A convenient access to allylic triflones with allenes and triflyl chloride in the presence of (EtO)2P(O)H

Article abstract of DOI:10.1039/c9cc03096d

A simple method for the preparation of allylic triflones from allenes and triflyl chloride in the presence of (EtO)₂P(O)H has been developed. The features of this reaction are catalyst-free and simple starting substrates. This method tolerates diverse functional groups and substituted allylic triflones are obtained in moderate to good yields.

Full text of DOI:10.1039/c9cc03096d

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. ni, Y. jiang, Z.
An, J. Lan and R. Yan, Chem. Commun., 2019, DOI: 10.1039/C9CC03096D.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
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
author guidelines.
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, outlined
in our author and reviewer resource centre, 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.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
Page 1 of 4
ChemComm
View Article Online
DOI: 10.1039/C9CC03096D
Journal Name
COMMUNICATION
A Convenient Access to Allylic Triflones with Allenes and Triflyl
chloride in the Presence of (EtO)2P(O)H
Jixiang Ni,a Yong Jiang, b Zhenyu An,a Jingfeng Lan,a Rulong Yan*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Previous work:
A simple method for the preparation of allylic triflones from
allenes and triflyl chloride in the presence of (EtO)2P(O)H has been
developed. The features of this reaction are catalyst-free and
simple starting substrates. This method tolerates diverse
functional groups and substituted allylic triflones are obtained in
moderate to good yields.
R1
Braverman's work
OH
O
[2,3]-sigmatropic
rearrangement
R1
O
O
R1
S
S
CF3
O
CF3
minor product
yield < 10%
O
F3C
S
Cl
O
For several years, organofluorines in chemistry have
experienced a strong acceleration of interest.1 Among them,
the trifluoromethanesulfonyl (CF3SO2) group has attracted
substantial attention both from the academic community and
the pharmaceutical industry, because it substantially improve
Ar
(EtO)2P(O)H
SCF3
Ar
Electrophilic attack
This work:
R1
R1
R2
3
durg’s chemical, physical, and biological properties.2, For
O
(EtO)2P(O)H
PhMe, 100 oC, air
R2
S
C
CF3SO2Cl
CF3
instance, compound I has been developed as potential
antiproliferative agent4 and Compound II has been used as an
API intermediate of potential pharmaceutiacal chemicals.5
O
H
Scheme 1 The reactions of trifluoromethylthiolation and
fluoroalkylthiolation.
O
CF3
S
O
reagents
trifluoromethanesulfinate,
have
been
used,
such
as
sodium
O
F3C
S
O
lithium/sodium/potassium
O
H
O
trifluoromethanesulfonate, trifluoromethyl sulfinic acid, and
trifluoromethane sulfonyl chloride.7 The trifluoromethane
sulfonyl chloride as a readily accessible substrate is received
extensive attentions and then significant progress has been
developed in the trifluoromethylthiolation. The Braverman’s
group reported a method for the preparation of allylic triflones
through rearrangement of cinnamyl triflinate which
synthesized from allylic alcohol with trifluoromethane sulfonyl
chloride.8 The group of Yi developed a method of the
fluoroalkylthiolation the electron-rich arenes and thiols with
the CF3SO2Cl/(EtO)2P(O)H reaction system via electophilic
O
HO
OH
II
. Ethyl (R)-4-phenyl-2-[[(trifluoro-
methyl)sulfonyl]oxy]butyrate
I
. (+)-3 AU-16-ene-25-SO2-CF3
Fig. 1 Pharmaceutical and bioactive compounds contain CF3SO2
moiety.
To meet the growing demand for CF3SO2-containing
compounds, few successful strategies have been developed to
introduce the CF3SO2 group into molecules.6 In those
transformations, some different trifluoromethylthiolating
fluoroalkylthiolation.9
The
related
reports
on
trifluoromethylthiolation with trifluoromethane sulfonyl
chloride are very rare and the reaction system of
CF3SO2Cl/(EtO)2P(O)H is used for introducing the SCF3 group.
So using the reaction system of CF3SO2Cl/(EtO)2P(O)H that
provides the trifluoromethanesulfonyl moiety through radical
pathway is still a great challenge so far. Herein, we disclose a
regioselective radical addition of CF3SO2Cl/(EtO)2P(O)H with
a. State Key Laboratory of Applied Organic Chemistry, College of Chemistry and
Chemical Engineering, Lanzhou University, Lanzhou, 730000, People’s Republic of
China..
Fax: 0931-8912596 E-mail: yanrl@lzu.edu.cn
b. School of Chemistry and Chemical Engineering, Yangtze Normal University,
Chongqing, China.
† Electronic Supplementary Information (ESI) available: Experimental procedures
spectroscopic data. See DOI: 10.1039/c000000x/
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
COMMUNICATION
Journal Name
Table 1 Optimization of reaction conditions a
corresponding products
View Article Online
DOI: 10.1039/C9CC03096D
Table 2 Scope of substituted allenes a
R1
O
(EtO)2P(O)H
R1
O
S
(EtO)2P(O)H
C
CF3SO2Cl
Ph
S
PhMe, 100 oC, air
R2
C
CF3
Ph
CF3SO2Cl
O
H
PhMe, 100 oC, air
CF3
R2
O
H
1a
3aa
2a
1
2a
3
Yield of 3aa
Entry
Variation from the “standard conditions”
3aa
(75%, E)
(71%, E)
(43%, E)
(80%, E)
[%]b
R = H
O
R = 4-Me
3ba
3ca
3da
3ea
S
1
2
3
4
5
6
standard conditions
Ar instead of Air
75
61
12
0
R = 2-OMe
R = 4-OMe
CF3
R
O
H
(70%, E) R = 4-OEt
Ph2P(O)H instead of (EtO)2P(O)H
Without (EtO)2P(O)H
1a : 2a = 1 : 1.5
3fa
3ga
3ha
(72%, E)
(60%, E)
(73%, E)
R = 3,4-diMe
R = 3,4-diOMe
R = 4-Ph
54
45
20
3ia
(50%, E)
R = 4-F
R = 4-Cl
R = 4-Br
3ja
(43%, E)
(40%, E)
at 80 oC
3ka
7c
THF instead of toluene
O
O
S
O
O
a
S
Standard conditions: 1a (0.3 mmol, 1.0 equiv), 2a (0.9 mmol, 3.0
CF3
CF3
O
o
O
H
H
equiv), additive (0.6 mmol, 2.0 equiv) in 2 mL toluene at 100 C for
8 h, under air. b Isolated yields. c THF = tetrahydrofuran.
3ma (56%)
3la (52%)
allenes to form the allylic triflones through direct allylic
trifluoromethanesulfonylation.
R'
3na
3oa
3pa
R = H, R' = H
(81%)
b
(70%, E/Z = 61/39)
R = 4-Me, R' = H
The reaction of buta-2,3-dien-2-ylbenzene 1a and
trifluoromethane sulfonyl chloride 2a was chosen as the model
reaction to optimize the reaction conditions (Table 1). The
reaction was found to be facile with 3.0 equiv of 2a in the
presence of (EtO)2P(O)H (2.0 equiv) in toluene at 100 oC under
air and it afforded the (E)-(4-((trifluoromethyl) sulfonyl)but-2-
en-2-yl)benzene 3aa in 75% isolated yield (Table 1, entry 1).
However, the use of Ar in place of Air could lead to the
formation of the desired product 3aa in 61% yield. When
Ph2P(O)H was employed in place of (EtO)2P(O)H, the yield
declined significantly from 61% to 12% (Table 1, entry 3). What
was more, synthesis of 3aa was not be observed without
(EtO)2P(O)H (Table 1, entry 4). Unfortunately, changing the
ratio of two components 1a and 2a to 1:1.5 reduced the yield
b
(61%, E/Z = 72/28) R = 4-OMe, R' = H
O
b
S
3qa
3ra
3sa
3ta
(63%, E/Z = 65/35)
R = 3,4-diMe, R' = H
R = 4-Ph, R' = H
R
CF3
O
b
H
(58%, E/Z = 65/35)
b
(41%, E/Z = 50/50) R = 4-Cl, R' = H
b
(40%, E/Z = 49/51)
R = 4-Br, R' = H
3ua
3va
(69%)
R = 4-Me, R' = 4-Me
b
(50%, E/Z = 65/35) R = 4-F, R' = 4-OMe
Et
O
S
O
S
CF3
CF3
O
O
H
H
3wa
(trace)
3xa
(20%, E)
Ph
O
O
S
o
S
(Table 1, entry 5). At a lower temperature of 80 C, the result
CF3
CF3
O
H
O
was found inferior than those observed under the standard
conditions (Table 1, entry 6). The THF instead of toluene
H
3ya
(trace)
3za
(trace)
O
delivered
trifluoromethylthiolating
trifluoromethanesulfinate/trifluoromethanesulfonate
also employed for this transformation and no desired product
was detected. Finally, we found that solvents, temperature
and other factors highly influence the yield of 3aa (see the
Supporting Information for details).
a
lower yield (Table 1, entry 7). Other
C
S
reagents,
such
as
sodium
were
CF3
(EtO)2P(O)H
PhMe, 100 oC, air
O
H
CF3SO2Cl
4aa
(trace)
1ab
2a
a
Reaction conditions: 1 (0.3mmol), 2a (0.9mmol), (EtO)2P(O)H (0.6mmol) in
2mL of toluene at 100 oC under air for 8h. E/Z selectivity of the allylic
b
1
triflones determined by H NMR analysis of the crude reaction mixture and
Having identified the optimized conditions, preliminary
investigation of the scope of allenes was performed in Table 2.
nuclear overhauser effect.
3ia-3ka were obtained with moderate yields. The substrates
1l-1m were also subject to the optimized conditions and the
target products 3la-3ma were isolated in 52-56% yields. Even
changing R1 from alkyl to aryl, the aimed products 3na-3va
were also generated from moderate to good yields with
moderate E/Z selectivity. Disappointingly, the substrates 1w-1z,
1ab failed to undergo with this process, no desired products
were detected except the product 3xa obtaining in 20% yield.
Gratifyingly,
a broad range of allenes with different
substitution patterns was used in this reaction, affording the
corresponding products from moderate to excellent yields.
Substrates 1a-1b, 1d-1f, 1h bearing electron-rich groups on
the phenyl ring of allenes reacted smoothly with
trifluoromethane sulfonyl chloride and provided the desired
products in 70-80% yields. Moreover, 1i-1k with electron-poor
groups, such as F, Cl, Br, were also well tolerated and the
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 4
ChemComm
Please do not adjust margins
Journal Name
COMMUNICATION
To shed light on the mechanism of this transformation, trifluoromethane sulfonyl radical adds to the substrate 1a to
View Article Online
several control experiments were carried out as described in form radical intermediate A. Finally,DOthI:e10.1in03te9/rCm9eCdCi0a3t0e96AD
Scheme 2. Only a trace amount of desired product 3aa was converts to the desired product 3aa through the capture
detected when TEMPO was employed for this reaction. hydrogen radical from the (EtO)2P(O)H.
Meanwhile, the hydrogen radical was captured by TEMPO and
In conclusion, we develop a convenient and efficient method
the important intermediate of m/z = 157 was detected by the to achieve the allylic triflylation. In the presence of (EtO)2P(O)H,
GCMS, which was 2,2,6,6-tetramethylpiperidin-1-ol (Figure S1). various substituted groups on allenes proceed smoothly, and
When BHT was added to the reaction system, none of the the desired products are afforded with moderate to good
desired product was observed. Thus, this result suggested that yields.
the reaction was a radical process. As the only trace amount of
This work was supported by the National Natural Science
the target product 3aa was detected without (EtO)2P(O)H, this Foundation of China (21672086) and the Fundamental
result demonstrated that hydrogen was derived from Research Funds for the Central Universities (lzujbky-2018-81).
(EtO)2P(O)H. And the GC-MS measurement was also
performed with A by following the standard conditions for 60
min. The important peaks at m/z = 172 was observed and the
Notes and references
(EtO)2POCl was also confirmed (Figure S2). These results
indicated that (EtO)2P(O)Cl and hydrogen radical exist in this
1
(a) X.-H. Xu, K. Matsuzaki and N. Shibata, Chem. Rev. 2015,
115, 731; (b) T. Liang, C. N. Neumann and T. Ritter, Angew.
Chem. 2013, 125, 8372; Angew. Chem., Int. Ed. 2013, 52,
8214; (c) T. Besset, T. Poisson and X. Pannecoucke, Chem.
Eur. J. 2014, 20, 16830; (d) W. K. Hagmann, J. Med. Chem.
2008, 51, 4359; (e) N. A. Meanwell, J. Med. Chem. 2011, 54,
2529; (f) J. Wang, M. Sanchez-Rosello, J. L. Acena, C. del Pozo,
A. E. Sorochinsky, S. Fustero, V. A. Soloshonok and H. Liu,
Chem. Rev. 2014, 114, 2432.
(a) Z. Yuan, H.-Y. Wang, X. Mu, P. Chen, Y.-L. Guo and G. Liu, J.
Am. Chem. Soc., 2015, 137, 2468; (b) K. Muller, C. Faeh and F.
Diederich, Science., 2007, 317, 1881; (c) S. Purser, P.-R.
Moore, S. Swallow and V. Gouverneur, Chem. Soc. Rev., 2008,
37, 320; (d) W.-K. Hagmann, J.Med. Chem., 2008, 51, 4359;
(e) N.-A. Meanwell, J. Med. Chem., 2011, 54, 2529; (f) M.
Cametti, B. Crousse, P. Metrangolo, R. Milani and G. Resnati,
Chem. Soc. Rev., 2012, 41, 31; (g) J. Wang, M. Sánchez-
Roselló, J.-L. Aceña, C. del Pozo, A.-E. Sorochinsky, S. Fustero,
V. A. Soloshonok and H. Liu, Chem. Rev., 2014, 114, 2432.
(a) G. Danoun, B. Bayarmagnai, M. F. Gruenberg and L. J.
Goossen, Chem. Sci., 2014, 5, 1312; (b) C. Matheis, K. Jouvin
and L. J. Goossen, Org. Lett., 2014, 16, 5984; (c) G. Danoun, B.
Bayarmagnai, M. F. Grünberg and L.-J. Gooßen, Angew.
Chem. Int. Ed., 2013, 52, 7972; (d) C. Hansch, A. Leo and R.-
W. Taft, Chem. Rev., 1991, 91, 165; (e) W. Sheppard, J. Am.
Chem. Soc., 1963, 85, 1314; (f) J. B. Hendrickson, A. Giga and
J. Wareing, J. Am.Chem. Soc., 1974, 96, 2275; (g) R. Goumont,
E. Kizilian, E. Buncel and F. Terrier, Org. Biomol. Chem., 2003,
1, 1741.
transformation.
Significantly,
submitting
(1-
cyclopropylvinyl)benzene to the standard conditions afforded
(E)-(1-((trifluoromethyl)sulfonyl)pent-2-en-2-yl)benzene 5aa in
40% yield, which meant that the trifluoromethane sulfonyl
radical existed in this transformation.
2
Scheme 2 Control experiments.
(EtO)2P(O)H(2.0 equiv)
TEMPO (2.0 equiv)
O
(1)
C
CF3SO2Cl
Ph
S
O
CF3
Ph
toluene, 100 oC, air
H
2a
3aa
1a
(trace)
(EtO)2P(O)H(2.0 equiv)
BHT (2.0 equiv)
O
S
O
C
CF3SO2Cl
Ph
Ph
(2)
(3)
(4)
CF3
Ph
Ph
toluene, 100 oC, air
H
2a
3aa
1a
(trace)
3
O
toluene, 100 oC, air
C
CF3SO2Cl
S
CF3
O
H
2a
3aa
1a
(trace)
(EtO)2P(O)H(2.0 equiv)
toluene, 100 oC, air
O
S
CF3
CF3SO2Cl
Ph
Ph
5aa
O
1ac
2a
(40%, E)
4
5
A. R. Usera, P.-M. Dolan, T. W. Kensler and G. H. Posner,
Bioorg. Med. Chem., 2007, 15, 5509.
Scheme 3 Proposed mechanism.
(a) H. Yanagisawa, S. Ishihara, A. Ando, T. Kanazaki. S.
Miyamoto, H. Koike, Y. Iijima, K. Oizumi, Y. Matsushita and T.
Hata, J. Med. Chem., 1987, 30, 1984; (b) M. H Ansari, M.
Ahmad and K. A Dicke, Bioorg. Med. Chem., 1993, 3, 1071.
(a) H. Yanai, M. Fujita and T. Taguchi, Chem. Commun., 2011,
47, 7245; (b) H. Kawai, Z. Yuan, E. Tokunaga and N. Shibata,
Org. Lett., 2012, 14, 5330; (c) X.-H. Xu, M. Taniguchi, X. Wang,
E. Tokunaga, T. Ozawa, H. Masuda and N. Shibata, Angew.
Chem. Int. Ed., 2013, 52, 12628; (d) H. Il. Kong, M. A. Gill, A.
H. Hrdina, J. E. Crichton and J. M. Manthorpe, J. Fluorine
Chem., 2013, 153, 151; (e) B. Alcaide, P. Almendros and C.
Lazaro-Milla, Chem. Commun., 2015, 51, 6992; (f) X. Zhao, Y.
Huang, F.-L. Qing and X.-H. Xu, RSC. Adv., 2017, 7, 47; (g) P.
Das and N. Shibata, J. Org. Chem., 2017, 82, 11915; (h) P. Das,
S. Gondo, E. Tokunaga, Y. Sumii and N. Shibata, Org. Lett.,
2018, 20, 558; (i) P. Das, S. Gondo, E. Tokunaga, Y. Sumii and
N. Shibata, Org. Lett., 2018, 20, 558.
O
S
O
S
(a)
F3C
Cl
F3C
Cl
(EtO)2P(O)Cl
O
O
6
2a
Cl
(EtO)2P(O)
(EtO)2P(O)H
CF3SO2
O
O
(b)
C
Ph
S
Ph
S
CF3
CF3
Ph
O
O
H
1a
A
3aa
Based on these experimental results and previous
mechanistic studies, a possible mechanism is proposed in
Scheme 3. Initially, trifluoromethane sulfonyl chloride 2a is
transformed into trifluoromethane sulfonyl radical and
chlorine radical under the standard conditions. Then the
7
(a) X. Creary, J. Org. Chem., 1980, 45, 2727; (b) J.-B.
Hendrickson, D. A. Judelson and T. Chancellor, Synthesis,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
COMMUNICATION
Journal Name
1984, 320; (c) B. Scott A and F. Cornelia, Eur. Pat. Appl., 1992,
EP 0473110 A1; (d) S. Braverman, T. Pechenick and Y. Zafrani,
Tetrahedron Lett., 2001, 42, 1391; (e) S. H. Oh, Y. R. Malpani,
N. Ha, Y.-S. Jung and S. B. Han, Org. Lett., 2014, 16, 1310; (f)
X. Q. Chu, H. Meng, X. P. Xu and S. J. Ji, Chem. Eur. J., 2015,
21, 11359; (g) L. Jiang, J. Qian, W. Yi, G. Lu, C. Cai and W.
Zhang, Angew. Chem., Int. Ed., 2015, 54, 14965; (h) L.-N. Hua,
H. Li, F.-L. Qing, Y. Huang and X.-H. Xu, Org. Biomol. Chem.,
2016, 14, 8443; (i) J. Liao, W. Guo, Z. Zhang, X. Tang, W. Wu
and H. Jiang, J. Org. Chem., 2016, 81, 1304; (j) T. Rawner, M.
Knorn, E. Lutsker, A. Hossain and O. Reiser, J. Org. Chem.,
2016, 81, 7139; (k) H. S. Han, Y. J. Lee, Y.-S. Jung and S.-B.
Han, Org. Lett., 2017, 19, 1962; (l) L. Chen, L. Wu, W. Duan, T.
Wang, L. Li, K. Zhang, J. Zhu, Z. Peng and F. Xiong, J. Org.
Chem., 2018, 83, 8607.
View Article Online
DOI: 10.1039/C9CC03096D
8
9
S. Braverman, T. Pechenick and Y. Zafrani, ARKIVOC, 2004, ii,
51.
(a) L. Jiang, W. Yi and Q. Liu, Adv. Synth. Catal., 2016, 358,
3700; (b) L. Jiang, J. Qian, W. Yi, G. Lu, C. Cai and W. Zhang,
Angew. Chem. Int. Ed., 2015, 54, 14965.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins