Merging Photoredox and Copper Catalysis: Enantioselective Radical Cyanoalkylation of Styrenes

Article abstract of DOI:10.1021/acscatal.8b01863

A photoredox and copper catalyzed asymmetric cyanoalkylation reaction of alkenes has been developed, which uses alkyl N-hydroxyphthalimide esters as alkylation reagents. In this radical cyanoalkylation reaction, the photoredox induced alkyl radical adds to styrene, and the generated benzylic radical couples with a chiral Box/CuII cyanide complex to achieve the enantioselective cyanation. This reaction features mild conditions, operational simplicity, broad substrate scope, high yields, and high enantioselectivities, which represents an efficient method for the asymmetric radical difunctionalization of alkenes.

Full text of DOI:10.1021/acscatal.8b01863

Letter
pubs.acs.org/acscatalysis
Cite This: ACS Catal. 2018, 8, 7489−7494
Merging Photoredox and Copper Catalysis: Enantioselective Radical
Cyanoalkylation of Styrenes
Wanxing Sha,† Lingling Deng,† Shengyang Ni, Haibo Mei,* Jianlin Han,* and Yi Pan
School of Chemistry and Chemical Engineering, State Key laboratory of Coordination Chemistry, Jiangsu Key Laboratory of
Advanced Organic Materials, Nanjing University, Nanjing, 210093, China
S
* Supporting Information
ABSTRACT: A photoredox and copper catalyzed asymmetric
cyanoalkylation reaction of alkenes has been developed, which
uses alkyl N-hydroxyphthalimide esters as alkylation reagents.
In this radical cyanoalkylation reaction, the photoredox induced
alkyl radical adds to styrene, and the generated benzylic radical
couples with a chiral Box/CuII cyanide complex to achieve the
enantioselective cyanation. This reaction features mild con-
ditions, operational simplicity, broad substrate scope, high
yields, and high enantioselectivities, which represents an
efficient method for the asymmetric radical difunctionalization
of alkenes.
KEYWORDS: asymmetric radical reaction, cyanoalkylation, photoredox, Cu catalysis, difunctionalization of alkene
arboxylic acids are the most common compounds in
Cnumerous biologically active natural products and drug
molecules. Furthermore, they are inexpensive and abundant in
nature, and also are among the most basic building blocks in
synthetic organic chemistry.1 In recent years, decarboxylation
of carboxylic acids has exhibited obvious advantages for
organic synthesis, such as inexpensive materials, CO2 as the
nontoxic byproduct, and so on. Importantly, radical decarbox-
ylation of alkyl carboxylic acid, catalyzed by a visible light-
induced photoredox catalyst, has witnessed a significant
advancement.2 Meanwhile, the alkyl N-hydroxyphthalimide
esters (NHP esters) derived from alkyl carboxylic acids have
been extensively developed as alkylating reagents in alkylation
cross-coupling reactions through the elimination of CO2.3
Difunctionalization of alkenes is a powerful and efficient tool
for organic synthesis, which can introduce two groups into an
alkene in one step via the addition of a C−C double bond,
enhancing the molecular complexity. Several functional groups,
such as cyano, trifluoromethyl, azido, amino, thiocyano, and so
on, have been introduced into molecules via these difunction-
alization reactions.4 However, the difunctionalization of
alkenes containing an alkylation process still includes great
challenges,5 as the previously reported related alkylation
reactions require harsh conditions, strong nucleophiles, or
explosive substrates.
(Scheme 1a).7 In 2016, the Liu group reported work realizing
enantioselective cyanation of benzylic C−H bonds via a
Scheme 1. Asymmetric Radical Difunctionalization of
Alkenes
In recent decades, asymmetric radical reactions have
tremendously enriched the research content of asymmetric
chemistry by trapping alky radicals with reactive chiral
transitional metal species.6 Compared to these previously
developed direct coupling reactions, the Buchwald group
realized an asymmetric cascade reaction by using unsaturated
carboxylic acids with Togni’s reagent and other reagents
Received: May 14, 2018
Revised: July 15, 2018
© XXXX American Chemical Society
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DOI: 10.1021/acscatal.8b01863
ACS Catal. 2018, 8, 7489−7494

ACS Catalysis
Letter
copper-catalyzed radical relay.8 Based on this report, they
proposed and developed a series of asymmetric radical
difunctionalizations of alkenes (Scheme 1b).9 Besides
TMSCN, boronic acid was also developed as a nucleophilic
reagent adding to alkenes in asymmetric radical reactions
(Scheme 1c).10
a
Table 1. Optimization of Reaction Conditions
Based on the photocatalyst’s activity, merging photoredox
and metal catalysis could realize some difficult transformations
under mild reaction conditions.11 In 2017, the Liu group
developed an enantioselective decarboxylative cyanation
reaction of N-hydroxy-phthalimide esters by merging photo-
redox catalysis with copper catalysis, which provides a new
access to chiral alkyl nitriles (Scheme 1).11c Recently, the
Macmillan, and Wang groups have independently developed
the decarboxylative cross-coupling of carboxylic acids with
electrophiles or nucleophiles.12 Notably, a radical generated via
photoredox catalysis and an aryl-metal(II) species are the two
key intermediates in these reactions. According to this strategy,
Fu and Macmillan realized an asymmetric decarboxylative
arylation reaction by using a photocatalyst, nickel catalyst, and
chiral ligand.12c Inspired by these elegant reports and our
previous work on asymmetric radical reactions,13 we proposed
a photoredox and copper-catalyzed asymmetric cyanoalkyla-
tion reaction of alkenes by using alkyl N-hydroxyphthalimide
esters as alkylation reagents (Scheme 1e). To the best of our
knowledge, an asymmetric cyanoalkylation reaction of alkenes
has never been developed. Furthermore, this work represents
the first example of photoredox and copper-catalyzed radical
difunctionalization of alkenes.
At the outset, we selected styrene 1a, cyclopentyl NHP ester
2a, and TMSCN as model substrates for the optimization of
racemic reaction conditions (for details, see Supporting
Information (SI)). We found that the reaction of 1a, 2a, and
TMSCN catalyzed by the combination of Ir(ppy)3/CuBr/2,6-
bis(4,5-dihydrooxazol-2-yl)pyridine (L7) with NMP as
solvent, under blue LEDs at room temperature, afforded
( )-3aa in 58% yield. Then, we carried out the study of
condition optimization for the asymmetric radical reaction.
First, we selected Cu(CH3CN)4PF6 as a metal catalyst, L1 as a
chiral ligand, and Ir(ppy)3 as a photocatalyst for this
asymmetric difunctionalization reaction. To our delight, the
corresponding product 3aa can be obtained with a 30% yield
and −59% ee at room temperature, under 5 W blue LEDs after
24 h (entry 1, Table 1). Next, other chiral ligands were tried in
this reaction to improve the reaction efficiency. We found that
the chiral ligand L4 could catalyze the reaction smoothly,
affording the desired product (R)-3aa14 with obviously
increased enantioselectivity (70% ee, entry 4). With L4 as
ligand and DCM as the solvent, different metal catalysts were
then screened for this system, and the results of entries 5−8
indicated that CuBr exhibited good performance (39% yield
and 79% ee, entry 5). To improve the yield and
enantioselectivity, several regular solvents were then tried for
this reaction (entries 13−18). The reactions with PhCl or
THF as the solvent resulted in product 3aa with excellent
enantioselectivity, but with poor yields (entries 10 and 14).
Prolonging the reaction time to 36 h has no effect on this yield
(entry 15). To our delight, increasing the loading amount of 1a
to 4.0 equiv resulted in the corresponding product 3aa with a
78% yield and 77% enantioselectivity (entry 16). To our
surprise, mixed solvent had a favorable effect on this reaction,
and the ee was further increased to 84% (entry 17). Finally,
control experiments demonstrated that a photocatalyst, visible
1a
yield
b
ee
c
entry (mmol)
catalyst
L
solvent
(%)
(%)
1
2
3
4
5
6
7
8
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.8
0.8
Cu(CH3CN)4PF6
Cu(CH3CN)4PF6
Cu(CH3CN)4PF6
Cu(CH3CN)4PF6
CuBr
CuCl
CuCN
CuOAc
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
L1 DMF
L2 DMF
L3 DMF
L4 DMF
L4 DCM
L4 DCM
L4 DCM
L4 DCM
L4 m-xylene
L4 PhCl
L4 NMP
L4 MeOH
L4 DMSO
L4 THF
L4 THF
L4 NMP
30
37
45
44
34
31
27
25
trace
26
58
trace
trace
41
41
78
75
−59
57
16
70
79
75
76
79
−
9
10
11
12
13
14
15
16
17
87
76
84
85
d
77
84
e
L4 NMP/
PhCl
NMP/
PhCl
e
18
19
20
0.8
0.8
0.8
−
−
−
−
−
−
ef
,
CuBr
CuBr
L4 NMP/
−
−
PhCl
eg
,
L4 NMP/
PhCl
a
Reaction conditions: 1a, 2a (0.2 mmol), TMSCN (1.1 equiv),
Ir(ppy)3 (0.5 mol %), metal catalyst (1.0 mol %), ligand (1.2 mol %),
solvent (1 mL), at room temperature, 5 W blue LEDs, 24 h. Isolated
yields. Determined by chiral HPLC. 36 h. NMP (0.4 mL) and
b
c
d
e
f
g
PhCl (0.6 mL). No photocatalyst. In the dark.
light, and a metal catalyst were all essential for this reaction
(entries 18−20).
With the optimized conditions in hand, we then explored
the reactivity of various alkenes by reacting with cyclopentyl
NHP ester 2a, and the results were summarized in Scheme 2.
First, we examined the styrene derivatives with substitution at
the para-position on the aromatic ring. As depicted in Scheme
2, both electron-donating and -withdrawing groups were well
tolerated in this system and afforded the desired product with
good reaction outcomes (3aa−3ga). In particular, the
substrate bearing para-phenyl gave an excellent yield and
high enantioselectivity (3ba, 88% yield and 92% ee). Then, the
styrene derivatives with the meta-substituted group on the
phenyl moieties were applied to this reaction. To our delight,
the reactions also proceeded very well to give the
corresponding product (3ha and 3ia) with moderate yields
but good enantioselectivities (87% ee and 84% ee,
respectively). Several styrenes with ortho-subsituted phenyl
were tried in this reaction to investigate the effect of steric
hindrance. As expected, these substrates 1j−1m worked better
in this system and resulted in good yields and excellent
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ACS Catalysis
Letter
a b c
, ,
with good yields and enantioselectivity. It should be mentioned
that the reaction showed excellent regioselectivity compared to
the previous methods.8,15 We also explored whether secondary
alkyl NHP esters could adapt to this reaction. It was noted that
both isopropyl NHP ester 2g and cyclobutyl NHP ester 2h
could be well tolerated, and the products 3ag and 3ah were
obtained with excellent yields and enantioselectivities. Finally,
the tertiary alkyl NHP ester was also found to be a suitable
substrate for this asymmetric radical reaction, and the
corresponding product 3ai could be obtained with a 52%
yield and 90% enantioselectivity.
Scheme 2. Substrate Scope of Different Alkenes
To gain the insight into this reaction mechanism, a radical
scavenger, TEMPO (2,2,6,6,-tetramethyl-1-piperidinyloxy),
was applied in the reaction. The reaction was totally
suppressed and the desired product 3aa was not detected,
which indicates that a radical process may be involved
(Scheme 4a). To confirm the formation of an alkyl radical,
Scheme 4. Mechanistic Investigation
a
Reaction conditions: 2a (0.2 mmol), alkenes 1 (4.0 equiv), TMSCN
(1.1 equiv), Ir(ppy)3 (0.5 mol %), CuBr (1.0 mol %), L4 (1.2 mol %),
NMP (0.4 mL), and PhCl (0.6 mL), at room temperature, 5 W blue
b
c
LEDs, for 24 h. Isolated yields. Enantioselectivity was determined
by chiral HPLC.
another radical scavenger 1,1-diphenylalkene was added to the
reaction under standard reaction conditions. The desired
product 3aa was again not detected. However, the adduct 4a of
the cyclopentyl radical with ethene-1,1-diyldibenzene was
detected by GC-MS (Scheme 4b).
enantioselectivities. Especially, in the case of ortho-bromostyr-
ene 1j, the highest enantioselectivity was obtained (3ja, 94%
ee). Finally, one inactive alkene, but-3-en-1-ylbenzene 1r, was
tried in this reaction. Unfortunately, almost no desired product
3ra was obtained.
According to the above experimental results and previous
studies, a possible mechanism was shown in Scheme
5.8−10,11c,12c,13,16 Initially, the photoredox catalyst Ir(ppy)3 is
irradiated to the activated state A, from which 2a abstracts an
electron to form a radical anion C and the photocatalyst
intermediate B. The radical anion C generates the alkyl radical
D, the phthalimide anion, via release of CO2. Subsequently, the
alkyl radical D adds to styrene 1a to generate the key benzylic
radical E. Meanwhile, the intermediate B oxidizes a copper(I)
Encouraged by the results from different alkenes with 2a, we
undertook another part of the substrate scope study of alkyl
NHP esters by using styrene 1a as the coupling partner, and
the results are shown in Scheme 3. Primary alkyl NHP esters
such as methyl, ethyl, and propyl worked very well in the
reaction and resulted in the corresponding product 3ab−3ad
with good yields and high enantioselectivity (84−88% ee).
Next, aryl ethyl and aryl propyl NHP ester were applied to this
reaction, which also proceeded smoothly to afford 3ae and 3af
Scheme 5. Proposed Mechanism
a b c
, ,
Scheme 3. Scope of Alkyl NHP Esters
a
Reaction conditions: NHP esters 2 (0.2 mmol), 1a (4.0 equiv),
TMSCN (1.1 equiv), Ir(ppy)3 (0.5 mol %), CuBr (1.0 mol %), L4
(1.2 mol %), NMP (0.4 mL), and PhCl (0.6 mL), at room
b
temperature, 5 W blue LEDs, for 24 h. Isolated yields.
c
Enantioselectivity was determined by chiral HPLC.
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(3) (a) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.;
Pan, C. M.; Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S.
Practical Ni-Catalyzed Aryl−Alkyl Cross-Coupling of Secondary
Redox-Active Esters. J. Am. Chem. Soc. 2016, 138, 2174−2177.
(b) Huihui, K. M.; Caputo, J. A.; Melchor, Z.; Olivares, A. M.;
Spiewak, A. M.; Johnson, K. A.; DiBenedetto, T. A.; Kim, S.;
Ackerman, L. K.; Weix, D. J. Decarboxylative Cross-Electrophile
Coupling of N-Hydroxyphthalimide Esters with Aryl Iodides. J. Am.
Chem. Soc. 2016, 138, 5016−5019. (c) Qin, T.; Cornella, J.; Li, C.;
Malins, L. R.; Edwards, J. T.; Kawamura, S.; Maxwell, B. D.; Eastgate,
M. D.; Baran, P. S. A General Alkyl-Alkyl Cross-Coupling Enabled by
Redox-Active Esters and Alkylzinc Reagents. Science 2016, 352, 801−
805. (d) Li, C.; Wang, J.; Barton, L. M.; Yu, S.; Tian, M.; Peters, D. S.;
Kumar, M.; Yu, A. W.; Johnson, K. A.; Chatterjee, A. K.; Yan, M.;
Baran, P. S. Decarboxylative Borylation. Science 2017, 356, eaam7355.
(e) Smith, J. M.; Qin, T.; Merchant, R. R.; Edwards, J. T.; Malins, L.
R.; Liu, Z.; Che, G.; Shen, Z.; Shaw, S. A.; Eastgate, M. D.; Baran, P.
S. Decarboxylative Alkynylation. Angew. Chem., Int. Ed. 2017, 56,
11906−11910. (f) Pratsch, G.; Lackner, G. L.; Overman, L. E.
Constructing Quaternary Carbons from N-(Acyloxy)phthalimide
Precursors of Tertiary Radicals Using Visible-Light Photocatalysis. J.
Org. Chem. 2015, 80, 6025−6036. (g) Yang, J.; Zhang, J.; Qi, L.; Hu,
C.; Chen, Y. Visible-Light-Induced Chemoselective Reductive
Decarboxylative Alkynylation under Biomolecule-Compatible Con-
ditions. Chem. Commun. 2015, 51, 5275−5278. (h) Gao, C.; Li, J. J.;
Yu, J. P.; Yang, H. J.; Fu, H. Visible-Light Photoredox Synthesis of
Internal Alkynes Containing Quaternary Carbons. Chem. Commun.
2016, 52, 7292−7294. (i) Jiang, M.; Yang, H. J.; Fu, H. Visible-Light
Photoredox Synthesis of Chiral α-Selenoamino Acids. Org. Lett. 2016,
18, 1968−1971. (j) Jin, Y.; Yang, H.; Fu, H. Thiophenol-Catalyzed
Visible-Light Photoredox Decarboxylative Couplings of N-(Acetoxy)-
phthalimides. Org. Lett. 2016, 18, 6400−6403. (k) Li, J. J.; Tian, H.;
Jiang, M.; Yang, H. J.; Zhao, Y. F.; Fu, H. Consecutive Visible-Light
Photoredox Decarboxylative Couplings of Adipic Acid Active Esters
with Alkynyl Sulfones Leading to Cyclic Compounds. Chem.
Commun. 2016, 52, 8862−8864. (l) Cheng, W. M.; Shang, R.;
Zhao, B.; Xing, W. L.; Fu, Y. Isonicotinate Ester Catalyzed
Decarboxylative Borylation of (Hetero)Aryl and Alkenyl Carboxylic
Acids through N-Hydroxyphthalimide Esters. Org. Lett. 2017, 19,
4291−4294. (m) Cheng, W. M.; Shang, R.; Fu, Y. Photoredox/
Brønsted Acid Co-Catalysis Enabling Decarboxylative Coupling of
Amino Acid and Peptide Redox-Active Esters with N-Heteroarenes.
ACS Catal. 2017, 7, 907−911.
(4) (a) Xu, L.; Mou, X. Q.; Chen, Z. M.; Wang, S. H. Copper-
Catalyzed Intermolecular Azidocyanation of Aryl Alkenes. Chem.
Commun. 2014, 50, 10676−10679. (b) He, Y. T.; Li, L. H.; Yang, Y.
F.; Zhou, Z. Z.; Hua, H. L.; Liu, X. Y.; Liang, Y. M. Copper-Catalyzed
Intermolecular Cyanotrifluoromethylation of Alkenes. Org. Lett. 2014,
16, 270−273. (c) Liang, Z.; Wang, F.; Chen, P.; Liu, G. S. Copper-
Catalyzed Intermolecular Trifluoromethylthiocyanation of Alkenes:
Convenient Access to CF3-Containing Alkyl Thiocyanates. Org. Lett.
2015, 17, 2438−2441. (d) Zhang, H.; Pu, W.; Xiong, T.; Li, Y.; Zhou,
X.; Sun, K.; Liu, Q.; Zhang, Q. Copper-Catalyzed Intermolecular
Aminocyanation and Diamination of Alkenes. Angew. Chem., Int. Ed.
2013, 52, 2529−2533. (e) Wang, F.; Qi, X.; Liang, Z.; Chen, P.; Liu,
G. Copper-Catalyzed Intermolecular Trifluoromethylazidation of
Alkenes: Convenient Access to CF3-Containing Alkyl Azides.
Angew. Chem., Int. Ed. 2014, 53, 1881−1886. (f) Li, J. A.; Zhang, P.
Z.; Liu, K.; Shoberu, A.; Zou, J. P.; Zhang, W. Phosphinoyl Radical-
Initiated α,β-Aminophosphinoylation of Alkenes. Org. Lett. 2017, 19,
4704−4706. (g) Zhang, P. Z.; Zhang, L.; Li, J. A.; Shoberu, A.; Zou, J.
P.; Zhang, W. Phosphinoyl Radical Initiated Vicinal Cyanophosphi-
noylation of Alkenes. Org. Lett. 2017, 19, 5537−5540.
catalyst to release photocatalyst Ir(ppy)3 and form the chiral
Box/Cu(II) state. Then, the chiral Box/Cu(II) is oxidized by
benzylic radical E and reacts with TMSCN to give the chiral
intermediate Box/Cu(III)17 F. Finally, the intermediate F
proceeds through reductive elimination to give the final
product 3aa and regenerates the Cu(I) catalyst for the next
catalytic cycle.
In summary, we have developed a novel photoredox and
copper catalyzed asymmetric cyanoalkylation of alkenes. In this
reaction, a photocatalyt and metal catalyst play a vital role.
This reaction can be compatible with various alkenes and
multiple alkyl NHP esters including primary, secondary, and
tertiary alkyl substituted esters. Furthermore, this reaction
features mild conditions, simple operation, moderate to
excellent yields, and high enantioselectivities, which enriches
the research content of the asymmetric radical reaction.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.8b01863.
■
S
Experimental details, characterization data, and NMR
spectra of new compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: meihb@nju.edu.cn.
*E-mail: hanjl@nju.edu.cn.
ORCID
Jianlin Han: 0000-0002-3817-0764
Author Contributions
†W.S. and L.D. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (Nos.
21472082, 21772085, 21761132021). The support from
Collaborative Innovation Center of Solid-State Lighting and
Energy-Saving Electronics and the Fundamental Research
Funds for the Central Universities (No. 020514380131) is also
acknowledged.
REFERENCES
■
(1) For recent reviews on decarboxylation reactions, see: (a) Weaver,
J. D.; Recio, A.; Grenning, A. J.; Tunge, J. A. Transition Metal-
Catalyzed Decarboxylative Allylation and Benzylation Reactions.
Chem. Rev. 2011, 111, 1846−1913. (b) Rodriguez, N.; Goossen, L.
J. Decarboxylative coupling reactions: a modern strategy for C−C-
bond formation. Chem. Soc. Rev. 2011, 40, 5030−5048. (c) Cornella,
J.; Larrosa, I. Decarboxylative Carbon-Carbon Bond-Forming Trans-
gormations of (Hetero)aromatic Carboxylic Acids. Synthesis 2012, 44,
653−676. (d) Wei, Y.; Hu, P.; Zhang, M.; Su, W. Metal-Catalyzed
Decarboxylative C-H Functionalization. Chem. Rev. 2017, 117, 8864−
8907.
(5) (a) Ji, J.; Liu, P.; Sun, P. Peroxide Promoted Tunable
Decarboxylative Alkylation of Cinnamic Acids to Form Alkenes or
Ketones under Metal-Free Conditions. Chem. Commun. 2015, 51,
7546−7549. (b) Ge, L.; Li, Y.; Jian, W.; Bao, H. Alkyl Esterification of
Vinylarenes Enabled by Visible-Light induced Decarboxylation. Chem.
- Eur. J. 2017, 23, 11767−11770. (c) Jian, W.; Ge, L.; Jiao, Y.; Qian,
(2) (a) Xuan, J.; Zhang, Z. G.; Xiao, W. J. Visible-Light-Induced
Decarboxylative Functionalization of Carboxylic Acids and Their
Derivatives. Angew. Chem., Int. Ed. 2015, 54, 15632−15641.
(b) Huang, H. C.; Jia, K. F.; Chen, Y. Y. Radical Decarboxylative
Functionalizations Enabled by Dual Photoredox Catalysis. ACS Catal.
2016, 6, 4983−4988.
7492
DOI: 10.1021/acscatal.8b01863
ACS Catal. 2018, 8, 7489−7494

ACS Catalysis
Letter
B.; Bao, H. Iron-Catalyzed Decarboxylative Alkyl Etherification of
Vinylarenes with Aliphatic Acids as the Alkyl Source. Angew. Chem.,
Int. Ed. 2017, 56, 3650−3654. (d) Qian, B.; Chen, S.; Wang, T.;
Zhang, X.; Bao, H. Iron-Catalyzed Carboamination of Olefins:
Synthesis of Amines and Disubstituted β-Amino Acids. J. Am.
Chem. Soc. 2017, 139, 13076−13082. (e) Li, W. Y.; Wang, Q. Q.;
Yang, L. Fe-Catalyzed Radical-Type Difunctionalization of Styrenes
with Aliphatic Aldehydes and Trimethylsilyl Azide via a Decarbon-
ylative Alkylation−Azidation Cascade. Org. Biomol. Chem. 2017, 15,
9987−9991.
F.; Jin, D. P.; Liu, X. Y. Merging Photoredox with Copper Catalysis:
Decarboxylative Difluoroacetylation of α,β-Unsaturated Carboxylic
Acids with ICF2CO2Et. Chem. Commun. 2016, 52, 11827−11830.
(c) Wang, D.; Zhu, N.; Chen, P.; Lin, Z.; Liu, G. Enantioselective
Decarboxylative Cyanation Employing Cooperative Photoredox
Catalysis and Copper Catalysis. J. Am. Chem. Soc. 2017, 139,
15632−15635. (d) Espelt, L. R.; McPherson, I. S.; Wiensch, E. M.;
Yoon, T. P. Enantioselective Conjugate Additions of alpha-Amino
Radicals via Cooperative Photoredox and Lewis Acid Catalysis. J. Am.
Chem. Soc. 2015, 137, 2452−2455. (e) Huo, H.; Shen, X.; Wang, C.;
Zhang, L.; Roese, 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. (f) Huo,
H.; Wang, C.; Harms, K.; Meggers, E. Enantioselective, Catalytic
Trichloromethylation through Visible-Light-Activated Photoredox
Catalysis with a Chiral Iridium Complex. J. Am. Chem. Soc. 2015,
137, 9551−9554. (g) Tan, Y. Q.; Yuan, W.; Gong, L.; Meggers, E.
Aerobic Asymmetric Dehydrogenative Cross-Coupling between Two
CspH Groups Catalyzed by a Chiral-at-Metal Rhodium Complex.
Angew. Chem., Int. Ed. 2015, 54, 13045−13048. (h) Huo, H.; Harms,
K.; Meggers, E. Catalytic, Enantioselective Addition of Alkyl Radicals
to Alkenes via Visible-Light-Activated Photoredox Catalysis with a
Chiral Rhodium Complex. J. Am. Chem. Soc. 2016, 138, 6936−6939.
(i) Wang, C.; Harms, K.; Meggers, E. Catalytic Asymmetric Csp3-H
Functionalization under Photoredox Conditions by Radical Trans-
location and Stereocontrolled Alkene Addition. Angew. Chem., Int. Ed.
2016, 55, 13495−13498.
(12) (a) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A.
G.; MacMillan, D. W. C. Merging Photoredox with Nickel Catalysis:
Coupling of α-Carboxyl sp3-Carbons with Aryl Halides. Science 2014,
345, 437−440. (b) Chu, L.; Lipshultz, J. M.; MacMillan, D. W. C.
Merging Photoredoxand Nickel Catalysis:The Direct Synthesis of
Ketones by the DecarboxylativeArylation of α-Oxo Acids. Angew.
Chem., Int. Ed. 2015, 54, 7929−7933. (c) Zuo, Z.; Cong, H.; Li, W.;
Choi, J.; Fu, G. C.; MacMillan, D. W. C. Enantioselective
Decarboxylative Arylation of α-Amino Acids via the Merger of
Photoredox and Nickel Catalysis. J. Am. Chem. Soc. 2016, 138, 1832−
1835. (d) Cheng, W. M.; Shang, R.; Yu, H. Z.; Fu, Y. Room-
TemperatureDecarboxylative Couplings of α-Oxocarboxylateswith
Aryl Halides by MergingPhotoredox with Palladium Catalysis.
Chem. - Eur. J. 2015, 21, 13191−13195. (e) Zhou, C.; Li, P. H.;
Zhu, X. J.; Wang, L. Merging Photoredox with Palladium Catalysis:
Decarboxylative ortho-Acylation of Acetanilides with α-Oxocarboxylic
Acids under Mild Reaction Conditions. Org. Lett. 2015, 17, 6198−
6201. (f) Xu, N.; Li, P. H.; Xie, Z. G.; Wang, L. Merging Visible-Light
Photocatalysis and Palladium Catalysis for C-H Acylation of Azo- and
Azoxybenzenes with α-Keto Acids. Chem. - Eur. J. 2016, 22, 2236−
2242.
(6) (a) Do, H. Q.; Chandrashekar, E. R. R.; Fu, G. C. Nickel/
Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic
Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-
Diarylalkanes. J. Am. Chem. Soc. 2013, 135, 16288−16291. (b) Binder,
J. T.; Cordier, C. J.; Fu, G. C. Catalytic Enantioselective Cross-
Couplings of Secondary Alkyl Electrophiles with Secondary
Alkylmetal Nucleophiles: Negishi Reactions of Racemic Benzylic
Bromides with Achiral Alkylzinc Reagents. J. Am. Chem. Soc. 2012,
134, 17003−17006. (c) Choi, J.; Fu, G. C. Catalytic Asymmetric
Synthesis of Secondary Nitriles via Stereoconvergent Negishi
Arylations and Alkenylations of Racemic α-Bromonitriles. J. Am.
Chem. Soc. 2012, 134, 9102−9105. (d) Wilsily, A.; Tramutola, F.;
Owston, N. A.; Fu, G. C. New Directing Groups for Metal-Catalyzed
Asymmetric Carbon−Carbon Bond-Forming Processes: Stereocon-
vergent Alkyl−Alkyl Suzuki Cross-Couplings of Unactivated Electro-
philes. J. Am. Chem. Soc. 2012, 134, 5794−5797. (e) Cherney, A. H.;
Reisman, S. E. Nickel-Catalyzed Asymmetric Reductive Cross-
Coupling Between Vinyl and Benzyl Electrophiles. J. Am. Chem. Soc.
2014, 136, 14365−14368. (f) Mao, J.; Liu, F.; Wang, M.; Wu, L.;
Zheng, B.; Liu, S.; Zhong, J.; Bian, Q.; Walsh, P. J. Cobalt−
Bisoxazoline-Catalyzed Asymmetric Kumada Cross-Coupling of
Racemic α-Bromo Esters with Aryl Grignard Reagents. J. Am. Chem.
Soc. 2014, 136, 17662−17668. (g) Jin, M.; Adak, L.; Nakamura, M.
Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-
Chloroesters with Aryl Grignard Reagents. J. Am. Chem. Soc. 2015,
137, 7128−7134. (h) Kainz, Q. M.; Matier, C. D.; Bartoszewicz, A.;
Zultanski, S. L.; Peters, J. C.; Fu, G. C. Asymmetric copper-catalyzed
C-N cross-couplings induced by visible light. Science 2016, 351, 681−
684. (i) Ding, W.; Lu, L. Q.; Zhou, Q. Q.; Wei, Y.; Chen, J. R.; Xiao,
W. J. Bifunctional Photocatalysts for Enantioselective Aerobic
Oxidation of β-Ketoesters. J. Am. Chem. Soc. 2017, 139, 63−66.
(7) (a) Zhu, R.; Buchwald, S. L. Enantioselective Functionalization
of Radical Intermediates in Redox Catalysis: Copper-Catalyzed
Asymmetric Oxytrifluoromethylation of Alkenes. Angew. Chem., Int.
Ed. 2013, 52, 12655−12658. (b) Zhu, R.; Buchwald, S. L. Versatile
Enantioselective Synthesis of Functionalized Lactones via Copper-
Catalyzed Radical Oxyfunctionalization of Alkenes. J. Am. Chem. Soc.
2015, 137, 8069−8077.
(8) Zhang, W.; Wang, F.; McCann, S. D.; Wang, D.; Chen, P.; Stahl,
S. S.; Liu, G. Enantioselective Cyanation of Benzylic C−H Bonds via
Copper-Catalyzed Radical Relay. Science 2016, 353, 1014−1018.
(9) (a) Wang, F.; Wang, D.; Wan, X.; Wu, L.; Chen, P.; Liu, G.
Enantioselective Copper-Catalyzed Intermolecular Cyanotrifluorome-
thylation of Alkenes via Radical Process. J. Am. Chem. Soc. 2016, 138,
15547−15550. (b) Wang, D.; Wang, F.; Chen, P.; Lin, Z.; Liu, G.
EnantioselectiveCopper-Catalyzed Intermolecular Amino- and Azido-
cyanation of Alkenes in aRadical Process. Angew. Chem., Int. Ed. 2017,
56, 2054−2058.
(10) (a) Wang, D.; Wu, L.; Wang, F.; Wan, X.; Chen, P.; Lin, Z.;
Liu, G. Asymmetric Copper-Catalyzed Intermolecular Aminoarylation
of Styrenes: Efficient Access to Optical 2,2-Diarylethylamines. J. Am.
Chem. Soc. 2017, 139, 6811−6814. (b) Wu, L.; Wang, F.; Wan, X.;
Wang, D.; Chen, P.; Liu, G. Asymmetric Cu-Catalyzed Intermolecular
Trifluoromethylarylation of Styrenes: Enantioselective Arylation of
Benzylic Radicals. J. Am. Chem. Soc. 2017, 139, 2904−2907.
(11) (a) Ye, Y.; Sanford, M. S. Merging Visible-Light Photocatalysis
and Transition-Metal Catalysis in the Copper-Catalyzed Trifluor-
omethylation of Boronic Acids with CF3I. J. Am. Chem. Soc. 2012,
134, 9034−9037. (b) Zhang, H. R.; Chen, D. Q.; Han, Y. P.; Qiu, Y.
(13) (a) Sha, W.; Zhu, Y.; Mei, H.; Han, J.; Soloshonok, V. A.; Pan,
Y. Catalytic Enantioselective Cyano-Trifluoromethylation of Styrenes.
ChemistrySelect 2017, 2, 1129−1132. (b) Sha, W.; Ni, S.; Han, J.; Pan,
Y. Access to Alkyl-Substituted Lactone via Photoredox-Catalyzed
Alkylation/Lactonization of Unsaturated Carboxylic Acids. Org. Lett.
2017, 19, 5900−5903. (c) Wang, Y.; Deng, L.; Zhou, J.; Wang, X.;
Mei, H.; Han, J. L.; Pan, Y. Synthesis of Chiral Sulfonyl Lactones via
Copper-Catalyzed Asymmetric Radical Reaction of DABCO·(SO2).
Adv. Synth. Catal. 2018, 360, 1060−1065.
(14) For the determination of absolute configurations, see the SI.
(15) Thiyagarajan, S.; Gunanathan, C. Facile Ruthenium(II)-
Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols Enabled
by Metal−Ligand Cooperation. ACS Catal. 2017, 7, 5483−5490.
(16) (a) Okada, K.; Okamoto, K.; Morita, N.; Okubo, K.; Oda, M.
Photosensitized Decarboxylative Michael Addition through N-
(Acyloxy)phthalimides via an Electron-Transfer Mechanism. J. Am.
Chem. Soc. 1991, 113, 9401−9402. (b) Lackner, G. L.; Quasdorf, K.
W.; Overman, L. E. Direct Construction of Quaternary Carbons from
Tertiary Alcohols via Photoredox-Catalyzed Fragmentation of tert-
Alkyl N-Phthalimidoyl Oxalates. J. Am. Chem. Soc. 2013, 135, 15342−
15345. (c) Lackner, G. L.; Quasdorf, K. W.; Pratsch, G.; Overman, L.
7493
DOI: 10.1021/acscatal.8b01863
ACS Catal. 2018, 8, 7489−7494

ACS Catalysis
Letter
E. Fragment Coupling and the Construction of Quaternary Carbons
Using Tertiary Radicals Generated From tert-Alkyl N-Phthalimidoyl
Oxalates By Visible-Light Photocatalysis. J. Org. Chem. 2015, 80,
6012−6024. (d) Pratsch, G.; Lackner, G. L.; Overman, L. E.
Constructing Quaternary Carbons from N-(Acyloxy)phthalimide
Precursors of Tertiary Radicals Using Visible-Light Photocatalysis. J.
Org. Chem. 2015, 80, 6025−6036.
(17) (a) Zhang, H.; Pu, W.; Xiong, T.; Li, Y.; Zhou, X.; Sun, K.; Liu,
Q.; Zhang, Q. Copper-catalyzed intermolecular aminocyanation and
diamination of alkenes. Angew. Chem., Int. Ed. 2013, 52, 2529−2533.
(b) Wang, F.; Wang, D.; Mu, X.; Chen, P.; Liu, G. Copper-catalyzed
intermolecular trifluoromethylarylation of alkenes: mutual activation
+
of arylboronic acid and CF3 reagent. J. Am. Chem. Soc. 2014, 136,
10202−10205. (c) Guo, Q.; Wang, M.; Wang, Y.; Xu, Z.; Wang, R.
Photoinduced, Copper-Catalyzed Three Components Cyanofluor-
oalkylation of Alkenes with Fluoroalkyl Iodides as Fluoroalkylation
Reagents. Chem. Commun. 2017, 53, 12317−12320.
7494
DOI: 10.1021/acscatal.8b01863
ACS Catal. 2018, 8, 7489−7494