Photoredox-Initiated 1,2-Difunctionalization of Alkenes with N-Chloro S-Fluoroalkyl Sulfoximines

Article abstract of DOI:10.1002/adsc.201801207

We describe herein the photoredox-initiated 1,2-difunctionalization of alkene derivatives with N-chloro S-fluoroalkyl sulfoximines yielding novel fluoroalkyl sulfoximine scaffolds. The reaction is proposed to proceed through an atom-transfer radical addition (ATRA) mechanism involving the generation of fluorinated nitrogen-centered sulfoximidoyl radicals. (Figure presented.).

Full text of DOI:10.1002/adsc.201801207

Title: Photoredox-initiated 1,2-Difunctionalization of Alkenes with
<i>N</i>-Chloro <i>S</i>-Fluoroalkyl Sulfoximines
Authors: Alexis Prieto, Patrick Diter, Martial Toffano, Jérôme
Hannedouche, and EMMANUEL MAGNIER
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801207
Link to VoR: http://dx.doi.org/10.1002/adsc.201801207

10.1002/adsc.201801207
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Photoredox-Initiated 1,2-Difunctionalization of Alkenes with N-
Chloro S-Fluoroalkyl Sulfoximines
Alexis Prieto,a,b Patrick Diter,a Martial Toffano,b Jérôme Hannedouche,b* and
Emmanuel Magnier a*
a
Institut Lavoisier de Versailles (ILV), UMR CNRS 8180, Université de Versailles, St Quentin en Yvelines, 45 av. des
Etats-Unis, 78035 Versailles Cedex, France
E-mail: emmanuel.magnier@uvsq.fr
Laboratoire de Catalyse Moléculaire, Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), UMR CNRS
b
8182, Université Paris-Sud, 91405 Orsay Cedex, France
E-mail: jerome.hannedouche@u-psud.fr
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))
nitrogen-centered sulfoximidoyl radicals.[8,9] The first
Abstract. We describe herein the photoredox-initiated
1,2-difunctionalization of alkene derivatives with N-
chloro S-fluoroalkyl sulfoximines yielding novel
fluoroalkyl sulfoximine scaffolds. The reaction is
proposed to proceed through an atom-transfer radical
addition (ATRA) mechanism involving the generation
of fluorinated nitrogen-centered sulfoximidoyl radicals.
report pointing out this reactivity was described by
Oae and co-workers.[8a] They demonstrated that UV-
light or thermal activations could initiate atom
transfer radical addition (ATRA) reactions to olefins
by homolytic cleavage of the N-X (X = Cl, Br) bond
of the sulfoximine (Scheme 1, a)). However, this
process is poorly effective yielding to the
dehalogenated sulfoximine as main product.
Keywords: Addition to alkenes; C-N bond formation;
Photocatalysis; Radicals; Fluorine.
Over the years, nitrogen-containing compounds
have displayed an incredible number of interesting
features in various fields including medicine,
agrochemistry and materials science.[1] Therefore,
strategies aiming the construction of C-N bond in a
selective manner have been widely investigated.
Among them, the transition-metal catalyzed cross-
coupling proved to be a powerful tool for their
formation,[2] but novel methodologies using milder
reaction conditions are still highly needed.
Photochemical processes appear as a promising
alternative for the promotion of challenging bond
constructions. While the creation of C-C bond in a
photocatalytic fashion is well established,[3] the
construction of C-N bond based on nitrogen-centered
radicals has been hitherto under-exploited.[4]
Sulfoximines have gained tremendous interest in
recent years owing to their unique properties,[5] and
have shown promising results in various areas such as
C-H activation, for which the sulfoximine moiety
served as a directing group.[6] Some of us have been
for a long time involved in the development of
transformations related to those derivatives with a
focus on S-perfluoroalkyl sulfoximine compounds
and their N-functionalization.[7] Recently, N-halo
sulfoximines have demonstrated their abilities to
trigger upon light irradiation the generation of
Scheme 1. Previous works and this work on regioselective
1,2-difunctionalisation of alkenes via generation of
nitrogen-centered sulfoximidoyl radicals.
In 2018, the Bolm group has elegantly updated this
reactivity using the photoredox catalysis concept and
has described an efficient procedure for the
difunctionalization of styrene derivatives using N-
thiocyanato sulfoximines which are ex-situ obtained
from
the
corresponding
N-bromocyanato
sulfoximines (Scheme 1, b)).[10,11] Despite its
efficiency, this procedure is restricted to arylalkenes
1
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10.1002/adsc.201801207
Advanced Synthesis & Catalysis
as the difunctionalization reaction is not operating
with aliphatic alkene derivatives. With these previous
works in mind, we considered to generate fluorinated
sulfoximidoyl radicals via photoredox processes and
explore their reactivities with radical acceptors.
Herein, we disclose our preliminary investigations
towards the regioselective photoredox-initiated 1,2-
difunctionalization of alkene derivatives with N-
chloro S-fluoroalkyl sulfoximines providing vicinal
chloro S-fluoroalkyl sulfoximine compounds in
moderate to excellent yields under mild reaction
conditions (Scheme 1, c)).
On the basis of our hypothesis, we selected
(chloroimino)(phenyl)(trifluoromethyl)-λ6-sulfanone
1a and styrene 2a as model substrates, and initiated
optimization studies. Gratifying, in our first
experiment, room-temperature treatment of 1a and 2a
in the presence of K2CO3 and Ir(ppy)3 as
photocatalyst (PC) under blue LEDs irradiation
afforded the corresponding addition compound 3a in
41% yield, and in a 1.2:1 diastereomeric ratio after
full conversion and despite the observation of side-
products (Table 1, entry 1). With this promising
result in hand, we next changed the photocatalyst
source and the base. While a change of photocatalyst
source for Ru(bpy)3(PF6) resulted in a significant
increase of yield to 89% (Table 1, entry 2), lower
yields were observed with the use of other inorganic
bases or without any base (Table 1, entries 3-5).
required for the reaction efficiency (Table 1, entries
9-10).
With the optimized reaction conditions in hand,
we next explored the scope of this photoredox-
initiated
chloro-sulfoximidation
transformation
(Scheme 2). Firstly, we evaluated the scope of the
olefin coupling partners (2) with sulfoximine 1a.
Good to high yields were observed for styrene
compounds, regardless the electron-donating or
electron-withdrawing nature and the position of the
substituents on the phenyl ring (3a-3h).[12] Our
methodology was next tested with olefins bearing
positions prone to H-atom transfer (HAT) processes
and with less reactive aliphatic alkene derivatives.
Pleasingly, the chloro-sulfoximidation transformation
proceeded well with styrene compound 2i bearing
several benzylic positions affording selectively
product 3i in good yield. Even when allylbenzene (2j)
was used as alkene acceptor, the transformation led to
the formation of the expected compound 3j, albeit in
moderate yield.
Table 1. Optimization studies of the chloro-
sulfoximidation reaction of 2a.a)
Entry
PC
Solvent
MeCN
Base
Yield (%)b)
1
2
3
4
5
Ir(ppy)3
KOAc
KOAc
K2CO3
K2HPO4
-
41
89
72
76
65
Ru(bpy)3(PF6)2 MeCN
Ru(bpy)3(PF6)2 MeCN
Ru(bpy)3(PF6)2 MeCN
Ru(bpy)3(PF6)2 MeCN
6
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
DMF
DCE
KOAc
KOAc
KOAc
KOAc
KOAc
41
74
7
8c)
9c)
Ru(bpy)3(PF6)2 MeCN
MeCN
89 (80d))
N.R.
N.R.
-
10c,e) Ru(bpy)3(PF6)2 MeCN
a)
Reaction conditions: 1a (0.3 mmol), 2a (1.5 mmol),
photocatalyst (2 mol%), base (0.6 mmol), solvent (0.6 mL)
b)
for 4 h.
Determined by 19F NMR spectroscopy using
α,α,α-trifluorotoluene as internal standard. c) 2 equiv. of 2a
were used. d) Isolated yield. e) No light irradiation, 72 h.
Scheme 2. Scope of the chloro-sulfoximidation of alkenes
2. Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol),
Ru(bpy)3(PF6)2 (2 mol%), KOAc (0.6 mmol), MeCN (0.6
mL) for 4 h. Isolated yields are given. All compounds are
isolated as a mixture of diastereomers (d.r = 1.2:1 to 1:1). a)
A short survey of polar solvents did not lead to any
further improvement of yield of 3a (Table 1, entries
6-7). Lowering the amount of 2a to 2 equivalents did
not affect the reaction outcome (Table 1, entry 8 vs 2).
Finally, control experiments showed that the
photocatalyst and the light irradiation are both
b)
Reaction time was extended to 18 h. 19F NMR yield is
given. The product was isolated with an impurity (<10%).
N.D = not determined.
2
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10.1002/adsc.201801207
Advanced Synthesis & Catalysis
Subsequently,
various
functionalized
and
unfunctionalized aliphatic alkenes (2k-2o) were
examined as coupling partners with 1a under our
optimized reaction conditions. To our delight, and in
contrast
to
the
photoredox-catalyzed
difunctionalization of alkenes with N-SCN
sulfoximines,[10] the transformation exhibited a good
efficiency with such C-C double bond derivatives.
Our methodology also displayed a good tolerance
towards various functional groups including ester
(3n), ketone (3m), cyano (3o), methoxyl (3c), halide
(3d-3f) and free alcohol (3t) and consequently offers
great
opportunities
for
further
structural
Scheme 4. Plausible mechanisms for the photoredox-
diversifications. Finally, the transformation was
explored with aryl sulfoximine derivatives bearing
diverse fluorinated chain patterns. Pleasingly,
whatever the fluorinated group, C4F9, CF2H, CF2Br or
CFCl2 engaged, the reaction afforded the
corresponding compounds in moderate to excellent
yields (3q-3t). It is worth noting that, for compound
2r, no side-products stemming from the likely
reduction of the CF2Br moiety was detected. Finally,
the synthesis of 3a was performed on a semi-
preparative 5 mmol scale without any decrease in
yield demonstrating the robustness of our
methodology (Scheme 3).
catalyzed chloro-sulfoximidation reaction.
In the path A, intermediate II would abstract a
chlorine atom from sulfoximine 1, leading meanwhile
to the formation of the compound 3 and the
generation of the new sulfoximidoyl radical I.
Regarding the path B, species II would undergo an
oxidation from the oxidation form of PC into the
cationic species III, which would restore the
photocatalyst to its original oxidation state. Finally,
species III would be trapped by a chloride atom
affording compound 3. To gain further insight into
the operating pathway, several control experiments
were performed (Scheme 5). We hypothesized that if
the reaction was going through the formation of the
cationic species III (via path B), the latter could be
trapped by the addition of an external nucleophile to
the reaction media. Thus, the transformation
reactivity was investigated with an alkene partner
bearing a free alcohol functionality on the tether
(Scheme 5, a)).
Scheme 3. Gram-scale experiment.
Based on previous reports,[13,14] two plausible
mechanisms could be evoked for this transformation
as displayed in Scheme 4. First, the photoexcitation
of the photocatalyst would promote the
photoreduction of the sulfoximine 1 by SET
reduction, that would give rise to the formation of the
sulfoximidoyl radical I. The latter would then react
with the alkene compound 2 affording the formation
of the radical intermediate II. At this stage, two
distinct mechanistic pathways might be considered,
namely the radical-chain pathway (Scheme 4, path A)
and the catalytic pathway (Scheme 4, path B).
Scheme 5. Control experiments.
Under these conditions, the ATRA-product 3t was
obtained in 75% yield as the sole product with no
trace of the rival cyclized product resulting from
direct intramolecular nucleophilic attack of the free
alcohol moiety on the potentially generated
carbocation intermediate III. Similarly, conducting
the photocatalyzed reaction of 1a and 2a in water as a
co-solvent only provides the chloro-sulfoximidation
product 3a. These control experiments are consistent
with a transformation proceeding via a radical-chain
mechanism (Scheme 4, path A).
3
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10.1002/adsc.201801207
Advanced Synthesis & Catalysis
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Experimental Section
General procedure
Preparation of N-functionalized sulfoximines (3a-3t). In
a glass tube, the selected alkene derivative (0.6 mmol, 2
equiv.), dry potassium acetate (58 mg, 0.6 mmol, 2 equiv.)
and the Ru(bpy)3(PF6)2 (5 mg, 2 mol%) were successively
added to a solution of the selected N-chlorosulfoximine
(0.3 mmol, 1 equiv.) in dry acetonitrile (0.6 mL). The
reactor was flushed with argon and sealed. The reaction
was stirred under visible light irradiation (Blue LED strip)
at ambient temperature for the appropriate time. Then the
reaction mixture was concentrated in vacuo and the residue
was purified by flash chromatography (silica gel,
appropriate mixture of hexane/ethyl acetate or pure
toluene) to afford the corresponding N-functionalized
sulfoximines as a mixture of diastereomers (d.r. between
1.2:1 and 1:1).
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Acknowledgements
AP is grateful to Labex Charmmmat for the postdoctoral
fellowship. We gratefully thank CNRS and the French Fluorine
Network (GIS fluor) for financial support. The authors thank
Guillaume Dagousset and Elsa Anselmi for helpful discussions.
4
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10.1002/adsc.201801207
Advanced Synthesis & Catalysis
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5
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Advanced Synthesis & Catalysis
COMMUNICATION
Photoredox-initiated 1,2-Difunctionalization of
Alkenes with N-Chloro S-Fluoroalkyl Sulfoximines
Adv. Synth. Catal. Year, Volume, Page – Page
Alexis Prieto, Patrick Diter, Martial Toffano,
Jérôme Hannedouche,* Emmanuel Magnier*
6
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