RETRACTED ARTICLE: Copper-Catalyzed Decarboxylative C(sp2)-C(sp3) and C(sp)-C(sp3) Coupling of Substituted Cinnamic Acids and 3-Phenyl Propiolic Acid with N-Tosyl Oxaziridines

Article abstract of DOI:10.1002/ejoc.201900982

A mild and efficient strategy for decarboxylative C(sp²)-C(sp³) and C(sp)-C(sp³) coupling of α,β-unsaturated carboxylic acids such as substituted cinnamic acids and 3-phenyl propiolic acid with N-Tosyl oxaziridines was developed. The corresponding products were achieved in moderate to good yields with excellent stereoselectivity. Base-free and oxidant-free conditions allow good functional group tolerance. Radical inhibitors such as TEMPO and BHT completely suppressed the reactions suggesting a radical mechanism was involved. This study is supposed to broaden the frontier of oxaziridines' chemistry and to open up a novel cascade for alkylating reagents.

Full text of DOI:10.1002/ejoc.201900982

A Journal of
Accepted Article
Title: Copper-catalyzed decarboxylative C(sp2)-C(sp3) and C(sp)-
C(sp3) coupling of substituted cinnamic acids and 3-phenyl
propiolic acid with N-Tosyl oxaziridines
Authors: Bich Ngoc Nguyen and Hai-Thuong Cao
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900982
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900982
Supported by

10.1002/ejoc.201900982
European Journal of Organic Chemistry
FULL PAPER
Copper-catalyzed decarboxylative C(sp2)-C(sp3) and C(sp)-C(sp3)
coupling of substituted cinnamic acids and 3-phenyl propiolic acid
with N-Tosyl oxaziridines
Bich-Ngoc Nguyen*[a] and Hai-Thuong Cao[a]
Abstract: A mild and efficient strategy for decarboxylative C(sp2)-
C(sp3) and C(sp)-C(sp3) coupling of -unsaturated carboxylic acids
such as substituted cinnamic acids and 3-phenyl propiolic acid with
N-Tosyl oxaziridines was developed. The corresponding products
were achieved in moderate to good yields with excellent
stereoselectivity. Base-free and oxidant-free conditions allow good
functional group tolerance. Radical inhibitors such as TEMPO and
BHT completely suppressed the reactions suggesting a radical
mechanism was involved. This study is supposed to broaden the
frontier of oxaziridines’ chemistry and to open up a novel cascade for
alkylating reagents.
electrophilic nitrogen source has also been disclosed. There
have been a number of aminations of primary and secondary
amines to produce hydrazides15 and hydrazines16. Enolates17,
alkoxides18, sulfides19 and even organometallic species20 can be
aminated in moderate to excellent yields. Nevertheless, the most
predominant application of oxaziridines is as electrophilic
oxygen atom transfer reagent21. Sulfides, with the aid of
oxaziridines, can be selectively converted to sulfoxides without
or with minor overoxidation to the corresponding sulfones22.
Moreover, the oxygen atom is successfully transferred to
phosphorus23, selenium24, nitrogen25 and carbon nucleophiles26.
In brief, oxidation and amination are the broad ranges of
oxaziridine chemistry.
The utility of these intriguing compounds in radical
reactions, in contrast, is quite rare. The pioneering research in
this field was described by Minisci27. Subsequently, Aubé and
coworkers reported the first study on intramolecular radical
cyclization of oxaziridines28. The similar work was published by
Black et al.29. Yoon et al. contributed copper- and iron-catalyzed
cycloaddition of N-Sulfonyl oxaziridines with alkenes30.
Introduction
Direct transition metal-catalyzed decarboxylative carbon-
carbon coupling of carboxylic acids has gained increasing
attention of chemists in recent years1 due to readily available
carboxylic acids as starting materials,
maximizing atom
economy and overcoming the constraint of organometallic
reagents. In this field, there is great interest in cinnamic acid as
alkenylarenes are widely used in pharmaceuticals, agriculture,
and material science2. In 2013, Qu3 introduced copper-silver
cocatalysis for the double decarboxylative cross-coupling
reaction of cinnamic acids with aliphatic acids (Scheme 1a).
However, this protocol only succeeded with secondary and
tertiary carboxylic acids. Recently, Pan4 and Li5 developed
cheaper methods using copper or iron-catalyzed decarboxylative
alkylation of cinnamic acids with cycloalkanes and cyclic ethers
(Scheme 1b). Mao6 reported the decarboxylation-methylation of
unsaturated carboxylic acids using FeCl3 (Scheme 1f).
Other attempts to construct alkenylbenzenes provided an E/Z
mixture of products7 (Scheme 1c-e). Meanwhile, a series of
decarboxylative C(sp2)-C(sp3) coupling reactions of vinylic
carboxylic acid were also described by Wu8, Liu9, Wang10 and
Guo11 (Scheme 1g-i). Notably, that transition metal-catalyzed
decarboxylative carbon-carbon formations, in common, utilize
peroxides or other oxidants restricts functional group tolerance.
Therefore, the necessity for
a mild and stereoselective
decarboxylative carbon-carbon coupling of cinnamic acids is still
in demand.
Oxaziridines, small organic heterocycles with unusual
stability as well as distinctive reactivities, have attracted a lot of
interest in the last decades and are potentially universal
reagents. Their exposure to chemical or photochemical stimuli
leads to various rearrangements to hydroxylamines or nitrones12,
isomerizations13, and eliminations14. Oxaziridines‘ role as
[a]
Bich-Ngoc Nguyen, Assoc. Prof. Hai-Thuong Cao
Department of Physics and Chemical Engineering
Le Quy Don Technical University
236 Hoang Quoc Viet Street, Cau Giay District, Hanoi, Vietnam
E-mail: bichngoc.nguyen@lqdtu.edu.vn
Scheme 1. Decarboxylative C(sp2)-C(sp3) coupling of cinnamic acids.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900982
European Journal of Organic Chemistry
FULL PAPER
As investigating oxaziridines’ reactivities, we found that
under copper catalysis, alkyl radicals can efficiently be
generated from N-Tosyl oxaziridines (Scheme 2). Inspired by
with p-nitro cinnamic acid. It is important to notice that
-substituted cinnamic acids were also tolerant in our reaction
giving products in moderate to good yields (3ka and 3ma).
Furthermore, heterocyclic acrylic acid such as (E)-3-
pyridineacrylic acid afforded the corresponding product 3na in
62% yield. Unfortunately, (E)-hex-2-enoic acid did not undergo
our transformation.
this discovery, we, herein, would like to introduce
a
decarboxylative alkylation of cinnamic acids using N-Tosyl
oxaziridines with high yields and excellent stereoselectivities.
Scheme 2. Alkyl radical generated from the N-Tosyl oxaziridine.
Results and Discussion
We initiated our study by heating a benzene solution of
trans-cinnamic acid 1a with N-Tosyl oxaziridine 2a in the
presence of a catalytic amount of copper (I) triflate (5 mol-%)
and 4,4′-di-tert-butyl-2,2′-dipyridyl as a ligand at 120 oC for 24
hours. To our delight, (E)-(3-methylbut-1-en-1-yl)benzene 3aa
was obtained in 29% yield as the sole isomer (Table 1, entry 1).
This result encouraged us due to unsymmetrical alkenes are
difficult to be achieved in a single step. Then, it was found that
with 2 equivalents of cinnamic acid, the yield significantly
increased to 58% (Table 1, entry 3). Changing in the amount of
catalyst or temperature did not enhance the result (Table 1,
entries 5-7). Surprisingly, in the presence of 1,2-dichloroethane
as a combination solvent, 3aa was furnished in 67% yield (Table
1, entry 8). The 1:3 (v/v) ratio of benzene and 1,2-dichloroethane
respectively was seemed to be the best with 81% product yield
(Table 1, entry 9).
Scheme 3. Scope of cinnamic acids.
Next, various N-Tosyl oxaziridines were investigated with
our protocol (Scheme 4). (E)-disubstituted ethylenes were
successfully installed in moderate to good yields. Interestingly,
coupling partner not only included alkyl-, cycloalkyl- but also
benzyl-, cyclic ether as well as alkyl moieties bearing other
functional groups (3gi). Thus, it seemed to provide an efficient
synthesis of aryl-substituted allylic esters.
Table 1. Optimization of the reaction conditions.
With the optimized conditions in hand, we examined the
scope of different substituted cinnamic acids. As shown in
Scheme 3, cinnamic acids with the electron-donating group gave
excellent yields (3ba, 3fa-3ia). Halogen - substituted cinnamic
acid also offered desired products in moderate yields (3ca-3ea).
The lower yield was obtained when p-trifluoromethyl cinnamic
acid was used as the substrate (3la) and no reaction occurred
Scheme 4. Scope of oxaziridines.
To evaluate the generality of our methodology, we
conducted the decarboxylative alkylation of 3-phenyl propiolic
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900982
European Journal of Organic Chemistry
FULL PAPER
acid. After 24 hours, (3-methylbut-1-yn-1-yl)benzene was
observed in about 20% yield. It was hypothesized that the
formation of stable (phenylethynyl)copper slowed down the
reaction so that Fe(OTf)2 was used instead of copper salt.
Undoubtedly, the yield increased up to 56%. Subsequently, a
variety of alkynylbenzenes 5aa–5af were obtained in moderate
yields (Scheme 5). However, 3-(p-tolyl)propiolic acid and pent-2-
ynoic acid did not undergo our protocol.
The detailed mechanism of the alkylation is still under
investigation but it is supposed to follow the screenplay
described in Scheme 7. Isopropyl radical is generated from N-
Tosyl oxaziridines under copper catalysis. Afterward, it is
trapped by the intermediate formed between cinnamic acid and
the copper salt. The reductive elimination step affords the
desired product and reproduces the catalyst itself.
Conclusions
In conclusion, we have developed a mild and efficient
strategy for stereoselective decarboxylative C(sp2)-C(sp3)
coupling of alkenyl carboxylic acids with N-Tosyl oxaziridines.
This protocol also provides an innovative approach for the direct
synthesis of alkyl phenyl acetylenes. Moreover, our research is
supposed to broaden the frontier of oxaziridines’ chemistry and
to open up a novel cascade for alkylating reagents. The detailed
mechanism of this reaction and other radical reactions of
oxaziridines have been investigated in our laboratory.
Scheme 5. Reactions between 3-phenyl propiolic acid and several oxaziridines.
Experimental Section
To the best of our knowledge, it is the first example that
alkyl aryl acetylenes are directly constructed from the transition
metal-catalyzed decarboxylative coupling of aryl alkynyl
carboxylic acids without oxidants and bases.
It is noteworthy that radical inhibitors such as TEMPO and
BHT completely suppressed our reactions suggesting a radical
process was involved (Scheme 6).
A mixture of cinnamic acid 1a (29.6 mg, 0.2 mmol, 2.0 equiv.), N-
Tosyl oxaziridine 2a (25.5 mg, 0.1 mmol, 1.0 equiv.), (CuOTf)2.Toluene
complex (1.3 mg, 0.0025 mmol, 5 mol-%) and ligand L (1.3 mg, 0.005
mmol, 5 mol-%) was dissolved in 0.25 mL benzene and 0.75 mL 1,2-
dichloroethane. The reaction mixture was heated in a sealed tube at
120 oC for 24 hours. After cooling to room temperature, 1 mL water was
added and the resulting mixture was extracted with dichloromethane. The
combined organic extracts were washed with brine, dried over anhydrous
MgSO4 and concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel with hexane as the eluent
affording 3aa (oil, 10.7 mg, 73%).1H NMR (400 MHz, CDCl3):  (ppm) =
7.34 (2H, d, J = 7.7 Hz), 7.29 (2H, d, J = 7.5 Hz), 7.18 (1H, d, J = 7.1 Hz),
6.34 (1H, d, J = 16.0 Hz), 6.19 (1H, dd, J = 16.0 Hz), 2.42-2.50 (1H, m),
1.09 (6H, d, J = 6.8 Hz). 13C NMR (125 MHz, CDCl3):  (ppm) = 138,
137.9, 128.4, 126.8, 126.7, 125.9, 31.5, 22.4. HRMS (ESI-TOF), Calcd.
for C11H14Na: 169.0988 ([M + Na]+), found: 169.0986 ([M + Na]+).
Scheme 6. Control experiment.
Keywords: decarboxylation • C-C coupling • oxaziridine •
cinnamic acid • copper
[1]
a) A.G. Myers, D. Tanaka, M. R. Mannion,J. Am. Chem. Soc., 2002,
124 (38), 11250–11251;b)D. Tanaka, A. G. Myers,Org. Lett., 2004, 6
(3), 433–436; c) L.J. Goossen, N. Rodríguez, B. Melzer, C. Linder, G.
Deng, L.M. Levy, J. Am. Chem. Soc., 2007, 129 (15), 4824–4833; d)
L.J. Goossen, N. Rodríguez,C. Linder, J. Am. Chem. Soc., 2008, 130
(46), 15248–15249; e) J. Moon, M. Jeong, H. Nam, J. Ju, J. H. Moon, H.
M. Jung, S. Lee,Org. Lett., 2008,10(5), 945-948; f) H. Kima, P.H.
Lee,Adv. Synth. Cat., 2009,351, 2827-2832; g) W.W. Zhang, X.G.
Zhang, J.H. Li,J. Org. Chem., 2010, 75 (15), 5259–5264, h) D. Zhao, C.
Gao, X. Su, Y. He, J. You, Y. Xue,Chem. Commun., 2010,46, 9049-
9051; i) L.J. Goossen, B. Zimmermann, T. Knauber,Beilstein J. Org.
Chem.2010,6, 43; j) Z.J. Fu, S.J. Huang, W. Su, M. Hong,Org. Lett.,
2010, 12 (21), 4992–4995; k) Z.M. Sun, J. Zhang, P. Zhao,Org. Lett.,
2010, 12 (5), 992–995; l) J.J. Dai,J.H. Liu,D.F. Luo, L. Liu, Chem.
Scheme 7. Proposed mechanism.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900982
European Journal of Organic Chemistry
FULL PAPER
Commun., 2011,47, 677-679; m) K. Takamatsu, K. Hirano, M.
Miura,Angew. Chem. Int. Ed., 2017,56, 5353-5357; n) X. Tan, Z. Liu, H.
Shen, P. Zhang, Z. Zhang, C. Li,J. Am. Chem. Soc., 2017, 139 (36),
12430–12433.
[26] a) P.Y. Toullec, C. Bonaccorsi, A. Mezzetti, A. Togni, P. Natl. Acad. Sci.
U. S. A., 2004,101,5810-5814; b) J.J. Jiang,J. Huang,D. Wang,M.X.
Zhao, F.J. Wang, M. Shi, Tetrahedron: Asymmetry, 2010,21, 794-799;
c) T. Ishimaru, N. Shibata, J. Nagai, S. Nakamura, T. Toru, S.
Kanemasa, J. Am. Chem. Soc., 2006, 128 (51), 16488–16489; d) S.
Takechi,N. Kumagai, M. Shibasaki, Tetrahedron Lett.,2011, 52, 2140-
2143; e) L. Zou, B. Wang, H. Mu, H. Zhang, Y. Song, J. Qu, Org. Lett.,
2013, 15 (12), 3106–3109.
[2]
[3]
C. Torborg, M. Beller,Adv. Synth. Cat., 2009, 351, 3027-3043.
W.P. Mai; G. Song; G.C. Sun; L.R Yang; J.W. Yuan; Y.M. Xiao; P.
Mao; L.B. Qu, RSC Adv., 2013, 3, 19264-19267.
[4]
a) J. Zhao, W. Zhou, J. Han, G.L.Y. Pan, Tetrahedron Letters, 2013, 54
(48), 6507-6510; b) J. Zhao; H. Fang; J. Han; Y. Pan, Beilstein J. Org.
Chem.,2013,9, 1718-1723.
[27]
F. Minisci; R. Galli; V. Malatesta; T. Caronna, Tetrahedron, 1970, 26
(17), 4083-4091.
[5]
[6]
[7]
C.Y. Wang; R.J. Song; W.T. Wei; J.H. Fan; J.H. Li, Chem. Commun.,
2015, 51, 2361-2363.
[28]
a) J. Aube, X. Peng, Y. Wang, F. Takusagawa, J. Am. Chem. Soc.,
1992, 114 (13), 5466–5467; b) J. Aubé; B. Gülgeze; X. Peng,
Bioorganic & Medicinal Chemistry Letters, 1994, 4 (20), 2461-2464.
D.StC. Black, G.L. Edwards, S.M. Laaman, Synthesis,2006, 12, 1981-
1990.
G. Rong, D. Liu, L. Lu, H. Yan, Y. Zheng, J. Chen, J. Mao, Tetrahedron,
2014, 70 (34), 5033-5037.
[29]
[30]
a) K. Xu; Z. Tan; H. Zhang; J. Liu; S. Zhang; Z. Wang, Chem. Commun.,
2017, 53, 10719-10722; b) C. Wang; Y. Lei; M. Guo; Q. Shang; H. Liu;
Z. Xu; R. Wang, Org. Lett., 2017, 19 (23), 6412-6415; c) H. Yang, P.
Sun, Y. Zhu, H. Yan, L. Lu, X. Qu, T. Li, J. Mao, Chem. Commun., 2012,
48, 7847-7849; d) H. Yang, H. Yan, P. Sun, Y. Zhu, L. Lu, D. Liu, G.
Ronga, J. Mao, Green Chem., 2013, 15, 976-981.
a) D.J. Michaelis, C.J. Shaffer, T.P. Yoon, J. Am. Chem. Soc., 2007,
129 (7), 1866–1867; b) D.J. Michaelis; M.A. Ischay; T.P. Yoon, J. Am.
Chem. Soc., 2008, 130 (20), 6610-6615; c) K.S. Williamson; T.P. Yoon,
J. Am. Chem. Soc., 2010, 132 (13), 4570-4571; d) K.S. Williamson; T.P.
Yoon,J. Am. Chem. Soc., 2012, 134 (30), pp 12370–12373.
[8]
[9]
M. Zhu, Z. Qiu, Y. Zhang, H. Du, J. Li, D. Zou, Y. Wu, Y. Wu,
Tetrahedron Letters, 2017, 58 (23), 2255-2257.
Z. Cui, X. Shang, X.F. Shao, Z.Q. Liu, Chem. Sci., 2012, 3, 2853-2858.
[10] Z. Fang, C. Wei, J. Lin, Z. Liu, W. Wang, C. Xu, X. Wang, Y. Wang,Org.
Biomol. Chem., 2017, 15, 9974-9978.
[11] J.F. Zhao, X.H. Duan, Y.R. Gu, P. Gao, L.N. Guo, Org. Lett., 2018, 20
(15), 4614–4617.
[12] T.Połiński, A.Chimiak, Tetrahedron Lett., 1974, 15, 2453-2456.
[13] a) A. Lattes, E. Oliveros, M. Riviere, C. Belzeck, D. Mostowicz, W.h
Abramskj, C. Piccinni-Leopardi, G. Germain, M. Van Meerssche, J. Am.
Chem. Soc., 1982, 104 (14), 3929–3934; b) J. Aubé, P. M.Burgett, Y.
Wang, Tetrahedron Lett., 1988, 29, 151-154.
[14] a) D.R. Boyd, R. Hamilton, N.T. Thompson, M.E. Stubbs, Tetrahedron
Lett., 1979, 20, 3201-3204; b) W.H. Rastetter, W.R. Wagner, M.A.
Findeis, J. Org. Chem., 1982, 47 (3), 419–422; c) K. Suda, F. Hino, C.
Yijima,J. Org. Chem., 1986,51 (22), 4232–4239.
[15] a) J. Vidal, J. Drouin, A. Collet, J. Chem. Soc., Chem. Commun., 1991,0,
435-437; b) J. Vidal, L. Guy, S. Sterin, A. Collet, J. Org. Chem., 1993,
58 (18), 4791–4793; c) J. Vidal, J.C. Hannachi, G. Hourdin, J.C.
Mulatier, A. Collet, Tetrahedron Lett., 1998, 39, 8845-8848; d) A.
Armstrong, L.H. Jones, J.D. Knight, R.D. Kelsey, Org. Lett., 2005, 7 (4),
713-716.
[16]
N.Richy, M. Ghoraf, J. Vidal, J. Org. Chem., 2012, 77 (23), 10972–
10977.
[17]
J. Vidal, J. Drouin, A. Collet, J. Chem. Soc., Chem. Commun., 1991, 0,
435-437.
[18] a) I.C. Choong, J.A. Ellman, J. Org. Chem., 1999, 64 (18), 6528–6529;
b) O.F. Foota, D.W. Knight, Chem. Commun., 2000,0, 975-976.
[19] a) A.Armstrong, R.S. Cooke, Chem. Commun., 2002, 0, 904-905; b) A.
Armstrong, R.S. Cooke, S.E. Shanahan, Org Biomol Chem., 2003, 1
(18), 3142-3143;c) A. Armstrong, L. Challinor, R.S. Cooke, J.H. Moir,
N.R. Treweeke, J. Org. Chem., 2006, 71 (10), 4028–4030;d) A.
Armstrong, L. Challinor, J.H. Moir, Angew. Chem. Int. Ed., 2007, 46
(28), 5369-5372.
[20] M. Ghoraf, J. Vidal, Tetrahedron Lett., 2008, 49, 7383-7385.
[21] K.S. Williamson, D.J. Michaelis, T.P. Yoon, Chem. Rev., 2014, 114 (16),
8016–8036.
[22] a) L. Bohé, M. Lusinchi, X. Lusinchi, Tetrahedron, 1999, 55, 155-166; b)
R.D. Mahale, M.R. Rajput, G.C. Maikap, M.K. Gurjar, Org. Process Res.
Dev., 2010, 14 (5), 1264–1268.
[23] A. Arnone, M. Pregnolato, G. Resnati, M. Terreni, J. Org. Chem., 1997,
62 (18), 6401–6403.
,
[24]
F.A.DavisJ.M.Billmers, O.D.Stringer,Tetrahedron Lett. 1983, 24, 3191-
3194.
,
[25] F.A.DavisA.C.Sheppard, Tetrahedron, 1989, 45, 5703-5742.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900982
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
C-C coupling*
Bich-Ngoc Nguyen*, Hai-Thuong Cao
Page No. – Page No.
Copper-catalyzed decarboxylative
C(sp2)-C(sp3) and C(sp)-C(sp3)
coupling of substituted cinnamic
acids and 3-phenyl propiolic acid with
N-Tosyl oxaziridines
We describe the copper-catalyzed decarboxylative alkylation of substituted
cinnamic acids using N-Tosyl oxaziridines with high yields and excellent
stereoselectivities. The (E)-alkene was achieved as the sole isomer in a single step.
Our protocol also gives an efficient approach for the construction of alkyl phenyl
acetylenes without oxidants and bases. Initial investigation suggested a radical
process was involved.
This article is protected by copyright. All rights reserved.