Asymmetric Propargylic Radical Cyanation Enabled by Dual Organophotoredox and Copper Catalysis

Article abstract of DOI:10.1021/jacs.9b02338

The first asymmetric propargylic radical cyanation was realized through a dual photoredox and copper catalysis. An organic photocatalyst serves to both generate propargyl radicals and oxidize Cu(I) species to Cu(II) species. A chiral Cu complex functions as an efficient organometallic catalyst to resemble the propargyl radical and cyanide in an enantio-controlled manner. Thus, a diverse range of optically active propargyl cyanides were produced with high reaction efficiency and enantioselectivities (28 examples, 57-97% yields and 83-98% ee). Moreover, mechanistic investigations including experiments and density functional theory calculations were performed to illustrate on the reaction pathway and stereochemical results.

Full text of DOI:10.1021/jacs.9b02338

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Communication
Asymmetric Propargylic Radical Cyanation Enabled
by Dual Organophotoredox and Copper Catalysis
Fu-Dong Lu, Dan Liu, Lei Zhu, Liang-Qiu Lu, Qian Yang,
Quan-Quan Zhou, Yi Wei, Yu Lan, and Wen-Jing Xiao
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 31 Mar 2019
Downloaded from http://pubs.acs.org on March 31, 2019
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Asymmetric Propargylic Radical Cyanation Enabled by Dual
Organophotoredox and Copper Catalysis
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Fu-Dong Lu,#,† Dan Liu,#,† Lei Zhu,‡ Liang-Qiu Lu,†,* Qian Yang,¶ Quan-Quan Zhou,† Yi Wei,† Yu
Lan,‡,* and Wen-Jing Xiao†,§,*
†CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College
of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, China
‡School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China
¶School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, 1037 Luoyu Road, Wuhan
430074, China
§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
Supporting Information Placeholder
allenylidene intermediates that can be captured by a series of
nucleophiles via two-electron pathways. However, one drawback
to this approach is that the mechanism renders the inner alkyne
analogues not applicable to this protocol, thus requiring new
strategies for developing the general catalytic asymmetric
propargylation process.
ABSTRACT: The first asymmetric propargylic radical
cyanation was realized through a dual photoredox and copper
catalysis. An organic photocatalyst serves to both generate
propargyl radicals and oxidize Cu(I) species to Cu(II) species. A
chiral Cu complex functions as an efficient organometallic
catalyst to resemble the propargyl radical and cyanide in an
enantio-controlled manner. Thus, a diverse range of optically
active propargyl cyanides were produced with high reaction
efficiency and enantioselectivities (28 examples, 66-97% yields
and 83-98% ee). Moreover, mechanistic investigations including
experiments and density functional theory (DFT) calculations
were performed to illustrate on the reaction pathway and
stereochemical results.
a) Nicholas reaction (1972): classic cation approaches
LG
R'
Nu
R'
1) Co2(CO)8
2) H+ or LA
3) Nu
R
R'
R
R
4) oxidant
(OC)3Co
Co(CO)3
Problems: multiple-step operation & highly toxic reagent and waste
b) Cu (1994) or Ru (2000) catalysis: current M-allenylidene approaches
M
•
•
LG
R'
Nu

Cu-cat.
Nu
R'
R'
H
H
or Ru-cat.
regenerate cat.
M
R'
Problem: no report on the cyanation due to its high affinity to transition metals
Alkynes are fundamentally important unsaturated compounds that
are ubiquitous in many natural isolates and artificial functional
materials (i.e., pharmaceuticals, agrochemicals and polymer
materials). In addition, the alkyne group is also one the most
versatile synthetic handles for obtaining many other functional
groups. Because of the unique physical, chemical and biological
properties of alkynes, a number of protocols have been developed
for their synthesis.1 Among the methods to prepare alkynes, the
elaboration of propargyl alcohols and their derivatives, pioneered
by Nicholas in the 1970s2 and later named as the Nicholas
reaction, has been demonstrated to be one of the most powerful
and widely used tools in laboratory synthesis and in the
pharmaceutical industry (Figure 1a).3 However, Nicholas himself
recognized that “Ultimately, systems for catalytic propargylation
eventually may be developed through careful selection of reaction
conditions, metal, and auxiliary ligand.”3a In 19944 and 2000,5
Cu- and Ru-catalyzed propargylic substitutions of propargyl esters,
chlorides and alcohols by heteroatom nucleophiles were reported,
respectively (Figure 1b). Benefiting from these pioneering
discoveries, various propargylic transformations, especially
catalytic asymmetric processes promoted by chiral ligands, have
flourished over the past two decades.6 Notably, the key to this
success is the catalytic formation of a γ-electrophilic metal-
c) This work:
asymmetric propargylic radical cyanations
organic
R
chiral
Cu catalyst
CN

LG
R'
photocatalyst
R'
R
R
TMSCN
(
)
R'
L*Cu(II) CN
(
)
2
dual catalysis + visible light + no noble metal
Challenge:
Significance:
1) green and economic conditions
2) syntheically flexible products
1) base-senstive products
2) excellent enantiocontrols
Figure 1. Strategies for propargylic substitution. LG, leaving group; Nu,
nucleophile; M, Cu or Ru; CN: cyanide.
Propargylic cyanides are belong to a class of versatile building
blocks in synthetic chemistry.7 To this end, in 1989, Stuart and
Nicholas disclosed the first cobalt-mediated propargylic cyanation
of propargyl ester and acetylenic acetals.8a In 1994, Marson and
Grabowska reported a propargylic cyanation of propargyl bromide
involving stoichiometric copper cyanide and lithium bromide.8b In
the following decades, to our knowledge, no catalytic propargylic
cyanation reactions have been reported, possibly due to the high
affinity of cyanide to many transition metals, which inhibits the
activity of catalysts by generating inactive complexes.9 Much
recently, the Liu group developed a series of elegant benzyl
radical cyanation reactions with high levels of enantiocontrol
through asymmetric copper catalysis.10 Inspired by the Liu
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cyanation and as a continuation of our long-time interest in
observed through H NMR analysis of the reaction mixture; the
allenyl nitrile was not detected. Employing other combinations of
Cu sources and chiral ligands (Table 1, entries 2-9) resulted in
substantially decreased reactivity and enantioselectivity,
excepting the combination of CuCl2 and L1 which provided a
similar result (Table 1, entry 4). Impressively, reducing the
loading of chiral Cu catalyst from 10 mol% to 2.5 mol% still
afforded the desired product with the same level of reaction
efficiency and enantiocontrol (Table 1, entry 10). Replacement of
the cyclopropane unit in the box ligand with an acyclic one did
not affect the enantioselectivity (Table 1, entries 10 and 11: L1 vs.
L2). Control experiments indicated that the Cu(MeCN)4BF4/L1
system, photocatalyst and visible light are indispensable for this
APRC reaction (Table 1, entries 12-14). Other propargyl esters
1a1-1a4, which lack sufficiently oxidative potentials (Figure S4-8),
cannot be used as efficient substrates (Table 1, entry 15).
visible-light-driven organic photochemical synthesis,11 we intend
to develop an asymmetric propargylic radical cyanation (APRC)
reaction through a photoredox/copper dual catalysis strategy. Here,
we disclose the first catalytic asymmetric propargylic radical
cyanation of propargyl esters by merging organophotoredox
catalysis with asymmetric copper catalysis (Figure 1c). This dual
catalysis strategy avoids
a
multiple-step operation and
stoichiometric metal activating reagents, thus providing
a
9
straightforward route to chiral propargyl cyanides with excellent
enantiocontrols under mild reaction conditions. In addition, this
study also constitutes a rare case of asymmetric cross-coupling
reactions synergistically catalyzed by photoredox catalysts and
chiral organometallic catalysts.12
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The design is depicted in Figure 2. It comprises an intertwined
photocatalysis cycle and a Cu catalysis cycle. We envisioned that
the redox-active propargyl esters (1a, LG = 3,5-2(CF3)2BzO:
E1/2[1a/1a•-] = -1.66 V vs. saturated calomel electrode (SCE) in
CH3CN)13 can accept a single electron from the excited state of
organo-photocatalyst Ph-PTZ* (E1/2[Ph-PTZ•+/Ph-PTZ*] = -
1.97 V vs. SCE),14a,b which reaches the excited state from the base
state of photocatalyst Ph-PTZ (absorption wavelength: 300-400
nm) upon irradiation with visible light. The homolysis of the
reduced species of propargyl ester 1 simultaneously generates a
propargyl radical I and a carboxylic anion LG-. Radical I, which
has a prochiral stereocenter, can be captured in a stereoselective
manner by L*Cu(II)(CN)2 to form chiral Cu(III) species III (II
→ III). Reductive elimination of intermediate II would deliver
the final chiral propargyl cyanide 3 and regenerate the chiral Cu(I)
catalyst. Cyanide anion (CN-) can be slowly released after the
reaction between the cyanide source, TMSCN, with the
carboxylic anion LG- and then, coordinate with the chiral Cu(I)
catalyst to form L*Cu(I)(CN)2 species.10a The SET process
between the oxidized state of Ph-PTZ+ (E1/2[Ph-PTZ•+/Ph-PTZ]
= 0.815 V vs. SCE) and L*Cu(I)(CN)2 (E1/2[Cu(II)/Cu(I)] = 0.36
V vs. SCE)10d encloses both photocatalysis and Cu catalysis
cycles. According to this design, the mild and base-free reaction
conditions avoid the isomerization of propargylic cyanides to
allenyl nitriles.15
Table 1. Condition Optimization of the APRC Reactiona
CN
LG
+
Cu
TMSCN
Ph
Ph
1a-1a4
2
3a
1a
1a1
for entries 1-14: LG = 3,5(CF3)2-BzO ( ); for entry 15: LG = AcO (
),
1a2
1a3
1a4
BocO (
), BzO (
), p-MeO-BzO ( )
entry
1
Cu source
chiral ligand
yield (%)b
90
eec
91
Cu(MeCN)4BF4
CuI
L1
L1
L1
L1
L1
L3
L4
L5
L6
L1
L2
L1
L1
L1
L1
2
NR
67
ND
82
3
Cu(OTf)2
4
CuCl2
88
89
5
Cu(acac)2
34
90
6
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
Cu(MeCN)4BF4
NR
NR
31
ND
ND
47
7
8
9
17
18
10d
11d
12d,f
13d,g
14d,h
15d,i
94 (91)e
88
92
radical
generation
cyanide
generation
LG
R'
CN-
LG-
+
TMSLG
-92
ND
ND
ND
ND
R
R
+
TMSCN
2
)
(
R'
1
I
NR
NR
NR
NR
R
Ph-PTZ*
Ph-PTZ+
R'
photocatalysis
cycle
L*Cu(II)(CN)2
oxidation
II
L*Cu(II)(CN)2
reduction
SET
process
Cu catalysis
cycle
R
Ph-PTZ
R'
Ph
N
III
L*Cu(I)(CN)2
L*Cu(III)(CN)2
aConditions: propargyl ester 1a (0.2 mmol), 2 (0.6 mmol), Cu source
(10 mol%), chiral ligand (12 mol%), Ph-PTZ (5 mol%) in anhydrous
product
formation
Key points:
S
o
L*Cu(I)-CN
THF (2 mL) at 30 C for 24 h under the irradiation of 2 x 3 W purple
I
1) efficient generation of propargylic radical
2) feasible SET between Ph-PTZ+ and
CN-
CN

LEDs (light intensity = 37.4 mw/cm2). bNMR yield using 1,3,5-
trimethoxybenzene as an internal standard. cDetermined by chiral
HPLC analysis. dUsing Cu source (2.5 mol%) and chiral ligand (3
L*Cu(I)(CN)
R
2
I
L*Cu(II)(CN)
2
3) asymmetric capturing of radical by
3
R'
mol%). eIsolated yield in parentheses. In dark. gIn the absence of
f
Figure 2. Reaction design: a photoredox/copper dual catalysis cycle for
the APRC reaction. Ph-PTZ: 10-phenyl-10H-phenothiazine; TMSCN:
trimethylcyanosilane.
h
i
photocatalyst. In the absence of chiral Cu catalysts. Propargyl ester
1a1, 1a2, 1a3 or 1a4 (0.2 mmol) was used in place of 1a. Ac, acetyl;
Boc, tert-butyloxycarboryl; Bz, benzoyl.
To substantiate the aforementioned reaction design, we
investigated the APRC reaction by evaluating various chiral
copper catalysts. After irradiating propargyl ester 1a and TMSCN
with visible light (2 × 3 W, purple LEDs, 390nm; Figure S1 and
S2) for 24 h in the presence of organic photocatalyst Ph-PTZ,
Cu(MeCN)4BF4 and chiral bisoxazoline (box) ligand L1, we were
delighted to detect the propargyl cyanide product 3a in 90% yield
and 91% ee. Notably, this product was the major regioisomer
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CN
CN
CN
CN
Ph
Ph
O
O
O
O
Ph
Ph
O
O
N
n-C5H11
Ph
Et
N
N
N
N
3a
3b
3c
3d
N
N
91% yield, 92% ee
85% yield, 94% ee
89% yield, 92% ee
83% yield, 93% ee
L1
L2
L3
CN
CN
CN
CN
O
Ph
Ph
O
Ph
Ph
3e
3f
3g
3h
O
O
O
O
O
O
PPh2
N
N
83% yield, 94% ee
87% yield, 97% ee
87% yield, 94% ee
87% yield, 96% ee
Ph
Ph
PPh2
N
N
N
N
CN
CN
Et
CN
CN
Ph
Ph
Ph
Ph
L4
L5
L6
O
9
Et
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
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45
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60
Ph
CO2t-Bu
Ph
OTBS
n-C5H11
O
MeO
3i
3j
3k
3l
After establishing the optimal reaction conditions, we sought
to define the generality of the methodology by exploring the
variety of propargyl esters. As summarized in Table 2, a wide
range of optically enriched propargyl cyanides were produced
through the visible-light-induced APRC reactions. For example,
various esters with alkyl substituents linked to the ester unit,
including linear, branched and cyclic substituents, can participate
in this asymmetric transformation very well. Functional groups
such as oxa-heterocycles, esters and OTBS were also compatible
with this dual catalysis system. In all of these cases, good reaction
efficiencies (3a-3j: 70-91% yields) were observed together with
high levels of enantiocontrols ranging from 86% ee to 97% ee.
We thereafter probed the variety of alkyne partner on the
propargyl ester under the standard conditions. As highlighted in
Table 2, a range of substrates with aryl alkynes are applicable to
this photochemical APRC process. Irrespective of the electronic
proprieties and positions of the substituents on the benzene ring,
the corresponding chiral propargyl cyanides were efficiently
afforded in generally good yields and with excellent
enantioselectivity (3k-3t: 57-91% yields and 88-98% ee).
Moreover, propargyl esters bearing heteroaryl substituents that
might affect the Cu catalyst were tolerated by this catalyst system
(3u: 85% yield and 90% ee; 3v: 75% yield and 91% ee). In
addition to the aryl- and heteroaryl-
79% yield, 86% ee
70% yield, 90% ee
74% yield, 95% ee
74% yield, 98% ee
CN
CN
CN
CN
Et
Et
Et
Et
Ph
NC
Br
3m
3n
3o
3p
79% yield, 96% ee
86% yield, 92% ee
70% yield, 91% ee
76% yield, 89% ee
CN
CN
CN
CN
F
Et
Et
Et
Et
F
3q
3r
3s
3t
91% yield, 94% ee
57% yield, 88% ee
80% yield, 95% ee
76% yield, 95% ee
CN
CN
CN
CN
Et
Et
Et
Et
S
N
3u
3v
5a
5b
85% yield, 90% ee
75% yield, 91% ee
66% yield, 98% ee
67% yield, 97% ee
CN
CN
CN
CN
Et
Ph
Et
BnO
TMS
n-C4H9
TMS
5c
5d
5e
5f
75% yield, 83% ee
75% yield, 87% ee
97% yield, 90% ee
84% yield, 89% ee
aAll the reaction were performed in 0.2 mmol scale; isolated yields; ee
values were determined by chiral HPLC or GC analysis. TBS: tert-
butyl dimethyl silicyl.
Table 2. Generality of APRC Reactionsa
Cu(CH CN) BF
2.5 mol%
L1
3
4
4
containing substrates, many other substrates with alkyl
substituents and functional groups such as alkenyl, ether and TMS
were proven successful for the present transformation.16 Generally,
good yields and excellent enantioselectivity were observed (5a-5e:
66-97% yields and 83-98% ee). More importantly, this APRC
reaction can be carried out at the gram scale, without obviously
effects on the reaction efficiency and enantiocontrol (Figure 3 and
S3). Notably, the redox-active elements, including the organic
photocatalyst Ph-PTZ and 3,5-(ditrifluoromethyl) benzoic acid,
were recovered in good yields.
CN
LG
Ph-PTZ
3 mol% , 5 mol%
R1
R1
+
TMSCN
2
0.1 M in THF, 30 °C, 24 h
2 x 3W purple LEDs
(LG = 3,5(CF3)2-BzO)
R2
R2
1a-1v 4a-4f
3a-3v 5a-5f
;
;
Cu(CH CN) BF
4
CN
Et
LG
Et
2.5 mol%
L1
3
4
Ph-PTZ
3 mol% , 5 mol%
TMSCN
(3.0 eq.), 0.1 M in THF
Ph
1b:
Ph
30 °C, 24 h, 2 x 5 W purple LEDs
(LG = 3,5(CF3)2-BzO)
3b:
1.37 g
81% yield and 95% ee
10 mmol
5 W
5 W
O
Ph
N
CF3
HO
S
CF3
Recoverd Ph-PTZ:
Recoverd acid:
85% yield
91% yield
Figure 3. A gram-scale APRC reaction performed in a 250 mL flask.
Next, we performed a set of experiments to determine the
reaction mechanism and stereochemical results. First,
luminescence quenching experiments indicated that the excited
state of photocatalyst Ph-PTZ was efficiently quenched by the
redox-active propargyl esters (Figure S9). Second, the light/dark
experiments (Figure S10) and the quantum yield (0.652)
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suggested a possible nonchain radical process for this APRC
a)
O
O
reaction. Third, control experiments using chiral propargyl ester
(S)-1a and two chiral box ligands were carried out under the
standard conditions. Given a well-established protocol for the Cu-
catalyzed stereospecific propargylic substitution of aryl Grignard
reagents by using chiral propargylic ammonium salts, there might
be a direct stereoselective interaction between Cu catalysts and
propargylic substrates.17 However, in our case, nearly the same
reaction profile and inverse enantio-induction were observed,
which excluded this possibility (Figure 4a). Fourth, a linear
relationship between the ee values of propargyl cyanide products
and box ligands was observed, which suggests a catalysis
mechanism involving a single Cu/L complex (Figure S12).18 Fifth,
a DFT calculation (DFT: density functional theory) of the
stepwise oxidation/reductive elimination process was carried out
to rationalize the experimentally observed stereochemical result.19
As shown in Figure 4b, the calculations suggest that the relative
free energy of the transition state corresponding to the addition of
the propargylic radical to Cu(II) species A (TS1) is lower than
that of reductive elimination to release product rac-3a and Cu(I)
species C (TS1), indicating the formation of the propargyl-Cu(III)
complex is reversible and that enantioselectivity is determined by
the reductive elimination step. Based on this information, we then
investigated the origin of enantioselectivity with the APRC
reaction of propargyl ester 1b as the model reaction. As shown in
Figure 4c, the relative free energy of transition state S-TS2
(leading to product S-3b) is 3.5 kcal/mol lower than that of R-TS2
(leading to product R-3b), consistent with experimental
observation. Further structural analysis showed that the structure
of R-TS2 would experience greater steric hindrance than that of
S-TS2. We therefore concluded that greater steric repulsion in R-
TS2 leads to the higher energy barrier observed in reductive
elimination for the R-product compared with that for the S-
product.
3
4
5
6
7
8
9
N
N
(1R, 2S)-L1
R-3a: 88% yield, -92% ee
O
O
N
N
(1S, 2R)-L1
S-3a: 84% yield, 91% ee
10
11
12
13
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CN
standard conditions
LG

(1S, 2R)-L1
(1 , 2 )-L1
Ph
(S)-1a
Ph chiral 3a
or
R
S
b)
O
O
O
O
Me
CN
G
(kcal/mol)
N
N
N
N
Cu
Cu
CN
NC
NC
Me
CN
Ph
rac-3a
Me
Ph
TS1
Ph
TS2
H
Me
-3.8
-7.6
TS2
-10.2
Ia
TS1
B
Ph
-18.1
A
rac-3a
O
O
O
O
O
O
N
N
N
N
N
N
Cu
Cu
Cu
CN
NC
-49.6
NC
CN
CN
Me
Ph
C
A
B
C
c)
We have successfully developed the first catalytic asymmetric
propargylic radical cyanation via a synergetic photoredox/copper
catalysis strategy. This strategy provides unprecedented access to
optically enriched propargyl cyanides with generally high reaction
efficiency and enantioselectivity under mild conditions. In
addition, a mechanistic investigation that included experimental
evidence and DFT calculations rationally illustrated the possible
reaction pathway and stereoinduction process. We believe that
this work not only opens a new window for catalytic asymmetric
propargylic functionalizations, but also provides a novel dual
catalysis system for visible-light-induced asymmetric chemical
bond formation.
Ph
Me
R-TS2:
S-TS2:
G = 0.0 kcal/mol
G = 3.5 kcal/mol
H
H
CN
Ph
CN
vs.
Cu
Cu
Me
CN
CN
Et
CN
CN
Ph
Ph
Et
R-3b
S-3b
Figure 4. Mechanistic investigations: a, reaction profiles of chiral
propargyl esters; b, DFT computational studies; c, proposed stereo-
induction models.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, and characterization data for all the
products. The Supporting Information is available free of charge
on the ACS Publications website.
AUTHOR INFORMATION
Corresponding Author
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luliangqiu@mail.ccnu.edu.cn; lanyu@cqu.edu.cn;
wxiao@mail.ccnu.edu.cn
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Boronic Acids with Dimethylmalononitrile. Angew. Chem., Int.
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P.-H.; Stahl, S. S.; Liu, G. Enantioselective Cyanation of Benzylic
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Chen, P.; Liu, G.; Enantioselective Copper-Catalyzed
Intermolecular Cyanotrifluoromethylation of Alkenes via Radical
Process. J. Am. Chem. Soc. 2016, 138, 15547-15550. (c) Wang, D.-
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Catalyzed Intermolecular Amino- and Azidocyanation of Alkenes
in a Radical Process. Angew. Chem. Int. Ed. 2017, 56, 2054-2058.
(d) Wang, D.-H.; Zhu, N.; Chen, P.-H.; Lin, Z.-Y.; Liu, G.
Author Contributions
#F.-D.L. and D.L. contributed equally to this work.
Notes
The authors declare no competing financial interests.
9
ACKNOWLEDGMENT
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We are grateful to the National Science Foundation of China (No.
21822103, 21820102003, 21822303, 21772052, 21772053,
21572074 and 21472057), the Program of Introducing Talents of
Discipline to Universities of China (111 Program, B17019), the
Natural Science Foundation of Hubei Province (2017AHB047)
and the International Joint Research Center for Intelligent
Biosensing Technology and Health for support of this research.
We thank Prof. Fang-Fang Pan in CCNU for the X-ray diffraction
analysis of single crystal, and thank Prof. Jia-Rong Chen in
CCNU for helpful discussions.
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(13) Please see the Supporting Information for the determination
of redox potentials of substrates 1a and 1a1-1a4.
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Light Photoredox-Catalyzed Deoxygenation of Alcohols. Beilstein
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Graphic Abstract:
Asymmetric Propargylic Radical Cyanations
5
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8
CN
LG
+
Cu
TMSCN
R
R
R'
R'
28 examples:
57-97% yields & 83-98% ee
redox-active
propargylic esters
significant
products
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• dual catalysis:
• no noble metal:
• mild condtions:
photoredox/copper catalysis
R
R'
organic photocat., chiral Cu cat.
visible light + ambient temperature
L*Cu(II) CN
(
)
2
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