A synergistic LUMO lowering strategy using Lewis acid catalysis in water to enable photoredox catalytic, functionalizing C-C cross-coupling of styrenes

Article abstract of DOI:10.1039/c8sc02106f

Easily available α-carbonyl acetates serve as convenient alkyl radical source for an efficient, photocatalytic cross-coupling with a great variety of styrenes. Activation of electronically different α-acetylated acetophenone derivatives could be effected via LUMO lowering catalysis using a superior, synergistic combination of water and (water-compatible) Lewis acids. Deliberate application of fac-Ir(ppy)₃ as photocatalyst to enforce an oxidative quenching cycle is crucial to the success of this (umpolung type) transformation. Mechanistic particulars of this dual catalytic coupling reaction have been studied in detail using both Stern-Volmer and cyclic voltammetry experiments. As demonstrated in more than 30 examples, our water-assisted LA/photoredox catalytic activation strategy allows for excess-free, equimolar radical cross-coupling and subsequent formal Markovnikov hydroxylation to versatile 1,4-difunctionalized products in good to excellent yields.

Full text of DOI:10.1039/c8sc02106f

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DOI: 10.1039/C8SC02106F
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EDGE ARTICLE
A Synergistic LUMO Lowering Strategy Using Lewis Acid Catalysis in
Water to Enable Photoredox Catalytic, Functionalizing C-C Cross-
Coupling of Styrenes
Received 00th January 20xx,
Accepted 00th January 20xx
Elisabeth Speckmeier, a Patrick J. W. Fuchs a and Kirsten Zeitler a
*
Easy available α-carbonyl acetates serve as convenient alkyl radical source for an efficient, photocatalytic cross-coupling with a
great variety of styrenes. Activation of electronically different α-acetylated acetophenone derivatives could be effected via
LUMO lowering catalysis using a superior, synergistic combination of water and (water-compatible) Lewis acids. Deliberate
application of fac-Ir(ppy)3 as photocatalyst to enforce an oxidative quenching cycle is crucial to the success of this (umpolung
type) transformation. Mechanistic particulars of this dual catalytic coupling reaction have been studied in detail using both
Stern-Volmer and cyclic voltammetry experiments. As demonstrated in more than 30 examples, our water-assisted
LA/photoredox catalytic activation strategy allows for excess-free, equimolar radical cross-coupling and subsequent formal
Markovnikov hydroxylation to versatile 1,4-difunctionalized products in good to excellent yields.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Visible light photocatalysis as a powerful tool for the selective
generation of radicals has given rise to numerous
unprecedented C-C-coupling reactions in recent years.1
Especially alkyl radicals2 have attracted great interest for the
formation of highly functionalized natural products and
pharmaceuticals.3 Back in 1985, Kellogg, one of the early
pioneers of visible light photocatalysis, explored the reactivity
of the electron deficient phenacyl radical generated by the
photocatalytic single electron reduction of the corresponding
phenacyl bromide.4 Since then, this electrophilic radical
species has enabled the access to a variety of interesting
radical trapping reactions for the implementation of new C-C-
coupling transformations.5 However, phenacyl bromide is well
known to promote radical polymerizations and also to be
susceptible to nucleophilic substitutions (and hence enabling
undesired polar reaction pathways) as for example,
demonstrated for pyridines6 or under basic conditions.7 We
Scheme 1 Design plan for a functionalizing sp3-sp2-photocatalytic cross-coupling
reaction.
corresponding α-acetoxy acetophenone (Ered = -1.72 V vs SCE) is
more negative than the reduction potential of bromo
acetophenone (Ered = -1.45 V vs SCE), we considered based on
our recent C-O-bond cleaving studies,11 that this reduced affinity
to accept electrons could, in addition, be beneficially utilized as
a promising, assistant tool to enhance reaction control and
selectivity by deliberate lowering of the carbonyl LUMO.
hence assumed, that less activated α-acetoxy acetophenone
could be a promising alternative for radical C-C coupling
reactions avoiding undesired pathways.
Especially, in addition, bromide itself cannot be considered as a
photochemically innocent leaving group based on its redox
properties: With an oxidation potential of only 0.66 V vs SCE
(Eox (Br●/Br-) = 0.66 V) mesolytically cleaved bromide anions can
easily get oxidized to the corresponding bromine radicals and
hence potentially may also form elemental Br2 by most common
Using synergistic photoredox catalysis with amino
organocatalysis MacMillan and co-workers could already
demonstrate that
with common
-bromo acetophenone12 and, very recently, as
well as with significantly less reactive -acetoxy derivatives as
non-traditional radical precursors.13 14 We hence questioned, if
α-alkylation of aldehydes can be achieved
α
α
, ,
photocatalysts.8 9 10 Although, as the reduction potential of the
,
such α-acetoxy derived radicals as “alkylation reagent” could
provide the required selectivity for a photocatalytic sp3-sp2 C-C
cross-coupling with styrenes followed by an oxidation to give
a.Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103
Leipzig, Germany. E-mail: kzeitler@uni-leipzig.de.
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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cation being crucial for achieving the targeted, additional
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Markovnikov functionalization. Two possDibOleI: 1p0a.1t0h3w9/aCy8sSCfo0r21t0h6iFs
supposed limitation could be considered to be operating:
Apart from a competitive oxidation of the reductive quencher
(e. g. R3N), well-established HAT (hydrogen atom transfer)
from the tertiary amine´s radical cation, being present in
increasing concentrations during the progress of the reaction,
could operate as an additional detrimental pathway. As
anticipated, no Markovnikov product was obtained while
conducting the reaction with tributylamine as electron donor,
following a reductive quenching cycle (Scheme 2 / right).
Instead, hydrogen atom abstraction took place as subsequent
reaction step after the catalytic cycle to provide the coupling
product
3 in an isolated yield of 83%. However, our attempts
to transfer these promising, “reductive quenching coupling
conditions”, which albeit miss the targeted additional
functionalization, to less reactive styrenes (instead of our
initial test substrate 1,1-diphenylethylene 2) were not met with
success. Further competitive reaction pathways (Scheme 3)
impede the coupling with styrene, such as the direct
abstraction of a hydrogen atom from the reductive quencher
by the phenacyl radical (product 5) (HAT), as well as the radical
addition onto an enamine species derived from the
degradation of the amine quencher providing the alternative
aldehyde coupling product 6 via aminocatalysis (Scheme 3).
Oxidative quenching conditions: fac-Ir(ppy)3, 0.5 mmol 1, 1.0 mmol 2 in MeCN/H2O 4:1,
irradiation with blue LEDs; yield of isolated product 4: 33%. Reductive quenching
conditions: 4CzIPN,15 1.5 equiv NBu3, 0.5 mmol 1, 1.0 mmol 2 in MeCN/H2O 4:1,
irradiation with blue LEDs; yield of isolated product 3: 83%.
Scheme 2. Oxidative vs reductive quenching conditions for the C–C coupling of α-acetoxy
acetophenone and 1,1-diphenylethylene and simplified comparison of the corresponding
different reaction pathways.
the respective Markovnikov-type functionalized products
(Scheme 1). This challenging photocatalytic/radical polar
crossover reaction would offer unprecedented access to
Scheme 3 Undesired side products present in cross-coupling reactions following
a reductive quenching cycle.
1,4-functionalized synthons, such as γ-hydroxyketones, being
Fortunately, employing fac-Ir(ppy)3 as photocatalyst in a redox
neutral oxidative quenching cycle mediates the targeted
functionalizing C-C coupling reaction to yield the desired
versatile building blocks for the synthesis of a variety of
bioactive compounds.16
1,4-functionalized product
phenone ( ) was reduced by fac-Ir(ppy)3 (E1/2 (Ir(III)*/Ir(IV)) = -1.73 V
vs SCE)17b without further attempts to lower the carbonyl LUMO.
Although the reduction potential of seems to be too negative for a
direct reduction (Ered = -1.72 V vs SCE), we could already obtain 33%
of the desired functionalized coupling product . Notably, this
4. Remarkably, the α-acetoxy aceto-
Results and Discussion
1
Based on our previous experience in C-O-bond activation,11 we
approached our cross-coupling investigations right from the
beginning with a focus on mechanism, especially considering
the crucial role of the quenching cycles of the photocatalyst
(Scheme 2).17 Initial test reactions employing simple oxidative
(Scheme 2 / left) and reductive quenching conditions (Scheme
1
4
preliminary finding indicated, that the carbonyl group may here
even be significantly activated for reduction, respectively for a
PCET-type reduction with water as omnipresent hydrogen bond
donor under our aqueous conditions.21
2 / right) for the coupling of α-acetoxy acetophenone (
1) as
radical precursor and 1,1-diphenylethylene as well-
(2)
established activated coupling partner,18 confirmed our
hypothesis, that a reductive quenching cycle would be
inappropriate for this intended reaction.
Having this in mind, we initiated a detailed screening, again using
styrene (7) as a more challenging, less activated coupling partner
(Table 1). Additional to water as H-bond donor present in our
solvent mixture, we evaluated different activation modes for the
LUMO lowering of carbonyl group,22 including Schreiner´s
thiourea,23 as well as different lanthanide-based, water-
Using tertiary amines as reductive quenchers typically offers
the great advantage of an extensive LUMO-lowering of the
carbonyl group via hydrogen bond/PCET19 activation or
2-center/3-electron interaction,20 respectively, effected by the
tertiary amine´s radical cation. However, we expected that
such a reductive quenching cycle would impede the necessary
oxidation of the benzylic radical to the corresponding benzylic
,
compatible Lewis acids.24 25 Interestingly, the choice of the
activation mode (entries 2, 3), as well as the choice of the
lanthanide Lewis acid (entry 5-9) seems to be insignificant for the
coupling product´s yield.
2 | Chem. Sci., 2018, 00, 1-3
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Table 1 Optimization of oxidative quenching conditions for styrene cross-coupling.
Table 2 Control experiments.
View Article Online
DOI: 10.1039/C8SC02106F
entry
1bcd
catalyst
additive
thioureae
1:7
yielda
19%
entry
deviation from the standard conditions
yielda
0%
1b
2b
3
no catalyst
no light
1 mol % fac-Ir(ppy)3
1:4
2bc
3bc
4c
5
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
1 mol % fac-Ir(ppy)3
0.5 mol% fac-Ir(ppy)3
thioureae
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Er(OTf)3
Gd(OTf)3
Dy(OTf)3
Nd(OTf)3
Nd(OTf)3
1:4
1:4
1:2
1:2
1:2
1:2
1:2
1:2
1:1
45%
46%
58%
82%
85%
88%
90%
91%
92%
0%
no Lewis acid
no water, but MeOH
no base
64%
0%c
61%
38%
0%
4
5
6
7
bromo acetophenone as radical source
Ir(dtbby)(ppy)2(PF6) as catalyst
6
7
a conditions: 0.5 mol % fac-Ir(ppy)3, 10 mol % Nd(OTf)3, 2 equiv K2CO3, 0.25 mmol
1, 0.25 mmol 7 in 1 mL MeCN/H2O 4:1, degassed, irradiation with blue LEDs, 2 h,
yield determined by GC-FID using mesitylene as internal standard; b 48 h reaction
time. c only minor conversion of 1; traces of 1,4-diphenylbut-3-en-1-one (corresp.
alkene to 8) and dimerization product 1,4-diphenylbutane-1,4-dione were
detected by GC/MS.
8
9
10
a
conditions: catalyst, 10 mol % additive, 2 equiv K2CO3, 0.25 mmol 1, 7 in 1 mL
MeCN/H2O 4:1, degassed, irradiation with blue LEDs, 2 h, yield determined by
b
c
The catalytic amount of Lewis acid strongly enhances the
effect on lowering the carbonyl`s LUMO; this may also be in
the context of the formation of Lewis acid water complexes to
GC-FID using mesitylene as internal standard; 20 mol % additive; without
degassing; d MeCN as solvent; e Schreiner´s thiourea catalyst.
,
promote PCETs as well-known for SmI2-water systems.27 28
However, Schreiner´s thiourea catalyst proved to be rather
unstable under these photocatalytic conditions. To avoid large
catalyst loadings and additional side products formed via the
degradation of the thiourea catalyst, we decided to continue
our investigations with neodymium triflate as Lewis acid in a
dual activation, synergistic catalysis.26 Furthermore, the yield
of coupling product could be dramatically increased by
degassing the reaction (entries 4, 5), to 91% (entry 9).
Additionally, decreasing the styrene equivalents to an
equimolar amount, as well as lowering the catalyst loading to
0.5 mol % had no negative influence nor on the yield neither
on the reaction time (2 h) (entry 10 (92%)). Notably, these
optimized reaction conditions allow for equimolar cross-
However, without the addition of water Nd(OTf)3 is almost
insoluble in acetonitrile and therefore cannot effectively
contribute to the carbonyl activation (entry 4). The exchange of
the acetate leaving group with bromide (entry 6) significantly
decreased the yield of the desired coupling product
8 to 38%.
While full conversion of the bromo acetophenone was still
reached after 2 h of irradiation, numerous, not further
determined side products were formed, clearly proving the
crucial role of the radical source for this cross-coup-
ling/functionalization protocol. An additional test reaction using
Ir(dtbbpy)(ppy)2(PF6) as strongly reductive catalyst for reductive
quenching cycles, but weaker reductive power of its excited
state (E(Ir(III)/Ir(II)) = -1.51 V vs SCE; E(Ir(III)*/Ir(IV)) = -0.96 V vs
SCE)17b failed to provide any product and further confirms the
oxidative quenching cycle of this cross-coupling.
coupling of radical precursor
1 and styrene 7 to the
1,4-functionalized product in excellent yield, avoiding typical
side reactions, such as styrene polymerization or hydrogen
abstraction of the α-acetylated acetophenone.
We then set out to prove the synergistic combination of water
and Lewis acid in a series of mechanistic studies. Initially, we
wanted to “visualize” and somewhat quantify the LUMO lowering
effect by cyclic voltammetry measurements29 to monitor the
influence of different additives on the reduction potential (Figure
1) and hence to gain a more detailed mechanistic understanding.
The control reactions (Table 2) confirmed the decisive role of
both catalyst and visible light, as without each no reaction
occurred during 48 h of elongated reaction time (entries 1, 2).
The omission of Lewis acid (entry 3) decreases the yield to only
64%. An experiment performed in acetonitrile without water,
but offering MeOH as alternative nucleophile (entry 4), did not
provide any of the corresponding methoxy adduct. In
combination with entry 3 this clearly shows the synergistic
interaction of both activation modes.21,26 Water can lower the
carbonyl LUMO only by weak hydrogen bonds, however
greatly contributes to the success of the reaction by creating a
two-phase system, which additionally shifts the equilibrium to
the cross-coupling process.
Insightfully, both the addition of water as well as of
neodymium triflate results in a significant decrease of the
measured reduction potential of
While without any additive the potential of
high for thermodynamically favorable reduction with
α-acetoxy acetophenone
1.
1
is slightly too
a
fac-Ir(ppy)3, the solvent mixture (MeCN/water 4:1 (v/v))
already lowers the reduction potential sufficiently to enable
the reduction of
1 and hence points to the often neglected,
however crucial role of solvents, especially water, for
(photo)redox processes.30
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performed in an acetonitrile/water mixture (4:V1iew(vA/rtvic)le),Ontlhinee
DOI: 10.1039/C8SC02106F
emission of fac-Ir(ppy)3 is clearly quenched by α-acetoxy
acetophenone
1. We further proved the importance of the
exclusion of oxygen (table 1, entries 4,5) in this reaction:
quenching study C shows energy transfer to O2 for the singlet
oxygen production31 to be a strongly preferred quenching
pathway of fac-Ir(ppy)3 in these solvent conditions.
Fc/Fc+
Based on these studies and our experimental results, we
propose the following mechanism for this functionalizing,
radical C-C-coupling reaction (Scheme 4) starting with the
excitation of the Ir catalyst followed by an oxidative quenching
via single electron transfer to the activated carbonyl group of
1
. The mesolytic cleavage of the C-O-bond leads to electron
deficient radical 9, which can now attack the styrene.
Subsequently, the newly created benzylic radical 10, which
may be stabilized by intramolecular cyclization5g to
radical 10cycl and hence suppress possible, undesired side
reactions (polymerization etc.), can be oxidized by the Ir(IV)
species. Upon regeneration of the photocatalyst this results in
a radical polar crossover to benzylic cation 11, respectively its
cyclized variant 11cycl. Final attack of water can then lead to
the formation of the 1,4-ketohydroxy product.
For details on electrodes, concentration and measurement conditions see ESI.
Fig. 1 LUMO-lowering effects on reduction potential of subject to different
conditions.
1
Notably, the combination of both activation modes, the
aqueous solvent system plus a water-compatible Lewis acid,27
significantly lowers the potential by 0.5 V and hence contributes
to an even more exergonic electron transfer process.
[Nd]
OAc
[Nd]
[Nd]
O
O
anthanide Lewis acid
for LUMO lowering
in aqueous solvent
l
O
-
OAc
Furthermore, we could confirm these observations by Stern-
Volmer experiments (Figure 2), also corroborating our initial
studies with diphenylethylene (see also Scheme 2).
Ar
Ar
Ar
R1
1
9
OAc
R2
R1
R2
O
[Nd]
O
*IrIII
IrIV
R1
Ar
oxidative
quenching
cycle
R2
IrIII
R1
Quenching Study A
Quenching Study B
600000
400000
200000
0
600000
400000
200000
0
Ar
O
R2
0 mM
1 mM
2 mM
3 mM
4 mM
5 mM
6 mM
7 mM
IrIV
0 mM
1 mM
2 mM
3 mM
4 mM
5 mM
6 mM
7 mM
10
Ar
10cycl
IrIII
Ar
[Nd]
O
O
R1
R1
H2O
R1
O
R2
R2
Ar
Ar
R2
11cycl
OH
11
Scheme 4 Proposed mechanism.
400
500
600
700
400
500
600
700
λ [nm]
λ [nm]
600000
400000
200000
0
8
6
4
2
0
Quenching Study C
Stern Volmer Plot
degassed
not degassed
Having optimized conditions and
a
mechanistic
understanding at hand, we set out to examine the scope of
the reaction starting with different styrenes (Scheme 5).
Notably, all tested vinyl benzenes could successfully be
coupled with the acetophenone radical. With exception of
product 17, whose styrene precursor is known to be
strongly prone to polymerization, all coupling products
were obtained in good to excellent yields (up to 96%).
Interestingly, there is no recognizable difference for the
coupling of styrenes with electron withdrawing (12-15) and
MeCN/H2
O 4:1
MeCN
400
500
600
700
0
2
4
6
8
c (Q) [mM]
λ [nm]
Fluorescence spectra for fac-Ir(ppy)3 (50 µM) with increasing amounts of α-acetoxy
acetophenone 1 (0-7 mM) as quencher. Quenching study A: in MeCN; quenching
study B: in MeCN/H2O 4:1; quenching study C: presence of oxygen. For further details,
see ESI.
electron donating substituents (16, 18, 19). The direct
Fig. 2 Stern-Volmer quenching studies.
comparison of the three different regioisomeric bromo
styrenes (12-14) nicely shows the insensitivity of the
transformation towards sterically hindrance being a typical
advantage of radical coupling reactions.32
While quenching study A shows no relevant decrease in the
photocatalyst´s fluorescence with increasing concentrations of
1
in pure (dry) acetonitrile, only in quenching study B,
4 | Chem. Sci., 2018, 00, 1-3
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DOI: 10.1039/C8SC02106F
a Conditions: 0.5 mol % fac-Ir(ppy)3, 10 mol % Nd(OTf)3, 2 equiv K2CO3, 0.5 mmol
1, 0.5 mmol styrene derivative in 2 mL MeCN/H2O 4:1, degassed, irradiation with blue
LEDs; isolated yields.
Scheme 5 Substrate scope for C-C-coupling with styrene derivatives.a
Even quaternary centers (e. g. tertiary alcohols) could be
generated in excellent yields by either employing
the attacking alkyl radical, respectively of the substrate´s
carbonyl group for the initial SET reduction.
α-methylstyrene (product 20) or 1,1-diphenylethylene
(product 4). To further elucidate the broad scope of our
approach for radical cross-couplings with styrenes, we then
investigated the trapping of radicals derived from different
substituted
α-acetoxy acetophenone precursors with a
selection of four different styrenes (Scheme 6). Gratifyingly,
we could obtain the desired products for all tested
combinations within our “4x5 matrix”. While the yields for
the combination of
styrenes are all consistently very good to excellent (82-96%;
see Scheme 5 products: 15 16 19,) the difference in
performance becomes more apparent for other,
substituted -acetylated acetophenones (Scheme 6:
acetophenones ). The cross-coupling of styrenes with
-tetralone derivative , as precursor for secondary radicals,
tolerates styrenes bearing an electron withdrawing group
21) as well as a mesomeric electron donating effect (22
α-acetoxy acetophenone 1 with these
8
,
,
,
α
I-V
α
I
(
)
(77-89%). However, the yield decreases to 53% in
combination with the sterically demanding and inductive
electron donating tert-butyl substituent present
(23).
Interestingly, the electron donating methyl group (II) and the
electron withdrawing chloro-substituent (III) did not show an
opposing trend for their performance as coupling partners.
According to this observed reactivity, the polarity match
seems to be of minor importance for the success of this
radical transformation. However, the mesomeric effect
of the para-methoxy substituent (acetophenone IV)
shows a notable decrease of all yields being best
explained by the lowering of the electron deficiency of
a
Conditions: 0.5 mol % fac-Ir(ppy)3, 10 mol % Nd(OTf)3, 2 equiv K2CO3, 0.5
mmol acetoxy substrate, 0.5 mmol styrene derivative in 2 mL MeCN/H2O 4:1,
degassed, irradiation with blue LEDs; isolated yields.
Scheme 6 Substrate scope for functionalizing radical polar cross-coupling
reaction with styrenes.a
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4
5
A. H. Mashraqui and R. M. Kellogg, 3-Methyl-2,3-
Altering the position of the substituent further illustrates
this effect with the observed increased yield for the
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dihydrobenzothiazoles as ReducingDAOgI:e1n0t..10D3y9e/CE8nSCh0a2n1c0e6dF
Photoreaction. Tetrahedron Lett., 1985, 26, 1449–1452.
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and E. Meggers, Asymmetric Photoredox Transition-Metal
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V
(Scheme 6/line 5: –I effect only).
Catalysis Activated by Visible Light. Nature, 2014, 515
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Conclusions
In summary, we have developed a novel equimolar cross-
coupling reaction of -acetoxy acetophenones and styrene
α
derivatives with a subsequent Markovnikov functionali-
zation to provide efficient access to versatile
1,4-substituted building blocks in good to excellent yields.
The reaction was realized by the oxidative quenching of
fac-Ir(ppy)3 in combination with effective synergistic
activation of the carbonyl group with water and Nd(OTf)3.
Detailed mechanistic investigations were performed,
including cyclic voltammetry and Stern-Volmer experi-
ments, to examine the LUMO-lowering effect in detail. Our
mechanistic studies reveal the impact of radical source and
choice of photocatalyst on both reactivity and selectivity
and support the crucial importance of the deliberate
application of fac-Ir(ppy)3 as an “oxidative quenching
cycle”-only catalyst for this challenging functionalizing
cross-coupling reaction. Moreover, our studies shed further
light on the often neglected, but critical role of aqueous
solvent systems in photoredox reactions.
α
-Carbonyl Alkyl Bromides and Benzyl Bromides. Chem.
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references reported therein.
Conflicts of Interest
6
(a) A. Fábián, F. Ruff and Ö. Farkas, Mechanism of
Nucleophilic Substitutions at Phenacyl Bromides with
Pyridines. A Computational Study of Intermediate and
Transition State. J. Phys. Chem., 2008, 21, 988–996. For an
example of using 4-methoxy pyridine to supposedly
There are no conflicts to declare.
Acknowledgements
This work was generously supported by the Deutsche
Forschungsgemeinschaft (DFG, GRK 1626).
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M. Sheridan, Y. Wang, D. Wang, L. Troian-Gautier, C. J.
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Org. Process Res. Dev., 2016, 20, 1134–1147. (b) M. D.
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10 See ESI for the cyclovoltammetric detection of bromide
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11 (a) E. Speckmeier, C. Padié and K. Zeitler, Visible Light
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12 D. A. Nicewicz and D. W. C. MacMillan, Merging
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T. M. Monos, G. Magallanes, L. J. Sebren and C. R. J.
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6
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16 A. P. Taylor, R. P. Robinson, Y. M. Fobian, D. C. Blakemore,
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26 For recent
reviews
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dual
activation
17 For selected recent reviews, see: (a) Special issue
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Res. 2016, 49. (b) C. K. Prier, D. A. Rankic and D. W. C.
MacMillan, Visible Light Photoredox Catalysis with
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18 Selected recent examples: (a) W. Liu, H. Cao, H. Zhang, H.
Zhang, K. H. Chung, C. He, H. Wang, F. Y. Kwong and A.
Lei, Organocatalysis in Cross-Coupling: DMEDA-Catalyzed
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27 For selected examples: (a) T. V. Chciuk, W. R. Anderson Jr.
and R. A. Flowers II, Proton-Coupled Electron Transfer in
the Reduction of Carbonyls by Samarium Diiodide−Water
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(b) S. Shi, R. Szostak and M. Szostak, Proton-Coupled
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SmI2–H2O: Implications for the Reductive Coupling of
Acyl-Type Ketyl Radicals with SmI2–H2O. Org. Biomol.
Chem., 2016, 14, 9151–9157. (c) T. V. Chciuk, W. R.
Anderson and R. A. Flowers II, High-Affinity Proton
Donors Promote Proton-Coupled Electron Transfer by
Catalysed Intermolecular Radical Addition of
α-Halo
Amides to Olefins. Chem. Commun., 2014, 50, 3619–3622.
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19 (a) M. H. V. Huynh and T. J. Meyer, Proton-Coupled
Electron Transfer. Chem. Rev., 2007, 107, 5004–5064.
(b) D. R. Weinberg, C. J. Gagliardi, J. F. Hull, C. Fecenko
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(c) K. E. C. Gentry and R. R. Knowles, Synthetic
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Chem. Res., 2016, 49, 1546–1556.
20 M. Nakajima, E. Fava, S. Loeschner, Z. Jiang and M.
Rueping, Photoredox-Catalyzed Reductive Coupling of
Aldehydes, Ketones, and Imines with Visible Light. Angew.
Chem., Int. Ed., 2015, 54, 8828–8832.
21 Please also see Stern-Volmer studies (figure 2 and ESI)
corroborating the pivotal role of water in the catalytic
system.
22 For a recent review, see: K. N. Lee and M.-Y. Ngai, Recent
Developments in Transition-Metal Photoredox-Catalysed
Reactions of Carbonyl Derivatives. Chem. Commun., 2017,
53, 13093–13112.
Samarium Diiodide. Angew. Chem., Int. Ed., 2016, 55
6033–6036.
,
28 The enhanced LUMO lowering effect by addition of
lanthanide Lewis acids within the aqueous solvent system
may also be considered as a case of “Lewis acid assisted
Brønstedt acid catalysis” (LBA) as classified by Yamamoto:
H. Yamamoto and K. Futatsugi, K. ”Designer Acids”:
Combined Acid Catalysis for Asymmetric Synthesis.
Angew. Chem., Int. Ed., 2005, 44, 1924–1942.
29 (a) R: S. Nicholson,. Theory and Application of Cyclic
Voltammetry for Measurement of Electrode Reaction
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mechanistic investigations by cyclic voltammetry see: T.
Liedtke, P. Spannring, L. Riccardi and A. Gansäuer, A.
Mechanism-Based Condition-Screening for Sustainable
Catalysis in Single Electron Steps by Cyclic Voltammetry.
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30 (a) see ref. 11b. For a recent instructive examples, also see:
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Markovnikov Hydroarylation of Unactivated Olefins via
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32 (a) G. L. Lackner, K. W. Quasdorf and L. E. Overman, Direct
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1 Ravelli, D.; Protti, S., Fagnoni, M. “Carbon–Carbon Bond Forming Reactions via Photogenerated Intermediates”, Chem. Rev., 2016, 116, 9850-9913.
2 Matsui, J. K.; Lang, S. B.; Heitz, D. R.; Molander, G. A. ACS Catal. 2017, 7, 2563–2575
3 a) Douglas, J. J.; Sevrin, M. J.; Stephenson, C. R. J. “Visible Light Photocatalysis: Applications and New Disconnections in the Synthesis of Pharmaceutical Agents” Org. Process Res. Dev., 2016,
20 (7), pp 1134–1147; b) Kärkäs, M. D.; Porco Jr., J. A.; Stephenson, C. R. J., “Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis” Chem. Rev., 2016, 116 (17),
pp 9683–9747
4 Mashraqui, A. H.; Kellogg, R. M. “3-Methyl-2,3-dihydrobenzothiazoles as reducing agent. Dye enhanced photoreaction.”, Tett. Lett., 1985, 1449-1452.
5 For a selection see: a) Huo, H.; Shen, X.; Wang, C.; Zhang, L.; Röse, P.; Chen, L.-A.; Harms, K.; Marsch, M.; Hilt, G.; Meggers, E. “Asymmetric photoredox transition-metal catalysis activated by
visible light”, Nature, 2014, 515, 100-103. b) Dange, N.; Jatoi, A. H.; Robert, F.; Landais, Y. “Visible-Light-Mediated Addition of Phenacyl Bromides onto Cyclopropenes”, Org. Lett., 2017, 19, 3652-3655.
c) Chen, W.; Liu, Z.; Tian, J.; Li, J.; Ma, J.; Cheng, X.; Li, G. “Building Congested Ketone: Subsituted Hantzsch Ester and Nitrile as Alkylation Reagents in Photoredox Catalysis”, J. Am. Chem. Soc.,
2016, 138, 12312-12315. and references reported herein.
6 Fábián A.; Ruff, F.; Farkas, Ö. “Mechanism of nucleophilic substitutions at phenacyl bromides with pyridines. A computational study of intermediate and transition state”, J. Phys. Chem., 2008, 21, 988-996.
7
Zhang, P.; Le, H.; Kyne, R. E.; Morken, J. P. „Enantioselective Construction of All-Carbo Quarternary Centers by Brach-Selective Pd-Catayzed Allyl-Allyl Cross-Coupling“ J. Am. Chem. Soc., 2011, 133,
9716-919.
8
Sheridan, M.; Wang, Y.; Wang, D.; Troian-Gautier, L.; Dares, C. J.; Sherman, B. D.; Meyer, T. J. Light-Driven Water Splitting Mediated by Photogenerated Bromine. Angew. Chem. Int. Ed. 2018, 57, 3449-
3453.
9 Hydrogen vs. electron transfer mechanisms in the chain decomposition of phenacyl bromides. Use of isotopic labeling
as a mechanistic probe Jocelyn Renaud and J.C. Scaiano Can. J. Chem. 74: 1724-1730 (1996).
10 Si HInweis CV mit phenacyl bromide
11 a) Speckmeier, E.; Padié C.; Zeitler, K. „Visible Light Mediated Reductive Cleacage of C-O Bonds Accessing a-Subsituted Aryl Ketones”, Org. Lett., 2015, 17, 4818-4821. b) Speckmeier, E.; Zeitler, K. “Desyl
and Phenacyl as Versatile, Photocatalytically Cleavable Protecting Group – A Classic Approach in a Different (Visible) Light”, ACS Catal., 2017, 7, 6821-6826.
12 Nicewicz, D. A.; MacMillan, D. W. C., „Merging Photoredox Catalysis with Organocatalysis: The Direct Asymmetric Alkylation of Aldehydes”, Science, 2008, 322, 77-80.
13 Nacsa, E. D.; MacMillan, D. W. C. „Spin-Center Shift-Enabled Direct Enantioselective a-Benzylation of Aldehydes with Alcohols”, J. Am. Chem. Soc, 2018, 140, 3322-3330.
14 Photochem photobiol Stephenson
15 Uoyama, H.; Goushi, K.; Shizu, K.; Nomura, H.; Adachi, C. Nature, 2012, 492, 234-238.
16 Taylor, A. P.; Robinson, R. P.; Fobian, Y. M.; Blakemore, D. C.; Jones, L. H.; Fadeyi, O. “Modern Advances in heterocyclic chemistry in drug discovery.” Org. Biomol. Chem. 2016, 14, 6611−6637.
17 For selected recent reviews, see: (a) Special issue “Photoredox
Catalysis in Organic Chemistry”: Acc. Chem. Res. 2016, 49. (b) Prier,
C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113,
5322−5363. (c) Zeitler, K. Angew. Chem., Int. Ed. 2009, 48, 9785−
9789.
18 W. Liu, H. Cao,H.Zhang,H.Zhang,K.H.Chung,C.He, H.
Wang,F.Y.Kwong,A.Lei, J. Am. Chem. Soc. 2010, 132,16737 –
16740
19 a) Huynh, M. H. V.; Meyer, T. J. “Proton-Coupled Electron Transfer” Chem. Rev., 2007, 107 (11), pp 5004–5064. b) Weinberg, D. R.; Gagliardi, C. J.; Hull, J. F.; Fecenko Murphy, C. .; Kent, C. A.; Westlake,
B. C.; Paul, A.; Ess, D. H.; Granville McCafferty, D.; Meyer, T. J. “Proton-Coupled Electron Transfer”, Chem. Rev., 2012, 112 (7), pp 4016–4093.
20 Nakajima, M.; Fava, E.; Loeschner, S.; Jiang, Z.; Rueping, M. „Photoredox-Catalyzed Reductive Coupling of Aldehydes, Ketones and Imines with Visible Light”, Angew. Chem. Int. Ed., 2015, 54, 8828-8832.
21 Hinweis auf Stern volmer als mech tool….
22 Ngai ChemComm2017 Review Carbonyl groups
23 A) Schreiner, P. R. Chem. Soc. Rev., 2003, 32, 289-296. B) Pihko, P. M. Angew. Chem. Int. Ed. 2004, 43, 2062 –2064.
24
For other successfull carbonyl activations with lanthan-based triflates also see: a) Du, J.; Skubi, K. L.; Schultz, D. M.; Yoon, T. P. “A Dual-Catalysis Approach to Enantioselective [2+2] Photocycloadditions
Using Visible Light”, Science, 2014, 344, 392-396. b) Amador, A. G.; Sherbrook, E. M.; Yoon, T. P. “Enantioselective Photocatalytic [3+2] Cycloadditions of Aryl Cyclopropyl Ketones”, J. Am. Chem. Soc.,
2016, 138, 4722-4725.
25 Ngai pyridine styrol Ln Activation
26 Reviews zur dualen Photokatalyse
27 PCET SmI2 and Water
28 Lewis acid assisted Bronsted Acid. Review Yamamoto
29
A) Nicholson, R. S. “Theory and Application of Cyclic Voltammetry for Measurement of Electrode Reaction Kinetics”, Anal. Chem., 1965, 37, 1351-1355. B) Jutand, A. “Contribution of Electrochemistry to
Organometallic Cataysis”, Chem. Rev., 2008, 108, 2300-2347. c) For other mechanistic investigations by cyclic voltammetry see: Liedtke, T.; Spannring, P.; Riccardi, L.; Gansäuer, A. “Mechanism-Based
Condition-Screening for Sustainable Catalysis in Single Electron Steps by Cyclic Voltammetry”, just accepted.
30 Role of water – Jui paper
31 Mulazzani, Q. G.; Sun, H.; Hoffman, M. Z.; Ford,
W. E.; Rodgers, M. A. J. J. Phys. Chem. 1994, 98, 1145–1150. (b) Tanielian,
C.; Wolff, C.; Esch, M. J. Phys. Chem. 1996, 100, 6555–6560.
32 a) Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem.
Soc. 2013, 135, 15342. b) Chu, L.; Ohta, C.; Zuo, Z.; MacMillan, D. W. C. J. Am. Chem. Soc.
2014, 136, 10886. c) Nawrat, C. C.; Jamison, C. R.; Slutskyy, Y.; MacMillan, D. W. C.; Overman, L. E. J. Am. Chem. Soc. 127, 35, 11270-11273.
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Table of Contents Entry
Synergistic LUMO activation by water and lanthanide Lewis acids allows for photocatalyzed C-O bond
breaking cross coupling of α-acetoxy carbonyl compounds with styrenes.
KEYWORDS C-C cross-coupling, alkyl radicals, LUMO lowering, photocatalysis, visible light
1