Hydrosulfonylation of Unactivated Alkenes by Visible Light Photoredox Catalysis

Article abstract of DOI:10.1021/acs.orglett.9b03636

The anti-Markovnikov hydrosulfonylation of unactivated alkenes with sodium sulfinates was realized via [Ir(dF(CF₃)ppy)₂(dtbbpy)]PF₆-mediated visible light photoredox catalysis. The presence of an acid such as acetic acid is essential for the reaction to take place. A variety of unactivated alkenes can be transformed into sulfones with good yield and high regioselectivity using this reaction, which is proposed to proceed by a radical mechanism.

Full text of DOI:10.1021/acs.orglett.9b03636

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Hydrosulfonylation of Unactivated Alkenes by Visible Light
Photoredox Catalysis
Juan-Juan Wang and Wei Yu*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou, Gansu 730000, China
S
* Supporting Information
ABSTRACT: The anti-Markovnikov hydrosulfonylation of
unactivated alkenes with sodium sulfinates was realized via
[Ir(dF(CF3)ppy)2(dtbbpy)]PF6-mediated visible light photo-
redox catalysis. The presence of an acid such as acetic acid is
essential for the reaction to take place. A variety of unactivated
alkenes can be transformed into sulfones with good yield and high regioselectivity using this reaction, which is proposed to
proceed by a radical mechanism.
corresponding sulfones in an anti-Markovnikov way by using
ulfones are versatile organic compounds that have
1
Smultifarious usefulness in various disciplines of chemistry. this method.
Recently, we developed a straightforward means for the anti-
Accordingly, many efforts have been made to gain access to
sulfonyl compounds of diverse structural features.2 Among the
numerous methods developed for this purpose, those employ-
ing alkenes as precursors are particularly attractive in view of
the availability of alkenes as feedstock chemicals.3 It has long
been known that sulfonyl radicals can add to alkenes to form
sulfones,4 but only during the past decade has the potential
usefulness of this methodology begun to be widely appreciated.
Sulfonyl radicals can be generated conveniently from various
precursors such as sulfonyl halides, sulfonyl hydrazides, sulfinic
acids, and sulfinates via single-electron reduction or oxidation,
which further enhances their practical usefulness in organic
synthesis.2,4 Much progress has been made recently in applying
the radical olefin sulfonylation to the preparation of vinyl
sulfones5 and β-functionalized sulfones.6 Notably, these
transformations can be realized under the mild conditions of
visible light photoredox catalysis,7 which is highly preferable
from the viewpoint of green chemistry.
Although many useful protocols have been developed for the
preparation of differently substituted sulfones from alkenes,
some issues still need to be investigated in this realm. For
example, the hydrosulfonylation of alkenes, a useful type of
transformation complementary to olefin sulfonylation−difunc-
tionalization, has been explored much less, despite the fact that
analogous hydrosulfonylation of alkynes is well-documented.8
Recently, Li9 and Wu10 reported several efficient visible light
catalytic protocols for the hydrosulfonylation of alkenes.
However, the scopes of their methods are limited to
electron-deficient alkenes, and there remains a need for
effective means of hydrosulfonylation of unactivated alkenes.
In this regard, we report herein a visible light-driven catalytic
protocol for the free radical hydrosulfonylation of unactivated
alkenes with [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as the photo-
catalyst and sodium sulfinates as the sulfonating agent. A broad
scope of unactivated alkenes can be converted to the
Markovnikov hydroazidation of alkenes under visible light
photoredox catalysis with [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as
the photocatalyst and TMSN3 as the azidating agent.11 The
reactions were found to be greatly facilitated by H2O and acids.
In view of the structural importance of sulfones, we wondered
if sulfones could be prepared in an analogous way through
reactions of alkenes with sodium sulfinates. Thus, compound
1a was used as the model compound to test the feasibility of
this idea. Initially, iridium complex [Ir(dF(CF3)-
ppy)2(dtbbpy)]PF6, which was found to be most effective for
the hydroazidation of alkenes, was used as the photocatalyst to
promote the reaction of 1a with sodium benzenesulfinate
(PhSO2Na·2H2O, 2a), and the representative result is listed in
Table 1.
It can be seen that the desired transformation took place
smoothly under visible light irradiation (blue light-emitting
diodes) with the assistance of acetic acid in chloroform,
affording sulfone 3a in good yield. The presence of an acid was
necessary for the reaction to occur (Table 1, entries 1 and 5).
Water also had a beneficial effect on the reaction. As such, a
yield of 98% was reached when the reaction system
incorporated 10 equiv of H2O and 4.5 equiv of acetic acid
with the molar ratio of 1a to 2a being 1:1.65 (entry 6). The
reaction took place equally well in dichloromethane (entry 8),
but other solvents such as acetonitrile, DMF, and ethanol are
unsuitable as the reaction media (entries 9−11, respectively).
Using 1 mol % [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 was enough to
guarantee a complete conversion and an excellent yield (entry
14). A control experiment indicated that the reaction did not
take place in the dark or without a photocatalyst (entry 16 or
17, respectively). Apart from [Ir(dF(CF3)ppy)2(dtbbpy)]PF6,
Received: October 15, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03636
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
the effectiveness of some other commonly used photocatalysts
was also tested, but they were found to be inferior to
[Ir(dF(CF3)ppy)2(dtbbpy)]PF6. Details of the optimization of
reaction conditions are presented in Tables S1−S4.
Table 1. Screening of Reaction Conditions
The optimal conditions were then applied to variously
substituted alkenes, and the results are illustrated in Scheme 1
and Figures 1−3 (The reactions were performed on 0.5 mmol
equiv
(H2O)
equiv
(AcOH)
time
(h)
yield of 3a
b
entry
solvent
(%)
1
2
3
4
5
6
7
8
0
0
0
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CH3CN
DMF
24
4
4
4
24
4
trace
77
77
94
no reaction
98
65
98
4.0
4.0
4.0
0
4.5
2.0
4.5
4.5
4.5
4.5
0
4.0
10
10
10
10
10
10
10
10
0
a
Figure 1. Scope for alkenes-2. The reaction was performed on a 4
10
4
mmol scale.
9
10
10
10
24
24
4
4
10
10
11
10
11
12
13
14
15
no reaction
trace
no reaction
no reaction
98
EtOH
EtOH
0
0
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
c
10
10
10
10
4.5
4.5
4.5
4.5
d
68
e
16
17
no reaction
trace
f
a
Figure 2. Scope for alkenes-3.
Reaction conditions: 0.2 mmol of 1a, 0.33 mmol of 2a (PhSO2Na·
2H2O), and 2 mol % [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 in 1 mL of
solvent under a nitrogen atmosphere unless otherwise specified.
scale). It can be seen that a broad scope of unactivated
terminal alkenes bearing diverse polar (Scheme 1) or nonpolar
(Figure 1) functionalities can react with sodium benzenesulfi-
nate, affording the hydrosulfonylation products in high yield
b
c
Isolated yield. With 1 mol % [Ir(dF(CF3)ppy)2(dtbbpy)]PF6.
With 1.3 equiv of 2a. Control experiment in the dark. In the
d
e
f
absence of a photocatalyst.
Scheme 1. Scope for Alkenes-1
B
DOI: 10.1021/acs.orglett.9b03636
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Proposed Mechanism
Figure 3. Scope for alkenes-4.
and with excellent anti-Markovnikov selectivity. Notably, the
reaction can be conducted on a gram scale without a loss of
yield (Figure 1, footnote a). When compound N-allyl-N-
phenylpent-4-enamide 1l bearing an N-allyl group as well as a
carbonyl-tethered carbon−carbon double bond was subjected
to the standard conditions, only 3l was obtained. 1,2-
Disubstituted alkenes can also be converted to sulfones in
this way [3ai-1 and 3ai-2 (Figure 2)], despite the fact that a
mixture of regioisomers would be formed. This protocol
worked as well for trisubstituted [3aj and 3ak (Figure 2)] or
tetrasubstituted olefins (3al).
To further test the scope of this protocol, the standard
conditions were applied to several electron-deficient and
electron-rich alkenes. As shown in Figure 3, this protocol can
be used to prepare 3am, 3an, and 3ap but is unsuitable for the
preparation of 3ao, 3aq, and 3ar.
radical A then adds to the alkene double bond to give carbon-
centered radical B. The existence of this step was confirmed by
the radical clock experiment with compounds 5 and 6. As
expected, these two compounds were transformed into 7 and
8, respectively, corresponding to radical cyclization and ring
opening, respectively (Scheme 4).
Scheme 4. Radical Clock Experiment
Subsequently, we investigated the reactions with several
other sodium sulfinates as the sulfonating agents, and the result
is depicted in Scheme 2. It was found that the structure of the
Scheme 2. Scope for Sodium Sulfinates
For the subsequent reaction of B, there are two possible
pathways.14 One (path a) involves its reduction by [IrII] to
carbanion C followed by protonation to give the final product.
In this way, the whole process would constitute an [Ir(dF-
(CF3)ppy)2(dtbbpy)]PF6-mediated redox catalytic cycle.
Alternatively, radical B might be directly converted to product
3 or 4 by abstracting a hydrogen atom from the in situ-
generated sulfinic acid through a radical chain process (path
b). This hydrogen atom transfer (HAT) is possible considering
the relative weakness of the O−H bond of sulfinic acids (BDE
∼ 78 kcal/mol15).
To see which pathway is more feasible under the current
circumstances, a deuterium experiment was conducted for the
reactions of p-ClPhSO2Na (unhydrated) with dodec-1-ene and
methyl cyclopent-1-ene 1-carboxylate (1am) (Scheme 5). We
assumed that if the reaction proceeds following path a, using
D2O and CD3COOD would not influence the reactions much
except that deuterium would be introduced into the
products.16 By contrast, if path b is the predominant pathway,
the efficacy of the reaction would be greatly reduced because it
is much more difficult to abstract a deuterium from the in situ-
generated p-ClPhSO2D.17 Our result showed that the yield of
the sulfonylation product decreased considerably under the
deuterated conditions for dodec-1-ene. Moreover, undeuter-
ated product 4d was also obtained along with its deuterated
counterpart 4d-D. The added hydrogen in 4d should come
from the residual [-OH] species in the deuterated reagents. A
similar phenomenon was observed in the study by Xu.17 These
results indicate the involvement of path b for the formation of
sulfinate has a strong influence on the outcome of the reaction.
While compounds 4a−4f and 4j were generated in good to
excellent yields, the preparation of 4g−4i was unsuccessful.
Our hydrosulfonylation reactions are believed to proceed
following a free radical mechanism, which is depicted in
Scheme 3. The reaction is probably initiated by single-electron
transfer (SET) between the photoexcited iridium catalyst and
sodium sulfinates, which would generate sulfonyl radical A,
with the photocatalyst being reduced to [IrII] at the same time.
This SET step should be a facile process according to the
reduction potential of [Ir(dF(CF3)ppy)2(dtbbpy)]PF6
[E1/2red(*IrIII/IrII) = 1.21 V vs SCE in MeCN]12 and the
oxidation potential of sodium benzenesulfinate (−0.37 V vs
SCE in MeCN for PhSO2Na).13 The thus formed sulfonyl
C
DOI: 10.1021/acs.orglett.9b03636
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 5. Deuterium Experiment
Scheme 6. Reaction of 1a with 4-Methylbenzenesulfinic
Acid
functionalities can be converted in good to excellent yields
with high anti-Markovnikov regioselectivity. We hope that this
method will find applications in the synthesis of structurally
useful sulfonyl compounds.
hydrosulfonylation products. In the case of lam, on the other
hand, using deuterated reagents did not influence the yield
much, and the percentage of the undeuterated product was
much lower than that of 4d. The latter result is more
consistent with path a. We reason that this discrepancy may be
caused by the difference in the electronic nature of these two
compounds. Compared with carbon radical B derived from
dodec-1-ene, that derived from 1am is easier to reduce to
anion C due to the stabilizing effect of the adjacent
methoxycarbonyl group, while its capacity to abstract a
hydrogen atom from the in situ-generated p-ClPhSO2H is
weakened for the same reason. As a result, path a became
competitive for the reaction of 1am. The fact that unactivated
alkenes reacted much better than electron-deficient alkenes
indicates that path b is more efficient, and it should be the
major pathway for the reaction of unactivated alkenes. In
addition to the deuterium experiment, the quantum yield was
also measured for the reaction of 1a with 2a, which gave a ϕ
value of 0.65 (details about the quantum yield measurement
are presented in the Supporting Information). This value is
smaller than expected (<1) but does not contradict a radical
chain process.14
As shown in Table 1, acetic acid plays a crucial role for the
reaction to proceed. We believe that the function of acetic acid
is to convert sodium sulfinates to the corresponding sulfinic
acids, which act as the hydrogen donor for the last HAT step.
It is also possible that acid helps to stabilize the photocatalyst
in the reaction system,6r,18 but on the basis of mechanistic
analysis mentioned above and our previous study,11 we believe
that this factor may not contribute much to the beneficial effect
of acid in these reactions.
According to the proposed mechanism, we expected that the
olefin hydrosulfonylation could also be realized by using
sulfinic acids as the sulfonating agent. Indeed, it was found that
compound 1a can react with 4-methylbenzenesulfinic acid
under photocatalysis to afford the desired product (Scheme 6).
However, the efficacy of this latter protocol is lower by
comparison, and it is more preferable to use sodium sulfinates
in practical synthesis.
In summary, we have achieved the anti-Markovnikov
hydrosulfonylation of unactivated alkenes with sodium
sulfinates under the conditions of visible light photocatalysis
by using [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as a photocatalyst.
The reaction is greatly facilitated by acetic acid and water. A
variety of unactivated terminal alkenes bearing diverse
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03636.
Experimental procedures, characterization data for the
products, and copies of 1H and 13C NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yuwei@lzu.edu.cn.
ORCID
Wei Yu: 0000-0002-3131-3080
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors thank the National Natural Science Foundation of
China (21772077 and 21372108) for financial support.
■
REFERENCES
■
(1) (a) Patai, S.; Rappoport, Z.; Stirling, C. J. M. The Chemistry of
Sulphones and Sulfoxides; Wiley: New York, 1988. (b) Whitham, G. H.
Organosulfur Chemistry; Oxford University Press: Oxford, U.K., 1995.
(2) Liu, N.-W.; Liang, S.; Manolikakes, G. Synthesis 2016, 48, 1939−
1973.
(3) (a) Pan, X.-Q.; Zou, J.-P.; Yi, W.-B.; Zhang, W. Tetrahedron
2015, 71, 7481−7529. (b) Glass, R. S. Top. Curr. Chem. 2018, 376,
22−42.
(4) (a) Skell, P. S.; Woodworth, R. C.; McNamara, J. H. J. Am.
Chem. Soc. 1957, 79, 1253−1256. (b) Cristol, S. J.; Davies, D. I. J.
Org. Chem. 1964, 29, 1282−1284. (c) Asscher, M.; Vofsi, D. J. Chem.
Soc. 1964, 86, 4962.
(5) For recent examples, see: (a) Luo, Y.-C.; Pan, X.-J.; Yuan, G.-Q.
Tetrahedron 2015, 71, 2119−2123. (b) Cai, S.; Xu, Y.; Chen, D.; Li,
L.; Chen, Q.; Huang, M.; Weng, W. Org. Lett. 2016, 18, 2990−2993.
̈
(c) Meyer, A. U.; Lau, V. W.; Konig, B.; Lotsch, B. V. Eur. J. Org.
Chem. 2017, 2017, 2179−2185. (d) Pramanik, M.; Choudhuri, K.;
Mal, P. Asian J. Org. Chem. 2019, 8, 144−150. (e) Li, P.; Wang, G.-W.
Org. Biomol. Chem. 2019, 17, 5578−5585.
(6) For representative examples, see: (a) Taniguchi, T.; Idota, A.;
Ishibashi, H. Org. Biomol. Chem. 2011, 9, 3151−3153. (b) Lu, Q.;
Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A. Angew. Chem., Int.
D
DOI: 10.1021/acs.orglett.9b03636
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Ed. 2013, 52, 7156−7159. (c) Wei, W.; Liu, C.; Yang, D.; Wen, J.;
You, J.; Suo, Y.; Wang, H. Chem. Commun. 2013, 49, 10239−10241.
(d) Shen, T.; Yuan, Y.; Song, S.; Jiao, N. Chem. Commun. 2014, 50,
4115−4118. (e) Jiang, Y.; Loh, T.-P. Chem. Sci. 2014, 5, 4939−4943.
(f) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H. Green Chem.
2014, 16, 2988−2991. (g) Zhu, R.; Buchwald, S. L. J. Am. Chem. Soc.
2015, 137, 8069−8077. (h) Yuan, Z.; Wang, H. Y.; Mu, X.; Chen, P.;
Guo, Y. L.; Liu, G. J. Am. Chem. Soc. 2015, 137, 2468−2471.
(i) Pagire, S.; Paria, S.; Reiser, O. Org. Lett. 2016, 18, 2106−2109.
(j) Yang, J.; Liu, Y.-Y.; Song, R.-J.; Peng, Z.-H.; Li, J.-H. Adv. Synth.
Catal. 2016, 358, 2286−2292. (k) Yang, D.; Huang, B.; Wei, W.; Li,
J.; Lin, G.; Liu, Y.; Ding, J.; Sun, P.; Wang, H. Green Chem. 2016, 18,
5630−5634. (l) Zhang, G.; Zhang, L.; Yi, H.; Luo, Y.; Qi, X.; Tung,
C.-H.; Wu, L.-Z.; Lei, A. Chem. Commun. 2016, 52, 10407−10410.
(m) Chen, F.; Zhou, N.-N.; Zhan, J.-L.; Han, B.; Yu, W. Org. Chem.
Front. 2017, 4, 135−139. (n) Zhang, J.; An, Y.; Wu, J. Chem. - Eur. J.
2017, 23, 9477−9480. (o) Qian, P.; Deng, Y.; Mei, H.; Han, J.; Zhou,
J.; Pan, Y. Org. Lett. 2017, 19, 4798−4801. (p) Xiong, Y.; Sun, Y.;
Zhang, G. Org. Lett. 2018, 20, 6250−6254. (q) Zuo, K.-L.; He, Y.-H.;
Guan, Z. Eur. J. Org. Chem. 2019, 2019, 939−948. (r) Hossain, A.;
Engl, S.; Lutsker, E.; Reiser, O. ACS Catal. 2019, 9, 1103−1109.
(7) (a) Zhu, J.; Yang, W.-C.; Wang, X.; Wu, L. Adv. Synth. Catal.
2018, 360, 386−400. (b) Guo, W.; Tao, K.; Tan, W.; Zhao, M.;
Zheng, L.; Fan, X. Org. Chem. Front. 2019, 6, 2048−2066.
(8) (a) Xi, Y.; Dong, B.; McClain, E. J.; Wang, Q.; Gregg, T. L.;
Akhmedov, N. G.; Petersen, J. L.; Shi, X. Angew. Chem., Int. Ed. 2014,
53, 4657−4661. (b) Wei, W.; Li, J.; Yang, D.; Wen, J.; Jiao, Y.; You, J.;
Wang, H. Org. Biomol. Chem. 2014, 12, 1861−1864. (c) Liu, Z.;
Chen, X.; Chen, J.; Qu, L.; Xia, Y.; Wu, H.; Ma, H.; Zhu, S.; Zhao, Y.
RSC Adv. 2015, 5, 71215−71218. (d) Chen, J.-Y.; Chen, X.-L.; Li, X.;
Qu, L.-B.; Zhang, Q.; Duan, L.-K.; Xia, Y.-Y.; Chen, X.; Sun, K.; Liu,
Z.-D.; Zhao, Y.-F. Eur. J. Org. Chem. 2015, 2015, 314−319. (e) Rong,
G.; Mao, J.; Yan, H.; Zheng, Y.; Zhang, G. J. Org. Chem. 2015, 80,
4697−4703. (f) Li, S.; Li, X.; Yang, F.; Wu, Y. Org. Chem. Front. 2015,
2, 1076−1079. (g) Wang, H.; Lu, Q.; Chiang, C.-W.; Luo, Y.; Zhou,
J.; Wang, G.; Lei, A. Angew. Chem., Int. Ed. 2017, 56, 595−599.
(h) Jia, S.; Chen, Z.; Zhang, N.; Tan, Y.; Liu, Y.; Deng, J.; Yan, H. J.
Am. Chem. Soc. 2018, 140, 7056−7060.
(9) Chen, Z.-Z.; Liu, S.; Hao, W.-J.; Xu, G.; Wu, S.; Miao, J.-N.;
Jiang, B.; Wang, S.-L.; Tu, S.-J.; Li, G. Chem. Sci. 2015, 6, 6654−6658.
(10) (a) Liu, T.; Li, Y.; Lai, L.; Cheng, J.; Sun, J.; Wu, J. Org. Lett.
2018, 20, 3605−3608. (b) Wang, X.; Yang, M.; Xie, W.; Fan, X.; Wu,
J. Chem. Commun. 2019, 55, 6010−6013.
(11) Wang, J.-J.; Yu, W. Chem. - Eur. J. 2019, 25, 3510−3514.
(12) (a) Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.;
Pascal, R. A., Jr.; Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17,
5712−5719. (b) Chen, D.-F.; Chu, J. C. K.; Rovis, T. J. Am. Chem.
Soc. 2017, 139, 14897−14900.
(13) Meyer, A. U.; Jager, S.; Prasad Hari, D.; Konig, B. Adv. Synth.
Catal. 2015, 357, 2050−2054.
(14) (a) Studer, A.; Curran, D. P. Angew. Chem., Int. Ed. 2016, 55,
58−102. (b) Buzzetti, L.; Crisenza, G. E. M.; Melchiorre, P. Angew.
Chem., Int. Ed. 2019, 58, 3730−3747.
(15) Griesser, M.; Chauvin, J.-P. R.; Pratt, D. A. Chem. Sci. 2018, 9,
7218−7229.
(16) Zhu, L.; Wang, L.-S.; Li, B.; Fu, B.; Zhang, C.-P.; Li, W. Chem.
Commun. 2016, 52, 6371−6374.
(17) Li, H.; Shen, S.-J.; Zhu, C.-L.; Xu, H. J. Am. Chem. Soc. 2019,
141, 9415−9421.
̈
(18) Foll, T.; Rehbein, J.; Reiser, O. Org. Lett. 2018, 20, 5794−5798.
E
DOI: 10.1021/acs.orglett.9b03636
Org. Lett. XXXX, XXX, XXX−XXX