Photocatalytic decarboxylative coupling between α-oxocarboxylicacids and alkenes

Article abstract of DOI:10.1007/s11426-019-9616-8

Photocatalytic decarboxylative cross-coupling which achieves the derivatization of widespread organic acids has become a hot topic in organic synthesis. As special acids, α-oxocarboxylicacids show the great potential in running decarboxylation to construc

Full text of DOI:10.1007/s11426-019-9616-8

SCIENCE CHINA
Chemistry
•COMMUNICATIONS•
SPECIAL ISSUE: Organic Free Radical Chemistry
https://doi.org/10.1007/s11426-019-9616-8
Photocatalytic decarboxylative coupling between α-
oxocarboxylicacids and alkenes
Ziyue Chen1, Fangling Lu1, Feng Yuan1, Juanjuan Sun1, Linyu Du1, Zhen Li1, Meng Gao1*,
Renyi Shi2* & Aiwen Lei1,2*
1National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China;
2The Institute for Advanced Studies (IAS), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China
Received June 19, 2019; accepted July 24, 2019; published online October 30, 2019
Photocatalytic decarboxylative cross-coupling which achieves the derivatization of widespread organic acids has become a hot
topic in organic synthesis. As special acids, α-oxocarboxylicacids show the great potential in running decarboxylation to
construct ketone derivatives. In this article, we have developed a photocatalytic decarboxylative cross-coupling of α-ox-
ocarboxylicacids and olefins to the synthesis of diverse aryl ketones. Various alkenes and α-oxocarboxylicacids were compatible,
generating the desired products in up to 90% yield. Preliminary mechanism studies suggest that a free radical pathway is
involved in this process.
photocatalysis, decarboxylative coupling
Citation:
Chen Z, Lu F, Yuan F, Sun J, Du L, Li Z, Gao M, Shi R, Lei A. Photocatalytic decarboxylative coupling between α-oxocarboxylicacids and alkenes.
Sci China Chem, 2019, 62, https://doi.org/10.1007/s11426-019-9616-8
Aryl ketones are vital structural building blocks in a huge
variety of molecules, including natural products, pharma-
ceutical drugs, photosensitizer and organic materials [1].
Additionally, aryl ketones are important intermediates for the
further transformation to other useful molecular fragment
[2]. The development of efficient methods for the synthesis
of aryl ketones constitutes a continuing hot research area in
synthetic chemistry. To the best of our knowledge, various
methods have been reported to the synthesis of aryl ketones
[3], like Friedel-Crafts acylation [4], transition-metal cata-
lyzed cross-coupling and so on [5]. However these protocols
suffer from poor selectivity, low atomic economy, use of rare
metal catalysts, pre-synthesized organometallic reagents and
toxic CO gas. Recently transition-metal catalyzed radical
cross-couplings of easily available aldehydes and olefins
have shown the potential in solving these problems above
[6]. Due to the inert aldehyde C–H bonds, peroxides and
harsh reaction conditions are always necessary for this
transformation. Hence, exploiting efficient and mild cata-
lysis to access aryl ketones is still significant and appealing.
As we know, α-oxocarboxylic acids which are widely used
in organic synthesis could be easily oxidized and dec-
arboxylated to give acyl radical [7]. So it is interesting and
meaningful to use α-oxocarboxylic acids instead of alde-
hydes in the radical cross-coupling to the synthesis of aryl
ketones. During the past decades, photocatalytic reaction has
shown its great potential in mild cross-coupling and attracted
more and more attention. In 2014, our group [8] has reported
the first example of visible-light-mediated decarboxylation/
oxidative amidation of α-keto acids with amines under mild
reaction conditions using O2 as the terminal oxidant. After
that, there are several works reporting the photocatalytic
decarboxylative cross-coupling of α-keto acids [9]. But it
still remains rare. Herein we have developed a mild photo-
catalytic decarboxylative cross-coupling of olefins and α-
*Corresponding authors (email: drmenggao@163.com; shirenyi.yz@hotmail.com;
aiwenlei@whu.edu.cn)
© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
chem.scichina.com link.springer.com

2
Chen et al. Sci China Chem
keto acids to access various aryl ketones (Scheme 1).
We initiated our investigation with the model reaction of
ethene-1,1-diyldibenzene (1a) and 2-oxo-2-phenylacetic
acid (2a) utilizing 2 mol% Ir(ppy)2(dtbbpy)PF6 as photo-
catalyst, 2 equiv. K3PO4 as base under the irradiation of 3 W
blue LED in toluene for 12 h. To our delight, the desired
product 1,3,3-triphenylpropan-1-one (3a) was obtained in
51% yield (Table 1, entry 1). The screening of various sol-
vents indicated that tetrahydrofuran (THF) was the best
solvent in this reaction (Table 1, entries 2–5). Then, different
bases were tested, showing that K3PO4 gave the highest
yield. While no product was achieved with NEt3 as the base
(Table 1, entries 6–8). Encouraged by the above results, next,
we tried to change the ratio of 1a/2a. When increasing the
amount of 2a to 1.5 and 2.0 equiv., the yield of 3a was
consequently increased to 70% and 80%, respectively (Table
1, entries 9, 10). Control experiments showed that photo-
catalyst, base and visible light were all essential to this re-
action (Table 1, entries 11–13).
the photocatalytic decarboxylative coupling reaction be-
tween 2a and different alkenes (Scheme 2). Firstly, various
1,1-diphenylethene derivatives were tested, giving the cor-
responding decarboxylative coupling products in good to
excellent yields (3a–3c). Halogens like F, Cl, Br were also
well tolerated in this reaction, providing the opportunities for
further functionalizations. Substrate with CF3 could run this
reaction smoothly to afford the desired product. When 2-(1-
phenylvinyl)naphthalene was utilized as the substrate, 78%
yield was obtained (3j). To our delight, styrenes were also
suitable substrates for this reaction. 86% yield was obtained
when 3-vinylpyridine was used as the substrate (3l). Styrenes
with halogens or electron-rich group in the benzene ring run
the reaction smoothly to give the desired products (3m–3q
and 3k).
To further explore the scope and generality of this proto-
col, different α-keto acids were tested, and the results were
listed in Scheme 2. α-Oxocarboxylicacids with methyl
groups on the para site of benzene ring could smoothly be
transferred to the desired products in good yields (3r and 3s).
Halogen substituents such as F (3t), could also be well tol-
erated in this reaction, generating the desired aryl ketones in
82% yield. To show the potential application of this synthetic
protocol, the scale-up reaction was conducted, affording the
corresponding product in 78% yield (Scheme 3).
With the optimized reaction conditions in hand, we tested
To investigate the possible radical mechanism of the pre-
Scheme 1 Retrosynthetic analysis of ketones.
Table 1 Optimization of reaction conditionsa)
Entry
1
Photocatalyst
Solvent
Tol
Base
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Na2CO3
NH3•H2O
NEt3
Yield (%)b)
51
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
–
2
Dioxane
CH3CN
DMF
THF
56
3
45
4
30
5
57
6
THF
55
7
THF
20
8
THF
n.d.
70
9c)
10d)
11e)
12f)
13g)
THF
K3PO4
K3PO4
K3PO4
–
THF
80
THF
n.d.
n.d.
n.d.
Ir(ppy)2(dtbbpy)PF6
Ir(ppy)2(dtbbpy)PF6
THF
Scheme 2 Photocatalytic decarboxylative coupling between α-oxo-
carboxylicacids and alkenes. All the reaction were performed with 1a
(0.2 mmol), 2a (0.4 mmol), Ir(ppy)2(dtbbpy)PF6 (2 mol%), K3PO4 (2
equiv.) and THF (3 mL), at 3 W blue LED, room temperature under N2 for
16 h (see Supporting Information online for the detailed experimental
procedure). Isolated yield.
THF
K3PO4
a) Reactions conditions: 1a (0.2 mmol), 2a (0.2 mmol), photocatalyst (2
mol%), base (2 equiv.), solvent (3 mL), 3 W blue LED, rt, 16 h. b) Isolated
yield. c) 0.3 mmol 2a was used. d) 0.4 mmol 2a was used. e) without
photocatalyst. f) without base. g) without light. n.d.=not detected.

3
Chen et al. Sci China Chem
the Program of Introducing Talents of Discipline to Universities of China
(111 Program).
Conflict of interest The authors declare that they have no conflict of
interest.
Scheme 3 Scale-up reaction.
Supporting information The supporting information is available online at
http://chem.scichina.com and http://link.springer.com/journal/11426. The
supporting materials are published as submitted, without typesetting or
editing. The responsibility for scientific accuracy and content remains en-
tirely with the authors.
1
2
3
(a) Serratore NA, Anderson CB, Frost GB, Hoang TG, Underwood SJ,
Gemmel PM, Hardy MA, Douglas CJ. J Am Chem Soc, 2018, 140:
10025–10033; (b) Perez-Prieto J, Galian R, Miranda M. Mini-Rev Org
Chem, 2006, 3: 117–135
(a) Liu H, Wang M, Li H, Luo N, Xu S, Wang F. J Catal, 2017, 346:
170–179; (b) Trawny D, Vandromme L, Rabe JP, Reissig HU. Eur J
Org Chem, 2014, 2014(23): 4985–4992; (c) Namai H, Ikeda H, Kato
N, Mizuno K. J Phys Chem A, 2007, 111: 4436–4442
(a) Tan DW, Li HX, Zhu DL, Li HY, Young DJ, Yao JL, Lang JP. Org
Lett, 2018, 20: 608–611; (b) Genç S, Günnaz S, Çetinkaya B,
Gülcemal S, Gülcemal D. J Org Chem, 2018, 83: 2875–2881; (c) Cao
XN, Wan XM, Yang FL, Li K, Hao XQ, Shao T, Zhu X, Song MP. J
Org Chem, 2018, 83: 3657–3668; (d) Zhong S, Lu Y, Zhang Y, Liu Y,
Wan JP. Org Biomol Chem, 2016, 14: 6270–6273; (e) Iwai T, Tanaka
R, Sawamura M. Organometallics, 2016, 35: 3959–3969; (f) Ding W,
Song Q. Org Chem Front, 2016, 3: 14–18; (g) Han F, Zhang X, Hu M,
Jia L. Org Biomol Chem, 2015, 13: 11466–11471; (h) Chen W, Chen
H, Xiao F, Deng GJ. Org Biomol Chem, 2013, 11: 4295; (i) Song CX,
Cai GX, Farrell TR, Jiang ZP, Li H, Gan LB, Shi ZJ. Chem Commun,
2009, 90: 6002
Scheme 4 Scale-up reaction.
sent transformation, a radical-trapping experiment was car-
ried out. TEMPO, a radical-trapping reagent, was added into
the reaction (Supporting Information online). The formation
of desired product was suppressed, thus revealing that the
initial steps of the transformation probably were caused by a
radical process. On the basis of the experimental results and
previous works, a plausible mechanism was proposed
(Scheme 4). Firstly, excited state of photocatalyst Ir(III)*
was firstly formed by the irradiation of blue LED. Then, this
reactive catalyst species oxidative decarboxylize 2-oxo-2-
phenylacetic acid to generate benzoyl radical I while af-
fording the low-valent Ir(II) simultaneously. The acyl radical
can be trapped by the alkene to generate the radical II which
could be oxidized by Ir(II) to give cation intermediate III and
regenerate Ir(III). Finally, the cation intermediate would go
protonation to obtain the desired product.
In conclusion, we developed a new photocatalytic dec-
arboxylative coupling of α-oxocarboxylicacids and alkenes,
giving the ketones as the products. Various alkenes and α-
oxocarboxylicacids were well tolerated, giving up to 90%
yield. Moreover, gram-scale synthesis and functional group
transformation further show the usefulness of this protocol,
which provided straightforward and effective strategies for
the synthesis of some natural products.
4
(a) Boroujeni KP. Chin Chem Lett, 2010, 21: 1395–1398; (b) Earle
MJ, Hakala U, Hardacre C, Karkkainen J, McAuley BJ, Rooney DW,
Seddon KR, Thompson JM, Wahala K. Chem Commun, 2005, 1: 903–
905; (c) Sarvari MH, Sharghi H. J Org Chem, 2004, 69: 6953–6956;
(d) Kaur J, Kozhevnikov IV. Chem Commun, 2002, 2508–2509; (e)
Begtrup M, Taft RW, Kamlet MJ. J Org Chem, 1986, 51: 2130–2131
(a) Yin H, Kumke JJ, Domino K, Skrydstrup T. ACS Catal, 2018, 8:
3853–3858; (b) Zhao HY, Feng Z, Luo Z, Zhang X. Angew Chem Int
Ed, 2016, 55: 10401–10405; (c) Andersen TL, Frederiksen MW,
Domino K, Skrydstrup T. Angew Chem Int Ed, 2016, 55: 10396–
10400
(a) Kim J, Yi CS. ACS Catal, 2016, 6: 3336–3339; (b) Murphy SK,
Bruch A, Dong VM. Angew Chem Int Ed, 2014, 53: 2455–2459;
(c) Chen QA, Kim DK, Dong VM. J Am Chem Soc, 2014, 136: 3772–
3775; (d) Matcha K, Antonchick AP. Angew Chem Int Ed, 2013, 52:
2082–2086; (e) Pruet JM, Robertus JD, Anslyn EV. Tetrahedron Lett,
2010, 51: 2539–2540
(a) Wang XZ, Zeng CC. Tetrahedron, 2019, 75: 1425–1430; (b) Wang
Z, Yang M, Yang Y. Org Lett, 2018, 20: 3001–3005; (c) Wang Q,
Zhang X, Fan X. Org Biomol Chem, 2018, 16: 7737–7747; (d) Liu W,
Hu YQ, Hong XY, Li GX, Huang XB, Gao WX, Liu MC, Xia Y,
Zhou YB, Wu HY. Chem Commun, 2018, 54: 14148–14151; (e) Jing
K, Li ZY, Wang GW. ACS Catal, 2018, 8: 11875–11881; (f) Chen R,
Zeng L, Huang B, Shen Y, Cui S. Org Lett, 2018, 20: 3377–3380;
(g) Bogonda G, Kim HY, Oh K. Org Lett, 2018, 20: 2711–2715;
(h) Abenante L, Penteado F, Vieira MM, Perin G, Alves D, Lenardão
EJ. Ultrasons Sonochem, 2018, 49: 41–46; (i) Zhu Z, Tang X, Li J, Li
X, Wu W, Deng G, Jiang H. Chem Commun, 2017, 53: 3228–3231;
(j) Wei Y, Hu P, Zhang M, Su W. Chem Rev, 2017, 117: 8864–8907;
(k) Chaubey NR, Singh KN. Tetrahedron Lett, 2017, 58: 2347–2350;
(l) Mal K, Naskar S, Sen SK, Natarajan R, Das I. Adv Synth Catal,
2016, 358: 3212–3230; (m) Yan K, Yang D, Wei W, Zhao J, Shuai Y,
Tian L, Wang H. Org Biomol Chem, 2015, 13: 7323–7330; (n) Rong
5
6
7
Acknowledgements This work was supported by the National Natural
Science Foundation of China (21520102003, 21702081, 21702152), the
Hubei Province Natural Science Foundation of China (2017CFA010), and

4
Chen et al. Sci China Chem
G, Mao J, Liu D, Yan H, Zheng Y, Chen J. RSC Adv, 2015, 5: 26461–
Goossen LJ, Rudolphi F, Oppel C, Rodríguez N. Angew Chem Int Ed,
2008, 47: 3043–3045; (ac) Jiang G, Wang S, Zhang J, Yu J, Zhang Z,
Ji F. Adv Synth Catal, 2019, 361: 1798–1802
Liu J, Liu Q, Yi H, Qin C, Bai R, Qi X, Lan Y, Lei A. Angew Chem Int
Ed, 2014, 53: 502–506
(a) Pawar GG, Robert F, Grau E, Cramail H, Landais Y. Chem
Commun, 2018, 54: 9337–9340; (b) Bai QF, Jin C, He JY, Feng G.
Org Lett, 2018, 20: 2172–2175; (c) Zhang M, Xi J, Ruzi R, Li N, Wu
Z, Li W, Zhu C. J Org Chem, 2017, 82: 9305–9311; (d) Yang S, Tan
H, Ji W, Zhang X, Li P, Wang L. Adv Synth Catal, 2017, 359: 443–
453; (e) Xu WT, Huang B, Dai JJ, Xu J, Xu HJ. Org Lett, 2016, 18:
3114–3117; (f) Xiao T, Li L, Zhou L. J Org Chem, 2016, 81: 7908–
7916; (g) Gu L, Jin C, Liu J, Zhang H, Yuan M, Li G. Green Chem,
2016, 18: 1201–1205; (h) Wang GZ, Shang R, Cheng WM, Fu Y. Org
Lett, 2015, 17: 4830–4833; (i) Chu L, Lipshultz JM, MacMillan
DWC. Angew Chem Int Ed, 2015, 54: 7929–7933; (j) Pan C, Jin H,
Liu X, Cheng Y, Zhu C. Chem Commun, 2013, 49: 2933–2935
26464; (o) Mao W, Zhu C. Org Lett, 2015, 17: 5710–5713; (p) Jiang
Q, Jia J, Xu B, Zhao A, Guo CC. J Org Chem, 2015, 80: 3586–3596;
(q) Kim M, Kumar Mishra N, Park J, Han S, Shin Y, Sharma S, Lee
Y, Lee EK, Kwak JH, Kim IS. Chem Commun, 2014, 50: 14249–
14252; (r) Yang Z, Chen X, Liu J, Gui Q, Xie K, Li M, Tan Z. Chem
Commun, 2013, 49: 1560–1562; (s) Park J, Kim M, Sharma S, Park E,
Kim A, Lee SH, Kwak JH, Jung YH, Kim IS. Chem Commun, 2013,
49: 1654–1656; (t) Miao J, Ge H. Org Lett, 2013, 15: 2930–2933;
(u) Kim M, Park J, Sharma S, Kim A, Park E, Kwak JH, Jung YH,
Kim IS. Chem Commun, 2013, 49: 925–927; (v) Wang H, Guo LN,
Duan XH. Org Lett, 2012, 14: 4358–4361; (w) Li M, Wang C, Ge H.
Org Lett, 2011, 13: 2062–2064; (x) Collet F, Song B, Rudolphi F,
Gooßen LJ. Eur J Org Chem, 2011, 2011(32): 6486–6501; (y) Xiao B,
Fu Y, Xu J, Gong TJ, Dai JJ, Yi J, Liu L. J Am Chem Soc, 2010, 132:
468–469; (z) Li M, Ge H. Org Lett, 2010, 12: 3464–3467; (aa) Fang
P, Li M, Ge H. J Am Chem Soc, 2010, 132: 11898–11899; (ab)
8
9