl2–2NH(CH2)5–2HCl
(CuCl as catalyst)
K2CO3
K2CO3
PhOH
PhOH
100
100
3
4
CuCl2–2NH(CH2)5–2HCl
Cu(NO3)2–(CH2)5NH
K2CO3
Et3N
PhOH
PhN(CH2)5
1a
100
64
5
6
7
8
9
Cu(NO3)2–(CH2)5NH
Cu(NO3)2–(CH2)5NH
Cu(NO3)2–(CH2)5NH
Cu(NO3)2–(CH2)5NH
Cu(NO3)2–(CH2)5NH
PhOH
100
50
48
45
36
Under the optimised condition, the results obtained with
boronic acids and Cu(NO3)2 complexes of amines are shown
in Table 2. The results indicate clearly that this protocol is
general and is applicable for reactions of a wide variety of
electron-rich, electron-deficient, and neutral arylboronic acids
NaHCO3 PhN(CH2)5
Na2CO3 PhN(CH2)5
K2CO3
NaOH
PhN(CH2)5
PhN(CH2)5
a Reaction conditions: phenylboronic acid (1 mmol), metal com-
plexes of piperidine (1 mmol) and base (1.2 mmol) were stirred
in water (2 mL) at 30 °C for 2 hours.
* Correspondent. E-mail: jrli@bit.edu.cn

382 JOURNAL OF CHEMICAL RESEARCH 2012
Table 2 Amination of boronic acid a
Entry
Boronic acid b
Cu(NO3)2 complex of Amine
Product
Yield/%c
1
2
PhB(OH)2
Cu(NO3)2–NH2(CH2)2CH3
Cu(NO3)2–NH(CH3)2
Cu(NO3)2–NH(CH2CH2)2O
Cu(NO3)2–NH2C6H5
PhNH(CH2)2CH3 2a
58
60
63
51
68
65
62
59
54
48
40
PhN(CH3)2 2b
3
PhN(CH2)4O 2c
PhNHPh 2d
4
5
4-CF3–C6H4–B(OH)2
4-Cl–C6H4–B(OH)2
2-Naphth-B(OH)2
4-CH3–C6H4–B(OH)2
Cu(NO3)2–NH(CH2CH2)2O
Cu(NO3)2–NH(CH2CH2)2O
Cu(NO3)2–NH(CH2CH2)2O
Cu(NO3)2–NH2(CH2)2CH3
Cu(NO3)2–NH(CH2CH2)2O
Cu(NO3)2–NH2C6H5
4-CF3–C6H4–N(CH2CH2)2O 2e
4-Cl–C6H4–N(CH2CH2)2O 2f
2-Naphth–N(CH2CH2)2O 2g
4-CH3–C6H4–NH(CH2)2CH3 2h
4-CH3–C6H4–N(CH2CH2)2O 2i
4-CH3–C6H4–NHC6H5 2j
Ph–CH=CH–NH(CH2)2CH3 2k
6
7
8
9
10
11
Ph–CH=CH–B(OH)2
Cu(NO3)2–NH2CH2CH2CH3
a Reaction conditions: boronic acid (1mmol), Cu(NO3)2 complex of Amine (1mmol), Et3N (1.2 mmol) were stirred in water (2 mL) at
30 °C for 2 hours. b All boronic acids were obtained from J&K chemical. c Yields refers to isolated pure product.
Scheme 1 The possible intermediate.
5
6
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Received 4 January 2012; accepted 3 April 2012
Paper 1201080 doi: 10.3184/174751912X13364681530823
Published online: 26 June 2012
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