Metal and base free synthesis of primary amines via ipso amination of organoboronic acids mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA)

Article abstract of DOI:10.1039/c5ob01070e

A metal and base free synthesis of primary amines has been developed at ambient temperature through ipso amination of diversely functionalized organoboronic acids, employing a combination of [bis(trifluoroacetoxy)iodo]benzene (PIFA)-N-bromosuccinimide (NBS) and methoxyamine hydrochloride as the aminating reagent. The amines were primarily obtained as their trifluoroacetate salts which on subsequent aqueous alkaline work up provided the corresponding free amines. The combination of PIFA-NBS is found to be the mildest choice compared to the commonly used strong bases (e.g. n-BuLi, Cs₂CO₃) for activating the aminating agent. The reaction is expected to proceed via activation of the aminating reagent followed by B-N 1,2-aryl migration.

Full text of DOI:10.1039/c5ob01070e

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: N. Chatterjee and
A. Goswami, Org. Biomol. Chem., 2015, DOI: 10.1039/C5OB01070E.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/obc

Organic & Biomolecular Chemistry
Page 1 of 5Journal Name
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C5OB01070E
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTICLE TYPE
Metal and Base Free Synthesis of Primary Amines via ipso Amination of
Organoboronic Acids Mediated by [bis(trifluoroacetoxy)iodo]benzene
(PIFA)
Nachiketa Chatterjee and Avijit Goswami*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
primary aromatic amines are the metal mediated reductions of the
nitro compounds and treatment of metal amide in liquid ammonia
to the benzynes.1c,1d,4 Later on, transition metal catalyzed
45 amination of aryl halides with ammonia were achieved.5
However, these transformations have several drawbacks of their
own, such as, limited functional groups compatibility, use of
metal and harsh reaction conditions, the concomitant formation of
undesired diaryl amines and many often the requirement of costly
50 ligands. From the pharmaceutical point of view, metal free
processes are always preferred over metal promoted methods. In
this perspective, transition metal free protocols towards syntheses
of primary amines from organoboronic acids have been
documented using ArONH2/Cs2CO3,6 MeONH2.HCl/n-BuLi7 and
55 HSO3ONH2/NaOH8 as the aminating agents (Scheme 1).
A metal and base free synthesis of primary amine has been
developed at ambient temperature through ipso amination of
diversely functionalized organoboronic acids, employing a
10 combination of [bis(trifluoroacetoxy)iodo]benzene (PIFA) –
N-Bromosuccinimide (NBS) and methoxyamine
hydrochloride as the aminating reagent. The amines were
primarily obtained as their trifluoroacetate salts which on
subsequent aqueous alkaline work up provided the
15 corresponding free amines. The combination of PIFA-NBS is
found to be the mildest choice compared to the commonly
used strong bases (e.g. n-BuLi, Cs2CO3) for activating the
aminating agent. The reaction is expected to proceed via
activation of the aminating reagent followed by B-N 1,2- aryl
20 migration.
Previous work:
Amines, both aromatic and aliphatic, are ubiquitous in various
natural products, pharmaceuticals, agrochemicals and dyes.1 As a
result, these compounds have significant applications in the
25 pharmaceutical industry and medicinal chemistry (Figure 1).2
Therefore, developing novel methodologies to access variedly
functionalized aromatic and aliphatic amines always have a great
research importance.
reaction
conditions
R-B(OH)2
reaction conditions
1. C6H3(NO2)2ONH2/Cs2CO3; 50 0C, 24-48 h; ref.6
2. MeONH2.HCl/n-BuLi; -78 0C - 60 0C, 12 h; ref.7
3. HSO3ONH2/NaOH ; RT, 16 h; ref.8
R-NH2
NH2
NH2
H3CO
This work:
reaction
conditions
N
H3CO
R-B(OH)2
R-NH2
Matrix for Glycopeptides,
Carbohydrates, and Phosphopeptides2a
OCH3
mescaline
hallucinogenic2b
reaction conditions
PIFA/NBS/MeONH2.HCl; RT, 2-3 h
F3C
NH2
Scheme 1 Transition metal free syntheses of primary amines
from organoboronic acids
EtO2C
NH2
60
benzocaine
a topical anesthetic2d
helps in biosynthesis of DNA in the
liver, kidney, thymus and spleen of rats2c
In spite of the novelties associated with these protocols, these
methods suffer from certain drawbacks. In the presence of
aminating reagent HSO3ONH2 or excess amount of very strong
base like n-BuLi, the functional groups like carbonyls, nitriles
65 and esters could not be expected to tolerate the reaction
conditions9 and this phenomenon imposes a limitation to the
functional group compatibility of these protocols. Furthermore,
no documentation has been made in the above mentioned
literature for amination of the N-heteroarylboronic acids.
30 Figure 1 Selected bio-active primary amines
In this context, it is needless to say that over the recent decades,
significant advancements have taken place in the field of
syntheses of secondary and tertiary anilines starting from
35 palladium catalyzed Buchwald-Hartwig coupling of aryl halides
and cupper catalysed Chan-Lam coupling of arylboronic
acids/esters.3 In spite of such notable progress in the
methodologies for syntheses of N-substituted arylamines, much
less attention has been drawn towards the development of
40 advanced protocols for facile syntheses of primary amines under
mild reaction conditions. The traditional approach to prepare the
70 In the present work, attention has been devoted to overcome
these problems by using easily available aminating reagent
MeONH2.HCl without using a base so that a wide range of
functional groups could tolerate the reaction conditions. In this
connection, it is mention worthy that our group has reported a
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 5
View Article Online
DOI: 10.1039/C5OB01070E
novel methodology for ipso nitration10 of organoboronic acids
where the combination of PIFA11 and NBS is anticipated to
produce a succinimidyl radical which could be used as an 35 Bromophenlylboronic acid (1b), taken as the model substrate for
The primary investigations were carried out with 4-
effective as well as milder proton scavenger compared to a base,
required to activate the aminating reagent for the amination
reaction to take place. With this idea from our earlier work, we
obtaining 4-bromoaniline (2b). An initial screening of the
organo-hypervalent iodine species disclosed that the reagents I
and II were unable to provide the desired arylamines regardless
of the presence or absence of NBS as additive, whereas, the
5
herein report
a facile PIFA-NBS mediated regioselective
amination of aryl-, N-heteroaryl- and alkylboronic acids by using 40 hypervalent iodine (III) was successful to promote the reaction
easily available methoxyamine hydrochloride (MeONH2.HCl) as
10 the aminating reagent. To the best of our knowledge, it is the first
example of using novel combination of PIFA-NBS-
MeONH2.HCl to generate primary amines under base and metal
free conditions.
and the arylamines were obtained in high yield in the presence of
NBS as an additive (Figure 2).
a
Table 1 represents the optimization results of PIFA-NBS
mediated ipso amination of organoboronic acids in open air under
45 ambient temperature. Early experiments confirmed that for the
reaction to be successful, the presence of both PIFA and NBS are
essential (entries 1 and 2). The optimization process revealed that
complete conversion of 1b to its corresponding trifluoroacetate
salt took place when 2.0 eq. of PIFA and NBS were employed
50 using acetonitrile as solvent (entries 3-5). Dichloromethane and
ethanol were examined as solvent for the said reaction. In
F3COCO
OCOCF3
HO
OTs
AcO
OAc
I
I
I
I
III
(87%)b
II
(0%)a
dichloromethane amination was found to occur in
a
(0%)a
15
comparatively lower yield (entry 6) whereas, in ethanol no
amination was found to take place (entry 7). No significant
55 change in the reaction outcome was noticed while performing the
reaction under inert environment (entry 8).
Keeping the optimized reaction conditions in mind, the
investigations were further explored to other substrates in order to
figure out the substrate scope of this methodology and the results
60 are documented in Scheme 2.
ano amination took place with these reagents; b isolated yield
Figure 2 Different organohypervalent iodine reagents employed
for the amination reaction
20
Table 1 Optimization of reaction conditionsa
B(OH)2
NH2.CF3CO2H
NH2
PhI(OCOCF3)2 - NBS
MeONH2.HClb
aq. NaOH
1.
PhI(OCOCF3)2 - NBS
MeONH2.HCl
CH3CN, rt, 2 h
a
Ar'-B(OH)2
Ar'-NH2
Br
1b
Br
2b
Br
CH3CN, rt, 2-3 h
1
(Ar' = aryl, N-heteroaryl)
2
2b'
2. aq. NaOH
entry
eq. of
PIFA
eq. of
solvent
yield
NBS as an
additive
-
(%)c
n.rd
n.re
49
NH2
NH2
NH2
NH2
Cl
Cl
1
2
3
3.0
-
CH3CN
CH3CN
CH3CN
Br
F
2d (84%)
2c (71%)
NH2
2a (78%)
NH2
2b (87%)
3.0
1.0
NH2
CH3
NH2
H3C
I
2e (80%)
1.0
H3C
2h (82%)
2g (74%)
2f (78%)
NH2
NH2
NH2
NH2
NH2
4
5
2.0
2.0
1.0
2.0
CH3CN
CH3CN
66
87f
MeO2C
NC
H3CO
OCH3
2i (79%)
2l (77%)
2j (86%)
2k (75%)
6
7
8
7
8
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
CH2Cl2
THF
69
64
NH2
NH2
NH2
H3COC
F3C
O2N
2o (66%)
2n (78%)
2p (82%)
2m (73%)
NH2
CHCl3
EtOH
67
NH2
n.rd
85g
N
N
NH2
N
2s (74%)b
2q (83%)b
2r (78%)b
CH3CN
65 areaction conditions: 1 (2.0 mmol), PhI(OCOCF3)2 (4.0 mmol),
MeONH2.HCl (2.0 mmol), NBS (4.0 mmol), CH3CN (6 mL), rt, 2-3
b
h, open air; the reactions with 1q, 1r and 1s were carried out in 3.0
mmol scale
aoptimized reaction conditions: 1b (2.0 mmol, 1.0 eq.),
PhI(OCOCF3)2 (4.0 mmol, 2.0 eq.), MeONH2HCl (2.0 mmol, 1.0
b
25 eq.), NBS (4.0 mmol, 2.0 eq.), CH3CN (6 mL), rt, 2 h, open air; all
optimization reactions were carried out with 2.0 mmol of
MeONH2.HCl; cisolated yield of 2b; no amination took place by
d
70 Scheme 2 PIFA Mediated ipso-Amination of Arylboronic Acids
stirring the reaction mixture for 24 h at room temperature; eno
amination was observed; however, bromination took place on
Employing this methodology, variedly functionalized arylboronic
acids were efficiently transformed to their corresponding amines
which demonstrated the excellent functional group (e.g. halide,
75 nitro, ester, keto and nitrile) compatibility of the protocol. The
0
30 heating the mixture at 60 C for 4 h; these reaction conditions were
f
g
taken as optimized reaction conditions; the reaction was carried out
under argon atmosphere
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 5
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C5OB01070E
arylboronicacids with a wide range of substitution in the ortho-, with NBS, in a radical pathway, to form N-aminosuccinimide (7)
meta- and para position were successfully converted to the 55 which then reacted with arylboronic acid in the same fashion as
corresponding arylamines indicating the negligible steric (2e, 2f
and 2i) and electronic effect (2j-2n) on the reaction outcome.
However, with fluorinated arylboronic acids, the amination was
found to undergo in lower yield (2c and 2o). It was delightful to
find that using the optimized reaction conditions, N-hetero-
arylboronic acids are also conveniently transformed to their
corresponding amines (2q, 2r and 2s) in excellent yields which
proposed by Petasis et al. for bromination of organoboronic
acids/esters by NBS.13
O
O
5
1. NH2NHCO2CMe3
CHCl3, reflux, 3 h
1b
N
NH2
O
2b
CH3CN, rt, 24 h
2. dry HCl in Et2O
then aq. NaOH
O
O
6
7
10 were not possible to synthesize through the previously mentioned
reported protocols for synthesizing primary amines from
organoboronic acids. On the other hand, aryl- and
heteroboronates were not found to undergo amination under this
reaction conditions.
Scheme 5 Preparation of N-aminoosuccinimide (7) and its
60 reaction with 1b
However, in
a separate reaction performed at ambient
temperature with NBS and MeONH2.HCl in the presence of
PIFA, formation of 7 was not observed in GC-MS analysis of the
65 crude reaction mixture. Furthermore, 4-bromoaniline (2b) was
not obtained when 4-bromophenylboronic acid (1b) was allowed
to react with 7, synthesized separately following the reported
literature procedure (Scheme 5).14 Thus, this pathway could also
be eliminated.
15
1.
PhI(OCOCF3)2 - NBS
MeONH2.HCl
R-B(OH)2
R-NH2
CH3CN, rt, 3 h
2. aq. NaOH
4
3
NH2
NH2
NH2
NH2
70
Br
4d (70%)
4a (65%)
4b (76%)
4c (78%)
reaction conditions: 3 (3.0 mmol), PhI(OCOCF3)2 (6.0 mmol),
MeONH2.HCl (3.0 mmol), NBS (6.0 mmol), CH3CN (6 mL), rt, 3 h,
20 open air
N
O
O
O
Ph
PhI(OCOCF3)2
N
I
OCOCF3
O
F3CCO2Br
F3CCO2H + Br2
Scheme 3 PIFA Mediated ipso-Amination of Alkylboronic Acids
PhI
O
To further explore the spectrum of this protocol, the alkylboronic
25 acids were also employed for amination reactions (Scheme 3).
Greatly, through this newly developed protocol, primary aliphatic
amines (4a-d) were successfully synthesized in high yields.
There might be three probable mechanistic rationales for this
ipso amination reaction of the organoboronic acid to happen. It
30 was hypothesised that if in the presence of the combination of
PIFA-NBS, methoxyamine hydrochloride and arylboronic acid
could produce the MeONH and an aryl radical respectively, then
these two radicals (aryl and MeONH) might combine to provide
arylamines in a single pot. Therefore, in order to be confirmed for
35 the radial mechanistic pathway, radical scavenging experiment
with TEMPO was performed.12 It was observed in the presence of
TEMPO, no amination took place at ambient temperature after 3
h which clearly confirms the radical pathway for this amination
reaction of the organoboronic acids.
MeONH2.HCl
Cl2
+
MeONH2
O
N
ArB(OH)2
O
H
H
N
O
N
O
N
H
H
N
H
H
HO
HO
HO
O
OMe
OMe
B
B
HO
Ar
Ar
CF3CO2H
Ar-NH2.CF3CO2H
Ar-NHB(OH)2
Scheme 6 Tentative reaction pathway
As the reaction is occurring in the absence of a base and having a
75 radical nature, the third possibility of PIFA-NBS mediated
activation of the aminatig reagent via a radical pathway followed
by B-N 1,2- aryl migration sounds logical for the reaction to
proceed. Based on the above mentioned experimental facts, it
could be speculated that PIFA readily reacts with NBS to
80 generate a succinimidyl radical10 along with generation of
trifluoroacetic acid and evolution of bromine gas. The
succinimdyl radical is expected to activate the aminating reagent
by abstracting the proton10 of the associated HCl molecule,
leaving behind the chlorine radical to go out as chlorine gas.
85 Then, nucleophilic attack of the activated methoxyamine takes
place to the boron centre of organoboronic acid to provide the
tetracoordinated boronate species. Finally, amine salts are
produced via intermolecular B-N 1,2-aryl migration from the
tetracordinated boronate species (Scheme 6).
40
B(OH)2
PIFA (3.0 eq)
NBS (2.0 eq.)
Br
Br
CH3CN
argon
5
Br
1b
R
Scheme 4 Reactions of 1b with PIFA-NBS in attempted
syntheses of biaryls
45 On the other hand, in a separate reaction, the arylboronic acid 1b
when applied to react with PIFA and NBS (Scheme 4) did not
afford any biaryl compound (5) which suggests that aryl radical is
not getting formed in the course of the reaction. Hence the
combination of aryl radical and metoxyamine radical for the
50 generation of the arylamines might be ruled out, although a
radical nature of the reaction pathway is being indicated.
90 Afterwards, the amination reaction was performed on a gram
scale to understand its practicality (Scheme 7). When 1b and 1k
were subjected for primary amination on a 10.0 mmol scale, the
corresponding primary amines were obtained in comparable
Second probable reaction pathway might be such that in the
presence of PIFA, methoxyamine hydrochloride could combine
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 5
View Article Online
DOI: 10.1039/C5OB01070E
yields as obtained on the low scale experiments demonstrating
the practical applicability of the protocol.
iodobenzene and other less polar impurities. The solid was then
dissolved to its optimum extent in minimum volume of water.
60 The solution was made completely alkaline with saturated aq.
NaOH solution under cold condition and the aq. solution was
extracted with ethyl acetate (5×20 mL). The combined organic
phase was washed with distilled water (3×7 mL) and was dried
over Na2SO4. After evaporating the solvent, the residue was
65 purified by column chromatography over silica gel using
pentane/ether as eluent to provide the pure target products (2/4).
B(OH)2
NH2
PhI(OCOCF3)2/NBS
MeONH2.HCl
CH3CN, rt, 3 h
aq. NaOH
R
R
R = Br (2b); 81%
= CN (2k); 71%
R = Br (1b)
= CN (1k)
1
Aniline (2a): pale yellow liquid (78%, 145.1 mg); H NMR (400
5
reaction conditions: 1b (2.0 g, 10.0 mmol)/1k (1.47 g, 10 mmol)
PhI(OCOCF3)2 (20.0 mmol), MeONH2.HCl (10.0 mmol), NBS (20.0
mmol), CH3CN (20 mL), rt, 3 h, open air
MHz, CDCl3): δ 7.19-7.23 (m, 2H), 6.80-6.84 (m, 1H), 6.71-6.73
70 (m, 2H), 3.58 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 146.3,
129.3, 118.3, 115.2.
4-Bromoaniline (2b): off-white solid (87%, 299.2 mg); 1H NMR
(400 MHz, CDCl3): δ 7.23 (dd, J = 6.8 Hz, 1.8 Hz, 2H), 6.55 (dd,
J = 6.4Hz, 2.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 145.3,
75 132.1, 116.8, 110.1.
Scheme 7 PIFA Mediated ipso-amination of arylboronic acids on
10 gram-scale
In conclusion, we have developed a novel metal and base free
methodology for synthesising primary amines via ipso amination
of organoboronic acids using a combination of PIFA-NBS and
15 MeONH2.HCl as the aminating agent. The method is applicable
for aryl-, heteroaryl-, and alkylboronic acids and produces amino
compounds at ambient temperature in significantly less reaction
time. The reaction conditions employed in the protocol show a
wide range of functional groups tolerance especially to the
20 carbonyl, nitrile ester and halogen which are hard to synthesise
through some of the previously reported methods. The simplicity,
use of easily available inexpensive reagents and the utilization of
PIFA-NBS combination, as a milder alternative to a base as
1
4-Fluoroaniline (2c): light brown liquid (71%, 157.6 mg); H
NMR (400 MHz, CDCl3): δ 6.83-6.87 (m, 2H), 6.59-6.63 (m,
2H), 3.45 (s, br, 1H); 13C NMR (100 MHz, CDCl3): δ 157.6,
155.3, 142.4, 116.2, 116.1, 115.8, 115.6.
1
80 3,4-Dichloroaniline (2d): grey solid (84%, 272.2 mg); H NMR
(400 MHz, CDCl3): δ 7.16 (d, J = 8.7 Hz, 1H), 6.75 (d, J = 2.8
Hz, 1H), 6.48-6.51 (m, 1H), 3.71 (s, br, 1H); 13C NMR (100
MHz, CDCl3): δ 146.1, 132.7, 130.6, 121.2, 116.9, 114.9.
1
2-Iodoaniline (2e): brownish solid (80%, 350.4 mg); H NMR
85 (400 MHz, CDCl3): δ 7.63 (dd, J = 8.2 Hz, 1.4Hz, 1H), 7.13 (dt, J
= 7.3 Hz, 1.8 Hz, 1H), 6.75 (dd, J = 8.2 Hz, 1.8 Hz, 1H), 6.47 (dt,
J = 8.2 Hz, 1.8 Hz, 1H) 4.08 (s, br, 2H); 13C NMR (100 MHz,
CDCl3): δ 146.8, 139.2, 129.4, 119.6, 114.5, 84.2.
proton scavenger, are the remarkable features of this method
.
25
1
2-Methylaniline (2f): pale yellow liquid (78%, 166.9 mg); H
90 NMR (400 MHz, CDCl3): δ 7.07-7.10 (m, 2H), 6.76 (t, J = 7.4
Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 3.61 (s, 3H), 3.96 (s, br, 1H),
2.20 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 144.9, 131.2, 127.0,
121.8, 118.6, 114.6, 17.4.
Experimental
General experimental section
1
3-Methylaniline (2g): light yellow liquid (74%, 158.4 mg); H
30
95 NMR (400 MHz, CDCl3): δ 7.08 (t, J = 7.8 Hz, 1H), 6.62 (d, J =
7.8 Hz, 1H), 6.52-6.54 (m, 2H), 3.54 (s, 2H), 2.30 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 146.2, 139.1, 129.0, 119.5, 116.0,
112.3, 21.8.
Chemicals and reagents were purchased from commercial
suppliers and used without further purification. Anhydrous
solvent (CH3CN) used in the reactions was dried and freshly
distilled before use. Thin layer chromatography (TLC) was
1
4-Methylaniline (2h): off-white semi-solid (82%, 175.5 mg); H
35 performed using pre-coated plates purchased from E. Merck
(silica gel 60 PF254, 0.25 mm). Column chromatography was
performed using E. Merck silica gel 60 (100–200 mesh). GC-MS
analyses were carried out on SHIMADZU GCMS-QP Ultra
2010 instrument. NMR spectra were recorded in CDCl3, on
40 JEOL JNM-ECS spectrometer at operating frequencies of 400
MHz (1H) or 100 MHz (13C) as indicated in the individual
spectrum. Chemical shifts (δ) are given in ppm relative to
residual solvent (chloroform, δ= 7.26 for 1H and 77.16 for
proton decoupled 13C NMR) and coupling constants (J) in Hz.
45 Multiplicity is tabulated as s for singlet, d for doublet, t for
triplet, q for quartet, dd for doublet of doublet, dt for doublet of
triplet and m for multiplet.
100 NMR (400 MHz, CDCl3): δ 6.97-6.99 (m, 2H), 6.61-6.64 (m,
2H), 3.39 (s, br, 2H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 143.9, 129.8, 127.9, 115.3, 20.5.
1
2-Methoxyaniline (2i): light yellow liquid (79%, 194.3 mg);. H
NMR (400 MHz, CDCl3): δ 6.73-6.83 (m, 4H), 3.86 (s, 3H), 3.69
105 (s, br, 2H); 13C NMR (100 MHz, CDCl3): δ 147.3, 136.1, 121.2,
118.2, 115.3, 110.4, 55.4.
4-Methoxyaniline (2j): off-white solid (86%, 211.6 mg); 1H
NMR (400 MHz, CDCl3): δ 6.75 (dd, J = 8.6 Hz, 2.3 Hz, 2H),
6.65 (dd, J = 8.7 Hz, 2.3 Hz, 2H), 3.74 (s, 3H), 3.19 (s, br, 2H);
110 13C NMR (100 MHz, CDCl3): δ 152.9, 139.8, 116.5, 114.7, 55.7.
1
4-cyanoaniline (2k): pale yellowish solid (75%, 177.0 mg); H
NMR (400 MHz, CDCl3): δ 7.40 (dd, J = 8.7 Hz, 1.8 Hz, 2H),
6.64 (dd, J = 8.6 Hz, 2.3 Hz, 2H), 4.17 (s, br, 2H); 13C NMR (100
MHz, CDCl3): δ 150.5, 133.9, 120.1, 114.5, 100.1.
General procedure for syntheses of the amino compounds:
50
115 Ethyl 4-aminobenzoate (2l): off-white solid (77%, 232.6 mg);
1H NMR (400 MHz, CDCl3): δ 7.85 (dd, J = 8.7 Hz, 2.3 Hz, 2H),
6.63 (dd, J = 8.7 Hz, 2.3 Hz, 2H), 4.31 (q, 2H), 4.05 (s, br, 2H);
13C NMR (100 MHz, CDCl3): δ 166.6, 150.7, 131.6, 120.1,
113.9, 60.1, 14.8.
120 4-nitroaniline (2m): brown solid (73%, 201.5 mg); 1H NMR
(400 MHz, CDCl3): δ 8.06 (d, J = 8.7 Hz, 2H), 6.62 (d, J = 9.2
To a stirred solution of appropriate boronic acids (1/ 3, 2.0
mmol/3.0 mmol, 1.0 eq.), PIFA (4.0 mmol/6.0 mmol, 2.0 eq.) and
NBS (4.0 mmol/6.0 mmol, 2.0 eq.) in CH3CN (6 mL),
MeONH2.HCl (2.0 mmol/3.0 mmol, 1.0 eq.) were added and the
55 mixture was stirred for 2-3 h. After completion of the reaction
(checked by TLC), the mixture was concentrated under vacuum.
The solid mass was washed with dry hexane to remove the
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 5
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C5OB01070E
Hz, 2H), 4.39 (s, br, 2H); 13C NMR (100 MHz, CDCl3): δ 152.4,
126.3, 122.0, 113.4.
3-Aminoacetophenone (2n): brownish solid (78%, 210.6 mg);
1H NMR (400 MHz, CDCl3): δ 7.24-7.26 (m, 1H), 7.14-7.19 (m,
2H), 6.78-6.81 (m, 1H), 3.66 (s, br, 2H), 2.49 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 198.9, 146.8, 138.1, 129.5, 119.9, 119.0,
113.8, 26.8.
1 (a) B. Schlummer and U. Scholz, Adv. Synth. Catal. 2004, 346, 1599;
(b) D. S. Surry and S. L. Buchwald, Angew. Chem. Int. Ed. 2008, 47,
65 6338; (c) S. A. Lawrence, Ed. Amines: Synthesis, Properties, and
Applications; Cambridge University Press: Cambridge, 2004; (d) Z.
Rappoport, Ed. The Chemistry of Anilines, Parts 1 and 2; John Wiley &
Sons: New York, 2007; (e) S. Tasler and B. H. Lipshutz,. J. Org. Chem.
2003, 68, 1190; (f) A. Ricci, Ed. Amino Group Chemistry: From
70 Synthesis to Life Sciences; wiley-VCH: Weinheim, 2008.
5
3-Trifluoromethylaniline (2o): light yellow liquid (66%, 212.5
1
mg); H NMR (400 MHz, CDCl3): 7.15 (t, J = 7.8 Hz, 1H), 6.90
2 (a) F. Yuko, F. Natsumi, T. Kohei, H. Yusaku, N. Takashi, K. Kaoru, K.
Shinichirou, I. Shinichi and T. Koichi, Analytical Chemistry,
2014, 86, 1937; (b) D. Crosby and J. McLaughlin, Lloydia, 1973, 36, 416;
(c) J. Seifert, H. Mostecka and G.F. Kolar, Toxicology, 1993, 83, 49; (d)
75 P. Demare and I. J. Regla, Chem. Educ. 2012, 89, 147.
10 (d, J = 7.8 Hz, 1H), 6.79 (m, 1H), 6.70-6.73 (m, 1H), 3.66 (s, br,
2H); 13C NMR (100 MHz, CDCl3): δ 146.7, 131.7, 131.5, 131.1,
129,8, 128.3, 125.6, 122.9, 118.0, 115.1, 115.0, 111.4, 111.3.
3 (a) J. P. Wolfe, S. Wagaw, J. F. Marcoux and S. L. Buchwald Acc.
Chem. Res. 1998, 31, 805; (b) J. F. Hartwig. Acc. Chem. Res. 2008, 41,
1534; (c) J. F. Hartwig, In Handbook of Organopalldium Chemistry for
Organic Synthesis; Wiely-interscience: New York, 2002; (d) S. L.
80 Buchwald and D. S. Surry, Chem. Sci. 2011, 2, 27; (e) J. X. Qiao and P.
Y. S. Lam, In Boronic Acids - Preparation and Applications in Organic
synthesis and Medicine, 2nd ed.; (f) J. X. Qiao and P. Y. S. Lam,
1
1-Aminonapthaline (2p): grey solid (82%, 234.5 mg); H NMR
(400 MHz, CDCl3): 7.81-7.84 (m, 2H), 7.46-7.48 (m, 2H), 7.29-
15 7.35 (m, 2H), 6.80 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 142.1, 134.4, 128.6, 126.4, 125.9, 124.9, 123.7, 120.8,
119.0, 109.7.
1
2-Aminopyridine (2q): light yellow solid (83%, 234.1 mg); H
Synthesis, 2011, 829; (g) T. D. Quach and R. A. Batey, Org. Lett. 2003,
4397; (h) S. S. Bhojgude, T. Kaicharla and A. T. Biju, Org. Lett. 2013,
85 15, 5452. (i) D. E. Olson, Mini-Rev. Org. Chem. 2011, , 341.
4 (a) T. Mallat, A. Baiker, W. Kleist and K. Koehler, Handb. Heterog.
Catal. 2nd ed. 2008,
, 3548; (b) H. U. Blaser, H. Steiner and M. Studer,
5,
NMR (400 MHz, CDCl3): 8.03-8.05 (m, 1H), 7.37-7.46 (m, 1H),
20 6.59-6.62 (m, 1H), 6.46 (d, J = 8.2 Hz, 1H), 4.52 (s, br, 2H); 13C
NMR (100 MHz, CDCl3): δ 158.2, 148.1, 137.8, 114.0, 108.2.
8
1
4-Aminopyridine (2r): white solid (78%, 219.9 mg); H NMR
7
(400 MHz, CDCl3): δ 8.20 (dd, J = 6.4 Hz, 1.4 Hz, 2H), 6.51 (dd,
J = 6.4 Hz, 1.4 Hz, 2H), 4.14 (s, br, 2H); 13C NMR (100 MHz,
25 CDCl3): δ 152.7, 150.4, 109.7.
ChemcatChem, 2009, 1, 210.
5 (a) H. Rao, H. Fu, Y. Jiang and Y. Zhao, Angew. Chem. Int. Ed. 2009,
90 48, 1114; (b) J. L. Klinkenberg and J. F. Hartwig, Angew. Chem. Int. Ed.
2011, 50, 86; (c) , H. Rao and H. Fu, Synlett, 2011, 745; (d) C. W.
Cheung, D. S. Surry and S. L. Buchwald, Org. Lett. 2015, 15, 3734.
6 C. Zhu, G. Li, D. H. Ess, J. R. Falck and L. Kurti, J. Am. Chem. Soc.
2012, 134, 18253.
1
3-Aminoquinoline (2s): brownish solid (74%, 319.7mg);. H
NMR (400 MHz, CDCl3): δ 8.49 (s, 1H), 7.94-7.96 (m, 1H),
7.55-7.58 (m, 1H), 7.39-7.44 (m, 2H), 7.21 (m, 1H), 3.65 (s, br,
2H); 13C NMR (100 MHz, CDCl3): δ 143.1, 142.6, 139.9, 129.2,
30 128.9, 127.0, 125.9, 125.7, 115.1.
95 7 S, C. Mlynarski, A. S. Karns and J. P. Morken, J. Am. Chem. Soc. 2012,
134, 16449.
1
Hexylamine (4a): light yellow liquid (65%, 196.9 mg); H NMR
8 S. Voth, J. W. Hollet and J. A. McCubbin, J. Org. Chem. 2015, 80
2545.
9 (a) J. K. Sanford, F. T. Blair, J. Arroya and K. W. Sherk, J. Am. Chem.
100 Soc., 1945, 67, 1941; (b) A. Citterio, A. Gentile, F. Minisci,
M. Serravalle and S. J. Ventura, Org. Chem. 1984, 49, 3364; D. G. Hall,
Ed.; Wiley-VCH: Weinheim, 2011.
,
(400 MHz, CDCl3): δ 2.64 (t, J = 7.3 Hz, 2H), 1.36-1.41 (m, 2H),
1.21-1.31 (m, 6H), 1.16 (s, br, 2H), 0.85 (t, J = 6.9 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 42.3, 39.9, 31.6, 26.4, 22.7, 14.0.
35 Benzylamine (4b): light yellow liquid (76%, 244.0 mg); 1H
NMR (400 MHz, CDCl3): δ 7.14-7.27 (m, 5H), 3.77 (s, 2H), 1.43
(s, 2H); 13C NMR (100 MHz, CDCl3): δ 143.2, 128.5, 127.1,
126.8, 46.5.
10 N. Chatterjee, D. Bhatt and A. Goswami, Org. Biomol. Chem. 2015,
13, 4828.
105 11 For other organo-hypervalent iodine promoted functionalization of
organic compounds: (a) N. Chatterjee, H. Chowdhury, K. Sneh and A.
Goswami, Tetrahedron Lett. 2015, 56, 172; (b) N. Chatterjee and A.
Goswami, Tetrahedron Lett. 2015, 56, 1524; for other functionalization of
organic compounds mediated by organic hypervalentiodine reagent see:
2-Phenylethylamine (4c): light brown liquid (78%, 283.1 mg);.
40 1H NMR (400 MHz, CDCl3): δ 7.28-7.32 (m, 2H), 7.19-7.23 (m,
3H), 2.96 (t, J = 6.9 Hz, 2H), 2.74 (t, J = 6.9 Hz, 2H), 1.24 (s, br,
2H); 13C NMR (100 MHz, CDCl3): δ 139.8, 128.9, 128.4, 126.0,
43.8, 40.0.
110 (a) V. V. Zhdankin
Structure and Synthetic Applications of Polyvalent Iodine Compounds
,
Hypervalent Iodine Chemistry: Preparation,
,
1
Cyclohexylamine (4d): colourless liquid (70%, 207.9 mg); H
John Wiley & Sons Ltd, 2014; (b) J. P. Brand and J. Waser, Chem Soc
Rev. 2012, 41, 4165; (c) M. Arisawa, S. Utsumi, M. Nakajima, N. G.
Ramesh, H. Tohma and Y. Kita, Chem. Commun. 1999, 469; (d) T. Dohi,
45 NMR (400 MHz, CDCl3): δ 2.53-2.60 (m, 1H), 1.74-1.78 (m,
2H), 1.63-1.68 (m, 2H), 1.52-1.57 (m, 1H), 1.34 (s, br, 2H), 0.94-
1.26 (m,6H); 13C NMR (100 MHz, CDCl3): δ 50.5, 36.9, 25.7,
25.2.
115 K. Morimoto, Y. Kiyono, H. Tohma and Y. Kita, Org. Lett. 2004,
(e) V. V. Zhdankin and P. Stang, Chem. Rev. 2008, 108, 5299; (f) D. Q.
Dong, S.H. Hao, Z. L. Wang and C. Chen, Org. Biomol. Chem. 2014, 12
7, 537;
,
4278; (g) K. Kiyokawa, S. Yahata, T. Kojima and Minakata, S. Org. Lett.
2014, 16, 4646; (h) E. A. Merritt and B. Olofsson, Angew. Chem. Int. Ed.
120 2009, 48, 9052; for functional group transformation in the absesence of
organohypervalent iodine, see: i) A. K. Chakraborti and Shivani, J. Org.
50
Acknowledgements
Chem. 2006, 71, 5785; (j) S. Bhagat and A. K. Chakraborti, J. Org. Chem
.
We are grateful to DST, New Delhi, India for their generous
financial support and IIT Ropar for infrastructural facilities. NC
would like to thank IIT Ropar for his fellowship.
2007, 72, 1263; (k) A. K. Chakraborti, A. Basak and V. Grover, J. Org.
Chem. 1999, 64, 8014; (l) S. V. Chankeshwara, R. Chebolu and A. K.
125 Chakraborti, J. Org. Chem. 2008, 73, 8615; (m) G.Yan and M. Yang,
Org. Biomol. Chem. 2013, 11, 2554.
55 Notes and references
12 see ESI
13 N. A.; Petasis and I. A. Zavialov, Tetrahedron Lett. 1996, 37, 567.
14 J. G. Krause, S. Kwon and B. J. Geor, Org. Chem. 1972, 37, 2040.
130
Department of Chemistry, Indian Institute of Technology, Ropar (IIT
Ropar), Nangal Road, Rupnagar, Punjab 140001, India
Tel: +91-1881-242121; E-mail: agoswami@iitrpr.ac.in
60 †Electronic Supplementary Information (ESI) available: See
DOI: 10.1039/b000000x
135
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5