Deoxygenation of tertiary amine N-oxides under metal free condition using phenylboronic acid

Article abstract of DOI:10.1016/j.tetlet.2017.01.051

A simple and efficient method for the deoxygenation of amine N-oxides to corresponding amines is reported using the green and economical reagent phenylboronic acid. Deoxygenation of N,N-dialkylaniline N-oxides, trialkylamine N-oxides and pyridine N-oxides were achieved in good to excellent yields. The reduction susceptible functional groups such as ketone, amide, ester and nitro groups are well tolerated with phenylboronic acid during the deoxygenation process even at high temperature. In addition, an indirect method for identification and quantification of tert-amine N-oxide is demonstrated using UV–Vis spectrometry which may be useful for drug metabolism studies.

Full text of DOI:10.1016/j.tetlet.2017.01.051

Accepted Manuscript
Deoxygenation of tertiary amine N-oxides under metal free condition using
phenylboronic acid
Surabhi Gupta, Popuri Sureshbabu, Adesh Kumar Singh, Shahulhameed Sabiah,
Jeyakumar Kandasamy
PII:
S0040-4039(17)30073-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.01.051
TETL 48554
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
13 December 2016
14 January 2017
16 January 2017
Please cite this article as: Gupta, S., Sureshbabu, P., Kumar Singh, A., Sabiah, S., Kandasamy, J., Deoxygenation
of tertiary amine N-oxides under metal free condition using phenylboronic acid, Tetrahedron Letters (2017), doi:
http://dx.doi.org/10.1016/j.tetlet.2017.01.051
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Deoxygenation of tertiary amine N-oxides
under metal free condition using
phenylboronic acid
Surabhi Gupta,a Popuri Sureshbabu,b Adesh Kumar Singh,a Shahulhameed Sabiah,b Jeyakumar Kandasamya*
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1
Tetrahedron Letters
journal homepage: www.elsevier.com
Deoxygenation of tertiary amine N-oxides under metal free condition using
phenylboronic acid
Surabhi Gupta,a Popuri Sureshbabu,b Adesh Kumar Singh,a Shahulhameed Sabiah,b Jeyakumar Kandasamy∗
aDepartment of chemistry, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh-221005.b Department of Chemistry, Pondicherry University,
Pondicherry-605014
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and efficient method for the deoxygenation of amine N-oxides to corresponding amines
is reported using the green and economical reagent phenylboronic acid. Deoxygenation of N, N-
dialkylaniline N-oxides, trialkylamine N-oxides and pyridine N-oxides were achieved in good to
excellent yields. The reduction susceptible functional groups such as ketone, amide, ester and
nitro groups are well tolerated with phenylboronic acid during the deoxygenation process even at
high temperature. In addition, an indirect method for identification and quantification of tert-
amine N-oxide is demonstrated using UV-Vis spectrometry which may be useful for drug
metabolism studies.
Available online
Keywords:
Reduction
Amine-N-Oxides
Arylboronic acid
Phenols
@2009 Elsevier Ltd. All rights reserved.
Green Chemistry
———
∗Corresponding author. Tel.: +91- 0542-6702879; fax: +91- 0542-6702876; e-mail: jeyakumar.chy@iitbhu.ac.in

2
Tetrahedron Letters
Amine N-oxides have found wide application in synthetic organic
report phenylboronic acid as an efficient reagent for the
deoxygenation of tert-amine N-oxides under mild conditions.
At the outset, 4-bromo-N,N-dimethylaniline N-oxide (1a) was chosen
as a model substrate for reaction optimization while phenylboronic
acid was used as a deoxygenating reagent (Table 1). In order to
identify a suitable solvent, the deoxygenation reactions were carried
out in different protic and aprotic solvents at room temperature using
equimolar amount of substrate and the reagent (Table 1, entries 1-
11). The protic solvents such as methanol, ethanol, t-butanol and
water gave incomplete reactions even after prolonged reaction time
(Table 1, entries 1-5). In the case of polar aprotic solvents (Table 1,
entries 6-11), dichloromethane was found to be very efficient,
providing a quantitative yield of the desired tert-amine within 5
minutes (Table 1, entry 10). In addition, tetrahydrofuran, 2-methyl
tetrahydrofuran (2-MeTHF) as well as dichloroethane also showed
comparable efficiency to that of dichloromethane (Table 1, entries 6,
7 and 11) while toluene and acetonitrile were found to be inefficient
media (Table 1, entries 8 and 9).
chemistry as starting materials, intermediates, oxidants, ligands,
organo catalysts, directing groups, etc.1 Besides their chemical
importance, N-oxides have also received considerable attention in
the field of biology and medicine.2 Many findings suggest that N-
oxides play a key role in the metabolism of drugs.2b Moreover, the
chemistry of deoxygenation of amine N-oxides has attracted
significant interest not only in synthetic organic chemistry3 but also
in biology.4 Recently, fluorescent probes have been developed based
on deoxygenation of N-oxides for sensing metal and non-metal
species found in biological assays (Figure 1).4a-c In medicine, N-
oxides have been suggested as less toxic bio-reductive prodrugs for
anticancer drugs (i.e. DNA intercalators) that are selectively
deoxygenated to the active drug by metabolic reduction under
hypoxic conditions (Figure 2). 4d, 4e
Considering the importance of deoxygenation processes in chemical
and biological transformations, numerous deoxygenation methods
have been developed using various metal and metal free reagents
including Pd-C/HCOONH4,5 Zn/NH4Cl,6 CuI,7 ZrCl4/NaBH4,8
SmI2,9 In/NH4Cl,10 titanium compounds,11 sulfur reagents,12
phosphorus reagents,13 diboron compounds14, etc. The major
limitations of these existing protocols are the use of toxic metals or
expensive reagents or reagents that are difficult to handle (e.g.
unpleasant odor, fuming, flammable or hygroscopic), requirement of
harsh and dry reaction conditions, longer reaction times, functional
group incompatibilities, etc.
After identifying dichloromethane as
a suitable solvent, the
optimization was further continued by examining the deoxygenation
process with electron rich and electron deficient arylboronic acids as
well as alkylboronic acids as reducing agent (Table 1, entries 12-15).
4-Methoxyphenylboronic acid showed equal efficiency to that of
simple phenylboronic acid while 4-nitrophenylboronic acid took
slightly longer time for completion of the reaction (Table 1, entries
12 and 13). On the other hand, alkylboronic acids such as methyl and
n-butylboronic acid showed less efficiency than arylboronic acids in
the deoxygenation process, perhaps due to migratory aptitude of
alkyl groups17 (Table 1, entries 14 and 15). Overall, phenylboronic
acid was found to be superior among the different boronic acids used
in this study in terms of not only higher reactivity but also
availability and cost effectiveness. Moreover, phenylboronic acid
produces environmentally benign by-products such as boric acid and
phenol during the deoxygenation process which can be easily
removed by simple basic workup procedures.
Figure 1. Example of N-oxide deoxygenation promoted turn-on fluorescent
probe.
It is important to mention here that recently diboron compounds such
as bis(pinacolato)diboron [(pinB)2], bis(catecholato)diboron [(catB)2]
and tetrahydroxydiboron have been explored as deoxygenating
reagents for the amine N-oxides.14 Despite the efficiency of diboron
compounds, their high cost and limited availability reduce their use
in organic synthesis.15a, 18 Moreover, in the case of diboron reagents
two boron atoms are required to deoxygenate one oxygen atom,
while only one boron atom is utilized in the case of phenylboronic
acid. Nevertheless, being an economical reagent, phenylboronic acid
showed a comparable efficiency to that of diboron compounds in the
deoxygenation process. For example, the deoxygenation of N-oxide
1a was achieved in a quantitative yield within 5 minutes using
diboron compounds (Table 1, entries 16-18) as well as
phenylboronic acid (Table 1, entry 10) in dichloromethane at room
temperature.
Figure 2. Structures of N-oxide based anticancer prodrugs.
Therefore, the development of an efficient and convenient method
for the selective reduction of amine N-oxides using green reagents
will have high significance not only in synthetic organic chemistry
but also in biological science, for example, drug metabolism
studies.11c
Organoboron compounds are important reagents in synthetic organic
chemistry which enable many chemical transformations in an
efficient manner.15 Among the different subclasses of organoboron
compounds, arylboronic acids remain the most popular and
extensively used in organic synthesis as building blocks,
intermediates, reagents and catalysts.15a Properties such as low
toxicity, high stability (against air, moisture and temperature) and
good chemical reactivity as well as ease of handling and storing
make arylboronic acids a more attractive class of compounds in
organic synthesis. Our research group is mainly interested in
developing eco-friendly methods for the preparation of important
organic compounds.16 In fact, we have recently reported efficient and
green methods for the oxidation of arylboronic acids into phenols
using hydrogen peroxide derivatives.16b, 16c In this context, here we
Table 1: Optimization of reaction conditions.a

3
minutes (Table 3, entry 4a). In addition, various cyclic, acyclic and
benzylic N-oxides were also successfully converted to corresponding
amines in excellent yields (Table 3, entries 4b-4g).
Table 2: Deoxygenation of N,N-dialkylaniline N-oxides using
phenylboronic acid.a,b
aReaction condition: aniline N-oxide (1 mmol) and boronic acid (1 mmol)
stirred in different solvents at room temperature. bIsolated yield. c(pinB)2:
bis(pinacolato)diboron. d(catB)2: bis(catecholato)diboron.
With optimized conditions in hand, the deoxygenation of various
aniline N-oxides was studied with phenylboronic acid at room
temperature (Table 2). Un-substituted N,N-dialkylaniline N-oxides as
well as naphthylamine N-oxides have been successfully reduced to
corresponding amines in excellent yields within 10 mins (Table 2,
entries 2b-2e). Similarly, electron donating (e.g. methoxy and
methyl) and withdrawing groups (e.g. chlorine, bromine and nitro)
functionalized aniline N-oxides underwent deoxygenation smoothly
to provide the desired products in high yield (i.e. > 90%) at room
temperature (Table 2, entries 2f-2n). In fact, no significant electronic
effects were observed in the deoxygenation process with respect to
different substituents present on the aryl ring. Moreover, sterically
hindered (i.e. ortho substituted) dialkylaniline N-oxides as well as N-
benzyl and N-phenyl aniline N-oxides also underwent deoxygenation
with same efficiency like simple aniline N-oxides (Table 2, entries
2g, 2h, 2j and 2o-2r).
Having successful results in hand, we have further examined the
reduction of trialkylic (cyclic and acyclic) and benzylic N-oxides
under optimized condition (Table 3). Initially, the deoxygenation of
N-methylmorpholine N-oxide was performed with one equivalent of
phenylboronic acid at room temperature. However, the reaction was
found to be slow and the desired product was obtained only in 65%
yield after 12 h (Table 3, entry 4a). Thus, the reaction was performed
at 80 oC in 1,2-dichloroethane (DCE) using one equivalent of
phenylboronic acid. It is interesting to note that the deoxygenation of
N-methylmorpholine N-oxide proceeded efficiently and gave the
desired product (i.e. N-methylmorpholine) in 93% yield within 30
aReaction condition: aniline N-oxide (1 mmol) and phenylboronic acid (1
mmol) was stirred in dichloromethane at room temperature. Isolated yield.
b
The deoxygenation of heteroaromatic N-oxides (e.g. pyridine N-
oxide) has found wide scope in synthetic organic chemistry.3 Being
successful in the case of deoxygenation of aniline and alkyl N-
oxides, we have attempted the deoxygenation of pyridine and
quinoline N-oxides with phenylboronic acid (Table 4). The reaction
provided the desired products in good to excellent yields with 1.5
equivalents of phenylboronic acid, however at high temperature (i.e.
120 oC). Pyridine N-oxides with electron donating groups such as
2,6-dimethyl
and
4-(N,N-dimethylamino)pyridine
N-oxides
underwent smooth conversion with good yield (75-90%) in a short
span of time (Table 4, entries 6a and 6b). On the other hand, electron
deficient pyridine N-oxides such as 2-chloro, 4-acetyl, 3-amido and
2,6-dimethyl esters functionalized pyridine-N-oxides took slightly
longer reaction time and gave the desired products in moderate
yields (Table 4, entries 6c-6f). In addition, similar to pyridine N-
oxides, quinoline and iso-quinoline N-oxides underwent
deoxygenation in 80% and 70% yields, respectively (Table 4, entries
6g and 6h). The stability of different functional groups under
standard reaction conditions plays a major role in organic synthesis.
It is noteworthy that many reduction susceptible functional groups
such as ketone, amide, esters and nitro groups are well tolerated with
phenylboronic acid during the deoxygenation even at high

4
T
etra
h
edr
on
Let
ters
temperature (Table 2 and 4). Thus, phenylboronic acid can be
will be interesting to find an inexpensive method that requires simple
instrumentation for a quick identification and quantification of amine
N-oxides. In this context, we anticipated that a simple indirect
method for the detection of tert-amine N-oxides is possible in UV-
regarded as a chemo-selective reducing agent.
Table 3: Deoxygenation of trialkyl and benzylamine N-oxides with
phenylboronic acid.a,b
Vis spectrometry by using 4-nitrophenylboronic acid as
a
O
PhB(OH)2
N
deoxygenating reagent. Because, 4-nitrophenylboronic acid will
produce 4-nitrophenol as a by-product during the deoxygenation of
N-oxides and it is detectable even at a trace amount at 400 nm in
UV-Vis spectrometer.22,23 Based on the concentration of 4-
nitrophenol, tert-amine concentration can be easily calculated using
Beer-Lambert’s law which will provide a significant information
regarding the concentration of N-oxide. Moreover, other metabolites
like sulfoxides and C-hydroxylation products can be easily
distinguished from N-oxides since they are un-reactive with
arylboronic acids.
N
R
R''
R
DCE, 80 oC
R''
R'
R'
3a-g
4a-g
O
O
N
Bn
N
Me
N
N
Bn
Bn
C6H13
C6H13
Me
Et
4a
4b
4c
4d
(12 h, 65%)c
(30 mins, 92%)
(45 mins, 90%)
(90 mins, 85%)
(30 mins, 93%)
As a case study, the deoxygenation of aniline N-oxide 1a with 4-
nitrophenylboronic acid was carried out in acetonitrile at room
temperature (Scheme 1).24 The progress of the reaction was
monitored by using UV-Vis spectrometry in every 15 minutes and
observed spectra are summarized in Figure 3. The spectrum clearly
shows an increase in absorption intensity at 400 nm in Tris-HCl
buffer solution, which corresponds to the formation of 4-nitrophenol
(Figure 3). The rate of the reaction was calculated from absorbance
vs time plot and found to be 1.41×10-4 s-1 (See supporting
information Figure S1 b). The amount of p-nitrophenol (p-NP)
formation can be directly correlated with the amount of formation of
tert-amine from corresponding N-oxide.
Et
N
Me
N
Me
N
Bn
Bn
4e
4f
4g
(90 mins, 82%)
(15 mins, 95%)
(25 mins, 95%)
aReaction condition: trialkyl N-oxide (1 mmol) and phenylboronic acid (1
o
b
c
mmol) was stirred in dichloroethane at 80 C. Isolated yield. Reaction was
carried out at room temperature.
Amine functionalities were found in many drug molecules and play
an important role in exerting their biological activity.19 It is well
known that in Phase I metabolism, drugs undergo different chemical
modifications like oxidation, reduction or hydrolysis to make more
water soluble compounds that can be excreted by various
processes.20 In this context, N-oxides have been observed as one of
the major metabolites of tert-amine drugs.2b For example, clozapine
N-oxide is a major metabolite of anti-depressant drug clozapine.21
The identification and quantification of N-oxide metabolites can play
an important role in developing newer drugs with high potential and
low toxicity.20
N
OH
HO
OH
N
O
B
+
+
NO2
Br
NO2
Br
(by-product)
2a
1a
Tris HCl Buffer
(PH:8.4)
Table 4: Deoxygenation of heteroaromatic N-oxides with
phenylboronic acid.a,b
O2N
O
PhB(OH)2
R
R
N
DCE, 120 o
C
N
O
Scheme 1. Deoxygenation of N-oxide 1a with 4-nitrophenylboronic
5a-h
6a-h
acid.
NMe2
COCH3
N
N
N
N
Cl
6a
(6 h, 75%)
6b
6d
6c
(10 h, 90%)
(12 h, 65%)
(24 h, 61%)
CONH2
MeO2C
N
CO2Me
N
N
N
6h
6f
(18 h, 60%)
6e
(16 h, 62%)
6g
(8 h, 80%)
(18 h, 70%)
aReaction condition: N-oxide (1 mmol) and phenylboronic acid (1.5 mmol)
was stirred in dichloroethane at 120 oC. bIsolated yield.
Recently, Kulanthaivel et al. have demonstrated
a chemical
deoxygenation method suitable for drug metabolism studies.11c
Titanium trichloride (TiCl3) has been employed as a selective
deoxygenating reagent of amine N-oxide metabolites while the
reaction progress and analysis were performed using liquid
Figure 3. Spectral profile showing the increase of p-NP band at 400 nm with
respect to time. The reaction was carried out in acetonitrile and spectra were
measured in tris-HCl buffer solution with 15 min interval.
It
b
f
T bl 5 th t i l t d i ld f t
t
i

5
Chem. Commun., 2015, 51, 9507; (d) Bernier, D.;
UV experiment. For example, after 60 minutes the isolated yield was
about 34% while the calculated UV yield was 39% (Table 5, entry
1). Similarly, the yields obtained in various intervals, for example,
after two hours and three hours (in both isolated as well as UV-Vis
experiment) were found to be similar (Table 5, entries 2 and 3),
which confirms our preliminary assumption.
Wefelscheid, U. K.; Woodward, S. Org. Prep. Proced. Int.,
2009, 41, 173; (e) Derdau, V.; Laschat, S.; Hupe, E.; Konig, W.
A.; Dix, I.; Jones, P. G. Eur. J. Inorg. Chem., 1999, 1001. (f)
Zhu, C.; Wang, R.; Falck, J. R. Org. lett., 2012, 14, 3494; (g)
Vanrheenen, V.; Kelly, R.C.; Cha, D.Y Tetrahedron Lett. 1976,
17, 1973; (h) Ley, S.; Norman, J.; Griffith, W. P.; Marsden, S.
P. Synthesis, 1994, 639.
Table 5. Yield comparison between isolated and calculated from UV
for the deoxygenation reaction of 1a with 4-nitrophenylboronic acid.
2. (a) Bickel, M. H. Pharmacol. Rev., 1969, 21, 325; (b) Hlavica,
P.; Damani, L. A. N-Oxidation of Drugs: Biochemistry,
pharmacology, toxicology, Springer, 1991.
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50, 9291; (b) Sun, W.; Xie, Z. G.; Liu, J.; Wang, L. Org.
Biomol. Chem., 2015, 13, 4596; (c) Kianmehr, E.; Rezaeefard,
M.; Khalkhali, M. R.; Khan, K. M. Rsc Adv, 2014, 4, 13764; (d)
Youssif, S. Arkivoc, 2001, 242.
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Adv, 2014, 4, 30398; (b) Hirayama, T.; Okuda, K.; Nagasawa,
H.Chem. Sci., 2013, 4, 1250; (c) Niwa, M.; Hirayama, T.;
Okuda, K.; Nagasawa, H. Org. Biomol. Chem., 2014, 12, 6590;
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Denny, W. A.; Wilson, W. R. Biochem. Pharmacol., 2000, 60,
969; (e) Wilson, W. R.; Denny, W. A.; Pullen, S. M.;
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Gilmer, J. F. Molecules, 2008, 13, 519.
aYield was calculated using Beer-Lambert’s law (A= cl) (Refer supporting
information). bYield from batch reaction in 1.0 mmol scale.
A plausible mechanism for the deoxygenation of amine N-oxide is
shown in Scheme 2. At first, N-oxide attacks the electrophilic
aryl/alkylboronic acid and forms an unstable amino-borate complex
A.15a Further, the aryl/alkyl group migrates from boron to N-oxide
oxygen which results in formation of tert-amine and borate ester.
The unstable borate ester further undergoes degradation to boric acid
and alcohol in the presence of water.
5. Balicki, R. Synthesis, 1989, 645.
6. Aoyagi, Y.; Abe, T.; Ohta, A. Synthesis, 1997, 891.
7. Singh, S. K.; Reddy, A. S.; Mangle, M.; Ganesh, K. R.
Tetrahedron, 2007, 63, 126.
8. Chary, K. P.; Mohan, G. H.; Iyengar, D. S. Chem. Lett., 1999,
1339.
9. Handa, Y.; Inanaga, J.; Yamaguchi, M. J. Chem. Soc. Chem.
Comm., 1989, 298.
10. Yadav, J. S.; Reddy, B. V. S.; Reddy, M. M. Tetrahedron Lett.,
2000, 41, 2663.
11. (a) McCall, J. M.; TenBrink, R. E. Synthesis, 1975, 335; (b)
Kano, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis, 1980,
695; (c) Kulanthaivel, P.; Barbuch, R. J.; Davidson, R. S.; Yi,
P.; Rener, G. A.; Mattiuz, E. L.; Hadden, C. E.; Goodwin, L. A.;
Ehlhardt. W. J. Drug Metab. Dispos., 2004, 32, 966.
Scheme 2. Plausible mechanism for the deoxygenation of amine N-
oxides to corresponding amines.
12. (a) Daniher, F. A.; HackleyJr. B. E. J. Org. Chem., 1966, 31,
4267; (b) Bonini, B. F.; Maccagnani, G.; Mazzanti, G.; Pedrini,
P. Tetrahedron Lett., 1979, 20, 1799; (c) Olah, G. A.;
Arvanaghi, M.; Vankar, Y. D. Synthesis, 1980, 660.
13. (a) Lutz, W. B.; Lazarus, S.; Klutchko, S.; Meltzer, R. I. J. Org.
Chem., 1964, 29, 1645; (b) HowardJr., E.; Olszewski, W. F. J.
Am. Chem. Soc., 1959, 81, 1483.
14. (a) Kokatla, H. P.; Thomson, P. F.; Bae, S.; Doddi, V. R.;
Lakshman, M. K. J. Org. Chem., 2011, 76, 7842; (b) Gurram,
V.; Akula, H. K.; Garlapati, R.; Pottabathini, N.; Lakshman, M.
K. Adv. Synth. Catal., 2015, 357, 451.
15. (a) Hall, D. G. Boronic Acids: Preparation and Applications in
Organic Synthesis, Medicine and Materials (Volume 1 and 2),
Wiley-VCH Verlag GmbH & Co. KGaA, Second Edition, 2011;
(b) Fernández, E.; Whiting, A. Synthesis and Application of
Organoboron Compounds, Springer, New York, 2015.
16. (a) Chaudhary, P.; Gupta, S.; Muniyappan, N.; Sabiah, S.;
Kandasamy, J. Green Chem, 2016, 18, 2323; (b) Gupta, S.;
Chaudhary, P.; Srivastava, V.; Kandasamy, J. Tetrahedron Lett,
2016, 57, 2506; (c) Gupta, S.; Chaudhary, P.; Seva, L.; Sabiah,
S.; Kandasamy, J. Rsc Adv, 2015, 5, 89133; (d) Chaudhary, P.;
Gupta, S.; Sureshbabu, P.; Sabiah, S.; Kandasamy, J. Green
Chem., 2016, 18, 6215.
In conclusion, we have demonstrated a simple and efficient method
for the deoxygenation of amine N-oxides to corresponding amines
using the green and economical reagent phenylboronic acid. The
N,N-dialkylaniline N-oxides, trialkylamine N-oxides and pyridine N-
oxides underwent deoxygenation smoothly to provide the desired
amines in good to excellent yields. The reduction susceptible
functional groups such as ketone, amide, ester, nitro and arylhalides
are well tolerated with phenylboronic acid during the deoxygenation
process even at high temperature. An indirect method for
identification and quantification of tert-amine N-oxide in UV-Vis
spectrometry is demonstrated by using 4-nitrophenylboronic acid as
a deoxygenating reagent. We believe that this technique will be
useful for drug metabolism studies.
Acknowledgements
J. K. gratefully acknowledges DST for young scientist start-up
research grant (YSS/2014/000236). S. G acknowledges IIT (BHU)
for a research fellowship. J. K. thanks to Dr. K. Murugan and Mr.
Albert Pape for
a helpful discussion during the manuscript
preparation. J. K. thanks Central Instrumentation Facility Center
(CIFC)-IIT BHU for the NMR facilities. S.S and P.S acknowledge
17. As per mechanism (see Scheme 3), migration of aryl or alkyl
group is necessary to obtain the desired amine. In general
migration efficiency of alkyl groups are relatively less when
compare to aryl groups. We belive it may be a reason for less
reactivity of alkylboronic acid in the deoxygenation.
Pondicherry University for NMR and MASS facilities. P.
acknowledges CSIR for senior research fellowship (SRF). A. K. S
acknowledges CSIR for junior research fellowship (JRF).
S
References and Notes
18. Cost of the organoboron compounds in Sigma Aldrich:
Phenylboronic acid 50 g is 73 $; Bis(pinacolato)diboron
[(pinB)2] 5g is 101 $; Bis(catecholato)diboron [(catB)2] 5g is
481$; and Tetrahydroxydiboron 5g is 103 $.
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Beitia, J.; Chavez, G.; Ilie, C.; Arman, H. D.; Larionov, O. V.

6
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22. (a) Bowers, Jr. G. N.; McComb, R. B.; Christensen, R. C.;
Schaffer, R. Clin.Chem., 1980, 26, 724; (b) Biggs, A. I. Trans.
Faraday Soc., 1954, 50, 800.
23. Brown, S. B. An Introduction to Spectroscopy for Biochemists,
Academic Press, London, 1980.
24. The reaction was carried out in acetonitrile due to its buffer
miscible properties for conducting UV experiments.

Highlights
1. Deoxygenation of amine N-oxides is achieved using the green and economical reagent
phenylboronic acid
2. Reaction proceeds under catalyst and metal free conditions
3. Reduction susceptible functional groups are well tolerated
4. Broad substrate scope, clean conversion and excellent yields are the advantages
5. An indirect method for identification and quantification of tert-amine N-oxide is
demonstrated using UV-Vis spectrometry

Table 1: Optimization of reaction conditions.a
Entry
Solvent
Boronic Acid
Time (mins)
Yield (2a) (%)b
1
CH3OH
CH3OH
C2H5OH
t-BuOH
H2O
PhB(OH)2
PhB(OH)2
60
12 h
60
60
60
30
15
60
60
5
25
80
32
50
30
89
95
46
32
97
97
97
94
40
2
3
PhB(OH)2
4
PhB(OH)2
5
PhB(OH)2
6
THF
PhB(OH)2
7
2- Me THF
Toluene
CH3CN
DCM
PhB(OH)2
8
PhB(OH)2
9
PhB(OH)2
10
11
12
13
14
PhB(OH)2
DCE
DCM
PhB(OH)2
10
5
p-Me-PhB(OH)2
p-NO2-PhB(OH)2
MeB(OH)2
DCM
DCM
120
60
15
16
17
18
DCM
DCM
DCM
DCM
n-BuB(OH)2
60
5
43
97
97
97
c
(pinB)2
d
(catB)2
5
B2(OH)4
5
aReaction condition: aniline N-oxide (1 mmol) and boronic acid (1 mmol) stirred in different
b
c
d
solvents at room temperature. Isolated yield. (pinB)2: bis(pinacolato)diboron. (catB)2:
bis(catecholato)diboron.

Table 2: Deoxygenation of N,N-dialkylaniline N-oxides using phenylboronic acid.a,b
2b
(5 mins, 98%)
2c
(5 mins, 98%)
2d
(5 mins, 95%)
2e
(10 mins, 96%)
2g
(20 mins, 93%)
2f
(10 mins, 98%)
2h
(20 mins, 92%)
2i
(10 mins, 95%)
2k
(10 mins, 97%)
2m
(15 mins, 96%)
2l
(5 mins, 96%)
2j
(20 mins, 97%)
2p
(30 mins, 91%)
2n
(15 mins, 97%)
2o
(30 mins, 92%)
2q
(20 mins, 93%)
2r
(30 mins, 97%)
aReaction condition: aniline N-oxide (1 mmol) and phenylboronic acid (1 mmol) was stirred in
b
dichloromethane at room temperature. Isolated yield.

Table 3: Deoxygenation of trialkyl and benzylamine N-oxides with phenylboronic acid.a,b
4c
(45 mins, 90%)
4a
(12 h, 65%)c
(30 mins, 93%)
4b
(30 mins, 92%)
Me
N
4e
(90 mins, 82%)
4f
(15 mins, 95%)
4d
(90 mins, 85%)
4g
(25 mins, 95%)
aReaction condition: trialkyl N-oxide (1 mmol) and phenylboronic acid (1 mmol) was stirred in
dichloroethane at 80 oC. bIsolated yield. cReaction was carried out at room temperature.

Table 4: Deoxygenation of heteroaromatic N-oxides with phenylboronic acid.a,b
6d
(12 h, 65%)
6a
(6 h, 75%)
6c
(24 h, 61%)
6b
(10 h, 90%)
CONH2
N
6h
(18 h, 70%)
6g
(8 h, 80%)
6f
(18 h, 60%)
6e
(16 h, 62%)
aReaction condition: N-oxide (1 mmol) and phenylboronic acid (1.5 mmol) was stirred in
dichloroethane at 120 oC. bIsolated yield.

Table 5. Yield comparison between isolated and calculated from UV for the deoxygenation
reaction of 1a with 4-nitrophenylboronic acid.
Entry
Time
UV yield (%)a
Isolated yield (%)b
1
2
3
1h
2h
3h
39
54
81
34
46
70
b
aYield was calculated using Beer-Lambert’s law (A=Ɛcl) (Refer supporting information). Yield
from batch reaction in 1.0 mmol scale.