Development of Br?nsted Base-Photocatalyst Hybrid Systems for Highly Efficient C-C Bond Formation Reactions of Malonates with Styrenes

Article abstract of DOI:10.1021/acscatal.0c02716

Br?nsted base-photocatalyst hybrid systems have been developed for reactions of malonates with styrene derivatives. The concept of this process lies in the photo-oxidation of catalytic amounts of the enolate to form reactive radicals that react with alken

Full text of DOI:10.1021/acscatal.0c02716

Subscriber access provided by Gothenburg University Library
Letter
Development of Brønsted Base–Photocatalyst Hybrid Systems for Highly
Efficient C–C Bond Formation Reactions of Malonates with Styrenes
Sebastian Bas, Yasuhiro Yamashita, and Shu Kobayashi
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.0c02716 • Publication Date (Web): 27 Jul 2020
Downloaded from pubs.acs.org on July 27, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 7
ACS Catalysis
1
2
3
4
5
6
7
8
9
Development of Brønsted Base–Photocatalyst Hybrid Systems for Highly Efficient C–C Bond
Formation Reactions of Malonates with Styrenes
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Sebastian Baś, Yasuhiro Yamashita* and Shū Kobayashi*
Department of Chemistry, School of Science,
The University of Tokyo
Bunkyo-ku, Tokyo, 113-0033, Japan
KEYWORDS photocatalysis • hybrid catalysis • Brønsted base • malonates • radical process.
ABSTRACT: Brønsted base–photocatalyst hybrid systems have been developed for reactions of malonates with styrene
derivatives. The concept of this process lies in the photooxidation of catalytic amounts of the enolate to form reactive
radicals that react with alkene double bonds under mild reaction conditions. This is an example of visible light activated
C–C bond formation reactions of malonates with alkenes to realize high atom economy under very mild reaction
conditions without using any transition metal catalysts.
Nucleophilic addition of carbanions to alkenes is
recognized as one of the most efficient C–C bond
formation reactions.1,2 In particular, when carbanions are
generated from stable and readily available precursors
using catalysts, the process is ideal in terms of atom
economy since simple proton transfer occurs from
starting materials to products via catalytic amounts of
carbanions. Malonic acid esters (malonates) are readily
available and their functional groups can be easily
converted into the desired target molecules; thus, they
are often employed as precursors of carbanions. While
the corresponding enolates are known to be stabilized
carbanions, their nucleophilicity is generally not sufficient
for reactions with alkenes without any electron-
withdrawing groups (simple alkenes). Reactions of
malonates with such alkenes catalyzed by transition
metals have been investigated; however, stoichiometric
amounts of Brønsted bases are needed in most cases.3
Towards truly efficient catalytic processes, we focused on
the development of reactions of malonates with alkenes
that proceed through the formation of radicals using
catalytic amounts of Brønsted base and redox activator
without using any transition metal catalysts.
generated via SET with alkenes promoted by a catalytic
amount of Mn(OAc)2 and a stoichiometric amount of
oxidant was disclosed; however, acetic acid was needed
as a solvent and applicable substrates were limited
A. Photooxidation of alkene to radical cation
17 eq. KOtBu
R2
R2 COOR1
COOR1
O
O
9-CP
30 mol%
+
R1O
OR1
MeCN, UV-light
Ar
Ar
33 eq.
CN
via
R2
Ar
9-CP
B. Oxidation of malonate to radical species using transition metals
Mn(OAc)2 (1-2 mol%)
COOR1
O
O
oxidant
AcOH
+
R2
COOR1
R1O
OR1
R2
via
O
O
R1O
OR1
C. This work
5 mol% KOtBu
4CzIPN
R2 COOR1
COOR1
R3
O
O
R3
Ar
1 mol%
+
Ar
R1O
OR1
MeCN, blue LED
R2
1.1 eq
high yields
lack of waste
clean reaction
Although reactions of malonates with simple alkenes
via single-electron photooxidation (SET) have been
reported, strong UV-light and the use of a large excess
of base and malonate are required (Scheme 1A).4,5 On
the other hand, reactions of 1,3-dicarbonyl radicals
N
NC
N
CN
N
N
ACS Paragon Plus Environment
4CzIPN

ACS Catalysis
Page 2 of 7
(Scheme 1B).6,7 We envisioned that modern visible-light
photocatalysis would be applicable to these types of
reactions.
6c
7c
8c
9c
3
3
3
3
MeCN 2 mol% 1 mol%
THF 5 mol% 1 mol%
77b
76d
20d
0b
1
2
3
4
DCM 5 mol% 1 mol%
Toluene 5 mol% 1 mol%
Scheme 1. Alkylation reactions of malonates with
alkenes. To date,
a
variety of metal and
5
organophotocatalysts have been developed and
employed in radical-mediated reactions.8 However, these
photocatalysts are not stable and their photoactivity is
significantly decreased under basic conditions. Therefore,
the effects that visible-light photocatalysts have on
Brønsted base-catalyzed reactions remain unclear. Here,
we have developed effective Brønsted base–
photocatalyst hybrid systems for catalytic alkylation
reactions of malonates with less electrophilic alkenes and
realized high atom economy under very mild reaction
conditions without using any transition metal catalysts
(Scheme 1C).
a
6
7
8
9
Reaction conditions: 4a (0.3 mmol), 5a (0.3 mmol),
KOtBu (0.1 mmol), and photocatalyst (0.01 mmol) in
anhydrous MeCN (5.0 mL) under argon at rt irradiated with
24W blue LED for 20 h; Determined by H NMR analysis
b
1
c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
with CH2Br2 as internal standard; Reaction conditions: 4a
(0.3 mmol), 5a (0.33 mmol), KOtBu, and 3 as described, in
anhydrous solvent (5.0 mL) under argon at rt irradiated with
24W blue LED for 20 h; d Isolated yield.
We next surveyed the scope of the reaction with
respect to alkenes under the optimized reaction
conditions. It was found that 1,1-diarylethylene
derivatives 5a–e afforded the desired products 6 in
excellent yields (Table 2, entries 1–5). Notably, after
simple work-up, an almost pure product was identified in
the reaction mixture, with only 3 and trace amounts of
The reaction of dimethyl malonate (4a) with 1,1-
diphenylethene (5a) was selected as a model reaction in
the presence of KOtBu as a base and photocatalysts 1–3
at room temperature (rt) in MeCN (Table 1). Whereas
photocatalysts 1 and 2 gave the product 6 in low yields
(entries 1 and 2), photocatalyst 3 provided 6 in 87% yield
(entry 3). Further optimization of the reaction conditions
enabled a decrease in the amount of the base and 3 to 5
and 1 mol%, respectively (entries 4–6). The target
reaction proceeded only in polar solvents such as MeCN
and THF (entries 4, 7–9). For further optimization, we
examined the use of organic photosensitizers to ensure
that 3 delivered the best results (see Table S1 in the
Supporting Information (SI)).
1
starting materials being observed (see H NMR spectra
of crude samples in the Supporting Information). An
exception was 5f, bearing two strong electron-donating
groups on Ar and R1 (entry 6). The R2-substituted alkenes
5g–i also gave lower yields (entries 7–9). While styrene
5j, its alkyl substituted derivatives 5k, 5l, and those with
electron-donating groups (5m, 5n) were reactive
substrates under the standard reaction conditions
(entries 10–12, see also Table S2 in the Supporting
Information), the yields were significantly improved by
using photocatalyst
7 instead of 3 (Table 2, in
parentheses). The effects of 3 and 7 were investigated as
part of a subsequent consideration of the mechanism
(see below). Styrenes with electron-withdrawing groups
5o–t reacted smoothly using 3 (entries 13–20). Whereas
only a trace amount of product 6au was obtained in the
reaction of -methylstyrene 5u using 3, 77% yield of 6au
was obtained using 7 (entry 21). The high reactivity was
also observed for alkenes 5v–zb bearing heterocyclic
rings, except for 5y (entries 22–28). For the latter alkene
and for non-terminal alkenes 5zc9 and 5zd, better yields
of the desired products were obtained using
photocatalyst 7 (entry 25 in parenthesis, entries 29, 30).
Interestingly, in case of styrenes 5p and 5j (only when 7
was used) the side products of double addition of alkene
to malonate have been detected (see, Scheme S3 in the
Supporting Information).
Table 1. Optimization of reaction conditions for the
reaction of 4a with 5a
X mol% KOtBu
Y mol% 1 or 2 or 3
O
O
Ph
COOMe
Ph COOMe
+
Ph
Ph
solvent, rt, 20 h
blue LED
MeO
OMe
4a
5a
6
O
O Cl O-
O
N
COOK
Br
NC
N
CN
N
Br
KO
O
O
N
N+
Br
Br
1
2
3
X
Y
Yield
Entry Photocatalyst Solvent
amount amount
(%)
0b
5b
1a
2a
3a
4c
5c
1
2
3
3
3
MeCN 30 mol% 3 mol%
MeCN 30 mol% 3 mol%
MeCN 30 mol% 3 mol%
MeCN 5 mol% 1 mol%
87b
91d
MeCN 5 mol% 0.5 mol% 79d
ACS Paragon Plus Environment

Page 3 of 7
ACS Catalysis
a
Reaction conditions: 4a (0.3 mmol), 5a–azi (0.33 mmol),
Table 2. Scope and limitations of the reaction with
1
2
3
4
5
6
7
8
KOtBu (0.015 mmol), 3 (0.003 mmol, Method A) in
anhydrous MeCN (5.0 mL) under argon at rt irradiated with
R2
5 mol% KOtBu
R2
R1
b
O
O
24W blue LED for 20 h. Isolated yield unless otherwise
Ar
COOMe
3
7
1 mol% or
+
c
noted. Determined by 1H NMR analysis with CH2Br2 as
MeO
OMe
MeCN, 20h, rt
blue LED, Ar
Ar
R1 COOMe
6
d
e
internal standard.
1.1 equiv. of 4a was used.
5
4a
Photocatalyst 7 was used instead of 3.
alkenesa
Next, we investigated the scope of the reaction with
malonates 4b–f. Whereas aliphatic esters gave nearly
quantitative yields of the expected products 6ba–da, low
reactivity was observed for 4e (both substrates remained
in the reaction mixture), and substitution at the
methylene group also inhibited the process (Table 3).
The lack of reactivity of 4f may be rationalized by
formation of stable tertiary radical species (see further
mechanistic discussion), thus thermodynamic force for its
recombination with alkene is significantly decreased. In
addition, other 1,3-dicarbonyl compounds like diketones
or ketoesters in the developed conditions undergo
competitive DeMayo reactions resulting in complex
product mixture formation. Moreover, the visible-light
activated DeMayo reaction in comparable conditions for
those substrates has been reported by König recently.10
Entry
Ar
R1
Ph
Ph
Ph
R2
H
H
H
5
6
Yield
91
97
9
1
2
3
Ph
p-tol
p-
5a
5b
5c
6aa
6ab
6ac
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
95
MeOC H
4
5
6
7
8
p-BrC6H4
Ph
p-ClC6H4
p-
Ph
p-FC6H4
H
H
H
5d
5e
5f
6ad
6ae
6af
6ag
6ah
6ai
6aj
6ak
6al
87
95
17c
37
30
p-ClC6H4
p-
Ph
p-FC6H4
Ph
Me 5g
Me 5h
9
Ph
H
H
H
H
Ph
H
H
H
H
5i
5j
5k
5l
5
17
10
11
12
13
Ph
p-tol
27 (77)d,e
21 (71)e
10 (64)e
p-tBuC6H4
p-MeOC6H4
6am
0 (28)e
A plausible mechanism for the reaction is outlined in
Scheme 2. The visible-light-excited photocatalyst
[Photocat]* oxidizes enolate I, resulting in the formation
of radical II, which undergoes recombination with alkene
5 to form radical III. Comparison of the oxidation
potentials for 5a [E(P/P•+) = +1.82 V vs. SCE in MeCN],11
enolates of malonates [ca. 0–0.6 V (for example 4b E(P–
/P•) = +0.59 V vs. SCE in MeCN)12] and photocatalyst 3
[E(P*/P•–) = +1.35 V and E(P/P•–) = –1.21 V vs. SCE in
MeCN]13 suggested that an electron-transfer event was
thermodynamically more feasible for the enolate than for
the alkene. Similar observations and conclusions
supported by spectroscopic and CV measurement
verification were reported by König.10
14 m-MeOC6H4
H
H
5n
6an
0c (78)e
15
16
p-ClC6H4
H
H
H
H
5o
5p
6ao
6ap
43 (80)e
55
p-O2NC6H4
17
o-O2NC6H4
H
H
5q
6aq
60
18
19
p-NCC6H4
p-AcC6H4
H
H
H
H
5r
5s
6ar
6as
56
45
20
p-MeO2CC6H4
H
H
5t
6at
94
21
22
23
24
25
26
27
28
29
Ph
Me
H
Me
Ph
H
H
H
H
H
H
H
H
H
H
H
H
5u
5v
5w
5x
5y
5z
5z
5z
5z
6a
tracec (77)e
2-pyridyl
2-pyridyl
2-pyridyl
3-pyridyl
4-pyridyl
2-quinolyl
3-quinolyl
Ph
6av
6aw
6ax
6ay
6az
6aza
6azb
6azc
80
49
99
Table 3. Scope and limitations of the reaction with
11 (46)e
85
51
41
5 mol% KOtBu
R2
O
O
COOR1
3
1 mol%
Ph
+
R1O
OR1
MeCN, 20h, rt
blue LED, Ar
Ph
Ph
Ph COOR1
-(CH2)4-
14 (70)e
R2
5a
6
4
5z
d
30
6azd
15 (59)e
malonatesa
Entry
R1
R2
4
6
Yield (%)b
Ph
CN
N
COOMe
6azc
1
2
3
4
5
Et
iPr
tBu
Allyl
Me
H
H
H
H
Me
4b
4c
4d
4e
4f
6ba
6ca
6da
6ea
6fa
94
99
92
18c
0c
N
N
F
COOMe
F
COOMe
6azd
COOMe
7
(3DPA2FBN)
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 7
a
Reaction conditions: 4b–i (0.3 mmol), 5a (0.33 mmol),
since 7 was reported to possess a higher ground-state
1
2
3
4
5
6
7
8
KOtBu (0.015 mmol), 3 (0.003 mmol), in anhydrous MeCN
(5.0 mL) under argon at rt irradiated with 24W blue LED for
reduction potential [(P/P•–) = –1.92 V vs. SCE in MeCN].16
In summary, we have developed a Brønsted base–
photocatalyst hybrid system that enabled reactions of
malonates with styrene derivatives. The reactions
proceeded cleanly with low loadings of base and
photocatalyst. Light-initiated single-electron transfer
oxidation of in situ generated enolates forming radicals
is one of the key steps. This is the first example of C–C
bond formation reactions of malonates with alkenes to
realize high atom economy under very mild reaction
conditions without using any transition metal catalysts.
b
c
20 h. Isolated yield unless otherwise noted. Determined
by 1H NMR analysis with CH2Br2 as internal standard.
Diarylalkenes result in the formation of highly stable
dibenzyl tertiary radicals, which is reflected in the high
yields of products. Newly formed radical III is reduced to
carbanion IV to regenerate photocatalyst 3. Further
deprotonation of another molecule of 4a by product-
base IV completes the catalytic cycle. When the reaction
was conducted in deuterated solvent (CD3CN) no
deuterium incorporation was found in the final product 6
structure, which excludes the possibility of solvent
participation in proton or hydrogen atom transfer (see
Table S4 in the Supporting Information).14
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
Supporting Information
This supporting information is available free of charge at
http://pubs.acs.org.
Materials, photoreactor structure, supporting experiments,
experimental methods, compounds characterization data
On the other hand, judging from the results presented in
Table 2, it was noted that some yields were influenced by
the reduction potential of the benzyl radicals to the
corresponding carbanions.
Scheme 2. Proposed mechanism based on the
AUTHOR INFORMATION
Corresponding Authors
O
O
MeO
OMe
Shū Kobayashi - Department of Chemistry, School of
Science, The University of Tokyo, Bunkyo-ku, Tokyo, 113-
0033, Japan, ORCID 0000-0002-8235-4368, e-mail:
shu_kobayashi@chem.s.u-tokyo.ac.jp
Yasuhiro Yamashita - Department of Chemistry, School of
Science, The University of Tokyo, Bunkyo-ku, Tokyo, 113-
0033, Japan , e-mail: yyamashita@chem.s.u-tokyo.ac.jp
R
4
5
O
O
Ar
-tBuOH
O-
tBuO-
O
MeO
OMe
II
MeO
OMe
[Photocat.]
I
Ar
COOMe
COOMe
R
[Photocat.]*
III
Authors
†Sebastian Baś - Department of Chemistry, School of
Science, The University of Tokyo, Bunkyo-ku, Tokyo, 113-
0033, Japan, ORCID 0000-0003-4692-5757
hv
[Photocat.]
Ar
COOMe
COOMe
Ar
COOMe
COOMe
R
R
IV
6
Present Addresses
O
O
†Faculty of Chemistry, Jagiellonian University, Gronostajowa
2, 30-387 Krakow, Poland
MeO
OMe
4
conducted investigation
Author Contributions
Benzyl radicals bearing electron-withdrawing groups on
the aromatic rings have higher reduction potentials [5r
(56% yield) (P•/P–) = –0.77 V; 5s (45% yield) (P•/P–) = –
0.71 V; 5o (43% yield) (P•/P–) = –1.40 V vs. SCE in MeCN]
than those with electron-donating groups [5m (0% yield)
(P•/P–) = –1.82 V; 5k (21% yield) (P•/P–) = –1.62 V; 5j
(27% yield) (P•/P–) = –1.43 V vs. SCE in MeCN] due to the
destabilizing/stabilizing effect of substituents.15 These
results suggested that a second electron-transfer process
that provided IV along with regeneration of
The manuscript was written through contributions of all
authors.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was partially supported by Japan Agency for
Medical Research and Development (AMED) (S.K.), and
Japan Society for the Promotion of Science (JSPS) KAKENHI
Grant Number JP 17H06448 (Y.Y.).
photocatalyst
3
might be
a
rate-limiting step.
Photocatalyst 7 improved the low yields of the reactions
with styrene bearing electron-donating substituents,
ABBREVIATIONS
ACS Paragon Plus Environment

Page 5 of 7
ACS Catalysis
Sakaguchi, S.; Ishii, Y. A Remarkable Effect of Bases on the
SET, single electron transfer, CV, cyclic voltammetry, SCE,
saturated calomel electrode, TLC, thin layer
chromatography, NMR nuclear magnetic resonance, LED,
light-emitting diode
1
2
3
4
5
6
7
8
Catalytic Radical Addition of Cyanoacetates to Alkenes Using a
Mn(II)/Co(II)/O2 Redox System. Bull. Chem. Soc. Jpn. 2005, 78,
1673–1676.
(8) For recent reviews on organic photocatalysis, see: (a) Marzo,
L.; Pagire, S. K.; Reiser, O.; König, B. Visible-Light Photocatalysis:
Does It Make a Difference in Organic Synthesis? Angew. Chem.
Int. Ed. 2018, 57, 10034–10072; (b) Romero, N. A.; Nicewicz, D.
A. Organic Photoredox Catalysis. Chem. Rev. 2016, 116, 10075–
10166; (c) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Dual Catalysis
Strategies in Photochemical Synthesis. Chem. Rev. 2016, 116,
10035–10074; (d) Revathi, L.; Ravindar, L.; Fang, W.-Y.; Rakesh, K.
P.; Qin, H.-L. Visible Light-Induced C-H Bond Functionalization:
A Critical Review. Adv. Synth. Catal. 2018, 360, 4652–4698; For
carbon–carbon bond-forming photoreactions, see: (a) Ravelli,
D.; Protti, S.; Fagnoni, M. Carbon–Carbon Bond Forming
Reactions via Photogenerated Intermediates. Chem. Rev. 2016,
116, 9850–9913; (b) Fagnoni, M.; Dondi, D.; Ravelli, D.; Albini, A.
Photocatalysis for the Formation of the C−C Bond. Chem. Rev.
2007, 107, 2725–2756.
(9) Product undergoes rearrangement with the carboxylic group
migrating. For more details see Scheme S2 in the Supporting
Information.
(10) Martinez-Haya, R. ; Marzo, L.; König, B. Reinventing the De
Mayo Reaction: Synthesis of 1,5-Diketones or 1,5-Ketoesters via
Visible Light [2+2] Cycloaddition of β-Diketones or β-Ketoesters
with Styrenes. Chem. Commun. 2018, 54, 11602–11605 (see
Supporting Information).
(11) Arnold, D. R.; Du, X.; Henseleit, K. M. The Effect of Meta-
and Para-Methoxy Substitution on the Reactivity of the Radical
Cations of Arylalkenes and Alkanes. Radical Ions in
Photochemistry. Part 26. Can. J. Chem. 1991, 69, 839–852.
(12) (a) Niyazymbetov, M. E.; Rongfeng, Z.; Evans, D. H.
Oxidation Potential as a Measure of the Reactivity of Anionic
Nucleophiles. Behaviour of Different Classes of Nucleophiles. J.
Chem. Soc., Perkin Trans. 2 1996, 1957–1961; (b) Daasbjerg, K.;
Knudsen, S. R.; Sonnichsen, K. N.; Andrade, A. R.; Pedersen, S. U.
Systematic Ranking of Nucleophiles as Electron Donors. Acta
Chem. Scand. 1999, 53, 938–948.
REFERENCES
(1) (a) Classic in Total Synthesis Eds.: Nicolaou, K. C.; Sorensen, E.
J.; Wiley-VCH, Weinheim, 1996, pp 1-19; (b) Classic in Total
Synthesis II Eds. Nicolaou, K. C.; Snyder, S. A.; Wiley-VCH,
Weinheim, 2003, pp 1-12; (c) Nicolaou, K. C.; Vourloumis, D.;
Winssinger, N.; Baran, P. S. The Art and Science of Total
Synthesis at the Dawn of the Twenty-First Century. Angew.
Chem. Int. Ed. 2000, 39, 41–122.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) Advanced Organic Chemistry Reactions, Mechanisms and
Structure (6rd Ed.) Smith, M. B.; March, J. John Wiley & Sons,
Hoboken, New Jersey, 2007, pp. 234-296 and 999-1251.
(3) (a) Dénès, F.; Pérez-Luna, A.; Chemla, F. Addition of Metal
Enolate Derivatives to Unactivated Carbon-Carbon Multiple
Bonds. Chem. Rev. 2010, 110, 2366–2447; (b) Dong, Z.; Ren, Z.;
Thompson, S. J.; Xu, Y.; Dong, G. Transition-Metal-Catalyzed C–
H Alkylation Using Alkenes. Chem. Rev. 2017, 117, 9333–9403.
(4) (a) Ohashi, M.; Nakatani, K.; Maeda, H.; Mizuno, K.
Photochemical Monoalkylation of Propanedinitrile by Electron-
Rich Alkenes. Org. Lett. 2008, 10, 2741–2743; (b) Ohashi, M.;
Nakatani, K.; Maeda, H.; Mizuno, K. Intramolecular Polar
Addition Reactions of Active Methylene Moieties to Aryl-
Substituted Alkenes via Photoinduced Electron Transfer.
Tetrahedron Lett. 2010, 51, 5537–5539; (c) Ohashi, M.; Nakatani,
K.; Maeda, H.; Mizuno, K. Selective Photochemical
Monoalkylation of Active Methylene Compounds by Alkenes. A
Green Pathway for Carbon–Carbon Bond Formation. J.
Photochem. Photobiol. A 2010, 214, 161–170.
(5) Arnold, D. R.; Chan, M. S. W.; McManus, K. A. Photochemical
Nucleophile-Olefin Combination, Aromatic Substitution (Photo-
NOCAS) Reaction, Part 12. Factors Controlling the
Regiochemistry of the Reaction with Alcohol as the Nucleophile.
Can. J. Chem. 1996, 74, 2143–2166.
(6) For enolate activation, see: (a) Ko, T. Y.; Youn, S. W.
Cooperative
Indium(III)/Silver(I)
System
for
Oxidative
(13) Luo, J.; Zhang, J. Donor–Acceptor Fluorophores for Visible-
Light-Promoted Organic Synthesis: Photoredox/Ni Dual
Catalytic C(sp3)–C(sp2) Cross-Coupling. ACS Catal. 2016, 6, 873–
877.
Coupling/Annulation of 1,3-Dicarbonyls and Styrenes:
Construction of Five-Membered Heterocycles. Adv. Synth. Catal.
2016, 358, 1934–1941; (b) Wetter, C.; Jantos, K.; Woithe, K.;
Studer,
Addition/Cyclization
A.
Intermolecular
Reactions
Radical
of Alkoxyamines
Addition
and
onto
(14) For examples of MeCN participation in the reaction
mechanism, see: (a) Iwata, Y.; Tanaka, Y.; Kubosaki, S.; Morita, T.;
Yoshimi, Y. A Strategy for Generating Aryl Radicals from
Arylborates through Organic Photoredox Catalysis: Photo-
Meerwein Type Arylation of Electron-Deficient Alkenes. Chem.
Commun. 2018, 54, 1257–1260; (b) Kumagai, Y.; Naoe, T.;
Nishikawa, K.; Osaka, K.; Morita, T.; Yoshimi, Y. Formation of
Carbanions from Carboxylate Ions Bearing Electron-
Withdrawing Groups via Photoinduced Decarboxylation:
Addition of Generated Carbanions to Benzaldehyde. Aust. J.
Chem. 2015, 68, 1668–1671.
(15) Sim, B. A.; Milne, P. H.; Griller, D.; Wayner, D. D. M.
Thermodynamic Significance of ρ+ and ρ- from Substituent
Effects on the Redox Potentials of Arylmethyl Radicals. J. Am.
Chem. Soc. 1990, 112, 6635–6638.
(16) Speckmeier, E.; Fischer, T. G.; Zeitler, K. A Toolbox Approach
To Construct Broadly Applicable Metal-Free Catalysts for
Photoredox Chemistry: Deliberate Tuning of Redox Potentials
Nonactivated Alkenes. Org. Lett. 2003, 5, 2899–2902; (c) Maeda,
H.; Takayama, H.; Segi M. Photoinduced Three-Component
Coupling Reactions of Electron Deficient Alkenes, Dienes and
Active Methylene Compounds. Photochem. Photobiol. Sci. 2018,
17, 1118–1126; (d) Lu, Z.-F.; Shen, Y.-M.; Yue, J.-J.; Hu, H.-W.; Xu,
J.-H.
Photoinduced
Three-Component
Reactions
of
Tetracyanobenzene with Alkenes in the Presence of 1,3-
Dicarbonyl Compounds as Nucleophiles. J. Org. Chem. 2008, 73,
8010–8015.
(7) (a) Linker, T.; Kersten, B.; Linker, U.; Peters, K.; Peters, E.-M.;
von Schnering, H. G. Manganese(III)-Mediated Radical Additions
of Dimethyl Malonate to Olefins. The Chemoselective Synthesis
of Diesters and Lactones. Synlett 1996, 468–470; (b) Hirase, K.;
Iwahama, T.; Sakaguchi, S.; Ishii, Y. Catalytic Radical Addition of
-
Carbonyl Compounds to Alkenes by Mn(II)/Co(II)/O2 System. J.
Org. Chem. 2002, 67, 970–973; (c) Kagayama, T.; Fuke, T.;
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 7
and Importance of Halogens in Donor–Acceptor Cyanoarenes. J.
Am. Chem. Soc. 2018, 140, 15353–15365.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

Page 7 of 7
ACS Catalysis
R3
5 mol% KOtBu
1 mol% photocat.
COOR1
COOR1
Ar
COOR1
COOR1
Ar
1
2
3
+
R2
MeCN, 20h, Ar
blue LED
R3
R2
4
5
6
N
N
NC
CN
F
F
7
8
N
N
N
N
N
CN
9
3DPA2FBN
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4CzIPN
7
ACS Paragon Plus Environment