Preparation of organophosphorus compounds from P-H compounds using o-(trimethylsilyl)aryl triflates as aryne precursors

Article abstract of DOI:10.1016/j.tet.2015.11.045

An efficient method was developed for the synthesis of a variety of arylphosphorus compounds from P-H compounds using o-(trimethylsilyl)aryl triflates as aryne precursors. The reaction provides a practical preparation of various arylphosphorus compounds via aryne intermediates utilizing diarylphosphine oxides and dialkyl phosphites as the nucleophiles.

Full text of DOI:10.1016/j.tet.2015.11.045

Accepted Manuscript
Preparation of organophosphorus compounds from P-H compounds using o-
(trimethylsilyl)aryl triflates as aryne precursors
Guoqiang Yang, Chaoren Shen, Mao Quan, Wanbin Zhang
PII:
S0040-4020(15)30230-1
10.1016/j.tet.2015.11.045
TET 27302
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 November 2015
Accepted Date: 19 November 2015
Please cite this article as: Yang G, Shen C, Quan M, Zhang W, Preparation of organophosphorus
compounds from P-H compounds using o-(trimethylsilyl)aryl triflates as aryne precursors, Tetrahedron
(2015), doi: 10.1016/j.tet.2015.11.045.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Preparation of Organophosphorus
Compounds from P-H Compounds using o-
(Trimethylsilyl)aryl Triflates as Aryne
Precursors
Leave this area blank for abstract info.
Guoqiang Yang, Chaoren Shen, Mao Quan, Wanbin Zhang*
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road,
Shanghai 200240, P. R. China

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Preparation of organophosphorus compounds from P-H compounds using o-
(trimethylsilyl)aryl triflates as aryne precursors
Guoqiang Yanga, Chaoren Shena, Mao Quana, and Wanbin Zhanga,
aSchool of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient method was developed for the synthesis of a variety of arylphosphorus compounds
from P-H compounds using o-(trimethylsilyl)aryl triflates as aryne precursors. The reaction
provides a practical preparation of various arylphosphorus compounds via aryne intermediates
utilizing diarylphosphine oxides and dialkyl phosphites as the nucleophiles.
Available online
2009 Elsevier Ltd. All rights reserved
.
words:
Organophosphorus compound
o-(Trimethylsilyl)aryl triflate
Aryne
P-arylation
P-H compound
1. Introduction
couplings, Diels−Alder reactions, 1,3-dipolar cycloadditions,
transition-metal-catalyzed reactions, and addition reactions with
a variety of nucleophiles.13 To date, there are only a handful of
reported examples concerning the preparation of arylphosphorus
compounds from aryne species generated from 1,2-dihalide arene
using a stoechoimetric quantity of base14 or a catalytic quantity of
base (usually butyllithium).15 In 2010, Jugé described the
synthesis of phosphonium salts via the reaction of primary,
secondary and tertiary phosphines with o-trimethylsilylaryl
triflate in acetonitrile at room temperature.16a Mhaske and
Hosoya groups reported the P-arylation of aryne with
alkoxyphosphine.16b,c Our group has developed the reaction of
insertion of arynes into arylphosphoryl amide P-N bond.17 Since
diarylphosphine oxide is more readily available than
alkoxyphosphine, we believe that insertion of H-P bond of
diarylphosphine oxide to aryne is a convenient method for
preparation of organophosphorus compounds. As a continuation
of our research interests concerning the construction of sp2 C-P
bonds,8j,9n we envisaged that a number of arylphosphorus
compounds could be obtained via an electrophilic aryne
generated in situ from o-(trimethylsilyl)aryl triflate using mild,
non-hazardous, fluoride-promoted conditions.18 To the best of our
knowledge, diarylphosphine oxides and dialkyl phosphites have
yet to be utilized for the synthesis of arylphosphorus compounds
via aryne intermediates.
Considerable interest has been attracted to developing
synthetic methods for organophosphorus compounds due to their
wide applications in organic synthesis,1 medicinal chemistry,2
polymers,3 and functional materials.4 Particularly in organic
synthesis, arylphosphines play important roles in organometallic
catalysis5 and organocatalysis.6 Continuing efforts have been
made to prepare arylphosphines oxide, arylphosphonates and
their derivative arylphosphines. Besides the direct coupling of
aryl halides with air-sensitive secondary phosphines, their
boranes, stannanes, potassium and lithium salts,7 the transition-
metal-catalyzed Arbuzov8 and Hirao9 reactions are the two most
widely-used methods employed for the preparation of
arylphosphorus compounds. Additionally, the Pd- and Cu-
catalyzed oxidative phosphonylation of arylboronic acids and
aryltrifluoroborates is a feasible method which can be used to
prepare arylphosphonates.10 Recently Zhao and Liang groups
have developed Cu-catalyzed coupling of N-tosylhydrazone and
H-phosphonates to prepare benzylphosphine oxides.11 The
methods mentioned above usually require a transition-metal,
ligand and additives. The reaction conditions also require an inert
atmosphere, high temperature and long reaction time. The
development of novel and efficient synthetic pathways to
construct sp2 C-P bond thus remains a challenge.
As a useful and highly reactive intermediate in organic
synthesis, the aryne group has been used for the construction of
various bonds.12 It undergos numerous reactions such as aryl
———
Corresponding author. Tel.: +86-021-5474-3265; fax: +86-021-5474-3265; e-mail: wanbin@sjtu.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and discussion
Our initial studies were performed by reacting o-
(trimethylsilyl)phenyl triflate with diphenylphosphine oxide. The
effect of reaction parameters on the yield is summarized in Table
1. Through the evaluation of several non-polar solvents (entries
1-5), we found that good yields were obtained in both MeCN and
DME (entries 1, 4). Elevating reaction temperature, using a
sealed tube with a Teflon plug valve as a reaction vessel and
prolonging the reaction time, can further improve the yield (entry
6). Cesium carbonate is used as a base in the reaction system, the
absence of which results in a reduction in yield (entry 7).
Table 1. Reaction condition screeninga
Entry
T (°C)
80
Solvent
MeCN
Toluene
THF
Isolated yield
78%
1
2
3
4
5
6
7
80
0%
70
0%
80
DME
85%
80
1,4-dioxane
DME
36%
100
100
93%b
67%c
DME
aUnless otherwise stated, reaction conditions: Ph2P(O)H (0.32 mmol), o-
(trimethylsilyl)phenyl triflate (0.30 mmol), CsF (0.90 mmol), Cs2CO3 (0.60
mmol), solvent (3 mL) under N2, reaction time was 8 h.
aReaction conditions: o-(trimethylsilyl)phenyl triflate (0.30 mmol), HP(O)Ar2
(0.32 mmol), CsF (0.90 mmol), Cs2CO3 (0.60 mmol), DME (3 mL), reaction
in sealed tube with Teflon plug valve, reac-tion time was 12 h.
bReaction in seal tube with Teflon plug valve, reaction time was 12 h.
cWithout Cs2CO3, reaction time was 12 h.
Table 3. Substrate scope of the coupling of o-
(trimethylsilyl)aryl triflate with dialkyl phosphitea
With the optimized reaction conditions in hand, substituent
effects of diarylphosphine oxides on the reaction outcome were
investigated (Table 2). We found that the introduction of
electron-donating groups at the para-position or meta-position of
the aromatic ring did not significantly affect the yields of the C–P
coupling products (entries 2-4). However, when an electron-
withdrawing group was present at the para-position of the phenyl
ring, the yield was slightly reduced (entry 5). A variety of o-
(trimethylsilyl)aryl triflates were examined for the C–P coupling
reaction with diphenylphosphine oxides (entries 6-8). Treatment
of the symmetrically substituted aryne precursors 2, 3 and 4 with
diphenylphospine oxide provided triarylphosphine oxides 11, 12
and 13 respectively in good yields. Strong steric effects were
observed when using the unsymmetrically substituted electron-
neutral aryne precursor 5, which showed good regioselectivity
(entry 9). The major regioisomer was found to be the 2-
substituted product according to 1H NMR spectra.
Table 2. Substrate scope of the reaction of diarylphosphine
oxides with o-(trimethylsilyl)aryl triflatea
aReaction conditions: o-(trimethylsilyl)aryl triflate (0.30 mmol), HP(O)(OR)2
(0.32 mmol), CsF (0.90 mmol), Cs2CO3 (0.60 mmol), MeCN (3 mL), reaction
in sealed tube with Teflon plug valve, reaction time was 12 h.
When we attempted to expand the scope of substrates to
dialkyl phosphite derivatives, we found that DME was not
suitable for the reaction of o-(trimethylsilyl)phenyl triflate 1 with

3
diethyl phosphite, and the expected product 14 was obtained only
in a trace amount. The reaction proceeded smoothly when the
solvent was changed from DME to acetonitrile (Table 3, entry 1).
The scope of the protocol for the synthesis of arylphosphonates
was validated using dimethyl phosphite and a number of o-
(trimethylsilyl)aryl triflates (Table 3, entries 2-6). Both weak
electron-rich aryne precursors 2 and 4, and symmetrically strong
electron-donating substituted aryne precursor 3 gave their
corresponding phosphonates in good yields (Table 3, entries 3-5).
Steric interactions also predominate in the case of silyl triflate 5,
which provides regioisomer 18 as the major product (Table 3,
entry 6).
Unless otherwise noted, all reagents were purchased from
ACCEPTED MANUSCRIPT
commercial suppliers and used without purification. Solvents
1,4-dioxane, DME and THF were distilled from sodium
benzophenone ketyl prior to use. Toluene was distilled at
atmospheric or reduced pressure over CaH2 prior to use. NMR
spectra were recorded on a Varian MERCURY plus-400 (400
MHz, 1H; 100 MHz, 13C; 162 MHz, 31P) spectrometer with
chemical shifts reported in ppm relative to the residual deuterated
solvent, the internal standard tetramethylsilane, or external 85%
H3PO4 for 31P. Mass spectrometry analysis was carried out using
an electrospray spectrometer Waters 4 micro quadrupole.
4.2. General procedures for the reaction of o-
Scheme 1. P-Arylation of ethyl phenylphosphinate and
(trimethylsilyl)aryl triflate with diarylphosphine oxide
diphenylphosphine
In a typical reaction, to an oven-dried 25 mL heavy walled
seal tube fitted with Teflon plug valve was added CsF (0.90
mmol), Cs2CO3 (0.60 mmol), o-(trimethylsilyl)aryl triflate (0.30
mmol) and diarylphosphine oxide (0.32 mmol). DME (3 mL)
was added via a syringe. The tube was sealed with Teflon plug
valve and then the reaction mixture was stirred at 100 °C for 12
h. The reaction was allowed to cool to room temperature. Then
reaction mixture was diluted with 5 mL water. The aqueous 3
layer was extracted with ethyl acetate (3 × 5 mL). The combined
organic layers were dried over Na2SO4, filtered and concentrated.
The product was isolated through preparative thin-layer
chromatography. General procedures for the reaction of o-
(trimethylsilyl)aryl triflate with dialkyl phosphate, trialkyl
phosphate or diphenyl phosphine are similar with the procedures
for the reaction of o-(trimethylsilyl)aryl triflate with
diarylphosphine oxide.
By applying our new methodology, ethyl diphe-
nylphosphinate 19 and triphenylphosphine 20 could be obtained
using MeCN and DME respectively, via the reaction between
aryne precursor
diphenylphosphine (Scheme 1).
1
and ethyl phenylphosphinate or
Scheme 2. Proposed Mechanism
4.2.1. Phosphoryl triphenyl (6).9m White solid, 31P NMR (CDCl3,
162 MHz): δ = 30.41; 1H NMR (CDCl3, 400 MHz): δ = 7.64-7.70
(m, 6H), 7.52-7.56 (m, 3H), 7.43-7.48 (m, 6H).
TMS
TfO
4.2.2. Bis(4-methylphenyl)phenyl phosphine oxide (7).9n White
solid, 31P NMR (CDCl3, 162 MHz): δ = 30.30; 1H NMR (CDCl3,
400 MHz): δ = 7.68-7.62 (m, 2H), 7.53 (dd, J = 8.0, 11.8 Hz,
4H), 7.48 (m, 1H), 7.24 (dd, J = 2.4, 8.4 Hz, 4H), 2.39 (s, 6H).
CsF
Cs
Cs2CO3
O
O
P
OH
P
R
R
R
P
R
R
4.2.3. Bis(3, 5-bismethylphenyl)phenylphosphine oxide (8).9n
H
R
1
White solid, 31P NMR (CDCl3, 162 MHz): δ = 30.89; H NMR
CsHCO3
(CDCl3, 400 MHz): δ = 7.68-7.63 (m, 2H), 7.55-7.51 (m, 1H),
7.47-7.42 (m, 2H), 7.26 (d, J = 12.4 Hz, 4H), 7.15 (s, 2H), 2.31
(s, 12H).
4.2.4. Bis(4-methoxyphenyl)phenylphosphine oxide (9).9n,19 White
solid, 31P NMR (CDCl3, 162 MHz): δ = 30.06; 1H NMR (CDCl3,
400 MHz): δ = 7.61-7.54 (m, 2H), 7.56 (dd, J = 11.2, 8.4 Hz,
4H), 7.51-7.49 (m, 1H), 7.45-7.41 (m , 2H), 6.94 (dd, J = 1.8, 6.4
Hz, 4H), 3.83 (s, 6H).
4.2.5. Bis(4-fluorophenyl)phenylphosphine oxide (10).19 White
solid, 31P NMR (CDCl3, 162 MHz): δ = 28.75; lH NMR (CDCl3,
400 MHz) δ = 7.76 (m, 6H), 7.53 (m, 2H), 7.19 (td, J = 2.4, 9.2
Hz, 4H).
Cs
H
O
P
protonation
R
R
P
R
R
O
21
We propose the following mechanism for this reaction
(Scheme 2), Firstly, the phosphine oxide is deprotonated by
Cs2CO3 and the CsF promotes the transfer of o-
(trimethylsilyl)aryl triflate to the aryne. The phosphine oxide
anion then attacks the aryne, resulting in the formation of the aryl
cesium intermediate 21. The desired product is then formed via
the protonation of 21.
4.2.6. 4-Diphenylphosphoryl-o-xylene (11). White solid, 31P
NMR (CDCl3, 162 MHz): δ = 30.36; H NMR (CDCl3, 400
3. Conclusions
1
In summary, we have developed a transition-metal-free
method for the sp2 C-P coupling of o-(trimethylsilyl)aryl triflates
with R1R2P(O)H to synthesize arylphosphonates, dia-
rylphosphinates, and arylphosphine oxides. The reaction provides
an efficient and practical synthesis of various arylphosphorus
compounds via aryne intermediates.
MHz): δ = 7.65 (m, 4H), 7.50 (m, 7H), 7.30 (dd, J = 3.6, 12.2 Hz,
1H), 7.19 (dd, J = 2.4, 6.0 Hz, 1H), 2.29 (s, 3H), 2.25 (s, 3H); 13
C
NMR (CDCl3, 100 MHz): δ = 141.4 (d, J = 2.6 Hz), 137.4 (d, J =
13 Hz), 133.2 (d, J = 9.2 Hz), 132.3 (d, J = 9.8 Hz), 133.0 (d, J =
103.6 Hz), 132.0 (d, J = 2.2 Hz), 129.9 (d, J = 2.8 Hz), 128.6 (d,
J = 11.2 Hz), 20.2, 20.0; HR-ESI-MS: [M+H]+ m/z calcd for:
307.1236, found: 307.1252.
4. Experiment
4.2.7. 1,3-Benzodioxol-5-yldiphenyl phosphine oxide (12).20
4.1. General informations
1
White solid, 31P NMR (CDCl3, 162 MHz): δ = 34.53; H NMR

4
Tetrahedron
ACCEPTED MANUSCRIPT
(CDCl3, 400 MHz): δ = 6.02 (s, 2H), 6.88 (dd, J = 7.9, 2.1 Hz,
References and notes
1H), 7.07 (d, J = 11.4 Hz, 1H), 7.18 (dd, J = 12.6, 8.0 Hz, 1H),
7.46 (t, J = 7.1 Hz, 4H), 7.54 (d, J = 7.1 Hz, 2H), 7.66 (dd, J =
7.5, 11.6 Hz, 4H).
1. (a) Engel, R. Chem. Rev. 1977, 77, 349; (b) Baumgartner T.;
Réau, R. Chem. Rev. 2006, 106, 4681
2. (a) Kim, Y. C.; Brown, S. G.; Harden, T. K.; Boyer, J. L.; Dubyak,
G.; King, B. F.; Burnstock, G.; Jacobson, K. A. J. Med. Chem.
2001, 44, 340; (b) Shie, J. J.; Fang, J. M.; Wang, S. Y.; Tsai, K.
C.; Cheng, Y. S.; Yang, A. S.; Hsiao, S. C.; Su, C. Y.; Wong, C.
H. J. Am. Chem. Soc. 2007, 129, 11892; (c) Kumar, T. S.; Zhou,
S. Y.; Joshi, B. V.; Balasubramanian, R.; Yang, T. H.; Liang, B.
T.; Jacobson, K. A. J. Med. Chem. 2010, 53, 2562; (d) Demmer,
C. S.; Krogsgaard-Larsen, N.; Bunch, L. Chem. Rev. 2011, 111,
7981.
4.2.8. 2-Naphthalenyldiphenyl phosphine oxide (13).21 White
1
solid; 31P NMR (CDCl3, 162 MHz) δ = 30.28; H NMR (CDCl3,
400 MHz) δ = 8.27 (d, J = 13.6 Hz, 1H), 7.88 (d, J = 9.6 Hz, 2H),
7.73-7.68 (m, 4H), 7.64-7.46 (m, 10H).
4.3. General procedures for the reaction of o-
(trimethylsilyl)aryl triflate with dialkyl phosphate
3. (a) Watson, K. A.; Palmieri, F. L.; Connell, J. W. Macromolecules
2002, 35, 4968; (b) Jin, Z.; Lucht, B. L. J. Am. Chem. Soc. 2005,
127, 5586; (c) Lin, Q.; Unal, S.; Fornof, A. R.; Armentrout, R. S.;
Long, T. E. Polymer 2006, 47, 4085; (d) Chen, R.-F.; Zhu, R.;
Fan, Q.-L.; Huang, W. Org. Lett. 2008, 10, 2913.
4. (a) Bock, T.; Möhwald, H.; Mülhaupt, R. Macromol. Chem. Phys.
2007, 208, 1324; (b) Chien, C. H.; Chen, C. K.; Hsu, F. M.; Shu,
C. F.; Chou P. T.; Lai, C. H. Adv. Funct. Mater. 2009, 19, 560; (c)
Hsu, F. M.; Chien, C. H.; Shu, C. F.; Lai, C. H.; Hsieh, C. C.;
Wang, K. W.; Chou, P. T. Adv. Funct. Mater. 2009, 19, 2834; (d)
Chou, H. H.; Cheng, C. H. Adv. Mater. 2010, 22, 2468; (e) Kim,
D.; Salman, S.; Coropceanu, V.; Salomon, E.; Padmaperuma, A.
B.; Sapochak, L. S.; Kahn, A.; Brédas, J. L. Chem. Mater. 2010,
22, 247; (f) Li, Z.; Ishizuka, H.; Sei, Y.; Akita, M.; Yoshizawa, M.
Chem. Asian J. 2012, 7, 1789; (g) Yu, D.; Zhao, F.; Zhang, Z.;
Han, C.; Xu, H.; Li, J.; Ma, D.; Yan, P. Chem. Commun. 2012, 48,
6157.
5. (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809; (b)
Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029; (c) Martin, R.;
Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (d) Surry, D. S.;
Buchwald, S. L. Chem. Sci. 2011, 2, 27; (e) Fernández-Pérez, H.;
Etayo, P.; Panossian, A.; Vidal-Ferran, A. Chem. Rev. 2011, 111,
2119.
6. For some selected reviews, see: (a) Lu, X.; Zhang, C.; Xu, Z. Acc.
Chem. Res. 2001, 34, 535; (b) Methot, J. L.; Roush, W. R. Adv.
Synth. Catal. 2004, 346, 1035; (c) Wei, Y.; Shi, M. Acc. Chem.
Res. 2010, 43, 1005; (d) Zhou, Z.; Wang, Y.; Tang, C. Curr. Org.
Chem. 2011, 15, 4083.
In a typical reaction, to an oven-dried 25 mL heavy walled
seal tube fitted with Teflon plug valve was added CsF (0.60
mmol), Cs2CO3 (0.90 mmol), o-(trimethylsilyl)aryl triflate (0.30
mmol) and dialkyl phosphate (0.32 mmol). MeCN (3 mL) was
added via a syringe. The tube was sealed with Teflon plug valve
and then the reaction mixture was stirred at 100 °C for 12h. The
reaction was allowed to cool to room temperature. Then reaction
mixture was diluted with 5 mL water. The aqueous 3 layer was
extracted with ethyl acetate (3 × 5 mL). The combined organic
layers were dried over Na2SO4, filtered and concentrated. The
product was isolated through preparative thin-layer
chromatography.
4.3.1. Diethyl phenylphosphonate (14).8j Colorless oil; 31P NMR
(CDCl3, 162 MHz): δ = 19.83; 1H NMR (CDCl3, 400 MHz): δ =
7.82 (m, 2H), 7.55 (m, 1H), 7.47 (m, 2H), 4.12 (m, 4H), 1.32 (t, J
= 7.2 Hz, 6H).
4.3.2. Dimethyl phenylphosphonate (15).8j Colorless oil; 31P
1
NMR (CDCl3, 162 MHz): δ = 22.79; H NMR (CDCl3, 400
MHz): δ = 7.80 (dd, J = 13.3, 7.5 Hz, 2H), 7.64 (m, 1H), 7.54 (m,
2H), 3.76 (d, J = 11.0 Hz, 6H).
4.3.3. Diethyl 3,4-dimethylphenylphosphonate (16).8j Colorless
1
oil; 31P NMR (CDCl3, 162 MHz): δ = 20.98; H NMR (CDCl3,
7. For examples of direct coupling of aryl halides with secondary
phosphines, their boranes, stannanes, potassium and lithium salts,
see: (a) Tunney, S. E.; Stille, J. K. J. Org. Chem. 1987, 52, 748;
(b) Ager, D. J.; East, M. B.; Eisenstadt, A.; Laneman, S. A. Chem.
Commun. 1997, 2359; (c) Cai, D.; Payack, J. F.; Bender, D. R.;
Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org. Synth. 1999,
76, 6; (d) Moncarz, J. R.; Brunker, T. J.; Jewett, J. C.; Orchowski,
M.; Glueck, D. S.; Sommer, R. D.; Lam, K.-C.; Incarvito, D.;
Concolino, T. E.; Ceccarelli, C.; Zakharov, L. N.; Rheingold, A.
L. Organometallics 2003, 22, 3205; (e) Shimizu, H.; Saito, T.;
Kumobayashi, H. Adv. Synth. Catal. 2003, 345, 185; (f) Lee, W.-
Y.; Liang, L.-C. Dalton Trans. 2005, 1952; (g) Blank, N. F.;
McBroom, K. C.; Glueck, D. S.; Kassel, W. S.; Rheingold, A. L.
Organometallics 2006, 25, 1742; (h) Brunker, T. J.; Anderson, B.
J.; Blank, N. F.; Glueck, D. S.; Rheingold, A. L. Org. Lett. 2007,
9, 1109; (i) Bonaterra, M.; Rossi, R. A.; Martín, S. E.
Organometallics 2009, 28, 933; (j) Lindner, R.; van den Bosch,
B.; Lutz, M.; Joost, N. H. R.; van der Vlugt, J. I. Organometallics
2011, 30, 499; (k) Franzke, A.; Pfaltz, A. Chem. Eur. J. 2011, 17,
4131.
8. For examples of Ni-catalyzed Arbuzov reaction, see (a) Tavs, P.
Chem. Ber. 1970, 103, 2428; (b) Balthazor, T. M.; Miles, J. A.;
Stults, B. R. J. Org. Chem. 1978, 43, 4538; (c) Balthazor, T. M. J.
Org. Chem. 1980, 45, 2519; (d) Heinicke, J.; Gupta, N.; Surana,
A.; Peulecke, N.; Witt, B.; Steinhauser, K.; Bansal, R. K.; Jones,
P. J. Tetrahedron 2001, 57, 9963; (e) Villemin, D.; Elbilali, A.;
Simeon, F.; Jaffrès, P.-A.; Maheut, G.; Mosaddak, M.; Hakiki, A.
J. Chem. Res. 2003, 436; (f) Von Mäkl, G.; Gschwendner, K.;
Rözer, I.; Kreitmeier, P. Helv. Chim. Acta. 2004, 87, 825; (g) Yao,
Q.; Levchik, S. Tetrahedron Lett. 2006, 47, 277; (h) Montoneri,
E.; Viscardi, G.; Bottigliengo, S.; Gobetto, R.; Chierotti, M. R.;
Buscaino, R.; Quagliotto, P. Chem. Mater. 2007, 19, 2671; (i)
Reddington, M. V. Bioconjugate Chem. 2007, 18, 2178; (j) Yang,
G.; Shen, C.; Zhang, W. Tetrahedron Lett. 2011, 52, 5032. For
examples of Cu- and Pd-catalyzed Arbuzov reactions: (k) Axelrad,
G.; Laosooksathit, S.; Engel, R. J. Org. Chem. 1981, 46, 5200; (l)
400 MHz): δ = 7.57 (d, J = 13.2 Hz, 1H), 7.52 (dd, J = 7.8, 13.4
Hz, 1H), 7.22 (dd, J = 4.2, 7.8 Hz, 1H), 4.09 (m, 4H), 2.30 (s,
6H), 1.31 (t, J = 7.0 Hz, 6H).
4.3.4. Diethyl benzo[d][1,3]dioxol-5-ylphosphonate (17).22
1
Colorless oil; 31P NMR (CDCl3, 162 MHz): δ = 20.10; H NMR
(CDCl3, 400 MHz): δ = 7.36 (ddd, J = 1.2, 8.0, 13.6 Hz, 1H),
7.19 (dd, J = 1.2, 13.2 Hz, 1H), 6.89 (dd, J = 3.4, 7.9 Hz, 1H),
6.01 (s, 2H), 4.04-4.13 (m, 4H), 1.32 (t, J = 7.1 Hz, 6H).
4.3.5. Diethyl naphthalen-2-yl phosphonate (18).9d Colorless oil;
1
31P NMR (CDCl3, 162 MHz): δ = 20.20; H NMR (400 MHz,
CDCl3): δ = 8.41 (d, J = 16.4 Hz, 1H), 7.84-7.93 (m, 3H), 7.71-
7.76 (m, 1H), 7.51-7.59 (m, 2H), 4.17-4.23 (m, 4H), 1.32 (t, J =
7.3 Hz, 6H).
4.3.6. Ethyl diphenylphosphinate (19).23 Colorless oil; 31P NMR
(CDCl3, 162 MHz): δ = 25.01; 1H NMR (CDCl3, 400 MHz): δ =
7.84–7.79 (m, 4H), 7.52–7.42 (m, 6H), 4.16–4.09 (m, 2H), 1.30
(t, J = 7.3 Hz, 3H).
Acknowledgments
We thank Professor Tsuneo Imamoto and Dr. Masashi Sugiya
for helpful discussion. This work was partially supported by the
National Natural Science Foundation of China (Nos. 21172143
and 21232004), Nippon Chemical Industrial Co., Ltd and
Shanghai Jiao Tong University. Our thanks also go to the
Instrumental Analysis Center of Shanghai Jiao Tong University.

5
Berrino, R.; Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Stabile, P.
Org. Biomol. Chem. 2010, 8, 4518.
Nakata, H.; Ohshita, J. Org. Lett. 2009, 11, 373; (g) Bonnafoux,
ACCEPTED MANUSCRIPT
L.; Colobert, F.; Leroux, F. R. Synlett 2010, 2953; (h) Diemer, V.;
Leroux, F. R.; Colobert, F. Eur. J. Org. Chem. 2011, 327; (i)
Diemer, V.; Begaud, M.; Leroux, F. R.; Colobert, F. Eur. J. Org.
Chem. 2011, 341; (j) Diemer, V.; Garcia, J. S.; Leroux, F. R.;
Colobert, F. J. Fluorine Chem. 2012, 134, 146. For selected recent
examples of nucleophilic addition, see: (k) Yoshida, H.; Sugiura,
S.; Kunai, A. Org. Lett. 2002, 4, 2767; (l) Yoshida, H.; Ikadai, J.;
Shudo, M.; Ohshita, J.; Kunai, A. J. Am. Chem. Soc. 2003, 125,
6638; (m) Lin, W.; Sapountzis, I.; Knochel, P. Angew. Chem. Int.
Ed. 2005, 44, 4258; (n) Yoshida, H.; Tanino, K.; Ohshita, J.;
Kunai, A. Chem. Commun. 2005, 5678; (o) Toledo, F. T.;
Marques, H.; Comasseto, J. V.; Raminelli, C. Tetrahedron Lett.
2007, 48, 8125; (p) Yoshida, H.; Morishita, T.; Ohshita, J. Org.
Lett. 2008, 10, 3845; (q) Morishita, T.; Fukushima, H.; Yoshida,
H.; Ohshita, J.; Kunai, A. J. Org. Chem. 2008, 73, 5452. (r)
Diemer, V.; Berthelot, A.; Bayardon, J.; Jugé, S.; Leroux, F. R.;
Colobert, F. J. Org. Chem. 2012, 77, 6117; (s) Chen, Y.; Willis,
M. C. Org. Lett. 2015, 17, 4786. (t) Pawliczek, M.; Garve, L. K.
B.; Werz, D, B. Org. Lett. 2015, 17, 1716.
9. (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Tetrahedron
Lett. 1980, 21, 3595; (b) Hirao, T.; Masunaga, T.; Ohshiro, Y.;
Agawa, T. Synthesis 1981, 56; (c) Hirao, T.; Masunaga, T.;
Yamada, N.; Ohshiro, Y.; Agawa, T. Bull. Chem. Soc. Jpn. 1982,
55, 909. For selected recent examples of further development and
modification to Hirao reaction: (d) Kalek, M.; Ziadi, A.;
Stawinski, J. Org. Lett. 2008, 10, 4637; (e) Kalek, M.; Stawinski,
J. Organometallics 2008, 27, 5876; (f) Belabassi, Y.; Alzghari,
S.; Montchamp, J. J. Organomet. Chem. 2008, 693, 3171; (g)
Kohler, M. C.; Sokol, J. G.; Stockland Jr., R. A. Tetrahedron Lett.
2009, 50, 457; (h) Laven, G.; Stawinski, J. Synlett 2009, 225; (i)
Kohler, M. C.; Grimes, T. V.; Wang, X.; Cundari, T. R.;
Stockland Jr., R. A. Organometallics 2009, 28, 1193; (j) Luo, Y.;
Wu, J. Organometallics 2009, 28, 6823; (k) Kalek, M.; Jezowska,
M.; Stawinski, J. Adv. Synth. Catal. 2009, 351, 3207; (l)
McDougal, N. T.; Streuff, J.; Mukherjee, H.; Virgil, S. C.; Stoltz,
B. M. Tetrahedron Lett. 2010, 51, 5550; (m) Zhang, X.; Liu, H.;
Hu, X.; Tang, G.; Zhu, J.; Zhao, Y. Org. Lett. 2011, 13, 3478; (n)
Shen, C.; Yang, G.; Zhang, W. Org. Biomol. Chem. 2012, 10,
3500; (o) Zhang, H.-Y.; Sun, M.; Ma, Y.-N.; Tian, Q.-P.; Yang,
S.-D. Org. Biomol. Chem. 2012, 10, 9627; (p) Zhao, Y.-L.; Wu,
G.-J.; Han, F.-S. Chem. Commun. 2012, 48, 5868; (q) Zhao, Y.-L.;
Wu, G.-J.; Li, Y.; Gao, L.-X.; Han, F.-S. Chem. Eur. J. 2012, 18,
9622; (r) Hayashi, M.; Matsuura, T.; Tanaka, I.; Ohta, H.;
Watanabe, Y. Org. Lett. 2013, 15, 628; (s) Xu, K.; Hu, H.; Yang,
F.; Wu, Y. Eur. J. Org. Chem. 2013, 319; (t) Xu, K.; Yang, F.;
Zhang, G.; Wu, Y. Green Chem. 2013, 15, 1055; (u) Stankevič,
M.; Włodarczyk, A. Tetrahedron 2013, 69, 73. For selected
reviews, see: (v) Prim, D.; Campagne, J.-M.; Joseph, D.;
Andrioletti, B. Tetrahedron 2002, 58, 2041; (w) Schwan, A. L.
Chem. Soc. Rev. 2004, 33, 218.
14. For nucleophilic addition of phosphines on arynes to synthesize
aryl quaternary phosphonium salts, see: (a) Wittig, G.; Benz, E.
Chem. Ber. 1959, 92, 1999; (b) Zbiral, E. Tetrahedron Lett. 1964,
25, 1649; (c) Wittig, G.; Maturza, H. Liebigs Ann. Chem. 1970,
732, 97; (d) Wittig, G.; Braun, H. Liebigs Ann. Chem. 1971, 751,
27;
15. For stereoselective addition of secondary phosphine to aryne: (a)
Bayardon, J.; Laureano, H.; Diemer, V.; Dutartre, M.; Das, U.;
Rousselin, Y.; Henry, J.-C.; Colobert, F.; Leroux, F. R.; Jugé, S. J.
Org. Chem. 2012, 77, 5759; (b) Rémond, E.; Bayardon, J.;
Takizawa, S.; Rousselin, Y.; Sasai, H.; Jugé, S. Org. Lett. 2013,
15, 1870; (c) Dutartre, M.; Bayardon, J.; Eymin, M.-J.; Jugé, S.
Phosphorus Sulfur, and Silican and Related Elements, 2015, 190,
955. (d) Bayardon, J.; Bernard, J.; Rémond, E.; Rousselin, Y.;
Malacea-Kabbara, R.; Jugé, S. Org. Lett. 2015, 17, 1216.
16. (a) Rémond, E.; Tessier, A.; Leroux, F. R.; Bayardon, J.; Jugé, S.
Org. Lett. 2010, 12, 1568; (b) Dhokale, R. A.; Mhaske, S. B. Org.
Lett. 2013, 15, 2218; (c) Yoshida, S.; Hosoya, T. Chem. Lett.
2013, 42, 583.
10. For metal-catalyzed oxidative coupling of arylboronic acid or
azole with secondary phosphonates, see: (a) Andaloussi, M.;
Lindh, J.; Sävmarker, J.; Sjöerg, P. J. R.; Larhed, M. Chem. Eur.
J. 2009, 15, 13069; (b) Qiao, J.; Lam, P. Synthesis 2011, 829; (c)
Zhuang, R.; Xu, J.; Cai, S.; Tang, G.; Fang, M.; Zhao, Y. Org.
Lett. 2011, 13, 2110; (d) Hou, C.; Ren, Y.; Lang, R.; Hu, X.; Xia,
C.; Li, F. Chem. Commun. 2012, 48, 5181.
11. (a) Miao, W.; Gao, Y.; Li, X.; Gao, Y.; Tang, G.; Zhao, Y. Adv.
Synth. Catal. 2012, 354, 2659; (b) Chen, Z.-S.; Zhou, Z.-Z.; Hua,
H.-L.; Duan, X.-H.; Luo, J.-Y.; Wang, J.; Zhou, P.-X.; Liang, Y.-
M. Tetrahedron 2013, 69, 1065.
17. Shen, C.; Yang, G.; Zhang, W. Org. Lett., 2013, 15, 5722.
18. (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
12, 1211; (b) Peña, D.; Cobas, A.; Pérez, D.; Guitian, E. Synthesis
2002, 1454; (c) Kovács, S.; Csincsi, Á. I.; Nagy, T. Z.; Boros, S.;
Timári, G.; Novák, Z. Org. Lett. 2012, 14, 2022.
12. For reviews on the use of arynes in organic synthesis, see: (a)
Kessar, S. V. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I., Eds.; Pergamon: New York, 1991; Vol. 4, pp 483-
515; (b) Chen, Y.; Larock, R. C. In Modern Arylation Methods;
Ackermann, L., Ed.; Wiley-VCH: New York, 2009; Chapter 12,
pp 401-473; (c) Wenk, H. H.; Winkler, M.; Sander, W. Angew.
Chem. Int. Ed. 2003, 42, 502; (d) Pellissier, H.; Santelli, M.
Tetrahedron 2003, 59, 701; (e) Sanz, R. Org. Prep. Proc. Int.
2008, 40, 215. (f) Tadross, P. M.; Stoltz, B. M. Chem. Rev. 2012,
112, 3550; (g) Dubrovskiy, A. V.; Markina, N. A.; Larock, R. C.
Org. Biomol. Chem. 2013, 11, 191.
19. Whitaker, C. M.; Kott, K. L.; McMahon R. J. J. Org. Chem. 1995,
60, 3499.
20. Xu, W.; Zou, J.-P.; Zhang, W. Tetrahedron Lett. 2010, 51, 2639.
21. Jutand, A.; Mosleh, A. J. Org. Chem. 1997, 62, 261.
22. Shimizu, H.; Ishizaki, T.; Fujiwara, T.; Saito, T. Tetrahedron:
Asymmetry 2004, 15, 2169.
23. Huang, C.; Tang, X.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem.
2006, 71, 5020.
Supplementary Material
13. For selected recent examples of aryne chemistry in synthesis, see:
(a) Liu, Z.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2005, 127,
15716; (b) Leroux, F. R.; Bonnafoux, L.; Heiss, C.; Colobert, F.;
Lanfranchi, D. A. Adv. Synth. Catal. 2007, 349, 2705; (c) Waldo,
J. P.; Zhang, X.; Shi, F.; Larock, R. C. J. Org. Chem. 2008, 73,
6679; (d) Shi, F.; Waldo, J. P.; Chen, Y.; Larock, R. C. Org. Lett.
2008, 10, 2409; (e) Waldo, J. P.; Zhang, X.; Shi, F.; Larock, R. C.
J. Org. Chem. 2008, 73, 6679; (f) Yoshida, H.; Morishita, T.;
Supplementary data related to this article can be found at
http://