Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates

Article abstract of DOI:10.1021/acscatal.7b01669

Alkyl radicals are obtained by photocatalytic oxidation of readily prepared or commercially available zinc sulfinates. The convenient benzylation and alkylation of a variety of electron-poor olefins triggered by the iridium(III) complex 6 Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ as photocatalyst is described. Moreover, it is shown that zinc sulfinates can be used for facile nonradical sulfonylation reactions with highly electrophilic Michael acceptors.

Full text of DOI:10.1021/acscatal.7b01669

Subscriber access provided by UNIVERSITY OF CONNECTICUT
Letter
Photocatalytic Radical Alkylation of Electrophilic
Olefins by Benzylic and Alkylic Zinc-Sulfinates
Andrea Gualandi, Daniele Mazzarella, Aitor Ortega Martinez, Luca Mengozzi, Fabio Calcinelli,
Elia Matteucci, Filippo Monti, Nicola Armaroli, Letizia Sambri, and Pier Giorgio Cozzi
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b01669 • Publication Date (Web): 07 Jul 2017
Downloaded from http://pubs.acs.org on July 7, 2017
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 free 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 accessible to all
readers and 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.
ACS Catalysis 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 8
ACS Catalysis
1
2
3
4
5
6
7
8
9
Photocatalytic Radical Alkylation of Electrophilic Olefins by Ben-
zylic and Alkylic Zinc-Sulfinates
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
Andrea Gualandi,*‡ Daniele Mazzarella,‡† Aitor Ortega-Martínez,‡± Luca Mengozzi,‡ Fabio
Calcinelli,‡ Elia Matteucci,§ Filippo Monti,*# Nicola Armaroli,# Letizia Sambri,§ and Pier Giorgio
Cozzi*‡
‡ Dipartimento di Chimica “G. Ciamician”, ALMA MATER STUDIORUM Università di Bologna, Via Selmi 2, 40126 Bolo-
gna, Italy
§ Dipartimento di Chimica Industriale “Toso Montanari”, ALMA MATER STUDIORUM Università di Bologna, Viale Ri-
sorgimento 4, Bologna, Italy
# Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bolo-
gna, Italy
† Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
± Departamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de
Síntesis Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante, 03080 Alicante, Spain
ABSTRACT: Alkyl radicals are obtained by photocatalytic oxidation of readily prepared or commercially available zinc sul-
finates. The convenient benzylation and alkylation of a variety of electron-poor olefins triggered by the iridium(III) complex
6 Ir[dF(CF3)ppy]2(dtbbpy)PF6] as photocatalyst is described. Moreover, it is shown that zinc sulfinates can be used for facile
non-radical sulfonylation reactions with highly electrophilic Michael acceptors.
KEYWORDS Sulfinates, photocatalysis, alkylation, benzylation, iridium catalyst
Sulfinates derivatives have been introduced in organic
chemistry since the early 1900’s.1 They are a class of easily
accessible or commercially available starting materials
with versatile reactivity, as they can be nucleophilic or
electrophilic depending on the reaction conditions.2 Many
sulfinates can be readily prepared up to the kilogram scale
and are stable under ambient conditions.3 Lately, oxidative
conditions were applied to the generation of radical spe-
cies starting from sulfinates,4 taking advantage of the fact
that oxidation potentials of sulfinates are lower compared
to other precursors of radicals, such as carboxylates.5 Ex-
trusion of SO2 induced by oxidative conditions generates
the corresponding aryl or alkyl radical.6 Recently, a radical-
based functionalization strategy7 that involves the use of
sodium and zinc bis(alkylsulfinate) reagents has been de-
veloped by Baran (Scheme 1).9 Alkyl sulfinates are also ac-
cessible by the procedures developed by Willis.8 Sulfinates
have been employed in different radical-based reactions.
Examples include Minisci type reactions,10,8c fluoroalkyla-
tion of thiols and enones11, sulfonylation of arylacetylene
acids,12 and decarboxylative fluoroalkylation of α,β-
unsaturated carboxylic acids.13
SCHEME 1. Baran’s synthetic procedures with zinc sul-
finate reagents.
On the other hand, benzyl- (and alkyl-) sulfinates have not
been yet investigated to accomplish photocatalytic radical
alkylation of electron poor olefins (Giese reaction)15. In-
deed, the use of benzyl radicals in photoredox reactions
was described by Nishibayashi16, Fagnoni,17 and Melchior-
re,18 but these intermediates are rather persistent and inef-
ficiently trapped by Michael acceptors. As pointed out by
Melchiorre,18 the large resonance stabilization of benzyl
radicals hampers ready addition to electron-poor olefins,
which results in the formation of dimeric bibenzyl deriva-
The use of sulfinates in photoredox catalysis, where radical
species are produced by an oxidation reaction induced by
the photo catalyst, has been also reported.14 In particular,
the photocatalytic sulfonylation of alkenes with aryl14a and
alkyl sulfinates5b has been described.
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 8
= +
III/II
tives. Therefore, Michael addition of benzylic radicals is
excited state *Ir[dF(CF3)ppy]2(dtbbpy)PF6] (E1/2*
1.21 V vs saturated calomel electrode).23
1
2
3
4
5
6
rather difficult. Recently, a more general benzylic alkyla-
tion of Michael acceptors was reported, using mesityl-10-
methylacridinium perchlorate.19 However, this strategy
requires a strong oxidizing power, because benzylic radical
cations are obtained by oxidation of alkylaryl derivatives
(E1/2red* photocatalyst = +2.06 vs SCE in MeCN).
7
8
9
Prompted by our interest in photoredox catalytic reac-
tions,20 herein we describe a new procedure to accomplish
the difficult radical benzylation of electrophilic alkenes, by
using benzylic sufinates in combination with commercially
available photocatalysts and visible light irradiation. Then,
we demonstrate that the scope of the reaction can be ex-
tended by using also alkylsulfinates.
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
As mentioned in the introduction, benzylic sulfinates are
readily accessible reagents. Indeed, sodium and zinc ben-
zylic sulfinates were prepared by reduction of the corre-
sponding sulfonyl chlorides (Scheme 2).10
SCHEME 3. Photoredox benzylation of alkylidene ma-
lonate (5a).
The reduced Ir[dF(CF3)ppy]2(dtbbpy) generated by oxida-
III/II
tive quenching is a strong reductant (E1/2
= - 1.37 V vs
saturated calomel electrode).23 Sodium alkyl sulfinates
-
5b
(Ered [RSO2·/RSO2 ] ≈ +0.45 V vs SCE) are suitable sub-
strates for the reaction. Unfortunately, even if we found
satisfactory conditions (Scheme 3), the reaction was quite
difficult to be reproduced. We found that benzylic sodium
sulfinates were unstable, even if stored under argon at -20
°C (see SI for details) and this was the origin of the ob-
served problems.24 Therefore, we turned on the more sta-
ble and less reactive zinc sulfinates; although they are
SCHEME 2. Preparation of benzylic sodium (3a) and
zinc sulfinates (4a-f).
more difficult to be oxidized5b (Ered [RSO2·/RSO2 ] ≈ +0.9 V
vs SCE) they proved to be suitable substrates for the reac-
-
Starting from the bromide analogues, sulfonyl chlorides
(2a-f) were synthesized in a two-step protocol by reaction
with Na2SO3, followed by treatment with POCl3 or other
reagents such as PCl5 or SOCl2. Sulfonyl chloride 2a was
reduced with sodium sulfite (Scheme 2) to give the corre-
sponding sodium sulfinate (3a). Zinc sulfinates (4a-f) were
conveniently prepared from sulfonyl chlorides (2a-f) by
reduction with zinc, which was activated with the Knochel
procedure.21
tion (Table 1).
Since water was necessary to solubilize the sulfinate, we
tested water miscible co-solvents. MeCN (entry 1), DMF
(entry 2), TFE (entry 3) and DME (entry 4) proved unsuit-
able. Instead, DMSO (entry 5) showed a lower conversion
rate compared to sodium sulfinate. The use of a mixture
1:4 H2O and EtOH (entry 6) gave a lower conversion com-
pared to a 4:1 (entry 7) or 1:1 (entry 8) that afforded fa-
vorable results, with the latter being the best solvent mix-
ture. In order to improve the solubility of the zinc reagent,
coordinating species able to bind this metal were also in-
vestigated (entries 9-11).25 Unfortunately, the conversion
was not improved even if zinc sulfinate seemed to be more
soluble under such conditions. Finally, a good conversion
was obtained with three equivalents of zinc sulfinate and
40 hours of irradiation (entry 12). With the optimized
conditions in hand, a variety of electrophilic alkenes were
then investigated (Scheme 4). With a variety of Michael ac-
ceptors (5b-k) the benzylated products (7b-k) were ob-
tained in moderate to good yields. Quite interestingly, the
outcome of the reaction was dependent from the alkene
derivative.26 Sulfones (8m-q) rather than derivatives (7)
were isolated as the major products in the reaction with
the alkenes (5m-q) (see discussion below and Scheme 8
for a plausible formation mechanism).
The alkylidene malonate (5a) was chosen as model com-
pound and the reaction with benzyl sodium sulfinate 3a
was evaluated by varying numerous parameters in the
presence of different photocatalysts (see SI for full details).
Satisfactory results were generally obtained by using a
mixture of EtOH or DMSO with H2O as reaction solvent, in
the presence of the iridium (III) photocatalyst (6). Other
photocatalysts with appropriate oxidative potential such
as eosin Y5b or 9-mesityl-10-methylacridinium tetra-
fluoroborate22 gave no conversion under the examined re-
action conditions.
By employing as photocatalyst the iridium(III) complex
(6), the thermodynamic limit for the electron transfer be-
tween (6) and sulfinate is dictated by the excited state
properties
of
the
photocatalyst.
Ir[dF(CF3)ppy]2(dtbbpy)PF6] (6) can absorb photons in the
visible spectral window, generating a powerful oxidizing
ACS Paragon Plus Environment

Page 3 of 8
ACS Catalysis
R2
R2
R2
R1
6
( ), 1 mol%
R1
1
2
3
R3
SO2Bn
8m-q
R3
5b-q
Bn
(
SO2)2Zn +
R3 or
1:1 EtOH:H2O, 40 h
blue led (24 W)
)
R1
Bn
7b-k)
TABLE 1. Optimization of the benzylation of alkylidene
5a with (BnSO2)2Zn.
4a
), 3 equiv
(
(
(
(
)
4
COOEt
COOMe
COOMe
5
6
MeOOC
Ph
Ph
Ph
COOMe
), 60 %
COOEt
7
8
9
7d
(
Ph
Ph
7b
(
), 62 %
7c
(
), 11 %
Ph
OMe
MeOOC
Ph
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
Ph
Entrya Solvent
Additive
Yieldb
25
OMe
COOMe
Ph
O
1
2
3
4
5
6
7
8
9
H2O:MeCN (1:1)
-
OMe COOEt
7e
(
), 40 %
7f
), 40 %
(
H2O:DMF (1:1)
H2O:TFE (1:1)
H2O:DME (1:1)
H2O:DMSO (1:4)
H2O:EtOH (1:4)
H2O:EtOH (4:1)
H2O:EtOH (1:1)
H2O:EtOH (1:1)
-
58
7g
(
), 40 %
Ph
Ph
-
31
O
COOEt
Ph
-
43
CHO
N(Bn)2
), 28 %
-
74
7h
), 49 %
7i
(
7j
( ), 39 %
(
-
27
O
O
O
O
SO2Bn
BnO2S
-
72
77 (57)c
NPh
N
O
-
O
2,6-lutidine
(4 equiv.)
2,2’-bipyridine
(2 equiv.)
1-Me-imidazole
(4 equiv.)
-
52
7k
), 85 %
8m
8n
( ), 61 %
(
(
), 57 %
Ph
SO2Bn
Ph
O
SO2Bn
10
11
H2O:EtOH (1:1)
H2O:EtOH (1:1)
H2O:EtOH (1:1)
72
SO2Ph
), 91 %
BnO2S
8q
Ph
Ph
O
8o
8p
78
(
), 44 %
(
), 63 %
(
12d
88 (69)c
SCHEME 4. Radical benzylation of different electro-
philic alkenes.
a
All the reactions were carried out under argon. The reaction
mixtures were degassed by three cycles of freeze-pump-thaw. The
reactions were performed using (4a) (0.2 mmol), (5a) (0.1 mmol)
in 1 mL of solvent mixture, in the presence of 1 mol% of the cata-
lyst 6. b Determined by 1H-NMR of the crude reaction mixture. c In
parenthesis isolated yields after chromatographic purification. d
Equivalents of (4a) were employed and the reaction mixture was
irradiated for 40 hours.
3
The effect of an aromatic substituent on the aryl moiety of
the benzylic sulfinates derivative was explored with dime-
thyl fumarate as acceptor (Scheme 5).
In general, it was possible to obtain satisfactory results
with a series of benzylic derivatives (4b-f), readily pre-
pared in moderate yields by the procedure described
above. In other cases, the desired zinc sulfinates com-
pounds were not obtained (see SI for details).
SCHEMES 5. Scope of reaction with different zinc ben-
zylic sulfinates.
We have briefly investigated the possibility to expand the
scope of the reaction by examining alkyl zinc sulfinates
(10, 11) which are commercially available or prepared by
the general procedure (see SI for details). Although the re-
action was observed, the yields of the products (12-14)
were lower with respect to the benzylic sulfinates, proba-
bly due to the lower stability of the generated alkyl radi-
cals. In the case of alkyl sulfinates, the alkene partners dic-
tated the product obtained: sulphones 12 and 13 or alkyl-
ated adduct 14 (Scheme 6).27
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 8
catalyst) and it is not blocked by radical scavengers
(Scheme 8). Formation of sulfonyl radical30 in our condi-
tions is unlikely to occur because reactions, in which the
sulfonyl radical is formed, are completely inhibited in the
presence of TEMPO.31 On the other hand, Pinnick has re-
ported the formation of sulfones by addition of sulfinates
salts (sodium, lithium, and magnesium sulfinates) to Mi-
chael acceptors.32 Zinc sulfinates are nucleophilic reagents
and are able to open epoxides in water affording the corre-
sponding β-hydroxysulfones.33 The presence of a zinc salt
is probably enhancing the electrophilicity of the Michael
acceptors.34
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
Based on these evidences, the sulfones are generated from
the nucleophilic attack of the zinc sulfinates on the elec-
trophilic alkenes partner. It is also worth mentioning that
with the less electrophilic substrate (5d), no sulfone, as
well as no product (7d), was isolated in the presence of
TEMPO (Scheme 7 (a)).
SCHEME 6. Reaction of alkyl zinc sulfinates with elec-
trophilic alkenes.
In order to prove that the mechanism involves the for-
mation of free radicals and that both light and photocata-
lyst are necessary, the model reaction was tested with 1.5
equivalents of the radical scavenger TEMPO (2,2,6,6-
tetramethylpiperidin-1-yl-oxyl) (a), in absence of light (b)
and without the Ir(III) catalyst (6) (c) (Scheme 7). In all
cases, no conversion was observed, proving that a radical
mechanism occurs and that both light and photocatalyst
are necessary.
a
Conversions measured by 1H-NMR on the crude mixture.
SCHEME 8. Formation of sulfones in a model reaction
in different reaction conditions.
In order to get a deeper insight into the mechanism and
the efficiency of this type of photoreactions, electrochemi-
cal and photochemical studies were carried out on the irid-
ium catalyst (6) and on the most representative reagents
tested above (i.e., the benzyl zinc sulfinate 4a, and the al-
kylidene malonate 5a).
SCHEME 7. Inhibition of the radical reaction in the
presence of TEMPO, and in the absence of light or pho-
tocatalyst.
First of all, the redox potentials of (4a) and (5a) were
characterized by square-wave voltammetry (Figure S3)
and compared to the excited-state redox potential of the Ir
(III) photocatalyst (6).30 In order to increase the solubility
of the zinc sulfinate (4a), four equivalents of 1-
methylimidazole MI were added to the acetonitrile solu-
tion. The results of the electrochemical experiments are
summarized in Table 2. The redox properties of MI are al-
so reported to demonstrate that this coordinating com-
pound does not take part in the photochemical reaction
and it simply acts as a solubilizing agent (i.e., its potentials
are outside the redox window of the excited iridium pho-
tocatalyst (6), see Table 2).
The intriguing formation of sulfone derivatives (8m-q) and
(12, 13) was investigated in detail. It is important to note
that only alkyl- and aryl-vinyl sulfones were obtained by
König, using eosin Y as photocatalyst,5b through the addi-
tion of sulfonyl radicals to alkenes, in combination with
sodium salts of alkyl and aryl sulfinates. Although the SO2
moiety is preserved with eosin, in our conditions zinc sul-
finates enable the alkylation of Michael acceptors. Organo-
sulfone mediated radical alkylation and vinylation reac-
tions were developed by Zard28 and are centered on the
facile decomposition of alkylsulfone radicals to give alkyl
radical with the liberation of sulfur dioxide.6 This desul-
fonylation is reversible and the equilibrium is shifted if the
radical is stabilized, as in our case.29 We found that this
process occurs also in the dark (in the absence of photo-
ACS Paragon Plus Environment

Page 5 of 8
ACS Catalysis
Table 2. Electrochemical data for the reaction partners (7a). The mechanistic picture for the radical benzylation is
1
2
3
4
5
6
7
8
illustrated in Figure 1 The proposed photocatalytic mech-
anism does not take into account a possible radical chain
reaction. However, this process is unlikely because the
quantum efficiency of the overall photochemical reaction is
estimated to be 0.37 ± 0.09, see SI for details.35
a
a
Eox
Ered
E*ox
[V]
E*red
[V]
[V]
[V]
(4a) + MI
+ 0.13 b ---
---
---
(4 equiv.)
In conclusion, we have shown that readily available zinc
sulfinates could be used in photoredox catalysis producing
benzylic radicals in an oxidative quenching cycle. The ben-
zylic radicals could be intercepted by suitable Michael ac-
ceptors. With strong electrophilic Michael acceptors, zinc
sulfinates can behave as nucleophiles leading to the corre-
sponding sulfone derivative, without radical formation.
(5a)
MI
(6)
a
---
– 2.42 b ---
---
---
+ 1.35 b ---
---
9
+ 1.32
– 1.73
≈ – 1.1
≈ + 0.7
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
See reference 20c for details. b Electrochemical data deter-
mined by square-wave voltammetry in room-temperature ace-
tonitrile solution + 0.1 M TBAPF6. All redox potentials are re-
ferred to the ferrocene/ferrocenium couple, used as internal
standard. Irreversible redox process with an estimated error of ±
0.05 V.
The excited-state reduction potential of the iridium com-
plex is high enough to oxidize the benzyl zinc sulfinate (4a)
(i.e., 0.7 > 0.13 V, see Table 2) and to catalyze the formation
of the corresponding radical. It is worth noting that the
same photocatalyst is not capable of oxidizing or reducing
the alkylidene malonate (5a) (see Table 2).
The electrochemical data are supported by the Stern-
Volmer quenching experiments summarized in Table 3
(see also Figure S4). As expected, the intramolecular re-
ductive quenching of complex (6) is only observed when
the benzyl zinc sulfinate (4a) is added to the photocatalyst
solution. The rate constant associated to this quenching
process (kq = 1.32 108 M–1 s–1, see Table 3) is comparable to
that of analogous processes involving the same iridium
photocatalyst, but different oxidable radical precursors.20c
FIGURE 1. Suggested mechanism for the benzylation
reaction with zinc sulfinates.
ASSOCIATED CONTENT
Supporting Information. Screening tests. Photophysical
measurements and quenching studies. Detailed procedures,
description and copies of NMR spectra for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org
Table 3. Stern–Volmer experiments carried out in oxy-
gen-free acetonitrile solutions at 298 K.a
AUTHOR INFORMATION
Corresponding Authors
KSV [mM–1]
kq b [108 M–1 s–1]
(4a)
+
MI (4 0.31 ± 0.01
1.32 ± 0.06
‡
equiv.)
(5a)
MI
Dipartimento di Chimica “G. Ciamician” ALMA MATER
STUDIORUM, Università di Bologna Via Selmi 2, 40126, Bolo-
gna, Italy. Email: andrea.gualandi10@unibo.it; piergior-
gio.cozzi@unibo.it.
Quenching not observed. c
Quenching not observed. c
a Data reported with a ± 95% confidence interval. In all cases,
the quality of the fitting is assured by a R2 > 0.98. Concentration of
photocatalyst: (6) = 0.015 mM; excitation wavelength: λmax = 330
nm. b kq = KSV / τ0 , where τ0 is the unquenched excited-state life-
# Istituto per la Sintesi Organica e la Fotoreattività, Consiglio
Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna,
Italy. Email: filippo.monti@cnr.it.
c
ORCID
time of the photocatalyst. There is no evidence of correlation
between the excited-state quenching of the photocatalyst and in-
creasing amounts of (5a) or MI for a concentration up to 5 mM.
Andrea Gualandi: 0000-0003-2403-4216
Daniele Mazzarella: 0000-0001-7121-9796
Aitor Ortega-Martínez: 0000-0002-8211-4479
Luca Mengozzi: 0000-0003-4472-1400
Elia Matteucci: 0000-0003-4206-817X
Filippo Monti: 0000-0002-9806-1957
Nicola Armaroli: 0000-0001-8599-0901
Letizia Sambri: 0000-0003-1823-9872
Pier Giorgio Cozzi: 0000-0002-2677-101X.
On the contrary, no quenching is found upon addition of
(5a) or of pure 1-methylimidazole. These findings unam-
biguously prove that the Michael acceptor cannot directly
react with (6), and that the only radicals which can be pho-
to-catalytically produced by the Ir (III) complex are those
generated by the oxidation of the zinc sulfinate derivative
(4a), through C-S bond dissociation and SO2 evolution.
Eventually, this radical can react with the Michael accep-
tor, affording a radical intermediate which can take up an
electron from the photochemically reduced iridium com-
plex. Then, the so-obtained carbanionic intermediate can
be protonated, leading to the desired reaction product
Author Contributions
The manuscript was written through contributions of all au-
thors. All authors have given approval to the final version of
the manuscript. A. G. was involved in the discovery and devel-
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 8
Collins, M. R.; Ornelas, M. A.; Ishihara, Y.; Baran, P. S. J. Am. Chem. Soc.
2014, 136, 4853-4856.
opment of the photochemical reaction. A. G., D. M., A. O.-M., F.
C. and L. M. performed the experiments. E. M. and L. S. pre-
pared the Ir(III) complexes used for the studies. F. M. and N. A.
designed and performed the photophysical measurements. P.
G. C. conceived and directed the project and wrote the manu-
script with contributions from all the authors.
1
2
3
4
5
6
7
8
(9)
(a) Flegeau, E. F.; Harrison, J. M.; Willis, M. C. Synlett, 2016,
27, 101-105; (b) Emmett, E. J.; Willis, M. C. Asian J. Org. Chem. 2015, 4,
602-611; (c) Deeming, A. S.; Russell, C. J.; Willis, M. C. Angew. Chem.
Int. Ed. 2015, 54, 1168-1171; (d) Deeming, A. S.; Emmett, E. J.; Rich-
ards-Taylor, C. S.; Willis, M. C. Synthesis, 2014, 46, 2701-2710; (e)
Deeming, A. S.; Russell, C. J.; Hennessy, A. J.; Willis, M. C. Org. Lett.
2014, 16, 150-153; (f) Richards-Taylor, C. S.; Blake-more, D. C.; Willis,
M. C. Chem. Sci. 2014, 5, 222-228.
(10) Minisci, F.; Fontana, F.; Vismara, E. J. Heterocycl. Chem.
1990, 27, 79-96.
(11) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765-825.
(12) Meesin, J.; Katrun, P.; Pareseecharoen, C.; Pohmakotr, M.;
Reutrakul, V.; Soorukram, D.; Kuhakarn, C J. Org. Chem. 2016, 81,
2744-2752.
(13) Li, Z., Cui, Z.; Liu, Z.-Q. Org. Lett. 2013, 15, 406-409.
(14) (a) Meyer, A. U.; Jäger, S.; Hari, D. P.; König, B. Adv. Synth.
Catal. 2015, 357, 2050-2054; (b) Meyer, A. U.; Lau, V. W. H.; König, B. ;
Lotsch, B. V. Eur. J. Org. Chem. 2017, 2179-2185; (c)Hering, T.; Uwe
Meyer, A.; König, B. J. Org. Chem. 2016, 81, 6927-6936, and ref. there-
in.
(15) Giese, B.; Gonzalez-Gomez, J. A.; Witzel, T. Angew. Chem. Int.
Ed. Engl. 1984, 23, 69-70. For a quite recent example, see: Qin T.; Ma-
lins, L. R.; Edwards, J. T.; Merchant, R. R.; Novak, A. J. E.; Zhong, J. Z.;
Mills, R. B.; Yan, M.; Yuan, C.; Eastgate, M. D.; Baran, P. S. Angew. Chem.
2017, doi: 10.1002/anie.201705107.
(16) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Chem. Commun.
2013, 49, 7854-7856.
(17) Capaldo, L.; Buzzetti, L.; Merli, D.; Fagnoni, M.; Ravelli, D. J.
Org. Chem. 2016, 81, 7102-7109.
(18) Silvi, M.; Verrier, C.; Rey, R. Y.; Buzzetti, L.; Melchiorre, P.
Nature Chem. 2017, DOI: 10.1038/NCHEM.2748.
(19) Zhou, R.; Liu, H.; Tao, H.; Yu, Y.; Wu, J. Chem. Sci. 2017, 8,
4654-4659.
(20) (a) Gualandi, A.; Marchini, M.; Mengozzi, L.; Natali, M.; Luca-
rini, M.; Ceroni, P.; Cozzi, P. G. ACS Catal. 2015, 5, 5927-5931; (b)
Magagnano, G.; Gualandi, A.; Marchini, M.; Mengozzi, L.; Ceroni, P.;
Cozzi P. G Chem. Commun. 2017, 53, 1591-1594; (c) Gualandi, A.;
Matteucci, E.; Monti, F.; Armaroli, N.; Sambri, L.; Cozzi, P. G. Chem. Sci.
2017, 8, 1613-1620.
Funding Sources
Bologna University, Fondazione Del Monte, SLAMM project
are acknowledged for financial support to A G. and L. M. N.A.
and F.M. thank the CNR for financial support through the pro-
jects PHEEL, N-CHEM, and bilateral CNR-CONICET.
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
S Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI. Details of all synthetic, elec-
trochemical, photophysical experiments.
ACKNOWLEDGMENT
A. O.-M. thanks the Spanish MINECO for a fellowship.
Notes
The authors declare no competing financial interest.
ABBREVIATIONS
Zinc trifluoromethanesulfinate (TFMS), zinc difluoro-
methanesulfinate (DFMS), zinc trifluoroethanesulfinate
(TFES) and zinc isopropyl-sulfinate (IPS), tetrabutylammoni-
um decatungstate (TBADT), trimethylsilyl (TMS), saturated
calomel electrode (SCE), acetonitrile (MeCN), dimethylsufox-
ide (DMSO), 2,2,6,6-tetramethylpiperidin-1-yl-oxyl (TEMPO),
REFERENCES
(1)
(a) Borsche, W.; Lange, W. Ber. Dtsch. Chem. Ges. 1906,
39, 2346-2356; (b) Smiles, S.; Le Rossignol, R. J. Chem. Soc. Trans.
1908, 93, 745-762.
(21) Chang, P.; Yeh, P.; Chen, H. G.; Knochel P. Org. Synth. 1992,
70, 195-202.
(2)
A. Org. Biomol. Chem. 2014, 12, 9743-9759.
(3) O'Hara, F.; Baxter, R.D.; O'Brien, A.G.; Collins, M.R.; Dixon,
For a review, see: Aziz, J.; Messaoudi, S.; Alami, M.; Hamze,
(22) Fukuzumi, S.; Kotani,H.; Ohkubo,K.; Ogo, S.; V. Tkachenko,
N. V.; Lemmetyinen, H. J. Am. Chem. Soc. 2004, 126, 1600-1601.
(23) Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R.
A.; Maliaras, G. G.; Bernhard, S. Chem. Mat. 2005, 17, 5712-5719.
(24) 1H-NMR signal of sodium sulfinates stored in air at r.t. were
showing the presence of other species after few hours. Also, storing
the sample at -20 °C the decomposition was only delayed. See SI for an
image.
J.A.; Fujiwara, Y.; Ishihara, Y.; Baran, P. S., Nature Protocols 2013, 8,
1042-1047.
(4)
2017, 82, 1224-1230.
(5)
(a) For hexanoate; Ered = + 1.16 vs SCE; see: Galicia, M.;
Wu, W. Q.; Yi, S. J; Yu, Y.; Huang, W.; Jiang, H. F. J. Org. Chem.
1/2
Gonzales, F. J. J. Electrochemical Soc. 2002, 149, D.46-D50. (b) For so-
dium alkyl sulfinates; Ered = +0.45 V vs SCE; see: Uwe Meyer, A.;
1/2
(25) For coordination of zinc sulfonates with a nitrogen contain-
ing heterocycle, see: Lindner, E.; Frembs, D. W. R.; Krug, D. Chem. Ber.
1975, 108, 291-300.
Strakov, K.; Slanina,T.; König, B. Chem. Eur. J. 2016, 22, 8694-8699.
(6)
Chatgilialoglu, C.; Lunazzi, L.; Ingold, K. U. J. Org. Chem.
1983,48, 3588-3589.
(26) Mayr has measured the electrophilicity of Michael accep-
tors in a series papers; see: (a) Chen, Q.; Mayer, P.; Mayr, H. Angew.
Chem. Int. Ed. 2016, 55, 12664; (b) Allgäuer, D. S.; Mayr, H. Eur. J. Org.
Chem. 2014, 2956; (c) Asahara, H.; Mayr, H. Chem. Asian J. 2012, 7,
1401 (d) Zenz, I.; Mayr, H. J. Org. Chem. 2011, 76, 9370; (e) Kaumanns,
O.; Lucius, R.; Mayr, H. Chem. Eur. J. 2008, 14, 9675-9682. Although
these kinetic investigations, a general method to predict the corre-
sponding reactivities and selectivities of Michael acceptors is still
missing. However, the relative reactivities of different families of Mi-
chael acceptors can be obtained by the thermodynamics of the rate-
determining step, as was recently found by Mayr: H. Mayr, personal
communication
(27) For the reduction potential and LUMO energy of a series of
α,β-unsaturated compounds, see: Moraleda, D.; El Abed, D.; Pellissier,
H.; Santelli, M. THEOCHEM 2006, 760, 113-119. Recently, the compu-
tational study of the addition of benzyl radical, generated through
photoredox conditions was reported: see Tutkovsky, B.; Meggers, E.;
Wiest, O. J. Am. Chem. Soc. 2017; DOI: 10.1021/jacs.7b01786. The
LUMO of the electron deficient alkene substrate and the SOMO of the
benzyl radical acting as a nucleophile are the orbitals involved in the
(7)
(a) A. Studer, D. P. Curran Angew. Chem. Int. Ed. 2016, 55,
58-102; (b) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. J. Am. Chem.
Soc. 2016, 138, 12692-12714.
(8)
Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. J. Am. Chem. Soc.
2016, 138, 12692-12714. For other radical reactions developed by
Baran group, see: a) Ji, Y.; Brueckl, T.; Baxter, R. D.; Fujiwara, Y.; Seiple,
I. B.; Su, S.; Blackmond, D. G.; Baran, P. S. PNAS, 2011, 108, 14411-
14415; (b) Fujiwara, Y.; Dixon, J. A.; Rodriguez, R. A.; Baxter, R. D.;
Dixon, D. D.; Collins, M. R.; Blackmond, D. G.; Baran, P. S. J. Am. Chem.
Soc. 2012, 134, 1494-1497; (c) Fujiwara, Y.; Dixon, J. A.; O'Hara, F.;
Funder, E. D.; Dixon, D. D.; Rodriguez, R. A.; Baxter, R. D.; Herlé, B.;
Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95-
99; (d) Zhou, Q.; Ruffoni, A.; Gianatassio, R.; Fujiwara, Y.; Sella, E.; Sha-
bat, D.; Baran, P. S. Angew. Chem. Int. Ed. 2013, 52, 3949-3952; (e)
O'Hara, F.; Blackmond, D. G.; Baran, P. S. J. Am. Chem. Soc. 2013, 135,
12122-12134; (f) Zhou, Q.; Gui, J.; Pan, C.-M.; Albone, E.; Cheng, X.; Suh,
E. M.; Grasso, L.; Ishihara, Y.; Baran, P. S. J. Am. Chem. Soc. 2013, 135,
12994-12997; (g) Gui, J.; Zhou, Q.; Pan, C.-M.; Yabe, Y.; Burns, A. C.;
ACS Paragon Plus Environment

Page 7 of 8
ACS Catalysis
process. The energy of the orbitals and their full structures were re-
ported in the article.
1
(28) a) Bertrand, F.; Quiclet-Sire, Z.; Zard, S. Z. Angew. Chem. Int.
Ed. 1999, 38, 1943-1946; (b) Quiclet-Sire, B.; Zard, S. Z. Beilstein J. Org.
Chem. 2013, 9, 557-576.
(29) Kim, S.; Kim, S. Bull Soc. Chim. Jpn. 2007, 80, 809-822.
(30) (a) Chatgilialoglu, C.; Mozziconacci, O.; Tamba, M.;
Bobrowski, K.; Kciuk, G.; Bertrand, M. P.; Gastaldi, S.; Timokhin, V. I. J.
Phys. Chem. A 2012, 116, 7623-7628; (b) Chatgilialoglu, C. in The
chemistry of Sulfone and Sulfoxides, Patai, S.; Rapaport, Z.; Stirling, J. J.
M. eds.; Wiley, Chichester 1988, pp. 1089.
2
3
4
5
6
7
8
(31) (a) Huang, Z.; Lu, Q.; Liu, Y.; Liu, D.; Zhang, J.; Lei, A. Org.
Lett. 2016, 18, 3940-3943; (b) Chen, F.; Meng, Q.; Han, S.-Q.; Han, B.;
Org. Lett. 2016, 18, 3390-3393.
(32) Pinnick, H. W.; Reynolds, M. A. J. Org. Chem. 1979, 44, 160.
(33) Chumachenko, N.; Sampson, P. Tetrahedron 2006, 62,
4540-4548.
(34) Zinc catalysis: applications in organic synthesis; Enthaler, S.;
Wu, X.-F. eds; Wiley-WCH, Weinheim 2015.
(35) The measured value of the quantum yield is similar to that
found in a photoredox radical decarboxylation reaction: Y. Miyake,
Nakajima, K.; Nishibayashi, Y. Chem. Commun. 2013, 49, 7854-7856.
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

ACS Catalysis
Page 8 of 8
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