Bis-Cyclometalated Indazole Chiral-at-Rhodium Catalyst for Asymmetric Photoredox Cyanoalkylations

Article abstract of DOI:10.1002/chem.201903369

A new class of bis-cyclometalated rhodium(III) catalysts containing two inert cyclometalated 6-tert-butyl-2-phenyl-2H-indazole ligands and two labile acetonitriles is introduced. Single enantiomers (>99 % ee) were obtained through a chiral-auxiliary-mediated approach using a monofluorinated salicyloxazoline. The new chiral-at-metal complex is capable of catalyzing the visible-light-induced enantioselective α-cyanoalkylation of 2-acyl imidazoles in which it serves a dual function as the chiral Lewis acid catalyst for the asymmetric radical chemistry and at the same time as the photoredox catalyst for the visible-light-induced redox chemistry (up to 80 % yield, 4:1 d.r., and 95 % ee, 12 examples).

Full text of DOI:10.1002/chem.201903369

A Journal of
Accepted Article
Title: Bis-Cyclometalated Indazole Chiral-at-Rhodium Catalyst for
Asymmetric Photoredox Cyanoalkylation
Authors: Philipp S. Steinlandt, Wei Zuo, Klaus Harms, and Eric
Meggers
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To be cited as: Chem. Eur. J. 10.1002/chem.201903369
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Bis-Cyclometalated Indazole Chiral-at-Rhodium Catalyst for Asymmetric Photoredox
Cyanoalkylation
Philipp S. Steinlandt, Wei Zuo, Klaus Harms, and Eric Meggers*
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg,
Germany
*
Corresponding author: meggers@chemie.uni-marburg.de
Abstract:
A new class of bis-cyclometalated rhodium(III) catalysts containing two inert cyclometalated 6-tert-
butyl-2-phenyl-2H-indazole ligands and two labile acetonitriles is introduced. Single enantiomers
(>99% ee) were obtained through a chiral-auxiliary-mediated approach using a monofluorinated
salicyloxazoline. The new chiral-at-metal complex is capable of catalyzing the visible-light-induced
enantioselective -cyanoalkylation of 2-acyl imidazoles in which it serves a dual function as the
chiral Lewis acid catalyst for the asymmetric radical chemistry and at the same time as the photoredox
catalyst for the visible-light-induced redox chemistry (up to 80% yield, 4:1 dr, and 95% ee, 12
examples).
1
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Introduction
Chiral transition metal complexes are a prominent and powerful class of asymmetric catalysts,
traditionally assembled from chiral organic ligands and metal salts or organometallic precursor
complexes.[1] The chiral organic ligands are typically involved in the asymmetric induction but also
control the relative and absolute configuration of the transition metal complexes. Following a
different strategy, we and others have recently demonstrated that chiral transition metal complexes
composed from entirely achiral ligands can be exquisite transition metal catalysts for a large variety
of asymmetric conversions, including asymmetric photocatalysis.[2-4] Such chiral-at-metal complexes
rely on a configurationally stable stereogenic metal center[5] for generating metal-centered chirality
which at the same time must be a reactive metal center for performing the asymmetric catalysis.[6]
Our initial design was based on bis-cyclometalated iridium(III) and rhodium(III) complexes,
in which two 5-tert-butyl-2-phenylbenzoxazoles (IrO[7] and RhO ) or 5-tert-butyl-2-
phenylbenzothiazoles (IrS[9] and RhS[10]) implement a stereogenic metal center with either a left-
handed (-configuration) or right-handed (-configuration) overall helical topology (Figure 1).
These two cyclometalated ligands are configurationally inert so that the overall stereochemical
information is retained in these complexes once they are generated in a non-racemic fashion. Two
additional monodentate acetonitrile ligands are labile and provide access of substrates or reagents to
the metal center.
[8]
We found that the nature of the cyclometalating ligand has a profound influence on the
reactivity and stereoselectivity of the bis-cyclometalated iridium(III) and rhodium(III) complexes[2]
and we were therefore seeking to investigate ligands that differ from our previous benzoxazole and
benzothiazole systems. Here we now introduce a new class of bis-cyclometalated chiral-at-metal
rhodium(III) catalysts which are based on two cyclometalated 6-tert-butyl-2-phenyl-2H-indazole
ligands (- and -RhInd). We demonstrate that this RhInd catalyst is superior for the visible-light-
induced enantioselective -cyanoalkylation of 2-acyl imidazoles in which RhInd serves a dual
function as the chiral catalyst but is also involved in the photochemical induction.
2
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Figure 1. Previous catalyst design and this work regarding bis-cyclometalated chiral-at-metal
rhodium and iridium catalysts for asymmetric conversions.
Results and Discussion
Design and synthesis of the rhodium catalyst
As part of our ongoing interest in expanding the structural diversity of bis-cyclometalated
rhodium-complexes, we chose 2-phenyl-2H-indazole as an interesting candidate. Bis-cyclometalated
iridium complexes with 2-phenyl-2H-indazoles are well established[11] but the analogous
rhodium(III) complexes have not been reported. The overall geometry of this ligand is comparable to
our previously applied benzoxazole and benzothiazole ligands, however, the electron-rich aromatic
system of 2H-indazoles provides significantly distinct electronics that might enable new catalytic
transformations. The chiral-auxiliary-mediated synthesis[12-14] of the enantiopure catalyst RhInd
started with the reaction of rhodium trichloride hydrate with 2.0 equiv. of 6-tert-butyl-2-phenyl-2H-
3
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10.1002/chem.201903369
indazole (1), followed by addition of 2.0 equiv. of AgPF
6
in MeCN to obtain bis-cyclometalated
rac-RhInd in 97% yield (Scheme 1). Afterwards, the racemic product was reacted with the
monofluorinated salicyloxazoline (S)-2[10,15,16] to provide the two diastereomers Λ-(S)-3 and Δ-(S)-4
in 40% and 48% yield, respectively, which were separated by column chromatography on deactivated
silica gel. The required high diastereomeric purity of the isolated auxiliary complexes was evaluated
by H-NMR and 19F-NMR spectroscopy. Cleavage of the auxiliary ligand was subsequently
performed under acidic conditions using trifluoroacetic acid (TFA), followed by anion exchange with
1
NH
4
PF to provide the individual enantiomers Λ-RhInd (95% yield) and Δ-RhInd (87% yield).
6
Scheme 1. Auxiliary-mediated synthesis of enantiopure Λ- and Δ-RhInd.
4
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The absolute configuration was assigned based on a crystal structure of Λ-RhInd (Figure 2a).
The CD spectra of Λ- and Δ-RhInd are shown in Figure 3 and confirm their mirror-imaged structures.
HPLC analysis on a chiral stationary phase exhibited an ee of > 99% for both the Λ- and the Δ-RhInd
complex (Figure 4). Superimposition of the crystal structures of RhInd and RhS showed a slightly
larger distance between the two quaternary carbon atoms of the tert-butyl groups for RhInd (11.3 Å)
making the catalytic site slightly larger compared to RhS (10.5 Å) (Figure 2b).[10a]
a)
b)
11.3 Å
(
RhInd)
10.5 Å
(
RhS)
Figure 2. a) Crystal structure of Λ-RhInd. ORTEP drawing with 50% probability thermal ellipsoids.
Hexafluorophospate counterion and solvent molecules are omitted for clarity. b) Superimposed
5
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crystal structure of Λ-RhInd (grey) with Λ-RhS (green). Fitted are the central metals together with
the metal-coordinated atoms.
100
-RhInd
-RhInd

50
0
-50
-100
200
300
400

(nm)
Figure 3. CD-spectra of Λ- and Δ-RhInd measured in MeOH (0.20 mM).
6
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10.1002/chem.201903369
Figure 4. HPLC traces of Δ, Λ, and racemic RhInd. HPLC conditions: Daicel CHIRALPAK IB-N5,

1
2
50 x 4.6 mm, column temp. = 25 °C, λabs = 254 nm, flow rate = 0.6 mL min , solvent A = 0.1%
aqueous TFA, solvent B = MeCN, gradient = 40% to 50% B in 180 min.
Initial experiments and optimization
With the new enantiopure complexes in hand, we next investigated the application of RhInd
for asymmetric photoredox catalysis.[17,18] After some initial reaction screening, we were delighted to
find that -RhInd (2.0 mol%) catalyzes the -cyanomethylation of 2-acyl imidazole 5a with
bromoacetonitrile (6a) in the presence of Na
2
HPO
4
and under irradiation with blue LEDs to provide
(
R)-7a with a high ee of 94% but in only 22% yield (Table 1, entry 1).[19] Table 1 shows the stepwise
optimization of this enantioselective visible-light-induced cyanoalkylation. First, different solvents
were investigated (entries 1-6) and it was found that MeOH/THF 4:1 provided the best results.
Changing the base from Na
2
HPO
4
to 2,6-lutidine or Cs
2
CO provided higher yields of 50% and 73%
3
but the enantioselectivity dropped to 87% and 4% ee. (entries 7 and 8). N,N-Diisopropylethylamine
(DIPEA) as base only provided 2% yield and 42% ee (entry 9). Despite the low yield, Na
2
HPO was
4
7
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selected as the most suitable base with respect to enantioselectivity. A higher catalyst loading afforded
better yields but a significantly lower enantioselectivity (entries 10 and 11). The reduced
enantioselectivity can be rationalized with a slow RhInd-catalyzed racemization of the product upon
product coordination, followed by deprotonation and reprotonation (see Supporting Information for
more details). Increasing the amount of bromoacetonitrile to 6.0 equiv. improved the yield while
maintaining a high ee (entry 12). Increasing the amount of base from 1.1 to 1.5 equiv. (entry 13) or
2
.0 equiv. (entry 14) provided further improved yields of 78% or 80%, respectively. Increasing the
amount of base further to 2.5 equiv. led to a sharp drop in the yield to 27%, probably due to the
resulting turbidity from the low solubility of Na HPO having a negative effect on the penetration by
2
4
the light into the reaction suspension (entry 15). Finally, it is worth noting that we found that small
amounts of water provide a beneficial effect, probably by facilitating rapid proton transfer, and
therefore stoichiometric amounts of water were added to each reaction shown in Table 1.
To summarize this part, we found reaction conditions for the photoinduced cyanoalkylation
reaction 5a + 6a  (R)-7a in 80% yield with 94% ee using 2 mol% of the chiral-at-rhodium complex

-RhInd as the single catalyst.
8
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Table 1. Initial experiments and optimization.[a]
Entry
Solvent
Base
Catalyst Equiv Yield [%] ee [%][b]
(
equiv)
(mol%)
of 6a
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
6.0
6.0
6.0
6.0
1
2
3
4
5
6
7
8
9
MeOH/THF 4:1
MeCN
Na
Na
Na
Na
Na
Na
2
2
2
2
2
2
HPO
4
4
4
4
4
4
(1.1)
(1.1)
(1.1)
(1.1)
(1.1)
(1.1)
2
2
2
2
2
2
2
2
2
4
8
2
2
2
2
22


15
17

50
73
2
47
99
76
78
80
27
94


80
79

87
4
42
78
56
94
94
94
92
HPO
HPO
HPO
HPO
HPO
THF
MeOH
MeOH/CH
2
Cl 1:1
2
MeOH/MeCN 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
MeOH/THF 4:1
2,6-Lutidine (1.1)
Cs CO (1.1)
DIPEA (1.1)
2
3
[
c]
1
1
1
1
1
1
0
1
2
3
4
5
Na
Na
Na
Na
Na
Na
2
2
2
2
2
2
HPO
HPO
HPO
HPO
HPO
HPO
4
4
4
4
4
4
(1.1)
(1.1)
(1.1)
(1.5)
(2.0)
(2.5)
[
(
(
a] Conditions: 2-Acyl imidazole 5a (0.10 mmol), Λ-RhInd (2-8 mol%) and the corresponding base
0.11-0.25 mmol) were dissolved in MeOH/THF 4:1 (0.5 mL) under inert gas atmosphere and H
0.56 mmol) was added. The resulting mixture was stirred for 5 min before bromoacetonitrile (0.30-
.60 mmol) was added and the mixture was degassed via freeze-pump-thaw for three cycles. The
reaction mixture was then stirred for 24 h under inert gas atmosphere at r.t. in front of blue LEDs
24 W, 10 cm distance). [b] Determined by HPLC analysis on chiral stationary phase. [c] DIPEA =
N,N-diisopropylethylamine.
2
O
0
(
9
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Substrate scope
After having established the optimized reaction conditions, we next investigated the scope of
the -cyanoalkylation with respect to 2-acyl imidazoles (5a-j) and -cyano bromides (6a-f) (Scheme
2
). Substrate 5a provided the best results with unbranched bromoacetonitrile (6a) with respect to yield
and enantioselectivity (7a). Interestingly, methyl substituted imidazole substrate 5b only gave 2%
yield and 80% ee (7b). Mesityl substituted imidazole substrate 5c provided 52% yield and an ee of
9
4% (7c). The addition of electron withdrawing and electron donating groups at the phenyl moiety
had a slightly disadvantageous effect on the yield as well as the enantioselectivity (7d-f). The
implementation of a naphthyl moiety resulted in a significantly lower yield and a moderate
enantioselectivity of 76% ee. (7g). 2-Thiophenyl substrate 5h showed no conversion at all, whereas
3
-thiophenyl substrate 5i provided 56% yield of 7i with 78% ee. This can be rationalized by a
bidentate coordination of the catalyst to the sulfur atom and the acyl oxygen of substrate 5h thus
impeding the conversion. Aliphatic substrate 5j only provided a low yield of 16% with 50% ee (7j).
Furthermore, five branched -cyano bromides were investigated. Diastereoselectivities were
1
validated by H-NMR spectroscopy of the crude products. Product 7k was formed in 64% yield with
a dr of 1.08:1. Both of the diastereomers showed high ee values of 94% and 95%. Product 7l was
formed with a dr of 3.01:1 with the major diastereomer exhibiting an ee of 94%. When -
bromophenylacetonitrile was used, the cyanoalkylation product 7m was obtained in 56% yield with
a dr of 4.01:1. Interestingly, the major diastereomer showed a very good ee of 95% while the minor
diastereomer was obtained with only 31% ee. Unfortunately, butyronitrile and isobutyronitrile did
not form any cyanoalkylation products (7n and 7o).
1
0
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Scheme 2. Substrate Scope. [a] Major diastereomer has the higher ee. [b] -RhInd was used instead
of the -enantiomer for product 7m.
1
1
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Mechanism of the cyanoalkylation
Mechanistic proposal. We previously reported a series of visible-light-induced
enantioselective α-alkylations of 2-acyl imidazoles using electron deficient benzyl bromides,
phenacyl bromides, perfluoroalkyl halides, and enantioselective trichloromethylations with
BrCCl
.[2,9a,20,21] These photoreactions were catalyzed most effectively with bis-cyclometalated
3
iridium complexes, whereas related photoinduced enantioselective -aminations of 2-acyl imidazoles
were catalyzed by the related bis-cyclometalated rhodium complexes.[2,22,23] These enantioselective
photoredox reactions serve as the basis for the proposed mechanism of the here introduced rhodium-
catalyzed photoinduced -cyanoalkylation of 2-acyl imidazoles. Accordingly, the catalytic reaction
begins with the coordination of the 2-acyl imidazole substrate (e.g. 5a) to the rhodium catalyst in a
bidentate fashion upon release of the two labile MeCN ligands of RhInd, thereby forming
intermediate I. A subsequent deprotonation induced by the added base Na
2
HPO generates the
4
rhodium enolate complex II which is a key intermediate of this asymmetric photoreaction. It fulfills
a dual function as reactive intermediate in the catalytic cycle and as the in situ assembled visible light
activatable photoredox catalyst. Upon absorption of visible light, the rhodium enolate acts as a
photoexcited reducing agent and transfers a single electron[24] to the -cyanoalkyl bromides (e.g. 6a),
which in turn fragments into bromide and the -cyanoalkyl radical V. This free radical V is electron
deficient due to the electron-withdrawing cyano group in -position and therefore rapidly reacts with
the electron-rich double bond of the rhodium enolate II to form the ketyl radical intermediate III
upon formation of a new C-C bond and a stereogenic carbon whose absolute configuration is
controlled by the chiral rhodium complex.[25] The ketyl radical III is a strong reducing agent and
either regenerates the oxidized photoredox mediator (IIIII) or it directly transfers an electron to a
new -cyanoalkyl bromide substrate to initiate a chain reaction. Either way, rhodium-coordinated
product IV is formed and after product release (e.g. 7a) the coordination of new substrate leads to
another catalytic cycle.
1
2
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+
Scheme 3. Proposed mechanism. [Rh] refers to the cationic, bis-cyclometalated fragment of RhInd.
Mechanistic control experiments. The proposed catalytic cycle is consistent with a number of
control experiments. First, the reaction requires both catalyst and Brønsted base for achieving
conversion (Table 2, entries 1 and 2), indicating the important role of the intermediate rhodium
enolate (intermediate II in Scheme 3). Under air, the C-C coupling product is completely suppressed
which is consistent with the interference of air with the proposed radical pathway, thus resulting in
the formation of -keto-2-acyl imidazole as an undesired side product (entry 3). Without any visible
light, only 20% yield with significantly lower enantioselectivity was observed (entry 4). We propose
that this product formation in the dark is the result of a non-radical S 2-pathway. When the
N
photoreaction was performed in the presence of the radical trapping reagent (2,2,6,6-
tetramethylpiperidin-1-yl)oxyl (TEMPO), the yield dropped to 25% (1.0 equiv. TEMPO) and 20%
(6.0 equiv. TEMPO), strongly indicating the involvement of a photoinduced radical mechanism
(
entries 5 and 6). A significant drop in enantioselectivity to 80% is observed when H O is excluded,
2
1
3
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demonstrating its crucial effect (entry 7). The benefit of small amounts of H
2
O can be rationalized
with an improved solubility of the base Na
2
HPO in the reaction solvent. We also determined a
4
quantum yield for this reactions, which is 0.046 for the reaction 5a + 6a  (R)-7a, which suggests
that the chain propagation plays at most a minor role and instead the rhodium enolate complex II
exerts the function of a real photoredox catalyst which is closely coupled to the asymmetric catalysis
[
2,9a,20,21]
cycle. This is different from our previous iridium-catalyzed -alkylations
and rhodium-
which apparently follow a chain mechanism (quantum yields >1).
Finally, UV/Vis-absorption spectra shown in Figure 5 demonstrate that the 2-acyl imidazole substrate
a, the catalyst RhInd, and the rhodium ketone complex I are not capable of significantly absorbing
[
2,22]
catalyzed -aminations
5
visible light but that the rhodium enolate complex II after deprotonation of I features a new absorption
band in the bathochromic region with a shoulder above 400 nm, which should be responsible for the
visible-light-induced photochemistry. It also explains why the shorter wavelength of blue LEDs
provides better results compared to a compact fluorescence light (CFL) bulb (entry 8).
Comparison with other catalysts. The performance of the new catalyst RhInd was compared
with some related and previously reported bis-cyclometalated complexes for the here introduced
photoinduced cyanoalkylation. The bis-cyclometalated phenylbenzothiazole complex Λ-IrS, which
was very successfully applied to a variety of enantioselective photoinduced -alkylations of 2-acyl
imidazoles,[2,9a,20,21] provided a high enantioselectivity of 94% ee but with just 23% yield (Table 2,
entry 10). The low yield can be explained by the inhibition of the catalyst by blocking the active site
of the catalyst through coordination of the bromoacetonitrile substrate or the cyanoalkylated product.
This is consistent with the fact that the bis-cyclometalated iridium catalyst displays a much slower
ligand exchange kinetics compared to its rhodium congener and thus should be more sensitive to
competing coordinating functional groups.[22] Indeed, when we increased the reaction temperature to
5
0 °C to speed up ligand exchange, -IrS gave a significantly higher yield of 62% but provided a
racemic mixture of the product, which might be due to an uncatalyzed background reaction at higher
temperatures (entry 11). On the other hand, the bis-cyclometalated phenylbenzothiazole complex Λ-
1
4
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RhS, which proved highly suitable for a variety of photoinduced -aminations of 2-acyl
imidazoles,[2,10,22,23] provided the cyanoalkylation product with 83% yield but a slightly lower
enantioselectivity of 90% ee (entry 12). At a first glance, this lower enantioselectivity is surprising
since the more constrained active site of the benzothiazole catalyst (see Figure 2b) should provide a
higher asymmetric induction. This is exactly what we observed for photoinduced -aminations of 2-
acyl imidazoles in which the benzothiazole catalyst RhS provided significantly higher ee values
compared to the benzoxazole analog RhO.[10a] We suggest that the higher enantioselectivity of RhInd
over RhS for the photoinduced cyanoalkylation is due to a slower S 2 background catalysis with
N
RhInd, and this is crucial because we observed a lower enantioselectivity for this reaction pathway.
Indeed, in the presence of air and absence of light, -RhS provided the cyanoalkylation product in
3
8% yield and with 88% ee (entry 13), as compared to a yield of only 20% with 86% ee for -RhInd
under the same conditions (entry 4). Finally, some modified RhInd-catalysts were also tested but
provided inferior results (entries 14-16).
1
5
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Table 2. Comparison with other catalysts and control reactions.[a]
Entry
Variations from standard
procedure
Catalyst
Yield [%]
ee [%][b]
1
2
3
4
5
6
7
8
9
without base
without catalyst
under air
Λ-RhInd










94
94
94
0
90
87
74



Λ-RhInd
Λ-RhInd
Λ-RhInd
Λ-RhInd
Λ-RhInd
Λ-RhInd
Λ-RhInd
Λ-IrS
[
c]
under air and without light
with 1.0 equiv TEMPO
with 6.0 equiv. TEMPO




26
80
23
62
83
38
73
43
13
without H
2
O
CFL lamp
none
none
50 °C
none
1
1
1
1
1
1
1
0
1
2
3
4
5
6
Λ-IrS
Λ-RhS
under air and without light
Λ-RhS
Λ-RhInd(Ph)[
d,e]
none
none
none
[
d,f]
rac RhInd(Ph-OMe)
rac RhInd(Ph-CF
[
d,g]
3
)
[
a] Conditions: 2-Acyl imidazole (0.10 mmol), catalyst (2 mol%) and Na
2
HPO
4
(0.20 mmol) were
dissolved in MeOH/THF 4:1 (0.5 mL) under inert gas atmosphere and H
2
O (0.56 mmol) was added.
The resulting mixture was stirred for 5 min before bromoacetonitrile (0.60 mmol) was added and the
mixture was degassed via freeze-pump-thaw for three cycles. The reaction mixture was then stirred
for 24 h under inert gas atmosphere at r.t. in front of blue LEDs (24 W, 10 cm). [b] Determined by
chiral HPLC analysis. [c] Exclusive formation of -keto-2-acyl imidazole as side product. For more
information, see Supporting Information. [d] For further information on modified catalysts see
Supporting Information. [e] R = Ph. [f] R = 4-(MeO)C
6
H
4
. [g] R = 4-(F
3
C)C
6
4
H .
1
6
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4
3
3
2
2
1
1
0
0
.0
.5
.0
.5
.0
.5
.0
.5
.0
RhInd
Substrate 5a
Enolate-Complex II
Imidazole-Complex I
200
300
400
500

(nm)
Figure 5. UV/VIS absorbance of RhInd, 2-acyl imidazole 5a, imidazole-complex I, and enolate-
complex II measured in CH
2
Cl (0.05 mM).
2
Conclusion
We here introduced a new chiral-at-metal rhodium(III) catalyst (RhInd) based on
cyclometalated 2-phenyl-2H-indazole ligands and developed a chiral-auxiliary-mediated synthesis of
the individual - and -enantiomer which provides virtually enantiopure complexes (ee > 99%). The
new 2-phenylindazole complex is structurally related to previously reported rhodium(III) catalysts
containing cyclometalated 2-phenylbenzoxazole and 2-phenylbenzothiazole ligands. However, the
indazole ligand apparently provides RhInd with distinct catalytic properties as demonstrated for an
efficient visible-light-induced asymmetric -cyanoalkylation of 2-acyl imidazoles. This
cyanoalkylation complements previous photoredox-mediated -alkylations using electron deficient
benzyl bromides, phenacyl bromides, perfluoroalkyl halides, and enantioselective
trichloromethylations with BrCCl
3
.[2,9a,20,21,26] Especially branched -cyano bromides afford
promising results with high enantioselectivities. Future work will investigate other applications of
1
7
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Chemistry - A European Journal
10.1002/chem.201903369
RhInd as a dual function catalyst for asymmetric photochemistry.
Experimental Section
General procedure for enantioselective α-alkylation of 2-acyl imidazoles. 2-Acyl
imidazole (0.10 mmol), Λ-RhInd (2.00 mol%) and Na HPO (0.20 mmol) were dissolved in
MeOH/THF 4:1 (0.5 mL) under inert gas atmosphere and H O (0.56 mmol) was added. The resulting
2
4
2
mixture was stirred for 5 min before bromoacetonitrile (0.60 mmol) was added and the mixture was
degassed via freeze-pump-thaw thoroughly for three cycles. The reaction mixture was then stirred for
2
4 h under inert gas atmosphere at r.t. in front of blue LEDs (24 W, 10 cm). Afterwards, the solvent
was evaporated under vacuum and the precipitate was purified by column chromatography on silica
gel (n-pentane/EtOAc 5:1  2:1) to afford pure products. For compounds 7k-m diastereomeric ratios
1
were determined by H-NMR spectroscopy of the crude products.
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Chemistry - A European Journal
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Graphical Abstract
A new chiral-at-metal rhodium(III) complex composed of two cyclometalated 2-phenyl-2H-
indazole ligands and two labile acetonitrile ligands permits the photoinduced enantioselective
cyanoalkylation of 2-acyl imidazoles. The new catalyst serves a dual function as a chiral Lewis acid
catalyst for the asymmetric radical chemistry and at the same time as the photoredox catalyst for the
visible-light-induced redox chemistry.
Keywords: chiral-at-metal, metal-centered-chirality, bis-cyclometalated, rhodium, asymmetric
catalysis, photoredox catalysis.
2
3
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