Metal-Free Deoxygenation of Amine N-Oxides: Synthetic and Mechanistic Studies

Article abstract of DOI:10.1002/cphc.202100108

We report herein an unprecedented combination of light and P(III)/P(V) redox cycling for the efficient deoxygenation of aromatic amine N-oxides. Moreover, we discovered that a large variety of aliphatic amine N-oxides can easily be deoxygenated by using only phenylsilane. These practically simple approaches proceed well under metal-free conditions, tolerate many functionalities and are highly chemoselective. Combined experimental and computational studies enabled a deep understanding of factors controlling the reactivity of both aromatic and aliphatic amine N-oxides.

Full text of DOI:10.1002/cphc.202100108

Accepted Article
Title: Metal-Free Deoxygenation of Amine N–Oxides: Synthetic and
Mechanistic Studies
Authors: Sami Lakhdar, William Lecroq, Jules Schleinitz, Mallaury
Billoue, Anna Perfetto, Annie–Claude Gaumont, Jacques
Lalevée, Ilaria Ciofini, and Laurence Grimaud
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemPhysChem 10.1002/cphc.202100108
Link to VoR: https://doi.org/10.1002/cphc.202100108
01/2020

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
Metal-Free Deoxygenation of Amine N–Oxides: Synthetic and
Mechanistic Studies
William Lecroq,[a], [‡] Jules Schleinitz,[b], [‡] Mallaury Billoue,[a] Anna Perfetto,[c] Annie–Claude Gaumont,[a]
Jacques Lalevée,[d] Ilaria Ciofini,[c] Laurence Grimaud,*[b] and Sami Lakhdar*[e]
Dedicated to memory of Prof. Jean-Michel Savéant
[a]
Dr. W. Lecroq, M. Billoue, Prof. Dr. A.–C. Gaumont and Dr. S. Lakhdar
Normandie Univ., LCMT, ENSICAEN, UNICAEN, CNRS,
6, Boulevard Maréchal Juin, Caen 14000 France
E-mail: lakhdar@chimie.ups-tlse.fr
[b]
J. Schleinitz and Dr. L. Grimaud
Laboratoire des biomolécules, LBM, Département de chimie, École normale
supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France.
E-mail : laurence.grimaud@ens.psl.eu
[c]
Ms. A. Perfetto and Dr. I. Ciofini
Institute of Chemistry for Life and Health Sciences (i-CLeHS), Chimie ParisTech, PSL University, CNRS,
11 rue P. et M. Curie, F-75005 Paris, France
[d] Prof. Dr. J. Lalevée
Université de Haute-Alsace, CNRS, IS2M UMR 7361, F-68100 Mulhouse, France
[e]
Dr. S. Lakhdar
Université Paul Sabatier, Laboratoire Hétérochimie Fondamentale et Appliquée (LHFA, UMR 5069),
118 Route de Narbonne, 31062, Toulouse Cedex 09, France
E-mail : lakhdar@chimie.ups-tlse.fr
[‡]
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of the document.
Abstract: We report herein an unprecedented combination of light
and P(III)/P(V) redox cycling for the efficient deoxygenation of
aromatic amine N-oxides. Moreover, we discovered that a large
variety of aliphatic amine N-oxides can easily be deoxygenated by
using only phenylsilane. These practically simple approaches
proceed well under metal–free conditions, tolerate many
functionalities and are highly chemoselective. Combined
reacts selectively with phosphine oxide and not with other
reagents present in the media.[4] While the P(III)↔P(V) redox
cycling approach has been frequently used in polar organic
reactions, it has, to the best of our knowledge, never been applied
to photoinduced processes, where phosphanes are used in
stoichiometric amounts.[5] This could be explained by the ability of
radicals, generated under photoinduced conditions, to react with
silanes through hydrogen atom transfer of Si–H bonds, thus
preventing the reduction of phosphine oxide to recover the
phosphine.
experimental and computational studies enabled
a
deep
understanding of factors controlling the reactivity of both aromatic and
aliphatic amine N-oxides.
Introduction
Trivalent organophosphorus compounds such as phosphines find
widespread use throughout numerous fields of synthetic
chemistry. Indeed, apart from their use as ligands in transition
metal catalysis or as organocatalysts, phosphanes have been
widely employed as stoichiometric reagents in various synthetic
transformations such as Wittig, Appel, Staudinger or Mitsunobu
reactions, to name a few.[1] The driving force for all these
transformations is the formation of high molecular weight
phosphine oxide as a byproduct, which poses separation and
waste disposal problems. Thus, the development of catalytic
variants of these reactions in organophosphorus reagent and
utilizing alternative feedstocks is highly important.[2] In this
context, the use of silanes as reducing agents of phosphine
oxides has appeared as an efficient solution enabling the
development of numerous interesting phosphane–catalyzed
processes.[3] Remarkably, in these polar reactions, the silane
Scheme 1. Deoxygenation of Amine N–oxides.
However, as many photochemical processes are known to
involve electronically neutral transient intermediates, we
reasoned that P(III)↔P(V) redox cycling might be applicable for
those reactions. In this context, the deoxygenation of
heteroaromatic N–oxides has captured our attention because of:
i) its great importance in various areas[6]ranging from synthesis
1
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
to catalysis[7]and biology[8], ii) the non–catalyzed version requires
a large amount of phosphane and proceeds at high temperature;[9]
iii) previous physical organic studies postulated the formation of
oxaziridine intermediate upon excitation of heteroaromatic N–
oxides with light.[10] This highly reactive intermediate should react
fast with phosphane to give the heteroaromatic compound along
with phosphine oxide. Based on this and on the fact that
phosphanes are more nucleophilic than silanes,[11]we assumed
silane would reduce the in situgenerated phosphine oxide rather
than reacting with the oxaziridine. Extension of this approach to
aliphatic amine N-oxide will also be investigated (Scheme 1).
12
13
2b (10)
2b (10)
CH3CN
traces[d]
99[e]
CH3CN
[a]
Reaction conditions: 1a (0.5 mmol, 1 equiv.), phenylsilane (0.65 mmol, 1.3
[b]
equiv.), organocatalyst (X mol %), solvent (5 mL), 16h.
NMR yields are
determined via 1H NMR spectroscopy vs internal standard. [c] In the absence of
[d]
[e]
phenylsilane.
In the absence of light.
The Schlenk-flask was irradiated
through a cut off filter ([NaNO2] = 0.72 M in aqueous solution, transparent for
light > 385 nm).
As depicted in Table 1, while triphenylphosphine oxide (2a, 20
mol%) failed to catalyze the reaction (entry 1) in acetonitrile,
phosphine oxides 2b and 2c gave the desired product in excellent
yields (entries 2-3, 99%). This might be attributed to the ability of
cyclic phosphine oxides to be easily reduced by silanes compared
to the acyclic ones.
It should be mentioned that a seminal study by Scaiano et al.
showed the efficiency of triethylphosphite to deoxygenate pyridine
N-oxide in acetonitrile under UV irradiation (max = 325 nm).[6a]
Results and Discussion
To test this hypothesis, we investigated the deoxygenation of 4–
cyanopyridine N–oxide 1a in the presence of a catalytic amount
of phosphine oxide 2, phenylsilane as a reducing agent, in
different solvents and under blue light irradiation.
When the same phosphite was used under our conditions (max
=
Table 1. Optimization of the reaction conditions.[a]
420 nm), no reaction was observed (see supporting information).
Based on these first results, the commercially available 3-methyl-
1-phenyl-phospholane oxide 2b was used for optimization. In this
context, a solvent screening including dichloromethane, toluene
and DMF (entries 4–6) showed a very low conversion compared
to acetonitrile (entry 2). While lowering the catalyst loading to 10
mol % (entry 7, 99%) did not affect the performance of the
reaction, reducing it to 5 and 2.5 mol% diminished the yield of the
reaction (93% and 83%, respectively, entries 8-9). Interestingly,
the organocatalyst (2b, entry 10), phenylsilane (entry 11) and light
(entry 12) were found to be essential for the deoxygenation
reaction as no conversion was observed in their absence. Finally,
to exclude the involvement of UV light, we irradiated the sample
through a UV filter (75% w/v NaNO2 solution, cut-off: λ =385 nm)
and a nearly full conversion has been attained (entry 13, 99%).
With the optimized conditions in hand, we next investigated the
scope of the photoreaction.
Entry
Organocatalyst
(X mol %)
Solvent
Yield [%][b]
1
2a (20)
2b (20)
2c (20)
2b (20)
2b (20)
2b (20)
2b (10)
2b (5)
CH3CN
CH3CN
CH3CN
CH2Cl2
Toluene
DMF
0
2
99
99
8
3
4
5
traces
2
6
7
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
99
93
83
0
8
9
2b (2.5)
–
10
11
2b (10)
0[c]
2
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
deoxygenated under our photochemical conditions and the
pyridine N–oxide (3zb) was deoxygenated using 1.3 equiv of
silane affording 3zb in 64% yield. It should be noted that a similar
chemoselective approach has recently been reported by Kim and
●
Lee, where [Ru(bpy)3]-Cl2 6H2O was used as a photocatalyst in
the presence of excess of hydrazine hydrate, which serves as
reductive quencher and hydrogen source.[6g]
To evaluate the general applicability of this photoorganocatalytic
approach, we investigated the deoxygenation of dialkylarylamine
N-oxide (Figure 2).
When optimizing the deoxygenation of N,N-dimethyl aniline N–
oxide, we were surprised to find that the reaction takes place
smoothly in the absence of both light and organocatalyst (2b). By
combining various aniline N–oxides and phenylsilane (1.3 equiv.)
in acetonitrile the corresponding anilines (5a–5g) can be obtained
within 10 min in very good yields (82–92%). Similarly, the
deoxygenation of a series of N-benzylpyrrolidine N-oxides,
bearing electron -donating and -withdrawing substituents on the
aromatic rings, works smoothly, delivering the amines (5h–5l) in
yields ranging from 59 to 87%. The deoxygenation of Rhodamine
B N–oxide can easily be performed under the optimized
conditions to yield the fluorescent dye 5m in good yield (83%).
Figure 1. Scope of the photochemical deoxygenation of heteroaromatic N–
oxides. Reaction conditions: 1 (0.5 mmol, 1 equiv.), phenylsilane (0.65 mmol,
1.3 equiv.), 2b (10 mol %), acetonitrile (5 mL), Blue LEDs (5 W), 16h.
As shown in Figure 1, the reaction proceeds well with pyridine N–
oxides para-substituted with either electron–withdrawing (3a–d)
or electron–rich (3e–h) groups in good to excellent yields.
Pyridine N–oxides bearing substituents at the meta (3i–k) or ortho
(3l,m) positions can be smoothly deoxygenated under the
optimized conditions. Notably, different functional groups (CF3 (3c,
93%), CO2Et (3d; 82%), CH2OH (3h; 57%), CN (3j; 94%) and
chloride (3l; 71%)) on the aromatic rings were well-tolerated.
Similarly, a large variety of quinoline oxides, bearing different
electronic substituents on the aromatic and/or heteroaromatic
rings (3m–3v), performed well under the optimized reaction
conditions, affording the corresponding reduced heterocycles in
good to excellent yields (69–94%). 5,6,7,8-tetrahydroquinoline–
N–oxide can also be deoxygenated to the corresponding
quinoline 3za in fair 54% yield.
Figure 2. Scope of the photochemical deoxygenation of aliphatic amine N–
oxides. Reaction conditions: 4 (0.5 mmol, 1 equiv.), phenylsilane (0.65 mmol,
1.3 equiv.), acetonitrile (5 mL).
More importantly, when starting with a bis–N–oxide, bearing both
a quinoline and a pyridine N-oxides, only the former is
3
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
Scheme 2. Working mechanistic hypotheses for the deoxygenation of 4–
cyanopyridine N–oxide (1a).
Mechanistic Investigations
In order to gain insights into the reaction mechanism of the photo-
deoxygenation of amine N–oxides (Figure 1), complementary
experimental and computational studies were performed.
We first focused our attention on the reaction mechanism of
deoxygenation of N-heterocyclic N-oxides.
Even if both reaction mechanisms have been previously
postulated in literature,[15] experimental evidence of the formation
of oxaziridine intermediates could be observed only in a few cases
since many heteroaromatic N-oxides do not show transient
absorption by laser flash photolysis.[10] We then turned our
attention to theoretical approaches to provide valuable insights.
To investigate the two possible reaction mechanisms, we resorted
on Density Functional Theory (DFT)[16] and Time Dependent
DFT[17] (as detailed in SI) to model ground and excited state
reactivity. First, to assess the photoisomerization hypothesis, we
computed the ground and excited state potential energy surfaces
(PES) describing the formation of the oxaziridine intermediate
(6a) from 1a, as this is supposed to be the key step of the process.
As relevant structural parameters, two angles (α and β in Figure
3) were considered. These two angles describe respectively, the
closure of the CNO ring and the out of plane position of the O
atom with respect to the heteroaromatic ring.
In order to confirm the generation of 3-methyl-1-phenyl-
phospholane (7) during the reaction, we reacted 3-methyl-1-
phenyl-phospholane oxide (2b) with phenylsilane under blue light
irradiation. As shown in Figure S1, almost 50% of the phosphane
was detected by 31P NMR spectroscopy after 16 h of irradiation.
Importantly, 30% and 70% of 7 were obtained when the same
reaction was carried out in the dark at room temperature and at
70 °C, respectively. These results indicate that the reduction of 2b
by phenylsilane is presumably a thermally driven process.
Noteworthy mentioning, the reaction of 3-methyl-1-phenyl-
phospholane (7, 1 equiv.) with 4–cyanopyridine N–oxide (1a, 1.2
equiv.) under blue irradiation gives rise to 4-cyanopyridine (3a) in
92% yield, which revealed the intermediacy of phospholane (6) in
the catalytic reaction.
As shown in Figure 3, the minima corresponding to 1a and 6a can
be located on the ground state (S0), the latter corresponding to an
α=56.8° and β=-107.7°, characteristic of the oxaziridine geometry.
Analysis of the ground and excited state PES reveals the
presence of a region, close to the transition state of the ground
state, with a small difference in energy (~5 kcal/mol) between S1
and S0. In this region, relaxation from the excited to the ground
state is likely to occur. On this basis, we can reasonably assume
the photoisomerization reaction occurs following a four-step
isomerization mechanism: after vertical absorption leading to the
population of the S1 excited state (step 1, dashed blue arrow),
vibrational relaxation leads to the S1 energy minimum (step 2, red
arrow) and if sufficient energy is provided, the region of S1→S0
vertical decay can be reached (step 3, dashed black arrow)
yielding the oxaziridine which can finally vibrationally relax toward
its corresponding minimum at the ground state (step 4, blue
arrow).
We next turned our attention to ascertain the nature of the
photoactive species involved in photodeoxygenation of 4–
cyanopyridine N–oxide (1a). To this end, we performed UV−vis
spectroscopic measurements on various combinations of 1a, 7
and phenylsilane in dichloromethane for each species (Figures
S2–S4, supporting information). Besides the pyridine N-oxide 1a
that absorbs slightly in the visible region, all of the other
components are silent in this region (> 390 nm). Furthermore,
addition of 7 did not induce any bathochromic shift to the spectrum
of 1a, ruling out the formation of an electron donor-acceptor
complex (EDA).[14]
These findings are consistent with simulated UV–visible spectra
reported in the supporting information (Figure S5). On this basis,
we assume a photo-activation of the pyridine N-oxide (1a) leading
to the formation of the (1a)* species. In aprotic solvents, two
scenarios can next be envisaged (Scheme 2): i)
a
photoisomerization leading to the formation of an unstable fused
oxaziridine 6a, which can further react with 7 to yield the pyridine
3a, or ii) a single electron transfer from the phosphane (7) to (1a)*
to generate the phosphoniumyl radical (7)●+ along with the
reduced pyridine N–oxide species (1a)●– (Scheme 2, grey arrows).
Figure 3. S0 and S1 free energy surfaces for the 4-cyano pyridine N-oxide (1a).
4
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
Finally, the mechanism of deoxygenation of dialkylarylamine N-
oxide remains to be elucidated. To this end, we considered the
reaction of phenylsilane with the parent pyridine N–oxide and with
N,N-dimethyl aniline N–oxide 4a.
In both cases, a pre-complex between phenylsilane and amine
N–oxide (1, 4a) is formed, the oxygen coordinated to the silicon
atom of the phenylsilane (detailed pathway is reported in the
supporting information).
In the case of 4a the energetic barrier to overcome for the
formation of the final product is found to be 18.6 kcal/mol. The
optimized transition state structure (TSa) shows that the oxygen
atom is bridging the nitrogen, the silicon and the hydrogen atoms
(O–N = 1.73 Å, O–Si = 1.76 Å, O–H = 1.66 Å) with a N-O-H quasi
linear arrangement. Though the reaction in the case of the
pyridine N-oxide 1 proceeds via a similar transition state (TSb),
the energy required for this reaction is around 20 kcal/mol higher
than that for the reaction of 4a with phenyl silane in agreement
with the experimental observation of the failure of pyridine N-
oxides to react with phenylsilane at room temperature. The
difference of reactivity between 1 and 4a stems to higher energy
NO bond in the latter compared to the former, due to conjugation
with the heterocycle.
Using this mechanistic modeling (full details in the supporting
information), we were able to quantify free energy difference
(GS1-oxa) between the N-oxide first excited state minimum and
the oxaziridine intermediate on the ground state PES, and
activation energy (G≠oxa) for the rate determining step of the
photocyclization i.e. the isomerization process from the first
excited state minimum of the N-oxide to the oxaziridine (step 2 to
step 3). From these data, the reaction of 1a is thermodynamically
favoured (GS1-oxa = -43.6 kcal/mol) and kinetically feasible at
room temperature (G≠oxa = 5 to 8 kcal/mol).
In order to test the single electron transfer mechanism displayed
in Scheme 2 we applied Marcus theory[18] (details in the
supporting information) to compute both activation and reaction
energies (reported in Table 2). This pathway was found to be
kinetically (ΔE≠
= 2.24 kcal/mol) and thermodynamically
SET
feasible (ΔESET = -29.2 kcal/mol). However, a direct comparison
between both mechanisms was not possible because of the
difficult evaluation of the entropic contribution.[19]
To overcome this issue we applied the same methodology to
three additional substrates, the electron–rich N’,N’–
dimethylaminopyridine N–oxide (1e) giving 3e in high yield and
two acridine N–oxides 1zc and 1zd, which failed to react under
the optimized experimental conditions (Figure 1). The results
presented in Table 2 show that, if SET is computed to be feasible
in all cases, it is found to be more favorable with acridine N–oxide
1zd than with the pyridine N–oxide 1e, which disagrees with
experimental results. The formation of the oxaziridine
intermediate is favored in the case of 1a,e showing the smallest
activation energies, while deoxygenation of 1zc,d is expected to
be unlikely to occur and indeed did not proceed under our
optimized conditions. On this basis, the computed
photoisomerization mechanism is consistent with the observed
yields.
60
TSb
40
TSa
D∆GG‡==1188..66kkccaall//mmooll
Precomplex
TSb
∆G‡=34.9 kcal/mol
DG=34.9 kcal/mol
20
0
+PhSiH3
N-oxide N,N dimethylaniline
pyridine N-oxide
-20
-40
-60
-80
+PhSiH2OH
TSa
Reaction coordinate
Table 2. Computed Free energies (GS1-oxa and ΔESET
)
activation energies (G≠ and ΔE≠SET) associated to the
oxa
photoisomerization yielding to the oxaziridine formation (oxa)
and the single electron transfer mechanism (SET). Refer to
Scheme 2 for detail.
Figure 4. DFT–calculated Gibbs energy profiles for the reactions of
phenylsilane with 1 and 4a, respectively.
Conclusion
In summary, this work demonstrates the efficiency of P(III)↔P(V)
redox cycling with light to drive practically simple deoxygenation
of a large variety of heteroaromatic N–oxides. Expensive and
highly sensitive catalysts, which are typically combined with
phenylsilane to reduce dialkylarylamine N-oxides, turned out to
be not required as such a deoxygenation proceeded within 10
minutes at room temperature. In order to understand factors
controlling both reactions, DFT calculations have been performed.
It was shown that the photochemical deoxygenation proceeds
most likely through the formation of a transient fused oxaziridine
as a key intermediate that reacts with phosphane to yield the
heteroarene. The reaction of dialkylarylamine N-oxides with
phenylsilane occurs according to a concerted pathway, with an
activation energy lower than that calculated for the deoxygenation
of pyridine N–oxide with phenylsilane. Given the importance of
deoxygenation of amine N–oxides in different domains going from
Substrate
ΔGS1-oxa
(kcal/mol)
ΔG≠
(kcal/mol)
ΔESET
(kcal/mol)
ΔE≠
SET
(kcal/mol)
oxa
1a
–43.61
–39.94
–15.26
–11.29
5 to 8
–29.20
5.95
2.24
10.54
9.97
2.58
1e
2 to 6
1zc
1zd
18 to 22
20 to 24
–4.69
–15.67
5
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
S. H. Cho, Angew. Chemie - Int. Ed. 2016, 55, 9690–9694. e) Z.
Zhang, C. Pi, H. Tong, X. Cui, Y. Wu, Org. Lett. 2017, 19, 440–443.
a) J. Kim, C. R. Bertozzi, Angew. Chemie - Int. Ed. 2015, 54, 15777–
15781. b) T. Hirayama, H. Tsuboi, M. Niwa, A. Miki, S. Kadota, Y.
Ikeshita, K. Okuda, H. Nagasawa, Chem. Sci. 2017, 8, 4858–4866.
E. Howard, W. F. Olszewski, J. Am. Chem. Soc. 1959, 81, 1483–
1484.
(a) K. Tokumura, H. Goto, H. Kashiwabara, C. Kaneko, M. Itoh, J.
Am. Chem. Soc. 1980, 102, 5643–5647. (b) for a recent article
discussing the formation of oxaziridines through irradiation of pyridine
N-oxides, see: (b) E. E. Hurlow, J. B. Lin, M. J. Dweck, S. Nuryyeva,
Z. Feng, T. K. Allred, K. N. Houk and P. G. Harran, J. Am. Chem.
Soc., 2020, 142, 20717–20724.
catalysis to biology, these simple approaches should find wide
applications.
[8]
[9]
Experimental Section
[10]
Experimental Details (see supporting information).
[11]
[12]
B. Kempf, H. Mayr, Chem. - A Eur. J. 2005, 11, 917–927.
M. Horn, L. H. Schappele, G. Lang-Wittkowski, H. Mayr, A. R. Ofial,
Chem. - A Eur. J. 2013, 19, 249–263.
Acknowledgements
[13]
[14]
A. M. Kirk, C. J. O’Brien, E. H. Krenske, Chem. Commun., 2020, 56,
1227-1230.
The authors thank the CNRS, Normandie Université, Région de
Normandie, Labex Synorg (ANR-11-LABX-0029), ENSCP Chimie
ParisTech, ENS, PSL for financial support. IC and AP
acknowledge support from the European Research Council
(ERC) for funding under the European Union’s Horizon 2020
research and innovation program (grant agreement No 648558,
STRIGES CoG grant).
For selected examples, see: a) M. Nappi, G. Bergonzini, P.
Melchiorre, Angew. Chemie - Int. Ed. 2014, 53, 4921–4925. b) S. R.
Kandukuri, A. Bahamonde, I. Chatterjee, I. D. Jurberg, E. C.
Escudero-Adán, P. Melchiorre, Angew. Chemie - Int. Ed. 2015, 54,
1485–1489. c) J. Davies, S. G. Booth, S. Essafi, R. A. W. Dryfe, D.
Leonori, Angew. Chemie - Int. Ed. 2015, 54, 14017–14021. e)T.
Morack, C. Mück-Lichtenfeld, R. Gilmour, Angew. Chemie - Int. Ed.
2019, 58, 1208–1212. f) G. E. M. Crisenza, D. Mazzarella, P.
Melchiorre, J. Am. Chem. Soc. 2020, 142, 5461–5476.
a) A. Albini, M. Alpegiani, Chem. Rev. 1984, 84, 43–71; b) A. Albini,
E. Fasani, A. M. Amer (1995) In: CRC handbook of organic
photochemistry and photobiology. CRC Press, Boca Raton FL, pp
879-891; c) A. Albini, M. Fagnoni (2004) CRC handbook of organic
photochemistry and photobiology, 2nd Edition. CRC Press, Boca
Raton FL, pp 1-21. d) O. Larionov (Ed.) Heterocyclic N-Oxides.
Topics in Heterocyclic Chemistry, 2017, vol 53.
C. Adamo, V. Barone, J. Chem. Phys., 1999, 110, 6158-6170; W. J.
Hehre, K. Ditchfield, J. A. Pople, J. Chem. Phys., 1972, 56, 2257-
2261; V. Barone, M. Cossi, J. Phys. Chem. A., 1998, 102, 11, 1995-
2001.
F. Furche, R. Ahlrichs, J. Chem. Phys., 2002, 117, 7433-7447.
R. A. Marcus, Annual Review of Physical Chemistry, 1964, 15, 155-
196.
[15]
[16]
Keywords: deoxygenation • mechanisms • photochemistry •
organocatalysis • selectivity
[1]
H. Guo, Y. C. Fan, Z. Sun, Y. Wu, O. Kwon, Chem. Rev. 2018, 118,
10049–10293.
[2]
[3]
S. Xu, Z. He, RSC Adv. 2013, 3, 16885–16904.
For selected contributions, see: a) C. J. O’Brien, J. L. Tellez, Z. S.
Nixon, L. J. Kang, A. L. Carter, S. R. Kunkel, K. C. Przeworski, G. A.
Chass, Angew. Chemie - Int. Ed. 2009, 48, 6836–6839. b) K. Fourmy,
A. Voituriez, Org. Lett. 2015, 17, 1537–1540. c) W. Zhao, P. K. Yan,
A. T. Radosevich, J. Am. Chem. Soc. 2015, 137, 616–619. d) M. L.
Schirmer, S. Adomeit, T. Werner, Org. Lett. 2015, 17, 3078–3081. e)
X. Han, N. Saleh, P. Retailleau, A. Voituriez, Org. Lett. 2018, 20,
4584–4588. f) T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A.
Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc. 2018,
140, 15200–15205. g) T. V. Nykaza, A. Ramirez, T. S. Harrison, M.
R. Luzung, A. T. Radosevich, J. Am. Chem. Soc. 2018, 140, 3103–
3113. h) L. Longwitz, A. Spannenberg, T. Werner, ACS Catal. 2019,
9, 9237–9244. i) C. Lorton, T. Castanheiro, A. Voituriez, J. Am.
Chem. Soc. 2019, 141, 10142–10147. j) L. Longwitz, T. Werner, Pure
Appl. Chem. 2019, 91, 95–102. k) A. Ghosh, M. Lecomte, S. H. Kim-
Lee, A. T. Radosevich, Angew. Chemie - Int. Ed. 2019, 58, 2864–
2869. l) L. Longwitz, T. Werner, Angew. Chemie - Int. Ed. 2020, 59,
2760–2763.
[17]
[18]
[19]
M. Besora, P. Vidossich, A. Lledos, G. Ujaque, F. Maseras, J. Phys.
Chem. A 2018, 122, 1392-1399.
[4]
[5]
For a recent review, see: A. Voituriez, N. Saleh, Tetrahedron Lett.
2016, 57, 4443–4451.
For selected articles, see: a) E. E. Stache, A. B. Ertel, T. Rovis, A. G.
Doyle, ACS Catal. 2018, 8, 11134–11139. b) M. Zhang, X. A. Yuan,
C. Zhu, J. Xie, Angew. Chemie - Int. Ed. 2019, 58, 312–316. c) P. J.
Xia, Z. P. Ye, Y. Z. Hu, D. Song, H. Y. Xiang, X. Q. Chen, H. Yang,
Org. Lett. 2019, 21, 2658–2662. d) J. I. Martinez Alvarado, A. B. Ertel,
A. Stegner, E. E. Stache, A. G. Doyle, Org. Lett. 2019, 21, 9940–
9944. e) Y. Q. Guo, R. Wang, H. Song, Y. Liu, Q. Wang, Org. Lett.
2020, 22, 709–713.
[6]
a) G. Bucher, J. C. Scaiano, J. Phys. Chem. 1994, 98, 12471–12473.
b) J. Jeong, K. Suzuki, M. Hibino, K. Yamaguchi, N. Mizuno,
ChemistrySelect 2016, 1, 5042–5048. c) F. Ding, Y. Jiang, S. Gan,
R. L. Y. Bao, K. Lin, L. Shi, European J. Org. Chem. 2017, 3427–
3430. d) A. Chardon, O. Maubert, J. Rouden, J. Blanchet,
ChemCatChem 2017, 9, 4460–4464. e) J. Jeong, K. Suzuki, K.
Yamaguchi, N. Mizuno, New J. Chem. 2017, 41, 13226–13229. f) R.
Rubio-Presa, M. A. Fernández-Rodríguez, M. R. Pedrosa, F. J.
Arnáiz, R. Sanz, Adv. Synth. Catal. 2017, 359, 1752–1757. g) S.
Gupta, P. Sureshbabu, A. K. Singh, S. Sabiah, J. Kandasamy,
Tetrahedron Lett. 2017, 58, 909–913. h) K. D. Kim, J. H. Lee, Org.
Lett. 2018, 20, 7712–7716. i) M. O. Konev, L. Cardinale, A. Jacobi
Von Wangelin, Org. Lett. 2020, 22, 1316–1320. j) H. Tinnermann, S.
Sung, B. A. Cala, H. J. Gill, R. D. Young, Organometallics 2020, 39,
6, 797–803. k) J. H. An, K. D. Kim and J. H. Lee, J. Org. Chem.2021,
86, 2876–2894
[7]
For selected examples on the use of heteroaromatic N–oxides in C–
H activation processes, see: a) L. C. Campeau, S. Rousseaux, K.
Fagnou, J. Am. Chem. Soc. 2005, 127, 18020–18021. b) H. P.
Kokatla, P. F. Thomson, S. Bae, V. R. Doddi, M. K. Lakshman, J. Org.
Chem. 2011, 76, 7842–7848. c) X. Zhang, Z. Qi, X. Li, Angew.
Chemie - Int. Ed. 2014, 53, 10794–10798. d) W. Jo, J. Kim, S. Choi,
6
This article is protected by copyright. All rights reserved.

10.1002/cphc.202100108
ChemPhysChem
ARTICLE
Entry for the Table of Contents
This work describes efficient metal-free approaches for chemoselective deoxygenation of amine N-oxides. Scope and reaction
mechanisms of these reactions are discussed.
Institute and/or researcher Twitter usernames: @samilakhdar1
7
This article is protected by copyright. All rights reserved.