Aryldiazenyl Radicals from Arylazo Sulfones: Visible Light-Driven Diazenylation of Enol Silyl Ethers

Article abstract of DOI:10.1002/adsc.201901424

A versatile protocol for the diazenylation of enol silyl ethers under visible light irradiation is presented herein. The reaction is based on the underused reaction of a nitrogen-based radical (the diazenyl radical) with an enol silyl ether. Arylazo sulfones were used as photoactivatable precursors of these diazenyl radicals. The resulting azaderivatives are potentially bioactive compounds as well as starting materials for the synthesis of N-containing heterocycles. (Figure presented.).

Full text of DOI:10.1002/adsc.201901424

Title: Aryldiazenyl Radicals from Arylazo Sulfones: Visible Light-Driven
Diazenylation of Enol Silyl Ethers
Authors: Havall Othman Abdulla, Simone Scaringi, Ahmed.A. Amin,
Mariella Mella, STEFANO PROTTI, and Maurizio Fagnoni
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10.1002/adsc.201901424
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Aryldiazenyl Radicals from Arylazo Sulfones: Visible Light-
Driven Diazenylation of Enol Silyl Ethers
Havall Othman Abdulla,a,b,‡ Simone Scaringi,a,‡ Ahmed A. Amin,b Mariella Mella,a
Stefano Protti,a,* and Maurizio Fagnonia,*
a
PhotoGreen Lab, Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy,
*E-mail: stefano.protti@unipv.it, fagnoni@unipv.it
b
Chemistry Department, College of Science, Salahaddin University, Erbil, Iraq
both authors contributed equally to the work.
‡
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
form III, Scheme 1b) was reported.[13] . Indeed, the
reaction rate of the coupling between the 4-
nitroaryldiazenyl radical with thiolate anion was
Abstract. A versatile protocol for the diazenylation of enol
silyl ethers under visible light irradiation is presented
herein. The reaction is based on the underused reaction of a reported to be very high (8.9×108 M-1 s-1).[13] In the
nitrogen-based radical (the diazenyl radical) with an enol
silyl ether. Arylazo sulfones were used as photoactivatable
precursors of these diazenyl radicals. The resulting
azaderivatives are potentially bioactive compounds as well
as starting materials for the synthesis of N-containing
heterocycles.
last years we embarked in the study of the
photoreactivity of arylazo sulfones IV (Scheme 1c)
and we found that, upon irradiation under visible light,
these compounds generate an aryl radical V via
homolytic cleavage of the N-S bond and nitrogen loss
of the so-obtained aryldiazenyl radical (I).[14] We
reasoned that if it was possible to divert the usual
reactivity of arylazo sulfones by shifting to valuable
diazenylation reactions.
Keywords: Arylazo sulfones; C-N Bond formation;
Diazenyl radicals; Enol silyl ethers; Visible light
photochemistry
Diazenylation reactions, namely the incorporation in
an organic compound of an aryl-N2 or an alkyl-N2
moiety is a process that mainly involves the reaction
of diazonium salts (in most cases generated in situ)[1]
or their analogues[2] with a suitable nucleophile
(Scheme
1a).
This
approach
led
to
carbodiazenylations (where two aryl moieties are
tethered to the nucleophile)[3] or made use of different
intermediates such as the aryldiazene cation radical.[4]
The intermediacy of an aryldiazenyl radical (I,
Scheme 1),[5] however, is a rare occurrence.[6] The
main reason is the poor stability at room temperature
in solution of this intermediate since it is known that
loss of dinitrogen took place to give an aryl radical[7]
with a fragmentation rate constant in the 0.4-4.0×105
s-1 range.[8,9] Nevertheless, such intermediates have
been found to play a key-role in both photochemical
and thermal transformation of a wide range of
azaderivatives including cyclic[10] and acyclic
azoalkanes,[11] as well as diazenes in general.[12]
These elusive radicals are claimed to be electrophilic
species due to the negatively polarized N=N group.[6a]
and in rare instances their reaction with negatively
charged nucleophiles to give either an aromatic
substitution (with malononitrile anion to form II) or
an azaderivative (e.g. by reaction with a thiolate to
Scheme 1.
Due to the electrophilic nature of I we envisaged that
nucleophilic partners such as enol silyl ethers of 1,3-
diketones,[15] that have been recently investigated as
coupling partners for N-centered radicals[16] could be
1
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10.1002/adsc.201901424
Advanced Synthesis & Catalysis
buffering agent (see SI for further details).
Gratifyingly, when this mixture was irradiated for 20
h by a 40 W LED Kessil lamp (456 nm), afforded the
corresponding azaderivative 2a in 75% yield
(Scheme 2).[19The scope of the reaction was thus
investigated by examining the use of differently
substituted arylazo sulfones (see Scheme 2).
ideal traps for this intermediate. Worth noting, the
thus formed azaderivatives have several applications
as bioactive compounds[17] as well as precursors of
azo-substituted heterocycles.[18]
]
Scheme 2. Photoinduced diazenylation of 1-
((trimethylsilyl)oxy)pent-3-en-2-one.
Scheme 3. Visible light-driven preparation of compounds
3,4
In order to test the feasibility of our proposal, we
initially focused on the visible light-induced reaction
between 4-((methylsulfonyl) diazenyl)acetophenone
(1a) and 1-((trimethylsilyl)oxy)pent-3-en-2-one and
the best reaction conditions obtained were the
following: 1a (0.05 M), 1-((trimethylsilyl)oxy)pent-
3-en-2-one (2.0 equiv) in argon saturated MeCN (1
mL), in the presence of 2 equiv of NaHCO3 as
Good results were obtained in the preparation of
azaderivatives
including a cyano group (2b and 2i, 66 and 50% yield
respectively), different halogens (2c-f, h) and even a
triple C-C bond (2g, 74% yield). Very good
diazenylation yields were likewise observed when
bearing
different
substituents
2
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10.1002/adsc.201901424
Advanced Synthesis & Catalysis
electron-donating substituents were present, including
t-butyl- (2l) and methoxy- substituents (2m-o).
Finally, discrete amounts of the dihalo-substituted
compound 2p and the 3-pyridyl derivative 2q have
been isolated under these conditions (37% yield in
both cases).
Scheme 4. Mechanistic proposal
The loss of N2 from intermediates 5 to form the
corresponding aryl radicals 6 (path c) was reported to
occur with an activation energy value ranging from
On contrast, only traces of the products were obtained
in the absence of light (see SI). Better results have
been even obtained when using the enol silyl ether of
46.2 to 25.2 kJ mol-1.[9] This path led to
[20]
hydrodeamination products 6’
(path c, c’) and it
has a role only under non optimized conditions (see
Table S1 for further details). Under the right
conditions, however, trapping of 5 by such peculiar
(and rather underutilized) radical traps[16] efficiently
competed with dediazoniation, and the silylated -
oxy-radical 7 is formed. Smooth oxidation and
following loss of the trimethylsilyl cation (paths e,
f)[21] resulted in the formation of the diazenylated
products 2-4.
dimedone
(5,5-dimethylcyclohexane-1,3-dione,
Scheme 3). In this case the desired products 3 were
all obtained in yields ranging from 76 to 94%,
independently from the aromatic substituents. We
also carried out few tests by employing 1,3-diphenyl-
3-((triethylsilyl)oxy)prop-2-en-1-one as the coupling
partner. Also in this case, both electron-poor (4a) and
electron-rich (4m,n) azaderivatives have been
isolated in excellent yields.
The sulfonyl radical is mainly converted to the
corresponding anion (path e) as demonstrated by an
ion chromatography analysis of the photolyzed
solution obtained from the reaction of 1b with 1-
((trimethylsilyl)oxy)pent-3-en-2-one (see SI, section
3) that revealed the presence of sulfinate anion in
66% yield.
Accordingly, trimethylsilyl methanesulfinate is
probably released in solution that upon hydrolysis by
adventitious water present in solution liberated
methanesulfinic acid. This acid may also derived in
part by direct hydrogen atom abstraction of the
sulfonyl radical from the reaction medium.[14a] Thus,
the presence of a buffering agent such as NaHCO3 is
beneficial for the reaction efficiency of the examined
reactions (compare entries 4 and 5 in Table S1)
probably avoiding acid-catalysed decomposition of
the enol silyl ethers employed.
To widen the scope of the reaction, we then
performed irradiation experiments on some arylazo
sulfones (1a, 1l) in the presence of another enol silyl
ether such as cyclohex-1-en-1-yloxy)triethylsilane
under the same conditions of Scheme 2. However, in
this case, no trapping of diazenyl radical was
observed, and reductive hydrodeamination to form
acetophenone and tert-butylbenzene, respectively,
was the only reaction occurring.
The reactivity observed may be explained by the
mechanistic proposal depicted in Scheme 4. As
hinted above, a n* transition occurs under visible
light irradiation of compounds 1a-q, and the resulting
singlet excited state undergoes homolytic cleavage of
the N-S bond, to form, along with a methanesulfonyl
radical, the corresponding aryldiazenyl radicals 5
(Scheme 4, paths a, b).[14a,b]
The intermediacy of diazonium salts 1’ (possibly
generated via heterolytic cleavage of the N-S bond,
path b’) has been also considered as an alternative
path. It is widely accepted that the photorelease of 1’
from arylazo sulfones occurred only under UV-light
irradiation[14a],[23] but a negligible formation of
compound 2 has been observed under photolysis at
366 nm (see Table S1).
In this work we were thus able to divert the
photoreactivity of arylazo sulfones, usually adopted
in arylation reactions, to perform valuable
diazenylation processes under very mild conditions
(upon visible light irradiation at room temperature).
This was possible by preventing the nitrogen loss
from the aryldiazenyl radical intermediate by
trapping with suitable enol silyl ethers of 1,3-
dicarbonyls. The use of this elusive species allowed
the formation of azaderivatives known to be bioactive
and at the same time interesting precursors for the
synthesis of different azo-substituted heterocycles.
Experimental Section
To a solution of the chosen arylazo sulfone (1a-q, 0.05 M,
0.25 mmol, 1 equiv) and the chosen silyl vinyl ether (0.1
M, 2 equiv) in MeCN (5 mL) were added 2 equiv of
3
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10.1002/adsc.201901424
Advanced Synthesis & Catalysis
NaHCO3. The resulting mixture was purged for 2 min with
nitrogen and the solution was irradiated for 20 h by means
of a 40 W LED Kessil Lamp (456 nm). The solvent was
then removed under reduced pressure and the crude
product was purified by column chromatography (eluant:
hexane: ethyl acetate) to afford the desired product.
[14] a) S. Crespi, S. Protti, M. Fagnoni, J. Org. Chem.
2016, 81, 9612–9621; b) M. Malacarne, S. Protti, M.
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Dossena, S. Sampaolesi, A. Palmieri, S. Protti, M. Fagnoni,
J. Org. Chem. 2017, 82, 10687–10692; d) C. Sauer, Y. Liu,
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Acknowledgements
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H. O. A. is grateful to the Chemistry Department, College of
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4
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10.1002/adsc.201901424
Advanced Synthesis & Catalysis
COMMUNICATION
Aryldiazenyl Radicals from Arylazo Sulfones:
Visible Light-Driven Diazenylation of Enol Silyl
Ethers
Adv. Synth. Catal. Year, Volume, Page – Page
H. O. Abdulla, S. Scaringi, A. A. Amin, M. Mella,
S. Protti,* and M. Fagnoni,*
5
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