Consecutive visible-light photoredox decarboxylative couplings of adipic acid active esters with alkynyl sulfones leading to cyclic compounds

Article abstract of DOI:10.1039/c6cc04386k

Novel and efficient consecutive photoredox decarboxylative couplings of adipic acid active esters (bis(1,3-dioxoisoindolin-2-yl)-substituted hexanedioates) with substituted 1-(2-arylethynylsulfonyl)benzenes have been developed under visible-light photocatalysis. The successive photoredox decarboxylative C-C bond formation at room temperature afforded the corresponding cyclic compounds in good yields with tolerance of some functional groups.

Full text of DOI:10.1039/c6cc04386k

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: J. Li, H. Tian, M.
Jiang, H. Yang, Y. Zhao and H. Fu, Chem. Commun., 2016, DOI: 10.1039/C6CC04386K.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

ChemComm
Page 1 ofC3 hemComm
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C6CC04386K
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
Communication
Consecutive visible-light photoredox decarboxylative couplings of adipic
acid active esters with alkynyl sulfones leading to cyclic compounds
Jingjing Li, Hua Tian, Min Jiang, Haijun Yang, Yufen Zhao and Hua Fu*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
as follows: Treatment of bis(1,3-dioxoisoindolin-2-yl)-substituted
hexanedioate (1) under visible-light photocatalysis produces
50 radical D, and intermolecular coupling (the first coupling) of D
with alkynyl sulfone (2) provides F. Subsequently, photocatalysis
of F forms radical J, and intramolecular coupling (the second
coupling) of J affords the target product (3).
Novel and efficient consecutive photoredox decarboxylative
couplings of adipic acid active esters (bis(1,3-dioxoisoindolin-
2-yl)-substituted hexanedioates) with substituted 1-(2-
arylethynylsulfonyl)benzenes have been developed under
10 visible-light photocatalysis. The successive photoredox
decarboxylative C-C bond formation at room temperature
afforded the corresponding cyclic compounds in good yields
with tolerance of some functional groups.
a) The previous researches
O
O
O
R1
N
Formation of carbon-carbon bonds is
a fundamental and
PC, visible light
O
RA R1
or
+
RA
H
15 important chemical transformation in organic synthesis. However,
it is a great challenge to develop consecutive formation of two C-
C bonds using readily available starting materials under mild
conditions. Carboxylic acids and their derivatives widely occur in
organic molecules and natural products, and their chemical
20 transformations provide diverse compounds.1 For example, the
decarboxylative strategy of carboxylic acids and their derivatives
has provided some valuable reactions in organic synthesis,2 such
as Heck-type reactions,3 allylations,4 redox-neutral cross-
coupling reactions,5 and oxidative arylations.6 Recently, visible-
25 light photoredox catalysis has attracted much attention, and it has
emerged as a powerful activation protocol in new chemical
transformations.7 Correspondingly, some achievements have been
gained on photoredox decarboxylative couplings of carboxylic
acids and their derivatives were used as the radical precursors.8
30 DiRocco and coworkers have developed the use of stable organic
acid peroxides activated by visible-light photoredox catalysis in
the presence of Ir(III) catalysts, and the reactions effectively
achieved the direct methyl-, ethyl-, and cyclopropylation of a
variety of biologically active heterocycles.9 Tunge and co-
35 workers have reported the decarboxylative allylation of amino
alkanoic acids and their esters via the dual catalysis of
Ir(ppy)2(bpy)[BF4] and Pd(PPh3)4.10 Organic carboxylic acid
active esters11 and free carboxylic acids12 as the radical precursors
have been used in the visible-light photoredox couplings in the
40 presence of photocatalysts (PC) and radical acceptors (RA) (see
Scheme 1a). More importantly, MacMillan and co-workers have
developed a pioneering photoredox decarboxylative coupings of
N-protected α-amino acids.13 To the best of our knowledge, there
is no report on photoredox decarboxylative coupling of
45 dicarboxylic acids and their derivatives thus far. Herein, we
report consecutive visible-light photoredox couplings of
substituted adipic acid active esters (Scheme 1b). Our strategy is
O
RA = radical acceptor
R1
OH
b) Our strategy
OPht
O
O
O
OPht
S
Ar
Ph
photocatalysis
visible light
R1
R1
O
Ar
R1
O
2
O
D
.
OPht
PhtO
F
1
O
Ar
N
Pht =
Ar
R1
photocatalysis
visible light
J
.
R1
3
O
55 Scheme 1 (a) The previous photoredox decarboxylative couplings of
carboxylic acid active esters or free carboxylic acids. (b) Our strategy on
consecutive photoredox decarboxylative couplings of adipic acid active
esters (1) with alkyne sulfones (2).
Consecutive photoredox decarboxylative couplings of bis(1,3-
60 dioxoisoindolin-2-yl)hexanedioate
(1a)
with
1-(2-
phenylethynylsulfonyl)benzene (2a) was selected as the model
reaction to optimize conditions including photocatalysts, solvents,
atmosphere and time (see Table S1 in Supporting Information).
The results showed that the optimal photoredox conditions are as
65 follows: 1.0 mol% [Ru(bpy)3]Cl2 as the photocatalyst, 4.4 equiv
of diisopropylethylamine (DIPEA) and 3.0 equiv of Hantzsch
ester (HE) (relative to amount of 2a) as the radical initiators and
reductants in dichloromethane (DCM) at room temperature under
argon atmosphere. After obtaining the optimized photoredox
70 conditions, we investigated the substrate scope on consecutive
decarboxylative couplings of various bis(1,3-dioxoisoindolin-2-
yl)-substituted
hexanedioates
(1)
with
1-(2-
arylethynylsulfonyl)benzenes (2) (Table 1). We first attempted
various substituted 1-(2-arylethynylsulfonyl)benzenes (2) using
75 bis(1,3-dioxoisoindolin-2-yl)hexanedioate (1a) as the partner.
Different substituted 1-(2-arylethynylsulfonyl)benzenes (2)
displayed obviously different reactivity, and substrates
containing electron-donating groups gave higher yields than those
containing electron-withdrawing groups. For example, alkyne
2
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

ChemComm
Page 2 of 3
sulfones with methyl, ethyl, methoxyl on aryl rings (see 3b-h)
25 isolated from coupling 1a and 2a under the standard conditions,
and its structure was confirmed by 1H and 13C NMR. Therefore, a
plausible mechanism on the consecutive visDibOlIe:-1l0ig.1h0t3Vp9i/heCwo6tAoCrtrCiec0lde4oO3xn8l6inKe
decarboxylative couplings is proposed in Scheme 2 according to
the results above and the previous references.7-14 Irradiation of
provided higher yields than those with ester groups (see 3p-r).
Alkyne sulfones containing biphenyl and naphthalene (see 3t and
3u) also donated the corresponding products in 52% and 66%
5
yields,
respectively. Other bis(1,3-dioxoisoindolin-2-yl)-
substituted hexanedioates (1) were investigated, and cis- and
trans-form products were obtained in good yields (Note: Z/E
ratios were determined by 1H NMR) (see 3v-ac). The consecutive
visible-light photoredox decarboxylicative couplings showed
10 tolerance of some functional groups including ether (see 3f-h, 3w
and 3ac), C-F bond (see 3i), C-Cl bond (see 3j-l, 3x and 3aa), C-
Br bond (see 3m-o), esters (see 3p-r and 3y) and amide (see 3s).
2+
30 Ru(bpy)3 with visible light leads to the oxidizing excited-state
II/I
[Ru(bpy)32+]* (E1/2
*
= +0.77 V vs SCE in MeCN7a), and the
red
photoexcited catalyst accepts an electron from DIPEA (E1/2
=
+0.65 V vs SCE in MeCN14) to provide Ru(bpy)3 , in which
+
+
DIPEA transforms into A. One electron in Ru(bpy)3 transfers to
35 phthalimide in 1 produces radical B regenerating catalyst
Ru(bpy)32+, and subsequent leaving of phthalimide anion (C) and
carbon dioxide from B gives radical D. Addition of D to alkyne
sulfone (2) leads to radical E, and homolytic cleavage C-S bond
Table 1 Consecutive photoredox decarboxylative couplings of bis(1,3-
dioxoisoindolin-2-yl)-substituted hexanedioates (1) with alkynyl sulfones
15 (2)a
·
in E donates F releasing radical PhSO2 . Reaction of PhSO2· with
OPht
O
O
40 Hantzsch ester (HE) provides PhSO2H and radical G,7a and
treatment of the photoexcited catalyst with G gives Ru(bpy)3+ and
[Ru(bpy)3Cl2], DIPEA
S
O
O
Ph HE, DCM, RT, Ar, 4-16 h
R1
R2
+
R1
40 W CFL
R2
2
+
3
OPht
H. Similarly, treatment of F with Ru(bpy)3 produces radical I
1
regenerating catalyst Ru(bpy)32+, and elimination of C and carbon
dioxide from I affords radical J. Intramolecular cyclization of J
45 forms radical K. Finally, treatment of K with HE generates the
desired target product (3) liberating G.
3 (Time, Yieldb)
Me
Me
Me
Me
3d (4 h, 71%)
3b (4 h, 73%)
3a (4 h, 90%)
3c (4 h, 76%)
.
EtO2C
or
CO2Et
Me
OMe
EtO2C
Me
CO2Et
Me
.
+
or
(iPr)2NEt
(iPr)2NEt
+
MeO
Me
N
H
G
A
N
H
Et
F
H
MeO
3h (4 h, 80%)
Cl
3e (8 h, 67%)
3i (4 h, 51%)
3m (4 h, 53%)
3g (4 h, 66%)
3f (4 h, 97%)
O
Cl
N
Pht =
O
+
Cl
[Ru(bpy)32+]*
Ru(bpy)3
OPht
3j (4 h, 74%)
3l (4 h, 65%)
3k (8 h, 56%)
O
O
Br
R1
Br
EtOOC
O
N
visible light
Br
3p (12 h, 45%)
2+
O
O
Ru(bpy)3
3n (8 h, 68%)
3o (4 h, 60%)
OPht
O
O
COOMe
R1
OPht
MeOOC
1
O
O
N
R1
Ph
(Boc)2N
Ph
-
3s (4 h, 44%)
-
D
.
3t (16 h, 52%)
O
O
.
O
3q (4 h, 65%)
O
O
3r (4 h, 52%)
S
N
+
CO2
2
Me
Me
OMe
Me
Me
O
C
Ar
B
.
EtOOC
SO2Ph
Ar
Cl
EtO2C
Me
CO2Et
Me
.
.
HE
PhSO2H
3v (4 h, 84%)
Z/E = 2:3
3x (4 h, 56%)
Z/E = 2:3
PhSO2
3w (4 h, 67%)
Z/E = 2:3
3y (4 h, 66%)
Z/E = 2:3
3u (8 h, 66%)
N
R1
H
O
Ar
OMe
G
R1
PhtO
E
O
Me
Cl
Me
PhtO
F
3aa (4 h, 62%)
Z/E = 1:1
3ab (4 h, 56%)
Z/E = 1:1
3z (4 h, 71%)
3ac (4 h, 66%)
Z/E = 1:1
+
Z/E = 1:1
2+
Ru(bpy)3
Ru(bpy)3
Ar
R1
Ar
O
O
a
R1
Reaction conditions: under irradiation of visible light and argon
atmosphere, bis(1,3-dioxoisoindolin-2-yl)-substituted hexanedioate (1)
(0.3 mmol), 1-(2-arylethynylsulfonyl)benzene (2) (0.2 mmol),
[Ru(bpy)3Cl2] (2 μmol), diisopropylethylamine amine (DIPEA) (0.88
mmol), Hantzsch ester (HE) (0.6 mmol), dichloromethane (DCM) (1.5
J
.
.
-
O
Ar
R1
K
-
N
O
N +
CO2
.
O
O
C
HE
G
o
b
mL), temperature (rt, ~25 C), time (4-16 h) in a sealed Schlenk tube.
Isolated yield. Boc = tert-butyloxycarbonyl.
Ar
I
R1
3
Scheme 2 A plausible mechanism on the consecutive visible-light
photoredox decarboxylative couplings.
In order to explore the visible-light photoredox
decarboxylative mechanism, reaction of bis(1,3-dioxoisoindolin-
2-yl) hexanedioate (1a) with 1-(2-phenylethynylsulfonyl)benzene
20 (2a) was performed in the presence of three equiv of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) as the radical-trapping
agent under the standard conditions, and the reaction did not
work, which implied that the reaction underwent a free-radical
intermediate process. In addition, PhSO2H as by-product was
OPht
O
O
[Ru(bpy)3Cl2], DIPEA
HE, DCM, RT, Ar, 4 h
S
Me
O
O
+
40 W CFL
3a (66%)
2u
OPht
1a
50
Scheme 3 Reaction of ((methylsulfonyl)ethynyl)benzene (2u) with 1a
under the standard conditions.
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 3
ChemComm
L. J. Goonβen, N. Rodríguez and K. Gooβenn, Angew. Chem. Int.
Ed., 2008, 47, 3100.
(a) A. G. Myers, D. Tanaka and M. R. Mannion, J. AVmie.wCAhretimcle. OSonclin.,e
Reaction of ((methylsulfonyl)ethynyl)benzene (2u) with 1a
was attempted under the standard conditions, and the target
product (3a) was obtained in 66% yield (Scheme 3).
3
2002, 124, 11250; (b) P. Forgione, M. C. Brochu, M. Stonge, K. H.
DOI: 10.1039/C6CC04386K
55
60
Thesen, M. D. Bailey and F. Bilodeau, J. Am. Chem. Soc., 2006, 128,
11350; (c) A. Maehara, H. Tsurugi, T. Satoh and M. Miura, Org.
Lett., 2008, 10, 1159; (d) P. Hu, J. Kan, W. Su and M. Hong, Org.
Lett., 2009, 11, 2341.
D. K. Rayabarapu and J. A. Tunge, J. Am. Chem. Soc., 2005, 127,
13510.
(a) L. J. Gooβen, G. Deng and L. M. Levy, Science, 2006, 313, 662;
(b) L. J. Gooβen, N. Rodríguez, B. Melzer, C. Linder, G. Deng and L.
M. Levy, J. Am. Chem. Soc., 2007, 129, 4824; (c) G. Hu, Y. Gao, Y.
Zhao, Org. Lett., 2014, 16, 4464.
We attempted 1-(oct-1-ynylsulfonyl)benzene (4) as the
radical accepter under the standard conditions. Unfortunately,
visible-light photoredox decarboxylative coupling of 1a with 4
5
4
5
gave
poor
yield
(Scheme
4a),
so
1-(2-
alkylethynylsulfonyl)benzenes are not good substrates. Further,
visible-light photoredox decarboxylative coupling of pimelic acid
10 active ester (6) with 2a was performed, and six-membered cycle
7 and internal alkyne 8 were obtained in 31% and 13% yields,
respectively (Scheme 4b).
65 6 (a) A. Voutchkova, A. Coplin, N. E. Leadbeater and R. H. Crabtree,
Chem. Commun., 2008, 6312; (b) C. Wang, I. Piel and F. Glorius, J.
Am. Chem. Soc., 2009, 131, 4194; (c) L. J. Goonβen, N. Rodríguez,
P. P. Lange and C. Linder, Angew. Chem. Int. Ed., 2010, 49, 1111.
OPht
O
O
S
[Ru(bpy)3Cl2], DIPEA
HE, DCM, RT, Ar, 4 h
Ph
O
O
(a)
+
40 W CFL
7
For selected reviews and books on visible-light photoredox catalysis,
see: (a) C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem.
Rev., 2013, 113, 5322; (b) T. P. Yoon, M. A. Ischay and J. Du, Nat.
Chem., 2010, 2, 527; (c) J. M. R. Narayanam and C. R. J.
Stephenson, Chem. Soc. Rev., 2011, 40, 102; (d) J. W. Tucker and C.
R. J. Stephenson, J. Org. Chem., 2012, 77, 1617; (e) K. Zeitler,
Angew. Chem. Int. Ed., 2009, 48, 9785; (f) L. Shi and W. Xia, Chem.
Soc. Rev., 2012, 41, 7687; (g) J. Xuan and W.-J. Xiao, Angew. Chem.
Int. Ed., 2012, 51, 6828; (h) D. P. Hari and B. König, Angew. Chem.
Int. Ed., 2013, 52, 4734; (i) Y. Xi, H. Yi and A. Lei, Org. Biomol.
Chem., 2013, 11, 2387; (j) Chemical Photocatalysis (Ed.: B. König),
De Gruyter, Stuttgart, 2013.
J. Xuan, Z.-G. Zhang and W.-J. Xiao, Angew. Chem. Int. Ed., 2015,
54, 15632.
Using carboxylic peroxides acids as the radical precursors, see: D. A.
DiRocco, K. Dykstra, S. Krska, P. Vachal, D. V. Conway and M.
Tudge, Angew. Chem. Int. Ed., 2014, 53, 4802.
4
OPht
5 (18% yield)
70
75
80
1a
O
O
S
7 (31% yield)
[Ru(bpy)3Cl2], DIPEA
HE, DCM, RT, Ar, 4 h
Ph
(b)
COOPht
COOPht
+
+
40 W CFL
2a
6
8 (13% yield)
Scheme 4 (a) Visible-light photoredox decarboxylative coupling of 1a with 1-
15 (oct-1-ynylsulfonyl)benzene (4). (b) Visible-light photoredox decarboxylative
coupling of pimelic acid active ester (6) with 2a.
8
9
In summary, we have developed novel and efficient
consecutive visible-light photoredox decarboxylative couplings
of substituted adipic acid active esters (bis(1,3-dioxoisoindolin-2-
85
90
10 Using amino alkanoic acids and esters as the radical precursors, see:
S. B. Lang, K. M. O’Nele and J. A. Tunge, J. Am. Chem. Soc., 2014,
136, 13606.
20 yl)-substituted
hexanedioates)
with
1-(2-
arylethynylsulfonyl)benzenes under the assistant of the
photocatalyst [Ru(bpy)3]Cl2 and visible-light, in which the
starting materials are readily available. Importantly, the reactions
were performed at room temperature, and the successive
25 photoredox decarboxylative couplings led to formation of two C-
C bonds. The present discovery should provide a novel and
practical strategy for synthesis of cyclic molecules, and we
believe that it will find wide applications in various fields.
11 Using carboxylic acid active esters as the radical precursors, see: (a)
D. H. R. Barton, D. Crich, Y. Hervé, P. Potier and J. Thierry,
Tetrahedron, 1985, 41, 4347; (b) D. H. R. Barton, D. Bridon, Y.
Hervé, P. Potier, J. Thierry and S. Z. Zard, Tetrahedron, 1986, 42,
4983; (c) K. Okada, K. Okamoto, N. Morita, K. Okubo and M. Oda,
J. Am. Chem. Soc., 1991, 113, 9401; (d) K. Okada, K. Okubo, N.
Morita and M. Oda, Tetrahedron Lett., 1992, 33, 7377; (e) M.
Zlotorzynska and G. M. Sammis, Org. Lett., 2011, 13, 6264; (f) M. J.
Schnermann and L. E. Overman, Angew. Chem. Int. Ed., 2012, 51,
9576; (g) G. L. Lackner, K. W. Quasdorf and L. E. Overman, J. Am.
Chem. Soc., 2013, 135, 15342; (h) J. Xie, P. Xu, H. Li, Q. Xue, H.
Jin, Y. Cheng and C. Zhu, Chem. Commun., 2013, 49, 5672; (i) J.
Yang, J. Zhang, L. Qi, C. Hu and Y. Chen, Chem. Commun., 2015,
51, 5275; (j) H. Huang, G. Zhang and Y. Chen, Angew. Chem. Int.
Ed., 2015, 54, 7872; (k) H. Tan, H. Li, W. Ji and L. Wang, Angew.
Chem. Int. Ed., 2015, 54, 8374.
95
Financial support for this work was provided by the National
30 Natural Science Foundation of China (Grant Nos. 21372139 and
100
21221062),
and
Shenzhen
Sci
&
Tech
Bureau
(CXB201104210014A).
105 12 Using carboxylic acids as the radical precursors, see: (a) J. C. T.
Leung, C. Chatalova-Sazepin, J. G. West, M. Rueda-Becerril, J.-F.
Paquin and G. M. Sammis, Angew. Chem. Int. Ed., 2012, 51, 10804;
(b) J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y. Lan and A. Lei,
Angew. Chem. Int. Ed., 2014, 53, 502.
110 13 Using N-Boc α-amino acids as the radical precursors, see: (a) A.
Noble and D. W. C. MacMillan, J. Am. Chem. Soc., 2014, 136,
11602; (b) L. Chu, C. Ohta, Z. Zuo and D. W. C. MacMillan, J. Am.
Chem. Soc., 2014, 136, 10886; (c) Z. Zuo and D. W. C. MacMillan,
J. Am. Chem. Soc., 2014, 136, 5257; (d) Z. Zuo, D. T. Ahneman, L.
Notes and references
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical
35 Biology (Ministry of Education), Department of Chemistry, Tsinghua
University, Beijing 100084, P. R. China. Fax: 86 10 62781695; E-mail:
fuhua@mail.tsinghua.edu.cn
†
Electronic supplementary information (ESI) available: General
40 procedure for visible-light photoredox synthesis of internal alkynes,
characterization data for compounds 3a-ac, references, and 1H and 13C
115
Chu, J. A. Terrett, A. G. Doyle and D. W. C. MacMillan, Science,
NMR
spectra
of
compounds
3a-ac.
See
2014, 345, 437.
http://dx.doi.org/10.1039/b000000x/
14 C. Gao, J. Li, J. Yu, H. Yang and H. Fu, Chem. Commun., 2016, 52,
7292.
45 1 (a) P. Gallezot, Chem. Soc. Rev., 2015, 41, 1538; (b) A. J. J. Straathof,
Chem. Rev., 2014, 41, 1871.
2
For recent reviews, see: (a) J. D. Weaver, A. Recio, III, A. J.
Grenning and J. A. Tunge, Chem. Rev., 2011, 111, 1846; (b) N.
Rodriguez and L. J. Gooβen, Chem. Soc. Rev., 2011, 40, 5030; (c) W.
I. Dzik, P. P. Lange and L. J. Gooβen, Chem. Sci., 2012, 3, 2671; (d)
50
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3