Metal-Free Aromatic Carbon-Phosphorus Bond Formation via a Sandmeyer-Type Reaction

Article abstract of DOI:10.1021/acs.joc.6b01820

An efficient metal-free phosphorylation process based on a Sandmeyer-type transformation with arylamines as the starting materials is developed. The transformation proceeds smoothly at room temperature without the exclusion of moisture or air. This phosphorylation reaction tolerates a wide range of functional groups and affords the phosphorylation products in moderate to good yields, thus providing a valuable method for the formation of aromatic carbon-phosphorus bonds.

Full text of DOI:10.1021/acs.joc.6b01820

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Article
Metal-Free Aromatic Carbon-Phosphorus Bond
Formation via a Sandmeyer-Type Reaction
Shuai Wang, Di Qiu, Fanyang Mo, Yan Zhang, and Jianbo Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01820 • Publication Date (Web): 28 Oct 2016
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Page 1 of 35
The Journal of Organic Chemistry
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MetalꢀFree Aromatic CarbonꢀPhosphorus Bond Formation via a
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SandmeyerꢀType Reaction
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Shuai Wang, Di Qiu, Fanyang Mo, Yan Zhang and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking
University, Beijing 100871, China
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
ABSTRACT. An efficient metalꢀfree phosphorylation process based on a Sandmeyerꢀtype
transformation with arylamines as the starting materials is developed. The transformation proceeds
smoothly at room temperature without the exclusion of moisture or air. This phosphorylation
reaction tolerates wide range of functional groups and affords the phosphorylation products in
moderate to good yields, thus providing a valuable method for the formation of aromatic
carbonꢀphosphorus bonds.
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INTRODUCTION
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Aryl phosphonates belong to an important class of organophosphorus compounds due to their
applications in medicinal chemistry,1 material sciences,2 and organic synthesis,3 which makes the
synthesis of this type of compounds of significant importance. The traditional methods to construct
the aromatic carbonꢀphosphorus bonds in these compounds involve nucleophilic substitution
reaction of organometallic reagent with electrophilic phosphine reagent (Scheme 1a),4
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MichaelisꢀArbuzov
reaction5
and
FriedelꢀCrafts
reaction.6
Additionally,
the
transitionꢀmetalꢀcatalyzed crossꢀcoupling reaction of aryl (pseudo)halides or some other compounds,
such as aryltriflates, tosylates, boronic acids and hydrazine with phosphorus(III) compounds has
been explored extensively since Hirao and coꢀworkers' pioneering work in 1980s.7,8 Due to the
excellent efficiency and remarkable functional group tolerance, the transitionꢀmetalꢀcatalyzed
coupling strategy has been widely utilized in carbonꢀphosphorus bond formation (Scheme 1b).
Despite of the significant progresses, these methods still suffer from some limitations, such as the
use of metal reagents and the requirement of relatively high temperature. Further efforts were made
to construct aromatic carbonꢀphosphorus bonds under mild conditions, for example, Xiao and
coꢀworkers have recently reported that the employment of visibleꢀlightꢀinduced photoredox catalysis
achieves the nickelꢀcatalyzed crossꢀcoupling of aryl halide with diarylphosphine oxides at room
temperature;9 Toste and coꢀworkers reported that, by employing dual gold and photoredox catalysis,
aryldiazonium salts could react with Hꢀphosphonates at room temperature to form
carbonꢀphosphorus bonds.10 In spite of these remarkable improvements, highly efficient approaches
for the construction of aromatic carbonꢀphosphorus bond under metalꢀfree mild conditions, which
could be served as alternative and supplementary methods for the synthesis of aryl phosphonate
compounds, is still limited.
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Scheme 1. Synthetic Methods for the Construction of Aromatic Carbon-Phosphorus Bonds
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On the other hand, the transformation of aryldiazonium salts into various functional groups,
such as halogen, hydroxyl group, cyano group, and sulfonates groups, known as Sandmeyerꢀtype
reactions, has been applied broadly both in laboratory research and industrial production.11 The
aryldiazonium salt intermediates, which could be in situ generated from aromatic amines,12 has been
recently explored in several new transformations.13,14 We have recently reported new approaches for
the synthesis of arylboronic pinacol esters, arylstannane compounds, and trifluoromethylated arenes
by using readily available arylamines as the starting materials.14Aryldiazonium salts have been
previously reported to react with phosphorus trihalides since 1950s,15 but these transformations often
suffer from poor yields and limited functional group tolerance. In view of the importance of aryl
phosphonates compounds and our continued interest in the development of the transformations with
aryldiazonium salts, we report herein an efficient approach for the metalꢀfree CꢀP Bond formation
through a similar Sandmeyerꢀtype transformation. The important feature of this method is the use of
triarylphosphites, which are stable and easy to handle, rather than the airꢀsensitive phosphorus
trihalides, as the phosphorylation reagents.
RESULTS AND DISCUSSIONS
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We began the study of the phosphorylation reaction with ethyl 4ꢀaminobenzoate (1a) as the
starting material. The arylamine 1a was firstly reacted with tꢀBuONO (tertꢀbutyl nitrite) in MeCN to
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form the corresponding aryldiazonium salt at 0 C, and then trimethyl phosphite (2a) was added in
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sequence. To our delight, the expected phosphorylation product 3aa was obtained in a yield of 44%
(Table 1, entry 1). As detected by GCꢀMS, the major byꢀproducts were ethyl benzoate, which was
generated by the reduction of aryldiazonium salt species, and trimethyl phosphate. Since our
previous study has indicated that acid can promote the generation of diazonium intermediate,14c we
thus proceed to study the effect of acid additives. Indeed, the reaction proceeded more efficiently
when TsOH was added (Table 1, entry 2), however, HCl and H2SO4 were found not suitable for this
transformation (Table 1, entries 3 and 4), and the reaction failed to give 3aa when typical Lewis acid
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BF3 Et2O was added (Table 1, entry 5). The product 3aa was formed in a lower yield when the
reaction was carried out in DCM (dichloromethane) or DCE (dichloroethane) (Table 1, entries 6 and
7). No apparent improvement was observed when the reaction temperature was raised to 80 oC
(Table 1, entry 8). Some other phosphorylation reagents were then explored. Triethyl phosphite (2b)
gave only trace amount of the corresponding product 3ab (detected by GCꢀMS, Table 1, entry 9).
Besides, only trace amount of ethyl benzoate was observed, because aryldiazonium salt was mainly
transformed into some nonꢀvolatile species under this condition. To our delight, when triphenyl
phosphite (2c) was employed as the phosphorus source, the corresponding product 3ac was produced
in a yield of 78% (Table 1, entry 10). The increase of concentration showed almost no influence on
the transformation (Table 1, entry 11). A low loading of tꢀBuONO and 2c led to the diminish of the
yields of 3ac (Table 1, entries 12 and 13). The yield of 3ac could be further improved with a higher
loading of 2c (Table 1, entry 14). One likely explanation for this result is that the higher equivalent
of 3c accelerates the phosphorylation process so that the generation of ethyl benzoate is inhibited.
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Table 1. Optimization of Reaction Conditionsa
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entry
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acid
solvent
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
temp
2, R
3, yield (%)b
3aa, 44
3aa, 54
3aa, 16
3aa, 20
3aa, ꢀꢀ
ꢀꢀ
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
0ꢀ80 oC
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
2a, Me
2b, Et
2c, Ph
2c, Ph
2
TsOH.H2O
HCl
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H2SO4
.
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BF3 Et2O
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TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
TsOH.H2O
3aa, 44
3aa, 17
3aa, 54
3ab, trace
3ac, 78
3ac, 79
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DCE
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MeCN
MeCN
MeCN
MeCN
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11c
12d
13e
14f
TsOH.H2O
TsOH.H2O
TsOH.H2O
MeCN
MeCN
MeCN
0 oCꢀrt
0 oCꢀrt
0 oCꢀrt
2c, Ph
2c, Ph
2c, Ph
3ac, 62
3ac, 51
3ac, 94
aUnless otherwise noted, the reaction conditions are as following: arylamine (0.2 mmol), tꢀBuONO
(0.3 mmol), P(OR)3 (0.4 mmol), acid (0.24 mmol), solvent (1.0 mL). Arylamine firstly reacted with
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tꢀBuONO and acid at 0 C for 15 min, and then the reaction system was allowed to warm to room
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b
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temperature and P(OR)3 was added. Isolated yield. 0.5 mL solvent was used. 0.3 mmol P(OR)3
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was added. e0.24 mmol tꢀBuONO was added. f0.6 mmol P(OR)3 was added.
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With the optimized reaction conditions in hand, we then examined the substrate scope of this
transformation with a series of functionalized arylamines using 2c as the phosphorylation reagent
(Scheme 2). The phosphorylation process has shown good functional group tolerance to both
electronꢀwithdrawing and electronꢀdonating groups on the aromatic ring, including nitro (3b), cyano
(3c), methyl (3d), halogen (3e and 3f), phenyl (3g), methylthio (3h), methoxy (3ic), acetyl (3j),
alkynyl (3ra and 3rb), alkenyl (3w), azo group (3v), hydrogen (3z). In all the cases, the
corresponding products were obtained in 40ꢀ98% yields. It is noteworthy that the tolerance of bromo
and chloro groups, which is normally not compatible in transitionꢀmetalꢀcatalyzed CꢀP bond
construction approaches, makes possible of further transformation of the products with
crossꢀcoupling reactions.
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Scheme 2. Substrate Scope of the Aniline Derivatives
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Reaction conditions: arylamine (0.2 mmol), tꢀBuONO (0.3 mmol), P(OPh)3 (0.6 mmol), TsOH.H2O
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(0.24 mmol), MeCN (1.0 mL). Arylamine was first reacted with tꢀBuONO and acid at 0 C for 15
min, and then the reaction system was warmed to room temperature and P(OPh)3 was added.
aIsolated yield after column chromatography. bThe reaction of arylamine with tꢀBuONO was carried
out at room temperature for 10 min. c3.0 mL MeCN was added.
The paraꢀsubstituted aryl amines with electronꢀwithdrawing groups could gave relatively higher
yields; while the substrate with electronꢀdonating paraꢀmethyl substituent afforded a moderate yield
of 66% (3d). The pꢀOMe substituted aniline gave a low yield of 40% (3ic). Similar yield could be
achieved with orthoꢀ and metaꢀsubstituted anilines (3kꢀq), indicating that the phosphorylation is not
sensitive to the steric effect. For the naphthylamine 1sa and 1sb, the diminished yield might be
attributed to the poor solubility of the corresponding diazonium salts.
We then expended the substrate scope of this phosphorylation reaction to the aromatic
heterocyclic amine derivatives. The results shown in Scheme 3 indicate that the phosphorylation of
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some aromatic heterocyclic amine derivatives also works, but giving the phosphorylation products in
low yields (5aꢀe). However, the phosphorylation reaction with some other aromatic heterocyclic
amine derivatives did not occur (5fꢀh).
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Scheme 3. Substrate Scope of Aromatic Heterocyclic Amine Derivatives
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Unless otherwise noted, the reaction conditions are as following: arylamine (0.2 mmol), tꢀBuONO
(0.3 mmol), P(OPh)3 (0.6 mmol), TsOH.H2O (0.24 mmol), MeCN (1.0 mL). Arylamine firstly
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reacted with tꢀBuONO and acid at 0 C for 15 min, and then the reaction system was warmed to
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room temperature and P(OPh)3 was added. Isolated yield with column chromatography. The
reaction of arylamine with tꢀBuONO was carried out at room temperature for 10 min.
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The Journal of Organic Chemistry
Next, the scope of a series of substituted triaryl phosphites (6aꢀd) was investigated and the results
are summarized in Scheme 4. Good yields were achieved for the chloroꢀ (7a) and bromoꢀ (7b)
substituted products, which could be convenient for further modifications. The tertꢀbutyl substituted
phosphite also gave a good yield of 89% (7d), but the reaction with methoxy substituted substrate
gave only diminished yield (7c).
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Scheme 4. Substrate Scope of the Triaryl Phosphites
Reaction conditions: arylamine (0.2 mmol), tꢀBuONO (0.3 mmol), P(OAr)3 (0.6 mmol), TsOH.H2O
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(0.24 mmol), MeCN (1.0 mL). Arylamine firstly reacted with tꢀBuONO and acid at 0 C for 15
minutes, and then the reaction system was warmed to room temperature and P(OPh)3 was added.
aIsolated yield after column chromatography.
For a further demonstration of the practical application of this method, the phosphorylation
reaction of three substrates was carried out in 20 mmolꢀscale for the gramꢀscale synthesis of
products 3ac, 3d, and 3ic, as shown in Scheme 5. To our delight, the reaction offered the
corresponding products with comparable yields.
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Scheme 5. Gram-Scale Synthesis
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aIsolated yield, the numbers in the brackets are the yields for the reaction carried out in 0.2
mmolꢀscale. b The reaction of arylamine with tꢀBuONO was carried out at room temperature for 10
min.
It is worth mentioning that the reaction using trialkyl phosphite (Table 1, 2a, b) as the
phosphorylation reagent could only give a low yield, which might be a potential limit for the
practical usefulness of this phosphorylation reaction. However, it was shown that the diphenyl
phosphonates could be easily transferred to various dialkyl phosphonates through ester exchange as
demonstrated by the example shown in eq 1,16 which could circumvent such limitation.
The mechanism of the reaction between arenediazonium salts and some phosphorus (III)
compounds was previously investigated by Yasui and coꢀworkers in 1995.17 In their study, it was
reported that a small amount of arylphosphonate was formed via a phosphonium ion intermediate
when arenediazonium salts were reacted with trialkyl phosphites in an alcoholic solvent under an
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The Journal of Organic Chemistry
argon atmosphere at 20 °C. Interestingly, according to the report 4ꢀnitrobenzenediazonium
fluoroborate gave a lower yield of arylphosphonate than 4ꢀmethylbenzenediazonium fluoroborate,
which showed an opposite electronic preference as compared with our phosphorylation reaction.
Also, the addition of acetonitrile, which is the best solvent in our phosphorylation reaction, was
reported to make the coupling of aryl radical generated from arenediazonium salts with phosphorus
species less favorable in Yasui's work. The observation of the opposite results indicates that our
phosphorylation reaction may proceed with a different pathway. To gain insights into the
mechanistic details of our transformation, the reaction of 1a in the presence of radical scavenger
TEMPO (2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀoxyl) was carried out (Scheme 6). When 10 mol% of
TEMPO was added, the yield of 3ac dropped from 94% to 83%. Moreover, the reaction was almost
blocked completely when 100 mol% or 150 mol% of TEMPO was added. These results indicate the
possibility that a radical process may be involved in this transformation.
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Scheme 6. Radical Trapping Experiments
Furthermore, experiments were carried out in order to reveal the influence of electronic effects of
the reaction. Thus, a 1:1 mixture of electronꢀwithdrawing group substituted aniline 1a and aniline 1z
was reacted under the optimized conditions and the reaction was stopped in 2 min in order to keep
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the reaction at low conversion of aryl amines. A 1.5:1 ratio of 3ac and 3z was observed (Scheme 7a),
indicating that the electronꢀdeficient 1a was more reactive. A 1.3:1 ratio of 3z and 3i was observed
in the similar competition experiment of 1z and methylꢀsubstituted aniline 1d (Scheme 7b). The
electronic preferences suggest that the decrease of positive charge on the active center occurs during
the transformation, which is in accordance with the generation of a radical species from a cationic
intermediate.
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Scheme 7. Studies on Electronic Effects
Based on the general understanding on Sandmeyerꢀtype reaction,18 and our previous mechanistic
investigation on Sandmeyerꢀtype borylation and stannylation,14 we have proposed a mechanism as
shown in Scheme 8. First, arylamine reacts with tꢀBuONO to generate diazonium salt intermediate A.
Then single electron transfer (SET) between A and triphenyl phosphite generates radical anion
species B and radical cation species C. Subsequently, phosphorous radical D is formed from C,
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followed by the reaction with B to afford the final phosphorylation product, along with the release of
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nitrogen.
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Scheme 8.Proposed Reaction Mechanism
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CONCLUSION
In summary, we have developed a Sandmeyerꢀtype phosphorylation method to synthesize aryl
phosphonates from easily available aryl amines. This metalꢀfree transformation can be conducted
under mild conditions without the exclusion of moisture or air. The reaction tolerates wide range of
functional groups and affords the phosphorylation products in moderate to good yields. In view of
the importance of aryl phosphonate compounds, we expect that this novel phosphorylation method
will find practical applications in the synthesis of these compounds and will be a supplementary
method for the construction of aromatic carbonꢀphosphorus bond. Detailed mechanistic study and
further expansion of the substrate scope are currently under investigation in our laboratory.
EXPERIMENTAL SECTION
General Methods. P(OMe)3, P(OEt)3, P(OPh)3 and the aniline derivatives were purchased from
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commercial suppliers and were used without further purifications. The solvents were all distilled
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prior to use. 200ꢀ300 mesh silica gels for the chromatography were used. Chemical shifts for H
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NMR (400 MHz) and 13CNMR (100 MHz) are reported relative to the chemical shift of
tetramethylsilane (TMS): chemical shifts (δ) were reported in ppm, and coupling constants (J) are in
Hertz (Hz). For 31P NMR (162 MHz) spectra 85% phosphoric acid (δ = 0) was served as external
standard. IR spectra are reported in wave numbers, cm−1. For HRMS measurements, the mass
analyzer is FTꢀICR. The substituted triaryl phosphites (6aꢀd) were prepared following the literature
procedure.19
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General procedure for the phosphorylation reaction.Arylamine (0.2 mmol) and TsOH·H2O (46
mg, 0.24 mmol) were added into a 10 mL reaction tube. After the addition of MeCN (1.0 mL), the
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turbid solution was stirred at 0 C. tꢀBuONO (31 mg, 0.3 mmol) was then added and the reaction
solution was stirred at 0 oC for 15 min, followed by the addition of P(OR)3 (0.6 mmol), the resulting
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reaction solution was stirred for 8 h at room temperature (around 25 C). The solution was then
concentrated under reduced pressure, and the crude residue was purified by silica gel column
chromatography to afford the pure products.
General procedure for gram scale phosphorylation reaction. Arylamine (1a, 1d, or 1i, 20 mmol)
and TsOH·H2O (4.56 g, 24 mmol) were added into a 200 mL reaction bulb. After the addition of
MeCN (40 mL), the turbid solution was stirred at 0 oC. tꢀBuONO (3.09 g, 30 mmol) was then added
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dropwise and the reaction solution was stirred at 0 C for 15 min, followed by the addition of
P(OPh)3 (18.06 g, 60 mmol), the resulting reaction solution was stirred for 8 h at room temperature
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(25 C). The solution was then concentrated under reduced pressure, and the crude residue was
purified by silica gel column chromatography to afford the pure product.
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The ester exchange experiment.16 The solution of sodium (130 mg, 5.7 mmol) dissolved in 3.0 mL
ethanol was added into a solution of 3ic (340 mg, 1.0 mmol) dissolved in 3 mL ethanol, the reaction
solution was stirred at room temperature for 2 h. Then the mixture was transferred into a 125 mL
separating funnel and 40 mL diethyl ether was added. The solution was washed by 1 M NaOH (40
mL), and then the water phase was extracted with 20 mL ethanol. The organic phase was then
washed by brine (30 mL). After drying by Na2SO4 and evaporation, the product 3ib was obtained
(215 mg, 88%) as an orange liquid.
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3ia was obtained as an orange liquid (205 mg, 84%) by using methanol as solvent under similar
conditions. For 3id (orange liquid, 134 mg, 55%), iꢀPrOH was used instead of ethanol and the
reaction was carried out at 60 oC for 2h.
The competition experiment. Arylamine 1a (83 mg, 0.5 mmol), 1z (47 mg, 0.5 mmol) and
TsOH·H2O (228 mg, 1.2 mmol) were added into a 50 mL reaction bulb. After the addition of MeCN
o
(10 mL), the turbid solution was stirred at 0 C. tꢀBuONO (155 mg, 1.5 mmol) was then added and
the reaction solution was stirred at 0 oC for 15 min, followed by the addition of P(OPh)3 (341 mg, 1.1
o
mmol). The resulting reaction solution was stirred for 2 min at room temperature (25 C). The
reaction was quenched by filtering the mixture through a short column of silica gel (eluent: ethyl
acetate). The solution was then concentrated under reduced pressure, and the crude residue was
purified by silica gel column chromatography to afford the pure product 3ac (38 mg, 20%) and 3z
(20 mg, 13%).
Ethyl 4ꢀ(dimethoxyphosphoryl)benzoate (3aa).20 Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 2:1) afforded 3aa (28 mg, 54%); yellow oil. H NMR (400 MHz, CDCl3) δ
8.16ꢀ8.13 (m, 2H), 7.91ꢀ7.86 (m, 2H), 4.41 (q, J = 7.1 Hz, 2H), 3.79 (d, J = 11.1 Hz, 6H), 1.42 (t, J =
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7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.7, 134.1 (d, J = 3.4 Hz), 131.9 (d, J = 9.9 Hz),
131.6 (d, J = 187.2 Hz), 129.4 (d, J = 15.2 Hz), 61.5, 52.9 (d, J = 5.6 Hz), 14.3; 31P NMR (CDCl3,
162 MHz) δ 20.6; IR (film): 1721, 1273, 1104, 1020, 830, 763 cmꢀ1; EIꢀMS (m/z, relative intensity):
257 (20), 230 (24), 213 (100), 185 (26), 136 (20), 91 (16); HRMS (ESI) calcd for C11H16O5P
[M+H]+ 259.0730; found 259.0728.
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Ethyl 4ꢀ(diphenoxyphosphoryl)benzoate (3ac).21Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 5:1) afforded 3ac (72 mg, 94%); yellow oil. H NMR (400 MHz, CDCl3) δ
8.17ꢀ8.14 (m, 2H), 8.07ꢀ8.01 (m, 2H), 7.31ꢀ7.26 (m, 4H), 7.19ꢀ7.14 (m, 6H), 4.41 (q, J = 7.1 Hz,
2H), 1.39 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.5, 150.1 (d, J = 7.7 Hz), 134.7 (d,
J = 3.19 Hz), 132.3 (d, J = 10.6 Hz), 131.3 (d, J = 192.93 Hz), 129.8, 129.6, 129,5, 120.6 (d, J = 4.6
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Hz), 61.6, 14.3; P NMR (CDCl3, 162 MHz) δ 10.6; IR (film): 1721, 1489, 1272, 1186, 1103, 932,
762 cmꢀ1; EIꢀMS (m/z, relative intensity): 381 (100), 337 (15), 289 (35), 242 (24), 170 (17), 77 (76);
HRMS (ESI) calcd for C21H20O5P [M+H]+ 383.1043; found 383.1043.
Diphenyl (4ꢀnitrophenyl)phosphonate (3b).16 Flash chromatography (silica gel, petroleum ether:ethyl
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acetate = 10:1) afforded 3b (68 mg, 95%); yellow liquid. H NMR (400 MHz, CDCl3) δ 8.35ꢀ8.32
(m, 2H), 8.19ꢀ8.14 (m, 2H), 7.34ꢀ7.30 (m, 4H), 7.19ꢀ7.18 (m, 6H);13C NMR (100 MHz, CDCl3) δ
150.7 (d, J = 4.0 Hz), 149.9 (d, J = 7.6 Hz), 133.8 (d, J = 191.8 Hz), 133.6 (d, J = 11.1 Hz), 130.0,
125.7, 123.6 (d, J = 16.2 Hz), 120.5 (d, J = 4.6 Hz); 31P NMR (CDCl3, 162 MHz) δ 8.2; IR (film):
1589, 1516, 1267, 1187, 945, 932, 777 cmꢀ1; EIꢀMS (m/z, relative intensity): 354 (89), 308 (14), 262
(14), 215 (34), 170 (16), 94 (19), 77 (100); HRMS (ESI) calcd for C18H15NO5P [M+H]+ 356.0682;
found 356.0682.
Diphenyl (4ꢀcyanophenyl)phosphonate (3c).16 Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 10:1) afforded 3c (66 mg, 98%); red liquid. H NMR (400 MHz, CDCl3) δ
8.11ꢀ8.05 (m, 2H), 7.80ꢀ7.77 (m, 2H), 7.33ꢀ7.26 (m, 4H), 7.20ꢀ7.16 (m, 6H);13C NMR (100 MHz,
CDCl3)δ 149.9 (d, J = 7.8 Hz), 132.8 (d, J = 10.4 Hz), 132.2 (d, J = 15.8 Hz), 132.0 (d, J = 192.4
Hz), 130.0, 125.6, 120.5 (d, J = 4.6 Hz), 117.6, 116.9 (d, J = 3.68 Hz); 31P NMR (CDCl3, 162 MHz)
δ 8.4; IR (film): 2233, 1590, 1489, 1271, 1185, 935, 767 cmꢀ1; EIꢀMS (m/z, relative intensity): 334
(91), 242 (19), 195 (42), 170 (18), 94 (20), 77 (100); HRMS (ESI) calcd for C19H15NO3P [M+H]+
336.0784; found 336.0786.
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Diphenyl pꢀtolylphosphonate (3d).16 Flash chromatography (silica gel, petroleum ether:ethyl acetate
= 20:1) afforded 3d (43 mg, 66%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.87ꢀ7.82 (m, 2H),
7.30ꢀ7.25 (m, 6H), 7.19ꢀ7.17 (m, 4H), 7.14ꢀ7.11 (m, 2H), 2.40 (s, 3H);13C NMR (100 MHz, CDCl3)
δ 150.5 (d, J = 7.4 Hz), 144.0 (d, J = 3.1 Hz), 132.3 (d, J = 10.9 Hz), 129.7, 129.4 (d, J = 16.4 Hz),
125.1, 123.5 (d, J = 195.1 Hz), 120.7 (d, J = 4.5 Hz), 21.8; 31P NMR (CDCl3, 162 MHz) δ 12.48; IR
(film): 1592, 1490, 1269, 1188, 1129, 926, 769 cmꢀ1; EIꢀMS (m/z, relative intensity): 323 (100), 231
(77), 213 (13), 184 (22), 170 (20), 77 (77); HRMS (ESI) calcd for C19H18O3P [M+H]+ 325.0988;
found 325.0994.
Diphenyl (4ꢀchlorophenyl)phosphonate (3e).16 Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 30:1) afforded 3e (59 mg, 86%); yellow liquid. H NMR (400 MHz, CDCl3) δ
7.92ꢀ7.87 (m, 2H), 7.50ꢀ7.47 (m, 2H), 7.35ꢀ7.26 (m, 4H), 7.21ꢀ7.14 (m, 6H);13C NMR (100 MHz,
CDCl3) δ 150.2 (d, J= 7.5 Hz), 140.0 (d, J = 4.2 Hz), 133.7 (d, J = 11.4 Hz), 129.8, 129.1 (d, J =
16.6 Hz), 125.4 (d, J = 195.9 Hz), 125.4, 120.6 (d, J = 4.5 Hz); 31P NMR (CDCl3, 162 MHz) δ 11.1;
IR (film): 1590, 1489, 1280, 1187, 1088, 930, 772 cmꢀ1; EIꢀMS (m/z, relative intensity): 343 (78),
251 (33), 233 (7), 204 (25), 170 (22), 77(100); HRMS (ESI) calcd for C18H15ClO3P [M+H]+
345.0442; found 345.0444.
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Diphenyl (4ꢀbromophenyl)phosphonate (3f). Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 30:1) afforded 3f (60 mg, 77%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.84ꢀ7.79 (m,
2H), 7.65ꢀ7.62 (m, 2H), 7.31ꢀ7.27 (m, 4H), 7.18ꢀ7.13 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 150.2
(d, J = 7.6 Hz), 133.8 (d, J = 11.2 Hz), 132.1 (d, J = 16.4 Hz), 129.8, 128.6 (d, J = 4.2 Hz), 125.9 (d,
J = 195.3 Hz), 125.3, 120.6 (d, J = 4.5 Hz); 31P NMR (CDCl3, 162 MHz) δ 11.4; IR (film) 1581,
1483, 1266, 1186, 1162, 930, 771 cmꢀ1; EIꢀMS (m/z, relative intensity): 389 (63), 295 (29), 248 (16),
170 (21), 77 (100), 51 (16); HRMS (ESI) calcd for C18H15BrO3P [M+H]+ 388.9937; found 388.9939.
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Diphenyl [1,1'ꢀbiphenyl]ꢀ4ꢀylphosphonate (3g).22 Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 20:1) afforded 3g (39 mg, 51%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ
8.06ꢀ8.00 (m, 2H), 7.73ꢀ7.70 (m, 2H), 7.62 (d, J = 7.4 Hz, 2H), 7.49ꢀ7.45 (m, 2H), 7.42ꢀ7.39 (m,
1H), 7.32ꢀ7.29 (m, 4H), 7.23ꢀ7.21 (m, 4H), 7.17ꢀ7.13 (m, 2H);13C NMR (100 MHz, CDCl3) δ 150.4
(d, J = 7.6 Hz), 146.0 (d, J = 3.4 Hz), 139.7, 132.8 (d, J = 10.8 Hz), 129.8, 129.0, 128.4, 127.3,
127.3 (d, J = 16.1 Hz), 125.3 (J = 194.7 Hz), 125.2, 120.7 (d, J = 4.5 Hz); 31P NMR (CDCl3, 162
MHz) δ 12.6; IR (film): 1591, 1488, 1274, 1188, 1133, 928, 761 cmꢀ1; HRMS (ESI) calcd for
C24H20O3P [M+H]+ 387.1145; found 387.1146.
Diphenyl (4ꢀ(methylthio)phenyl)phosphonate (3h). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 20:1) afforded 3h (37 mg, 52%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ
7.86ꢀ7.80 (m, 2H), 7.30ꢀ7.26 (m, 6H), 7.19ꢀ7.12(m, 6H), 2.45 (s, 3H);13C NMR (100 MHz, CDCl3)
δ 150.4 (d, J = 7.5 Hz), 146.2 (d, J = 3.6 Hz), 132.5 (d, J = 11.1 Hz), 129.8, 125.2, 125.1 (d, J = 16.1
Hz), 122.0 (d, J = 197.5 Hz), 120.6 (d, J = 4.7 Hz), 14.6; 31P NMR (CDCl3, 162 MHz) δ 12.7; IR
(film): 1589, 1489, 1278, 1187, 1085, 927, 773 cmꢀ1; EIꢀMS (m/z, relative intensity): 356 (100), 263
(94), 216 (23), 170 (12), 139 (9), 77 (68); HRMS (ESI) calcd for C19H18O3PS [M+H]+ 357.0709;
found 357.0708.
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1
Dimethyl (4ꢀmethoxyphenyl)phosphonate (3ia)10 Orange liquid (205 mg, 84%). H NMR (400 MHz,
CDCl3) δ 7.74 (dd, J = 12.7, 8.7 Hz, 2H), 6.98 (dd, J = 8.7, 3.3 Hz, 2H), 3.85 (s, 3H), 3.74 (d, J =
11.1 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 163.0 (d, J = 3.5 Hz), 133.9 (d, J = 11.2 Hz), 117.9 (d,
J = 196.1 Hz), 114.1 (d, J = 16.1 Hz), 55.3, 52.5 (d, J = 5.5 Hz);31P NMR (CDCl3, 162 MHz) δ
23.1IR (film): 2955, 1600, 1507, 1244, 1132, 1024, 812 cmꢀ1;EIꢀMS (m/z, relative intensity): 77 (15),
108 (30), 121 (69), 171 (80), 185 (24), 216 (100).
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Diethyl (4ꢀmethoxyphenyl)phosphonate (3ib).16 Orange liquid (215 mg, 88%). H NMR (400 MHz,
CDCl3) δ 7.78ꢀ7.72 (m, 2H), 6.98ꢀ6.95 (m, 2H), 4.17ꢀ4.00 (m, 4H), 3.85 (s, 3H), 1.31 (t, J = 7.0 Hz,
6H);13C NMR (100 MHz, CDCl3) δ 162.8 (d, J = 3.3 Hz), 133.7 (d, J = 11.3 Hz), 119.5 (d, J = 195.0
Hz), 114.0 (d, J = 16.1 Hz), 61.9 (d, J = 5.3 Hz), 55.3, 16.3 (d, J = 6.6 Hz); 31P NMR (CDCl3, 162
MHz) δ 20.3; IR (film): 1600, 1243, 1132, 1022, 962, 807 cmꢀ1; EIꢀMS (m/z, relative intensity): 244
(39), 216 (43), 188 (100), 171 (54), 135 (24), 108 (59); HRMS (ESI) calcd for C11H18O4P [M+H]+
245.0937; found 245.0930.
Diphenyl (4ꢀmethoxyphenyl)phosphonate (3ic).16 Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 10:1) afforded 3ic (27 mg, 40%); orange liquid. 1H NMR (400 MHz, CDCl3) δ
7.88 (dd, J = 13.4, 8.8 Hz, 2H), 7.30ꢀ7.26 (m, 4H), 7.19ꢀ7.11 (m, 6H), 6.98 (dd, J = 8.8, 3.8 Hz, 2H),
3.85 (s, 3H);13C NMR (100 MHz, CDCl3) δ 163.5 (d, J = 3.6 Hz), 150.5 (d, J = 7.4 Hz), 134.4 (d, J=
11.9 Hz), 129.7, 125.0, 120.7 (d, J = 4.5 Hz), 117.8 (d, J = 200.4 Hz), 114.2 (d, J = 16.9 Hz), 55.3;
31P NMR (CDCl3, 162 MHz) δ 13.3; IR (film): 1597, 1489, 1257, 1187, 1130, 926, 770 cmꢀ1; EIꢀMS
(m/z, relative intensity): 339 (72), 247 (100), 229 (8), 200 (16), 170 (18), 77 (67); HRMS (ESI) calcd
for C19H18O4P [M+H]+ 341.0937; found 341.0943.
Diisopropyl (4ꢀmethoxyphenyl)phosphonate (3id)10 Orange liquid (134 mg, 55%). H NMR (400
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MHz, CDCl3) δ 7.75 (dd, J = 12.5, 8.6 Hz, 2H), 8.96ꢀ8.94 (m, 2H), 4.69ꢀ4.61 (m, 2H), 3.84 (s, 3H),
1.36 (d, J = 6.0 Hz, 6H), 1.21 (d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.6 (d, J = 3.2
Hz), 133.7 (d, J = 11.4 Hz), 121.2 (d, J = 195.3 Hz), 113.8 (d, J = 16.1 Hz), 70.4 (d, J = 5.3 Hz),
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55.3, 23.9 (dd, J = 24.1, 3.9 Hz); P NMR (CDCl3, 162 MHz) δ 18.0; IR (film): 2979, 2923, 1601,
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1242, 1133, 1016, 979 cmꢀ1; EIꢀMS (m/z, relative intensity): 77 (14), 108 (37), 171 (55), 188 (100),
230 (24), 272 (16).
Diphenyl (4ꢀacetylphenyl)phosphonate (3j). Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 5:1) afforded 3j (62 mg, 89%); orange liquid. 1H NMR (400 MHz, CDCl3) δ 8.08ꢀ8.05 (m,
4H), 7.32ꢀ7.28 (m, 4H), 7.19ꢀ7.16 (m, 6H), 2.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 197.3,
150.1 (d, J = 7.5 Hz), 140.4 (d, J = 3.1 Hz), 132.7 (d, J = 10.4 Hz), 131.6 (d, J = 191.0 Hz), 129.8,
128.2 (d, J = 16.0 Hz), 125.4, 120.6 (d, J = 4.6 Hz), 26.8; 31P NMR (CDCl3, 162 MHz) δ 10.5; IR
(film): 1691, 1590, 1489, 1263, 1186, 930, 764 cmꢀ1; EIꢀMS (m/z, relative intensity): 353 (100), 337
(17), 259 (39), 212 (17), 170 (15), 77 (94); HRMS (ESI) calcd for C20H18O4P [M+H]+ 353.0937;
found 353.0939.
Diphenyl oꢀtolylphosphonate (3k).16 Flash chromatography (silica gel, petroleum ether:ethyl acetate
= 30:1) afforded 3k (45 mg, 69%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 15.2,
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7.6 Hz, 1H), 7.52ꢀ7.28 (m, 1H), 7.34ꢀ7.27 (m, 6H), 7.23ꢀ7.12 (m, 6H), 2.76 (s, 3H); C NMR (100
MHz, CDCl3) δ 149.3 (d, J = 7.9 Hz), 141.1 (d, J = 10.7 Hz), 133.5 (d, J = 11.1 Hz), 132.3 (d, J =
3.1 Hz), 130.5 (d, J = 15.9 Hz), 128.7, 124.7 (d, J = 15.8 Hz), 124.5 (d, J = 188.7 Hz), 124.1, 119.4
(d, J = 4.7 Hz), 20.5 (d, J = 3.6 Hz); 31P NMR (CDCl3, 162 MHz) δ 13.1; IR (film): 1593, 1490,
1187, 1163, 1025, 928, 757 cmꢀ1; EIꢀMS (m/z, relative intensity): 324 (100), 288 (19), 231 (22), 212
(29), 165 (22), 94 (27), 77 (72); HRMS (ESI) calcd for C19H18O3P [M+H]+ 325.0988; found
325.0988.
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The Journal of Organic Chemistry
Diphenyl (2ꢀcyanophenyl)phosphonate (3l). Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 5:1) afforded 3l (58 mg, 87%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.30ꢀ8.24 (m,
1H), 7.91ꢀ7.87 (m, 1H), 7.74ꢀ7.71 (m, 2H), 7.33ꢀ7.28 (m, 8H), 7.20ꢀ7.14 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 150.0 (d, J = 8.0 Hz), 135.7 (d, J = 9.4 Hz), 134.8 (d, J = 11.6 Hz), 133.4 (d, J = 2.6
Hz), 132.5 (d, J = 14.8 Hz), 129.9 (d, J = 192.9 Hz), 129.9, 125.6, 120.6 (d, J = 4.6 Hz), 117.0 (d, J
= 5.9Hz), 114.9 (d, J = 4.6 Hz); 31P NMR (CDCl3, 162 MHz) δ 6.1; IR (film): 2231, 1589, 1489,
1278, 1184, 944, 764 cmꢀ1; EIꢀMS (m/z, relative intensity): 335 (100), 242 (39), 224 (22), 195 (62),
170 (20), 77 (97); HRMS (ESI) calcd for C19H15NO3P [M+H]+ 336.0784; found 336.0787.
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Diphenyl (2ꢀchlorophenyl)phosphonate (3m). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 30:1) afforded 3m (55 mg, 80%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ
8.17ꢀ8.11 (m, 1H), 7.54ꢀ7.50 (m, 2H), 7.39ꢀ7.32 (m, 1H), 7.31ꢀ7.23 (m, 8H), 7.16ꢀ7.12 (m, 2H);13C
NMR (100 MHz, CDCl3) δ 150.2 (d, J = 7.4 Hz), 137.0, 136.9 (d, J = 8.8 Hz), 134.6, 131.1 (d, J =
10.6 Hz), 129.8, 126.7 (d, J = 14.7 Hz), 125.9 (d, J = 196.4 Hz), 125.3, 120.6 (d, J = 4.5 Hz); 31P
NMR (CDCl3, 162 MHz) δ 8.2; IR (film): 1587, 1489, 1268, 1186, 1052, 940, 757 cmꢀ1; EIꢀMS (m/z,
relative intensity): 344 (100), 309 (71), 251 (21), 215 (83), 168 (37), 77 (88); HRMS (ESI) calcd for
C18H15ClO3P [M+H]+ 345.0442; found 345.0441.
Diphenyl (3ꢀnitrophenyl)phosphonate (3n).23 Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 20:1) afforded 3n (59 mg, 69%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J =
13.3 Hz, 1H), 8.46 (d, J = 8.3 Hz, 1H), 8.29 (dd, J = 13.2, 7.6 Hz, 1H), 7.76ꢀ7.70 (m, 1H), 7.34ꢀ7.30
(m, 4H), 7.21ꢀ7.17 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 149.9 (d, J = 7.9 Hz), 148.1 (d, J = 19.1
Hz), 138.0 (d, J = 10.3 Hz), 130.1 (d, J = 16.5 Hz), 130.0, 129.5 (d, J = 196.5 Hz), 127.8 (d, J = 2.9
Hz), 127.2 (d, J = 12.1 Hz), 125.7, 120.5 (d, J = 4.7 Hz); 31P NMR (CDCl3, 162 MHz) δ 8.1; IR
(film): 1590, 1532, 1489, 1362, 1185, 936, 762 cmꢀ1; EIꢀMS (m/z, relative intensity): 355 (100), 338
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(17), 308 (308 (47), 170 (25), 94 (17), 77 (89); HRMS (ESI) calcd for C18H15NO5P [M+H]+
356.0682; found 356.0685.
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Diphenyl (3ꢀacetamidophenyl)phosphonate (3o). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 2:1) afforded 3o (31 mg, 42%); orange liquid.1H NMR (400 MHz, CDCl3) δ
9.30 (s, 1H), 8.41 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 15.9 Hz, 1H), 7.59 (dd, J = 13.4, 7.6 Hz, 1H),
7.48ꢀ7.43 (m, 1H), 7.26ꢀ7.21 (m, 4H), 7.14ꢀ7.10 (m, 6H), 1.82 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 169.4, 150.0 (d, J = 7.7 Hz), 139.7 (d, J = 20.2 Hz), 129.8, 129.6, 126.3 (d, J = 194.0 Hz), 126.2 (d,
J = 8.6 Hz), 125.5, 124.5 (d, J = 3.0 Hz), 123.2 (d, J = 13.6 Hz), 120.7 (d, J = 4.3 Hz), 24.0; 31P
NMR (CDCl3, 162 MHz) δ 12.8; IR (film): 3295, 2926, 1549, 1488, 1185, 935, 771 cmꢀ1; HRMS
(ESI) calcd for C20H19NO4P [M+H]+ 368.1046; found 368.1051.
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3ꢀ(Diphenoxyphosphoryl)phenyl acetate (3p). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 10:1) afforded 3p (59 mg, 81%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ
7.82 (dd, J = 13.6, 7.6 Hz, 1H), 7.72 (d, J = 15.1 Hz, 1H), 7.54ꢀ7.49 (m, 1H), 7.36ꢀ2.28 (m, 5H),
7.19ꢀ7.13 (m, 6H), 2.31 (s, 3H);13C NMR (100 MHz, CDCl3) δ 169.0, 150.7 (d, J = 21.3 Hz),
150.2 (d, J = 7.8 Hz), 130.0 (d, J = 18.1 Hz), 129.8, 129.6 (d, J = 9.8 Hz), 128.6 (d, J = 194.5 Hz),
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126.7 (d, J = 3.4 Hz), 125.4 (d, J = 11.1 Hz), 125.3, 120.6 (d, J = 4.5 Hz), 21.1; P NMR (CDCl3,
162 MHz) δ 10.6; IR (film): 1770, 1590, 1489, 1277, 1187, 933, 771 cmꢀ1; EIꢀMS (m/z, relative
intensity): 368 (14), 326 (100), 233 (14), 186 (7), 170 (9), 94 (6), 77 (29); HRMS (ESI) calcd for
C20H18O5P [M+H]+ 369.0886; found 369.0889.
Diphenyl (3ꢀbromophenyl)phosphonate (3q). Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 30:1) afforded 3q (67 mg, 86%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J =
14.3 Hz, 1H), 7.89 (dd, J = 13.6, 7.6 Hz, 1H), 7.74ꢀ 7.32 (m, 1H), 7.41ꢀ7.37 (m, 1H), 7.33ꢀ7.29 (m,
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4H), 7.19ꢀ 7.15 (m, 6H);13C NMR (100 MHz, CDCl3) δ 150.1 (d, J = 7.7 Hz), 136.3 (d, J = 2.9 Hz),
135.0 (d, J = 11.1 Hz), 130.7 (d, J = 9.7 Hz), 130.3 (d, J = 16.9 Hz), 129.9, 129.4 (d, J = 192.7 Hz),
125.4, 123.0 (d, J = 20.7 Hz), 120.6 (d, J = 4.6 Hz); 31P NMR (CDCl3, 162 MHz) δ 9.6; IR (film):
1590, 1488, 1275, 1186, 1137, 932, 763 cmꢀ1; EIꢀMS (m/z, relative intensity): 389 (56), 310 (16),
295 (24), 248 (16), 170 (28), 77 (100); HRMS (ESI) calcd for C18H15BrO3P [M+H]+ 388.9937;
found 388.9936.
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Diphenyl (4ꢀ((triisopropylsilyl)ethynyl)phenyl)phosphonate (3ra). Flash chromatography (silica gel,
petroleum ether:ethyl acetate = 50:1) afforded 3ra (64 mg, 65%); yellow liquid. 1H NMR (400 MHz,
CDCl3) δ 7.89 (d, J = 13.8, 8.1 Hz, 2H), 7.59ꢀ7.56 (m, 2H), 7.31ꢀ7.27 (m, 4H), 7.18ꢀ7.13 (m, 6H),
1.13 (s, 21H);13C NMR (100 MHz, CDCl3) δ 150.2 (d, J = 7.3 Hz), 132.2 (d, J = 6.6 Hz), 132.0 (d, J
= 12.2 Hz), 129.8, 128.5 (d, J = 3.7 Hz), 126.3 (d, J = 193.4 Hz), 125.3, 120.6 (d, J = 4.6 Hz), 105.7,
95.0, 18.6, 11.3; 31P NMR (CDCl3, 162 MHz) δ 11.5; IR (film): 2943, 2866, 1596, 1490, 1187, 1127,
932 cmꢀ1; EIꢀMS (m/z, relative intensity): 490 (3), 447 (100), 419 (24), 405 (26), 391 (33), 377 (44),
77 (26); HRMS (ESI) calcd for C29H36O3PSi [M+H]+ 491.2166; found 491.2165.
Diphenyl (4ꢀethynylphenyl)phosphonate (3rb). Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 20:1) afforded 3rb (32 mg, 48%); pale yellow liquid. H NMR (400 MHz,
CDCl3) δ 7.87ꢀ7.81 (m, 2H), 7.54ꢀ7.51 (m, 2H), 7.24ꢀ7.18 (m, 4H), 7.11ꢀ7.06 (m, 6H), 3.17 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 150.2 (d, J = 7.5 Hz), 132.3 (d, J = 2.3 Hz), 132.1 (d, J = 3.0 Hz),
129.8, 127.2 (d, J = 3.7 Hz), 127.2 (d, J = 193.6 Hz), 125.3, 120.6 (d, J = 4.5 Hz), 82.4, 80.5; 31P
NMR (CDCl3, 162 MHz) δ 11.1; IR (film): 1593, 1489, 1186, 1125, 930, 767 cmꢀ1; EIꢀMS (m/z,
relative intensity): 333 (100), 241 (60), 223 (16), 194 (46), 170 (20), 77 (97); HRMS (ESI) calcd for
C20H16O3P [M+H]+ 335.0832; found 335.0840.
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Diphenyl naphthalenꢀ1ꢀylphosphonate (3sa). Flash chromatography (silica gel, petroleum ether:ethyl
acetate = 20:1) afforded 3sa (25 mg, 35%); red liquid. 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 8.6
Hz, 1H), 8.40ꢀ8.34 (m, 1H), 8.09 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.74ꢀ7.69 (m, 1H),
7.63ꢀ7.59 (m, 1H), 7.56ꢀ7.51 (m, 1H), 7.31ꢀ7.24 (m, 4H), 7.20ꢀ7.16 (m, 4H), 7.14ꢀ7.10 (m, 2H);13C
NMR (100 MHz, CDCl3) δ 150.4 (d, J = 7.6 Hz), 135.8 (d, J = 10.0 Hz), 134.6 (d, J = 3.6 Hz), 133.6
(d, J = 13.6 Hz), 132.5 (d, J = 11.1 Hz), 129.7, 129.1, 128.0, 126.7, 126.5 (d, J = 4.3 Hz), 125.2,
124.6 (d, J =17.6 Hz), 123.2 (d, J = 187.8 Hz), 120.6 (d, J = 4.8 Hz); 31P NMR (CDCl3, 162 MHz) δ
12.7; IR (film): 1591, 1489, 1272, 1187, 996, 928, 774 cmꢀ1; EIꢀMS (m/z, relative intensity): 360
(99), 267 (100), 249 (42), 202 (26), 173 (26), 127 (28), 77 (59); HRMS (ESI) calcd for C22H18O3P
[M+H]+ 361.0988; found 361.0990.
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Diphenyl naphthalenꢀ2ꢀylphosphonate (3sb). Flash chromatography (silica gel, petroleum ether:ethyl
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acetate = 20:1) afforded 3sb (32 mg, 44%); orange solid, m.p. = 84ꢀ85 C. H NMR (400 MHz,
CDCl3) δ 8.57 (d, J = 16.4 Hz, 1H), 7.95ꢀ7.87 (m, 4H), 7.64ꢀ7.55 (m, 2H), 7.30ꢀ7.21 (m, 8H), 7.14ꢀ
7.11 (m, 2H);13C NMR (100 MHz, CDCl3) δ 150.4 (d, J = 7.5 Hz), 135.3 (d, J = 2.8 Hz), 135.2 (d, J
= 11.0 Hz), 132.3 (d, J = 17.7 Hz), 129.8, 129.2, 128.8, 128.6 (d, J= 15.0 Hz), 127.9, 127.2, 126.4 (d,
J = 10.2 Hz), 125.2 (d, J = 1.0 Hz), 123.8 (d, J = 193.1 Hz), 120.7 (d, J = 4.5 Hz); 31P NMR (CDCl3,
162 MHz) δ 12.6; IR (film): 1589, 1489, 1277, 1187, 1085, 926, 771 cmꢀ1; EIꢀMS (m/z, relative
intensity): 360 (100), 267 (73), 220 (22), 204 (21), 170 (11), 127 (28), 77 (67); HRMS (ESI) calcd
for C22H18O3P [M+H]+ 361.0988; found 361.0984.
Diphenyl (4ꢀnitronaphthalenꢀ1ꢀyl)phosphonate(3t). Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 10:1) afforded 3t (81 mg, 99%); yellow solid, m. p. = 106ꢀ109 C. H NMR
(400 MHz, CDCl3) δ 8.94 (d, J = 8.1 Hz, 1H), 8.49ꢀ8.40 (m, 2H), 8.05 (dd, J = 7.6, 3.3 Hz, 1H),
7.88ꢀ7.80 (m, 2H), 7.31ꢀ7.21 (m, 4H), 7.19ꢀ7.14 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 151.1 (d, J
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= 4.4 Hz), 150.0 (d, J = 7.4 Hz), 134.1 (d, J = 10.0 Hz), 133.9 (d, J = 12.0 Hz), 130.0, 129.6, 129.6
(d, J = 186.5 Hz), 129.3, 127.1 (d, J = 4.3 Hz), 125.6, 124.9 (d, J = 13.9 Hz), 123.6, 120.9, (d, J =
18.0 Hz), 120.4 (d, J = 4.7 Hz); 31P NMR (CDCl3, 162 MHz) δ 9.5; IR (film): 1590, 1257, 1489,
1278, 1184, 937, 766, 689 cmꢀ1; HRMS (ESI) calcd for C22H17NO5P [M+H]+ 406.0839; found
406.0844.
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Diphenyl (3ꢀfluoroꢀ4ꢀnitrophenyl)phosphonate (3u). Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 10:1) afforded 3u (50 mg, 67%); yellow solid, m.p. = 81ꢀ84 C. 1H NMR (400
MHz, CDCl3) δ 8.18ꢀ8.13 (m, 1H), 7.94ꢀ7.87 (m, 2H), 7.36ꢀ7.32 (m, 4H), 7.22ꢀ7.10 (m, 6H);13C
NMR (100 MHz, CDCl3) δ 154.9 (dd, J = 269.0, 22.82 Hz), 149.7 (d, J = 7.8 Hz), 140.2 (dd, J = 4.5,
2.2 Hz), 135.3 (dd, J = 185.9, 6.6 Hz), 130.1, 128.3 (dd, J = 9.5, 5.0 Hz), 126.5 (dd, J = 17.7, 2.7
Hz), 125.9 (d, J = 0.9 Hz), 122.6 (dd, J = 22.2, 11.5 Hz), 120.4 (d, J = 4.5 Hz); 31P NMR (CDCl3,
162 MHz) δ 5.1; IR (film): 1597, 1533, 1489, 1279, 1184, 942, 737 cmꢀ1; EIꢀMS (m/z, relative
intensity): 373 (98), 326 (20), 280 (8), 233 (35), 170 (20), 77 (97); HRMS (ESI) calcd for
C18H14FNO5P [M+H]+ 374.0588; found 374.0592.
Diphenyl (E)ꢀ(4ꢀ(phenyldiazenyl)phenyl)phosphonate (3v). Flash chromatography (silica gel,
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petroleum ether:ethyl acetate = 30:1) afforded 3v (35 mg, 42%); red liquid. H NMR (400 MHz,
CDCl3) δ 8.15ꢀ 8.09 (m, 2H), 8.01ꢀ7.94 (m, 4H), 7.55ꢀ7.52 (m, 3H), 7.34ꢀ7.28 (m, 4H), 7.23ꢀ7.14 (m,
6H);13C NMR (100 MHz, CDCl3) δ 155.2 (d, J = 3.9 Hz), 152.5, 150.3 (d, J = 7.5 Hz), 133.4 (d, J =
11.0 Hz), 132.0, 129.8, 129.2, 128.9 (d, J = 202.1 Hz), 125.3, 123.2, 122.8 (d, J = 16.4 Hz), 120.6 (d,
J = 4.5 Hz); 31P NMR (CDCl3, 162 MHz) δ 11.0; IR (film): 1593, 1489, 1274, 1187, 1125, 931, 769
cmꢀ1; HRMS (ESI) calcd for C24H20N2O3P [M+H]+ 415.1206; found 415.1212.
Ethyl (E)ꢀ3ꢀ(4ꢀ(diphenoxyphosphoryl)phenyl)acrylate (3w). Flash chromatography (silica gel,
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1
petroleum ether:ethyl acetate = 10:1) afforded 3w (41 mg, 50%); red liquid. H NMR (400 MHz,
CDCl3) δ 8.00ꢀ7.95 (m, 2H), 7.70ꢀ7.62 (m, 3H), 7.32ꢀ7.26 (m, 4H), 7.20ꢀ7.14 (m, 6H), 6.53 (d, J =
16.0 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
166.4, 150.2 (d, J = 7.8 Hz), 142.8, 139.0 (d, J = 3.5 Hz), 132.8 (d, J = 10.6 Hz), 129.8, 128.4 (d, J =
193.7 Hz), 128.0 (d, J = 16.1 Hz), 125.3, 121.3, 120.6 (d, J = 4.6 Hz), 60.8, 14.3; 31P NMR (CDCl3,
162 MHz) δ 11.3; IR (film): 2923, 1713, 1489, 1276, 1184, 936, 771, 681 cmꢀ1; HRMS (ESI) calcd
for C23H22O5P [M+H]+ 409.1199; found 409.1197.
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Diphenyl (3ꢀ(benzyloxy)phenyl)phosphonate (3x). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 20:1) afforded 3x (51 mg, 61%); yellow liquid. 1H NMR (400 MHz, CDCl3) δ
7.58ꢀ7.53 (m, 2H), 7.43ꢀ7.34 (m, 6H), 7.31ꢀ7.27 (m, 4H), 7.21ꢀ7.13 (m, 7H), 5.08 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 158.6 (d, J = 20.1 Hz), 150.4 (d, J = 7.5 Hz), 136.3, 130.0 (d, J = 18.7 Hz),
129.8, 128.7, 128.2, 128.0 (d, J = 191.9 Hz), 127.6, 125.2, 124.8 (d, J = 9.7 Hz), 120.6 (d, J = 4.5
Hz), 120.5 (d, J = 3.2 Hz), 117.8 (d, J = 12.0 Hz), 70.3; 31P NMR (CDCl3, 162 MHz) δ 12.1; IR
(film): 1592, 1488, 1230, 1185, 1025, 938, 755 cmꢀ1; HRMS (ESI) calcd for C25H22O4P [M+H]+
417.1250; found 417.1248.
Diphenyl (3,5ꢀdifluorophenyl)phosphonate (3ya). Flash chromatography (silica gel, petroleum
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ether:ethyl acetate = 30:1) afforded 3ya (42 mg, 61%); yellow liquid. H NMR (400 MHz, CDCl3)
δ7.52ꢀ7.46 (m, 2H), 7.34ꢀ7.30 (m, 4H), 7.20ꢀ7.16 (m, 6H), 7.07ꢀ7.02 (m, 1H);13C NMR (100 MHz,
CDCl3) δ 162.9 (ddd, J = 253.8, 26.8, 8.9 Hz), 150.0 (d, J = 7.7 Hz), 130.8 (d, J = 196.2 Hz), 129.9,
125.6, 120.5 (d, J = 4.5 Hz), 115.3 (dd, J = 26.6, 10.5 Hz), 108.9 (dt, J = 24.8, 2.5 Hz); 31P NMR
(CDCl3, 162 MHz) δ 8.2; IR (film): 1593, 1489, 1430, 1304, 1185, 936, 768 cmꢀ1; EIꢀMS (m/z,
relative intensity): 345 (100), 253 (18), 206 (34), 170 (20), 94 (15), 77 (86); HRMS (ESI) calcd for
C18H14F2O3P [M+H]+ 347.0643; found 347.0641.
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Diphenyl (3,4ꢀdifluorophenyl)phosphonate (3yb). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 20:1) afforded 3yb (56 mg, 81%); yellow solid, m.p. = 89ꢀ90 oC. 1H NMR (400
MHz, CDCl3) δ 7.82ꢀ7.70 (m, 2H), 7.32ꢀ7.28 (m, 5H), 7.19ꢀ7.14 (m, 6H);13C NMR (100 MHz,
CDCl3) δ 153.7 (ddd, J = 257.5, 12.5, 3.8 Hz), 150.4 (ddd, J = 253.1, 24.0, 12.7 Hz), 150.1 (d, J =
7.5 Hz), 129.9, 129.6 (ddd, J = 10.3, 7.4, 4.1 Hz), 125.5, 124.1 (dt, J = 198.3, 4.5 Hz), 121.7 (ddd, J
= 18.4, 11.9, 1.2 Hz), 120.5 (d, J = 4.5 Hz), 118.3 (t, J = 18.3 Hz); 31P NMR (CDCl3, 162 MHz) δ
9.1; IR (film): 1590, 1489, 1278, 1186, 1093, 934, 769 cmꢀ1; EIꢀMS (m/z, relative intensity): 345
(95), 254 (29), 206 (30), 170 (22), 77 (100), 51 (19); HRMS (ESI) calcd for C18H14F2O3P [M+H]+
347.0643; found 347.0647.
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Diphenyl phenylphosphonate (3z).16 Flash chromatography (silica gel, petroleum ether:ethyl acetate
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= 20:1) afforded 3z (49 mg, 79%); yellow solid, m.p. = 70ꢀ72 C. H NMR (400 MHz, CDCl3) δ
8.00ꢀ7.94 (m, 2H), 7.62ꢀ7.59 (m, 1H), 7.52ꢀ7.49 (m, 2H), 7.31ꢀ7.27 (m, 4H), 7.20ꢀ7.12 (m, 6H);13C
NMR (100 MHz, CDCl3) δ 150.4 (d, J = 7.5 Hz), 133.2 (d, J = 3.2 Hz), 132.3 (d, J = 10.4 Hz), 129.7,
128.7 (d, J = 15.9 Hz), 126.9 (d, J = 192.8 Hz), 125.1, 120.6 (d, J = 4.5 Hz); 31P NMR (CDCl3, 162
MHz) δ 12.3; IR (film): 1591, 1489, 1270, 1187, 1131, 926, 773, 689 cmꢀ1; EIꢀMS (m/z, relative
intensity): 309 (100), 217 (43), 199 (11), 170 (34), 152 (8), 77(57); HRMS (ESI) calcd for
C18H16O3P [M+H]+ 311.0832; found 311.0827.
Ethyl 5ꢀ(diphenoxyphosphoryl)benzofuranꢀ2ꢀcarboxylate (5a). Flash chromatography (silica gel,
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petroleum ether:ethyl acetate = 5:1) afforded 5a (49 mg, 58%); orange liquid. H NMR (400 MHz,
CDCl3) δ 8.38(d, J = 14.63 Hz, 1H), 8.06ꢀ8.00 (m, 1H), 7.74ꢀ7.70 (m, 1H), 7.58 (s, 1H), 7.31ꢀ7.26
(m, 4H), 7.20ꢀ7.13 (m, 6H), 4.46 (q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.1 Hz, 3H);13C NMR (100 MHz,
CDCl3) δ 159.0, 157.8, 150.3 (d, J = 7.5 Hz), 147.3, 130.7 (d, J = 12.2 Hz), 129.8, 128.8 (d, J = 12.1
Hz), 127.2 (d, J = 10.0 Hz), 125.3, 122.4 (d, J = 195.5 Hz), 120.6 (d, J = 4.5 Hz), 113.6, 113.1 (d, J
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= 16.9 Hz), 61.9, 14.3; 31P NMR (CDCl3, 162 MHz) δ 12.3; IR (film): 1728, 1590, 1489, 1186, 1087,
932, 767 cmꢀ1; EIꢀMS (m/z, relative intensity): 421 (100), 377 (9), 329 (58), 207 (11), 170 (12), 77
(60); HRMS (ESI) calcd for C23H20O6P [M+H]+ 423.0992; found 423.0996.
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Diphenyl (5ꢀbromopyridinꢀ3ꢀyl)phosphonate (5b). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 15:1) afforded 5b (21 mg, 27%); white solid, m.p. = 138ꢀ141 oC. 1H NMR (400
MHz, CDCl3) δ 9.03 (d, J = 5.6 Hz, 1H), 8.88 (s, 1H), 8.31 (d, J = 14.2 Hz, 1H), 7.35ꢀ7.31 (m, 4H),
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7.20ꢀ7.18 (m, 6 H); C NMR (100 MHz, CDCl3) δ 154.9, 150.5 (d, J = 11.8 Hz), 149.8 (d, J = 7.7
Hz), 142.1 (d, J = 9.1 Hz), 130.0, 125.7, 125.3 (d, J = 191.7 Hz), 121.1 (d, J = 14.9 Hz), 120.5 (d, J
= 4.5 Hz); 31P NMR (CDCl3, 162 MHz) δ 6.8; IR (film): 1589, 1488, 1265, 1185, 1160, 943, 770
cmꢀ1; EIꢀMS (m/z, relative intensity): 389 (56), 310 (31), 296 (36), 251 (8), 170 (16), 77 (100);
HRMS (ESI) calcd for C17H14BrNO3P [M+H]+ 389.9889; found 389.9892.
Diphenyl (6ꢀmethoxypyridinꢀ3ꢀyl)phosphonate (5c). Flash chromatography (silica gel, petroleum
ether:ethyl acetate = 10:1) afforded 5c (17 mg, 25%); yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.72
(dd, J = 7.0, 1.9 Hz, 1H), 8.02 (ddd, J = 12.2, 8.6, 2.2 Hz, 1H), 7.33ꢀ7.29 (m, 4H), 7.21ꢀ7.14 (m, 6H),
6.82 (dd, J = 8.6, 2.9 Hz, 1H), 3.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0, 152.4 (d, J = 15.4
Hz), 150.2 (d, J = 7.5 Hz), 141.7 (d, J = 10.4 Hz), 129.8, 125.3, 120.6 (d, J = 4.7 Hz), 115.3 (d, J =
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201.5 Hz), 111.3 (d, J = 13.3 Hz), 54.0; P NMR (CDCl3, 162 MHz) δ 11.2; IR (film) 1592, 1488,
1275, 1187, 1024, 929, 770, 689 cmꢀ1; EIꢀMS (m/z, relative intensity): 340 (100), 325 (9), 248 (75),
207 (12), 170 (14), 77 (46); HRMS (ESI) calcd for C18H17NO4P [M+H]+ 342.0890; found 342.0893.
Diphenyl (6ꢀ(trifluoromethyl)pyridinꢀ3ꢀyl)phosphonate (5d). Flash chromatography (silica gel,
petroleum ether:ethyl acetate = 15:1) afforded 5d (47 mg, 63%); white solid, m.p. = 129ꢀ132 oC. 1H
NMR (400 MHz, CDCl3) δ 9.17 (d, J = 5.7 Hz, 1H), 8.37 (dd, J = 13.4, 8.1 Hz, 1H), 7.75 (dd, J =
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The Journal of Organic Chemistry
7.8, 2.5Hz, 1H), 7.28ꢀ7.24 (m, 4H), 7.13ꢀ7.11 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 152.7 (d, J =
12.9 Hz), 149.7 (d, J = 7.7 Hz), 141.9 (d, J = 9.4 Hz), 130.1, 127.0 (d, J = 193.2 Hz), 125.8, 120.9 (q,
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J = 276.6 Hz), 120.4 (d, J = 4.7 Hz), 120.3 (d, J = 9.9 Hz); P NMR (CDCl3, 162 MHz) δ 6.6; IR
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(film): 2928, 1590, 1485, 1335, 1184, 1160, 1078, 945 cmꢀ1; EIꢀMS (m/z, relative intensity): 378
(100), 286 (33), 239 (20), 170 (12), 94 (9), 77 (68); HRMS (ESI) calcd for C18H14F3NO3P [M+H]+
380.0658; found 380.0658.
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Diphenyl (2ꢀmethylbenzo[d]thiazolꢀ5ꢀyl)phosphonate (5e). Flash chromatography (silica gel,
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petroleum ether:ethyl acetate = 5:1) afforded 5e (23 mg, 30%); orange solid, m.p. = 102ꢀ105 C. H
NMR (400 MHz, CDCl3) δ 8.54 (d, J = 15.3 Hz, 1H), 7.97ꢀ7.88 (m, 2H), 7.30ꢀ7.26 (m, 4H),
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7.22ꢀ7.18 (m, 4H), 7.16ꢀ7.12 (m, 2H), 2.87 (s, 3H); C NMR (100 MHz, CDCl3) δ 168.9, 153.0 (d,
J = 21.1 Hz), 150.3 (d, J = 7.6 Hz), 141.1, 129.8, 127.5 (d, J = 11.7 Hz), 126.8 (d, J = 11.1 Hz),
125.2, 124.4 (d, J = 195.0 Hz), 122.0 (d. J = 18.1 Hz), 120.6 (d, J = 4.6 Hz), 20.3; 31P NMR (CDCl3,
162 MHz) δ 12.1; IR (film): 1592, 1489, 1274, 1187, 1059, 931, 772, 689 cmꢀ1; HRMS (ESI) calcd
for C20H17NO3PS [M+H]+ 382.0661; found 382.0663.
Ethyl 4ꢀ(bis(4ꢀchlorophenoxy)phosphoryl)benzoate (7a). Flash chromatography (silica gel,
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petroleum ether:ethyl acetate = 15:1) afforded 7a (66 mg, 73%); yellow oil. H NMR (400 MHz,
CDCl3) δ 8.19ꢀ8.16 (m, 2H), 8.04ꢀ7.99 (m, 2H), 7.27ꢀ7.55 (m, 4H), 7.13ꢀ7.11 (m, 4H), 4.42 (q, J =
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7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H); C NMR (100 MHz, CDCl3) δ 165.4, 148.5 (d, J = 7.6 Hz),
135.0 (d, J = 3.5 Hz), 132.3 (d, J = 10.8 Hz), 131.0, 130.4 (d, J = 191.1 Hz), 129.9, 129.7 (d, J =
15.96 Hz), 121.9 (d, J = 4.6 Hz), 61.7, 14.3; 31P NMR (CDCl3, 162 MHz) δ 11.2; IR (film): 1724,
1486, 1273, 1192, 1102, 926 cmꢀ1; HRMS (ESI) calcd for C21H18Cl2O5P [M+H]+ 451.0263; found
451.0258.
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