K2S2O8-mediated metal-free direct P-H/C-H functionalization: A convenient route to benzo[: B] phosphole oxides from unactivated alkynes

Article abstract of DOI:10.1039/c6gc01009a

The first metal-free, facile and K₂S₂O₈-mediated radical addition/cyclization of unactivated alkynes with diarylphosphine oxides has been developed, affording a general and practical procedure to construct valuable benzo[b]phosphole oxides via sequential P-H/C-H functionalization.

Full text of DOI:10.1039/c6gc01009a

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Ma, W. Chen,
G. Hu, Y. Zhang, Y. Gao, Y. Yin and Y. Zhao, Green Chem., 2016, DOI: 10.1039/C6GC01009A.
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/greenchem

Please do not adjust margins
Green Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/C6GC01009A
Journal Name
COMMUNICATION
K S O -mediated metal-free direct P-H/C-H functionalization: a
2
2
8
convenient route to benzo[b]phosphole oxides from unactivated
alkynes
Received 00th January 20xx,
Accepted 00th January 20xx
a
c
b
b
*b
a
b
DOI: 10.1039/x0xx00000x
Dumei Ma, Weizhu Chen, Gaobo Hu, Yun Zhang, Yuxing Gao, Yingwu Yin and Yufen Zhao
www.rsc.org/
The first metal-free, facile and
K
2
S
2
O
8
-mediated radical
emerged as the most attractive and powerful approach for
making benzo[b]phosphole oxides because this pathway is
highly atom-economical and internal alkynes and
diarylphosphine oxides as reaction partners are highly stable
and readily available in a variety of substituted forms, making
them convenient precursor for building compounds of wide
substrate scope, however, these methods used a plenty of
environmentally unfriendly Mn or Cu salts or noble Ag salts as
catalysts, thus increasing the cost and restraining their
applications. Therefore, the development of cheap,
environmentally friendly and metal-free methods for the
direct preparation of benzo[b]phosphole derivatives from
readily available alkynes and diarylphosphine oxides is still
addition/cyclization of unactivated alkynes with diarylphosphine
oxides has been developed, affording a general and practical
procedure to construct valuable benzo[b]phosphole oxides via
sequential P-H/C-H functionalization.
Phosphorus-containing heterocycles has attracted much
attention for synthetic chemists over the past few decades
due to their wide applicability in organic synthesis, medicinal
1
chemistry
and
material
science.
Particularly,
benzo[b]phosphole derivatives, the phosphorous analogue of
indole, have attracted considerable attention as promising
organic optoelectronic materials because of their unique
2
physical and photoelectric properties. Yet, the methods for
desirable and essential.
the synthesis of these motifs are relatively lacking.
Traditionally, benzo[b]phospholes were mainly obtained from
alkynylarenes bearing ortho-phosphorus substituents via the
(a) Cyclization of alkynylarene having ortho-phosphorus functional group:
R2
R1
*
P = Mes PH,
R1
PhP(=O)H,
P
R3
PhPNEt2 .
3
P
(X) X = O, S
intermolecular cyclization (Scheme 1a) , which suffers from
(
(
b) Transition-metal-catalyzed cycloaddition of internal alkyne:
R2
the requirement of the complicated multistep reactions for
H
R2
I
II
Ag (4 equiv.) or Cu
R
+
R1
each cyclization precursor and
a
lack of functionality
H
R
P
MnIII (3.5 equiv.)
P
R3
O
tolerance owing to using strong bases. Until recently, a few of
novel and efficient methods for the synthesis of
R
3
O
R
1
c) This work: Transition-metal-free P-radical addition/cyclization:
R2
4
benzo[b]phosphole species including silver- or manganese-
4a-
H
R
2
Transition-
Metal-Free
R
H
+
R1
b
5
R
mediated
and
copper-catalyzed
intermolecular
P
P
R3
2 2 8
K O S
R3
O
R1
O
cycloadditions of internal alkynes with phosphine derivatives
Scheme 1b), multicomponent approaches reported by
Scheme 1 Synthetic methods of benzo[b]phospholes
(
6
Over the past several years, the development of
transtition-metal-free transformations has become an active
8
topic in organic synthesis since metal-free catalyzed process
Yoshikai et al., and our group’s work on TBAI-catalyzed
radical addition/cyclization of diaryl(arylethynyl)phosphine
7
oxides with toluene derivatives, have continuously emerged.
is advantageous in terms of elimination of cost saving, metal
toxicity and minimization of environmental pollution, and is
regarded as an important subject in green chemistry. Such
methodologies are extremely valuable as promising
alternatives and beneficial complements to transition-metal-
catalyzed processes. Particularly, the transition-metal-free
direct C-H functionalization has emerged as one of the most
important strategies for the preparation of a wide range of
useful molecular frames in modern organic synthesis
chemistry due to its avoidance of prefunctionalization of
starting substrates and its remarkable advantages of both
Among them, transition-metal-catalyzed intermolecular
cycloaddition of phosphine derivatives to internal alkynes has
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
Green Chemistry
Page 2 of 6
View Article Online
DOI: 10.1039/C6GC01009A
COMMUNICATION
Journal Name
step- and atom-economy and environmental sustainability in
industrial and green chemistry, and made significant
2 2 8
could react with 2a in the presence of 5 equivalents of K S O
as the oxidant in 1,4-dioxane at 60 °C for 12 h to afford the
desired product 3a in 53% yield (entry 1). Encouraged by this
result, the effect of solvents was detected, such as toluene,
DMSO, ethanol and acetonitrile, which categorically
approved acetonitrile as the most suitable choice (entries 2-
5). When the reaction temperature was increased to 90 °C,
the yield of 3a was improved significantly (75% yield, entry 6).
Gratifyingly, increasing the reaction time to 24 h led to an
excellent yield of 90% (entry 7). To advance the process
9
progress. On the other hand, the cheap, commercially
available and nontoxic K
for chemical synthesis from environmental and economic
points of view. It is well known that K can play as a
radical initiator to produce sulfonyl radicals from sulfinates,
2 2 8
S O as catalyst is highly attractive
2 2 8
S O
1
0
which could lead to the formation phosphorus-centered
radicals followed by the radical reaction for the synthesis of
1
1
organic phosphorus compounds. However, to the best of
our knowledge, the example of benzo[b]phosphole oxides
formation via metal-free radical addition/cyclization of
internal alkynes with diarylphosphine oxides has yet to be
reported (Scheme 1c). As part of our on-going efforts to
develop environmentally friendly new methods for the P-C
further, other oxidants such as (NH
oxone were also investigated, with the finding that
(NH and Na gave unsatisfactory yields of 69% and
4 2 2 8 2 2 8
) S O , Na S O and
4
)
2
S
2
O
8
2 2 8
S O
51%, respectively, and oxone was ineffective for the reaction
(entries 8-10). Notably, no desired product was detected in
1
2
bond formation, herein, we first disclosed K
2
S
2
O
8
-mediated
2 2 8 2 2 8
the absence of K S O , revealing that K S O was essential to
metal-free oxidative radical addition/cyclization of
unactivated alkynes towards the structurally diverse
achieve a high yield of product 3a. (entry 11). Subsequently,
we checked the effect of additives including pyridine, AcOH
and TBAB (tetrabutyl ammonium bromide) and found that a
sharp decrease of the yield was observed using pyridine and
AcOH, but the addition of 1 equiv. of TBAB completely
suppressed this reaction, demonstrating that the addition of
the additive is less effective (entries 12-14). Increasing or
decreasing the temperature from 90 °C gave rise to a
significant decrease in reaction yield (entries 15-16). Similarly,
benzo[b]phosphole oxides via sequential
P-H/C-H
functionalization along with the formation of one C-C and
one C-P bond. This metal-free strategy enables a simple,
efficient and environment-benign access to structurally
complex benzo[b]phosphole oxide frameworks of importance
in material science through a simple one-pot process.
a
Table 1 Optimization of the reaction conditions
2 2 8
an increase in the K S O loading did not improve this
reaction, and a low loading (4 equiv.) resulted in a decrease
of the yield (entries 17-18).
With the optimized conditions in hand, the scope of this
method was extended to the reaction of a wide range of
alkynes with different diarylphosphine oxides. As shown in
Table 2, various alkynes bearing different electron-
withdrawing and electron-donating substituents were all
efficiently reacted with diarylphosphine oxides via this novel
Temp (°C)/
Yield
b
(%)
Entry Oxidant
Additive
Solvent
Time (h)
60/12
60/12
60/12
60/12
60/12
90/12
90/24
90/24
90/24
90/24
90/24
90/24
90/24
90/24
80/24
100/24
90/24
90/24
K
2
S
2
O
8
53
49
24
39
60
75
90
69
51
0
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
-
dioxane
toluene
DMSO
K
K
2
S
S
2
O
O
8
8
-
2 2 8
metal-free K S O -mediated radical addition/cyclization
2
2
-
reactions to afford diverse benzo[b]phosphole oxides with
moderate to high yields (3a-3s), demonstrating that this
protocol is a general and practical tool for the preparation of
various valuable benzo[b]phosphole oxide motifs. Generally,
both electron-rich and electron-deficient diarylacetylenes 1a-
1i were all suitable for this method, and the corresponding
oxidative addition/cyclization products were obtained in
moderate to excellent yields of 43-90% (3a–3i). Thus, a
variety of substituents on the aromatic ring, such as methyl,
ethyl, t-butyl, methoxyl, fluoro, chloro, bromo and
trifluoromethyl groups, were all tolerated under the reaction
conditions, revealing that electronic effects were not evident
in this transformation. Notably, fluoro-, chloro- and bromo-
substituted diarylacetylenes could be successfully converted
into the desired products (3e-3g), which indicated the
potential of this new procedure to allow access to highly
K
K
K
2
2
2
S
S
S
2
O
O
O
8
-
2 5
C H OH
2
2
8
8
-
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
-
K
2
S
2
O
8
-
(NH
Na
4
)
2
S
2
O
8
-
2
S
2
O
8
-
0
1
2
3
4
5
6
7
8
oxone
-
-
-
0
K
K
K
K
K
K
K
2
2
2
2
2
2
2
S
2
S
2
S
2
S
2
S
2
S
2
S
2
O
8
O
8
O
8
O
8
O
8
O
8
O
8
pyridine
56
58
0
AcOH
TBAB
-
-
-
-
65
50
83
60
c
d
1
a
Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), oxidant (5 equiv.),
c
additive (1 equiv.), solvent (2 mL), under Ar. Isolated yields. Using
b
13
functionalized targets by next coupling of halide products.
d
(6 equiv.). Using K
K
2
S
2
O
8
2
S
2
O
8
(4 equiv.).
Encouraged by the above results, we next examined the
oxidative addition/cyclization reactions of various
asymmetrical phenylacetylenes with 2a. It is worth noting
Our initial efforts focused on the model reaction of 1,2-
diphenylethyne (1a) with diphenylphosphine oxide (2a) to
optimize the reaction conditions (Table 1). To our delight, 1a
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 6
Pleas Ge rd eo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C6GC01009A
Journal Name
COMMUNICATION
a
Table 2
K
2
S
2
O
8
-mediated radical addition/cyclization of diarylphosphine oxides
2
with unactivated alkynes
1
b
b
Entry
1
Alkyne
1
Product
3
Yield (%)
90
Entry
11
Alkyne
1
Product
3
Yield (%)
60
2
3
4
5
75
63
70
51
12
13
14
15
61
48
51
33
6
7
8
9
55
57
50
16
17
18
53
38
57
c
61
43
53
19
20
1
0
63
a
b
c
CN (2mL), at 90 °C for 24 h under Ar. Isolated yields. Two regioisomers were
Reaction conditions:
generated and were not separated by column chromatography on silica gel owing to their very similar polarity. The ratio of two regioisomers of 3s was
1
(0.3 mmol),
2
(0.9 mmol), K
2
S
2
O
8
(1.5 mmol), CH
3
3
determined by P NMR analysis.
1
that various asymmetrical phenylacetylenes 1j-1s reacted
with 2a or 2b in a high regioselective manner to afford the 2-
substituted 1,3-diphenyl-1H-phosphindole-1-ones 3j-3r in
moderate yields without the observation of other
of 3o and 3q. Notably, steric hindrance significantly affected
the reaction efficiency. For example, the ethyl 3-(p-
tolyl)propiolate 1l and meta-substituted counterpart 1m
afforded moderate yields of 61% and 48%, respectively, but
sterically demanding ethyl 3-(o-tolyl)propiolate only gave a
3
1
regioisomers by in situ P NMR analysis. This result revealed
that the phosphorus atom was installed at the less hindered
position of alkynes preferentially. Interestingly, a series of
aryllpropiolates (1j-1q) having different functional groups,
such as methyl, fluoro, bromo, methoxyl and trifluoromethyl
groups, still underwent a similar process to give the
corresponding products 3j-3q, albeit in somewhat low yields
trace
of
product.
Furthermore,
diethyl
(phenylethynyl)phosphonate 1r is also a suitable reaction
partner to extend the applicability of the present procedure.
To gain more insight into the substrate scope, substituted
secondary arylphosphine oxide 2b was further evaluated. It
was found that 2b could also participate in this
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
Green Chemistry
Page 4 of 6
View Article Online
DOI: 10.1039/C6GC01009A
COMMUNICATION
Journal Name
transformation, but a mixture of regioisomeric products (3s
)
diarylphosphine oxides, affording rapid and environment-
benign strategy for structurally diverse array of
benzo[b]phosphole oxides via sequential P-H/C-H
were obtained as a result of a radical mechanism involving
a
4
,14
similar radical aryl migration rearrangement. In addition,
ethyl(phenyl)phosphine oxide 2c smoothly reacted with 1k
and led to the corresponding product 3t in a good yield.
To demonstrate the synthetic application of the present
protocol, a gram-scale experiment was performed on 1a (20
mmol, 3.6g) using 2a under the optimal reaction conditions
functionalization under mild reaction conditions. Importantly,
the use of commercially available, inexpensive and
2 2 8
environmentally benign K S O as oxidant represents a
prominent advantage of the method. Most attractively, the
present method avoids metals and other additives, and
various valuable benzo[b]phosphole oxide moieties could be
(Scheme 2a). The desired product 3a was obtained in a good
yield of 65% (3a, 4.9 g), revealing this method could be easily
adopted for the large scale preparations with the high
efficiency. In addition, as expected, 2a could react with diyne
conveniently obtained in a simple one-step process.
Therefore, the present protocol eliminates any possibility
that residual heavy metal in the product would affect its
performance when it is applied to organic electronic devices.
In addition, the operational simplicity and environment-
friendliness associated with this approach suggest its great
potential for widespread application in the construction of
important benzo[b]phosphole oxide frameworks in material
science. Further mechanistic investigations and application
researches will be pursued.
1u
to generate
a
bis(benzophosphole-3-yl)benzene
framework, which is of interest for applications in thin-film
photovoltaics and organic light-emitting diodes (Scheme
3
b).
a,15
2
Scheme 2 Application studies
To understand the mechanism of the current reaction, the
radical scavenger effect was examined by the reaction of 1a
with 2a, and the addition of 6 equivalents of TEMPO or BHT
as a radical scavenger dramatically suppressed this reaction
(
Scheme 3). Furthermore, the BHT adduct 10 was detected by
Scheme 4 Proposed mechanism
the ESI-HRMS analysis. These results showed that the
reaction probably proceeded via a free radical process.
We are grateful for the financial support from the Chinese
National Natural Science Foundation (21202135, 41576081)
and the National Basic Research Program of China
(2012CB821600).
O
K2S2O8 (5 equiv.)
1
a
a
+
+
Ph
P
H
H
+
+
TEMPO
3a
CH3CN
90 oC, 24 h
Ph
2
a
(6 equiv.)
17% yield
Bu-t
O
O
K2S2O8 (5 equiv.)
CH3CN
90 oC, 24 h 15% yield
1
Ph
P
BHT
3a
O
PPh2
Ph
Notes and references
2a
(6 equiv.)
Bu-t
10
1
(a) M. Stolar and T. Baumgartner, Chem. Asian J., 2014,
1
Niemeyer and J. Pohl, J. Med. Chem.,1999, 42, 2542; (c) M.
M. Mader and P. A. Bartlett, Chem. Rev., 1997, 97, 1281; (d)
J. W. Darrow and D. G. Drueckhammer, J. Org. Chem., 1994,
9,
212; (b) V. Gilard, R. Martino, M. Malet-Martino, U.
Scheme 3 Radical Trapping Study
4
,11
Based on the above results and previous reports,
a
plausible mechanism is proposed in Scheme 4. Initially, the
·
-
2 2 8 4
homolysis of K S O easily generated the SO anion radical,
59, 2976; (e) A. Kumar, P. V. Sharmar, K. Gurram and N.
which abstracted hydrogen from the P-H bond of 2a
,
Rane, Bioorg. Med. Chem. Lett., 2006, 16, 2484; (f)
Phosphorus Heterocycles II, Bansal, R. K., Ed. Topics in
Heterocyclic Chemistry, Springer, Berlin, 2010, Vol. 21; (g)
Phosphorus Ligands in Asymmetric Catalysis: Synthesis and
Applications, Börner, A., Ed. Wiley-VCH: Weinheim, 2008,
Vols. 1−3; (h) Phosphorus Compounds: Advanced Tools in
Catalysis and Material Sciences, Peruzzini, M., Gonsalvi, L.,
Ed. Springer, Berlin, 2011; (i) F. Bu, E. Wang, Q. Peng, R. Hu,
A. Qin, Z. Zhao and B. Tang, Chem. –Eur. J. 2015, 21, 4440.
-
11
providing a phosphinoyl radical
Then, the selective addition of the P-radical
bond of the alkyne 1a afforded an alkenyl radical
the radical might undergo two pathways to give the desired
4
and nontoxic HSO
to the triple
. Finally,
4
salt .
4
5
5
product 3a on the basis of the generation of two
regioisomeric products via a similar process originally
4
proposed by Miura and Duan.
2
Selected publications: (a) Y. Matano, A. Saito, T.
Fukushima, Y. Tokudome, F. Suzuki, D. Sakamaki, H. Kaji, A.
Ito, K. Tanaka and H. Imahori, Angew. Chem. Int. Ed., 2011,
Conclusions
50, 8016; (b) A. Fukazawa, E.Yamaguchi, E. Ito, H. Yamada,
J. Wang, S. Irle and S. Yamaguchi, Organometallics, 2011,
In conclusion, we have successfully developed the first
3
0
, 3870; (c) Y. Ren and T. Baumgartner, J. Am. Chem. Soc.,
011, 133, 1328; (d) Y. Matano and H. Imahori, Org. Biomol.
, 1258; (e) J. Crassous and R. Réau, Dalton
efficient,
2 2 8
K S O -mediated metal-free oxidative radical
2
addition/cyclization of various unactivated alkynes with
Chem., 2009,
7
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 6
Pleas Ge rd eo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C6GC01009A
Journal Name
COMMUNICATION
Trans., 2008, 6865; (f) Y. Ren and T. Baumgartner, Dalton
Trans., 2012, 41, 7792; (g) E. Yamaguchi, C. Wang, A.
Fukazawa, M. Taki, Y. Sato, T. Sasaki, M. Ueda, N. Sasaki, T.
Higashiyama and S. Yamaguchi, Angew. Chem. Int. Ed.,
9
Selected recent examples: (a) H. J. Kim, J. Kim, S. H. Cho and
S. Chang, J. Am. Chem. Soc., 2011, 133, 16382; (b) T. Truong
and O. Daugulis, J. Am. Chem. Soc., 2011, 133, 4243; (c) S.
Ghosh, S. De, B. N. Kakde, S. Bhunia, A. Adhikary and A.
Bisai, Org. Lett., 2012, 14, 5864; (d) Y. Liu, B. Jiang, W.
Zhang and Z. Xu, J. Org. Chem., 2013, 78, 966; (e) Y.-F. Liang
and N. Jiao, Angew. Chem. Int. Ed., 2014, 53, 548; (f) Q. Ke,
2
015, 54, 4539.
3
(a) H. Tsuji, K. Sato, L. Ilies, Y. Itoh, Y. Sato and E. Nakamura,
Org. Lett., 2008, 10, 2263; (b) T. Sanji, K. Shiraishi, T.
Kashiwabara and M. Tanaka, Org. Lett., 2008, 10, 2689; (c)
A. Fukazawa, Y. Ichihashi, Y. Kosaka and S. Yamaguchi,
B. Zhang, B. Hu, Y. Jin and G. Lu, Chem. Commun., 2015, 51
,
1012; (g) J. K. Laha, K. P. Jethava and S. Patel, Org. Lett.,
2015, 17, 5890.
Chem. Asian J., 2009, 4, 1729; (d) A. Fukazawa, M. Hara, T.
Okamoto, E.-C. Son, C. Xu, K. Tamao and S. Yamaguchi, Org.
Lett., 2008, 10, 913; (e) A. Fukazawa, H. Yamada and S.
Yamaguchi, Angew. Chem. Int. Ed., 2008, 47, 5582; (f) Y.
Zhou, Z. Gan, B. Su, J. Li, Z. Duan and F. Mathey, Org. Lett.,
2015, 17, 5722; (g) B. Wu and N. Yoshikai, Org. Biomol.
Chem., 2016, DOI: 10.1039/c6oB00219f.
10 Z. V. Todres, Ion-Radical Organic Chemistry: Principles and
Applications, CRC Press, New York, 2nd Ed., 2009.
11 (a) Y.-M. Li, Y. Shen, K.-J. Chang and S.-D. Yang, Tetrahedron,
2014, 70, 1991; (b) L. Zhu, H. Yu, Q. Guo, Q. Chen, Z. Xu and
R. Wang, Org. Lett., 2015, 17, 1978; (c) P. Xu, Z. Wu, N.
Zhou and C. Zhu, Org. Lett., 2016, 18, 1143; (d) M. Gao, Y. Li,
4
(a) Y. Unoh, K. Hirano, T. Satoh and M. Miura, Angew.
Chem. Int. Ed., 2013, 52, 12975; (b) Y.-R. Chen and W.-L.
Duan, J. Am. Chem. Soc., 2013, 135, 16754; (c) W. Ma and L.
Ackermann, Synthesis, 2014, 46, 2297.
P. Zhang, Y. Gao, L. Zhang, Z. Li, Y. Liu, G. Tang and Y. Zhao,
Adv. Synth. Catal., 2016, 358, 138.
(a) B. Wu, M. Santra and N. Yoshikai, Angew. Chem. Int. Ed.,
L. Xie, R. Chauvin and X. Cui, Chem. Commun., 2016, 52,
2846.
12 (a) G. Hu, Y. Gao and Y. Zhao, Org. Lett., 2014, 16, 4464; (b)
G. Hu, Y. Zhang, Y. Gao and Y. Zhao, Org. Biomol. Chem.,
2015, 13, 8221; (c) G. Hu, W. Chen, T. Fu, Z. Peng, H. Qiao,
Y. Gao and Y. Zhao, Org. Lett., 2013, 15, 5362; (d) Y. Gao, G.
Wang, L. Chen, P. Xu, Y. Zhao, Y. Zhou and L.-B. Han, J. Am.
Chem. Soc., 2009, 131, 7956.
13 (a) Metal-Catalyzed Cross-Coupling Reactions, ed. A. de
Meijere and F. Diederich, Wiley-VCH, New York, 2004, and
references therein; (b) D.-G. Yu, B.-J. Li and Z.-J. Shi, Acc.
Chem. Res., 2010, 43, 1486.
5
6
2014, 53, 7543; (b) B. Wu, R. Chopra and N. Yoshikai, Org.
Lett., 2015, 17, 5666.
7
8
Y. Zhang, G. Hu, D. Ma, P. Xu, Y. Gao and Y. Zhao, Chem.
Commun., 2016, 52, 2815.
Selected recent reviews: (a) S. Roscales and A. G. Csákÿ,
Chem. Soc. Rev., 2014, 43, 8215; (b) C. Zhua and J. R. Falck,
Adv. Synth. Catal., 2014, 356, 2395; (c) R. Rossi, M. Lessi, C.
Manzini, G. Marianetti and F. Bellina, Adv. Synth. Catal.,
14 A. Studer and M. Bossart, Tetrahedron, 2001, 57, 9649.
15 (a) H. Tsuji, K. Sato, Y. Sato and E. Nakamura, Chem. Asian J.,
2010, 5, 1294; (b) H. Tsuji, K. Sato, Y. Sato and E. Nakamura,
2
2
015, 357, 3777; (d) C.-L. Sun and Z.-J. Shi, Chem. Rev.,
014, 114, 9219.
J. Mater. Chem., 2009, 19, 3364.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Green Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C6GC01009A
K S O -mediated metal-free direct P-H/C-H
2
2
8
functionalization: a convenient route to benzo[b]phosphole
oxides from unactivated alkynes
Dumei Ma, Weizhu Chen, Gaobo Hu, Yun Zhang, Yuxing Gao, Yingwu Yin and Yufen Zhao
2 2 8
A metal-free and K S O -mediated radical addition/cyclization of internal alkynes leading to
benzo[b]phosphole oxides was developed, which eliminates residual heavy metal contamination
in the product.
R2
R2
H
P
Transition-
Metal-Free
R
+
R1
H
R
K O S
2 8
P
3 O
2
R3
O
R1
R
2
1 examples
up to 90% yield