CDI-promoted direct esterification of P(O)-OH compounds with phenols

Article abstract of DOI:10.1016/j.tetlet.2017.05.036

A novel and efficient N,N′-carbonyl diimidazole-catalyzed protocol for the direct esterification of P(O)-OH compounds using phenols as efficient esterification reagents is illustrated. It is a simple way to synthesis a broad spectrum of functionalized O-aryl phosphinates, phosphonates, and phosphates from basic starting materials with moderate to excellent yields.

Full text of DOI:10.1016/j.tetlet.2017.05.036

Accepted Manuscript
CDI-Promoted Direct Esterification of P(O)-OH Compounds with Phenols
Biquan Xiong, Chenghong Hu, Haotian Li, Congshan Zhou, Pangliang Zhang,
Yu Liu, Kewen Tang
PII:
S0040-4039(17)30620-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.05.036
TETL 48929
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
31 March 2017
10 May 2017
12 May 2017
Please cite this article as: Xiong, B., Hu, C., Li, H., Zhou, C., Zhang, P., Liu, Y., Tang, K., CDI-Promoted Direct
Esterification of P(O)-OH Compounds with Phenols, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/
j.tetlet.2017.05.036
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.

Graphical Abstract
CDI-Promoted Direct Esterification of P(O)-
OH Compounds with Phenols
Leave this area blank for abstract info.
Biquan Xiong,* Chenghong Hu, Haotian Li, Congshan Zhou, Pangliang Zhang, Yu Liu, Kewen Tang*
Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang,
414006, P.R.China.

1
Tetrahedron Letters
CDI-Promoted Direct Esterification of P(O)-OH Compounds with Phenols
Biquan Xiong,* Chenghong Hu, Haotian Li, Congshan Zhou, Pangliang Zhang, Yu Liu, Kewen Tang*
Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, P.R.China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel and efficient N,N’-carbonyl diimidazole-catalyzed protocol for the direct esterification
of P(O)-OH compounds using phenols as efficient esterification reagents is illustrated. It is a
simple way to synthesis a broad spectrum of functionalized O-aryl phosphinates, phosphonates,
and phosphates from basic starting materials with moderate to excellent yields.
Available online
2015 Elsevier Ltd. All rights reserved.
Keywords:
N,N’-carbonyl diimidazole
Esterification
P(O)-OH compounds
Phenols
1. Introduction
convenient than those reported in the literature for the synthesis
of O-aryl organophosphorus compounds without the use of
Phosphonic and phosphoric acids are widely existed in natural
resources, especially certain phosphoryl esters are important
motifs in natural products, pharmacological agents, amino acid
analogues, and synthetic precursors. In recent years, due to the
wide application of O-aryl substituted phosphonic and
phosphoric acids derivatives in industrial materials, medicinal
chemicals, lubricants, and phosphine ligands, there is a growing
interest in these kinds of compounds. [1-7]
diaryliodonium salts and metal salts. Compared with P(O)-H or
P-Cl compounds, P(O)-OH compounds are more air- and/or
moisture-stable, and the use of them is more cost-saving and
effective.[11-13]
For their preparation, orthodox nucleophlic substitution of
toxic phosphorus halides with phenols are commonly adopted.
The Atherton-Todd reaction of P(O)-H compounds with phenols
is also extensively used for the synthesis of the compounds, but
the protocol suffers from the low tolerance of functional groups
and substrate limitations, as well as the introduction of toxic
reagents.[8] In 2014, Feringa et al first disclosed the synthesis of
mixed alkyl aryl phosphonates using easily available
phosphonates with diaryl iodonium triflates over copper
catalysts, where the P=O bond coordinates with copper
efficiently to activate the phosphonates.[9] In addition, we
recently reported the functionalization of P(O)-OH compounds
using diaryl iodonium triflates or phenols for the synthesis of O-
aryl organophosphorus compounds, and where the copper salts
and CCl4 is essential for the reaction of P(O)-OH compounds
with phenols.[10]
Scheme 1. Methods for the synthesis of P[O]-OAr compounds.
2. Results and Discussion
The reaction of diphenyl phosphinic acid with phenol at room
temperature with the assistance of N,N’-carbonyl diimidazole
(CDI) and Et3N in THF under N2 atmosphere gives O-phenyl
diphenyl phosphinate 3a in 31% yield (Table 1, entry 1). The
introduction of CDI is crucial for the reaction. Then we
concentrated on the optimization of reaction conditions. Different
solvents (THF, DCM, DCE, DMF, 1,4-dioxane, EtOAc, CH3CN)
were screened for the reaction, and CH3CN is found to be the
best, affording 3a in 43% yield (Table 1, entries 1-7). Among the
coupling reagents tested (CDI (N,N’-carbonyl diimidazole),
TBTU (N,N,N',N'-Tetramethyl-O-(benzotriazol-1-yl) uronium
tetrafluoroborate), HATU (1-[bis (dimethyl-lamino) methylene]-
As an ongoing effort on the activation of P(O)-OH
compounds, we studied the direct esterification of P(O)-OH
compounds with phenols under mild conditions using N,N’-
carbonyl diimidazole as the coupling reagent. Herein we report
this efficient and simple protocol that is more economical and
1H-1,2,3-triazolo-[4,5-b]
pyridinium
3-oxid
hexafluoro

phosphate),
oxoethylidenaminooxy) dimethyl amino-morpholino-carbenium
hexafluorophosphate), BOP ((benzotriazol1yloxy)-tris-
COMU
((1-cyano-2-ethoxy-2-
withdrawing group on the aromatic ring should have a lower
redox potential than hydroquinone, suggesting that the another
hydroxyl of hydroquinone cannot be esterificated by diphenyl
phosphinic acid. For most cases, electron-donating groups (Table
2, 3b-3d, 3m-3q) or electron-withdrawing groups (Table 2, 3e-
3g, 3j, 3l-3m, and 3r) of phenols do not change the yields
significantly.
(dimethylmino) phosphonium hexafluophosphate)), their
efficiency is in the order: CDI > COMU > TBTU > HATU >
BOP, and CDI gives the best result (Table 1, entries 8-11).[14]
Besides Et3N, we further tested other bases such as DBU, N,N-
dimethylaniline, N,N-diethylaniline, and diisopropyl ethyl amine.
It is apparent that N,N-dimethylaniline is the best, and 99% yield
of 3a is obtained at a “diphenyl phosphinic acid:PhNMe2 molar
ratio” of 1:1.5 (Table 1, entries 12-16).
Table 2
Scope of phenols a
Table 1
Optimization of the esterification of 1a with 2a a
Entry
Coupling reagent
(1.0 eq)
CDI
Solvent
Base (1.0 eq)
Yield b
1
2
3
THF
DCE
DCM
DMF
Et3N
Et3N
Et3N
31%
11%
13%
5%
CDI
CDI
CDI
4
Et3N
5
6
7
8
CDI
CDI
CDI
TBTU
HATU
COMU
BOP
CDI
CDI
CDI
CDI
CDI
-
-
Dioxane
EtOAc
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
DBU
PhNMe2
PhNEt2
DIEA
PhNMe2
PhNMe2
PhNMe2
2%
13%
43%
39%
33%
41%
27%
31%
71%
57%
49%
99% c
0%
9
10
11
12
13
14
15
16
17
18
a
Reaction conditions: diphenyl phosphinic acid (0.5 mmol), phenols (0.5
0% d
mmol), CDI (0.5 mmol), PhNMe2 (0.75 mmol), CH3CN (1.0 mL), N2, room
b
c
a
temperature, 12 h. Isolated yields. Yield was determined by GC analysis,
and dodecane was used as internal standard.
Reactions were carried out with diphenyl phosphinic acid (0.5 mmol),
phenol (0.5 mmol) and base (0.5 mmol) in solvent (1.0 mL), under N2
b
atmosphere stirred at room temperarure for 12 h. Yield was determined by
c
d
GC analysis, and decane was used as internal standard. PhNMe2 (1.5 eq).
100 oC, air.
Table 3
Scope of P(O)-OH compounds a
It turned out that the present esterification reaction is generally
applicable for the transformation of P(O)-OH compounds to O-
aryl organophosphorus compounds. As shown in Table 2,
phenols such as p-cresol, 4-tert-butyl phenol, 4-methoxy phenol,
4-bromo phenol, 4-fluoro phenol, 4-iodo phenol and 4-phenyl
phenol react efficiently with diphenyl phosphinic acid (1a) under
the optimized reaction conditions to afford the corresponding
products of O-aryl phosphoryl compounds 3a-h in moderate to
excellent yields. Ortho-substituted phenols such as 2-phenyl
phenol, 2-fluoro phenol and 2-methyl phenol are also well
tolerated in the reaction, yielding the desired esterification
products of 3i-k in 76-95% yields. In addition, the reactions of 1a
with 4-nitro phenol and 4-trifluoromethyl phenol also afford the
desired product in 81% and 89% yields, respectively. As stated
above, it is observed that specials phenols (.e.g., hydroquinone,
2-methyl-5-iso-propyl phenol, 1-(2-hydroxy-4-methoxyphenyl)
ethanone, 2,4,6,-tribromo phenol, 1-naphthol and 2-naphthol)
also exhibit high reactivity, generating the corresponding
products in 75-93% yields, respectively (Table 2, 3o-3t). When
hydroquinone is used as the starting materials, there is not found
the generation of the di-esterification product. This result is also
consistent with the expectation that 3o bearing an electron-
a
Reaction conditions: P(O)-OH compounds (0.5 mmol), phenol (0.5 mmol),
CDI (0.5 mmol), PhNMe2 (0.75 mmol), CH3CN (1.0 mL), N2, room
temperature, 12 h. b Isolated yields. c N.D. = Not detected.
As depicted in Table 3, we investigated a variety of substituted
P(O)-OH compounds (1b-1i) with phenol under the optimized
conditions. It is clear that aryl substituted diphenyl phosphinic
acids such as di-(4-methyl phenyl) phosphinic acid and di-(4-
trifluoromethyl phenyl) phosphinic acid are also good substrates

for the reaction, and the expected esterification products of 4a
and 4b are generated in 97% and 92% yields, respectively. In
A plausible mechanism for the present esterification of P(O)-
OH compounds with phenols is proposed as illustrated in Scheme
3. P(O)-OH compound (A) first attacks N,N’-carbonyl
diimidazole to afford the 1H-imidazole-1-carboxylic phosphoryl
anhydride (B) and one molecular of 1H-imidazole (C).
Intermediate B could also be attacked directly by phenol to give
the esterification product. In the presence of a base, the 1H-
imidazole attacks the phosphorus center of intermediate B to give
the activated intermediate D, with the release of H-imidazole and
carbon dioxide via the cleavage of P-O bond. Finally, the
esterification path is completed via the reaction of activated
inermediate D with nucleophiles (phenol) with the elimination of
one molecular of 1H-imidazole.
addition,
dibutyl
phosphinic
acid,
ethyl
hydrogen
phenylphosphonate,
and 6-hydroxy-6H-dibenzo[c,e][1,2]
oxaphosphinine 6-oxide also react with phenol (2a) efficiently to
give the corresponding O-aryl phosphoryl products 4c-4e in 78-
94% yields. However, phenyl diphenyl phosphate (4f) and phenyl
dibutyl phosphonate (4g) were generated only in 11% and 13%
yields when diphenyl hydrogen phosphate and dibutyl hydrogen
phosphate employed. In addition, when phenylphosphonic acid
(1i) is adopted, there is no detection of the corresponding
esterification product. It is maybe ascribe to the great acidity of
this type compounds (1g-i). So, as described above, the
efficiency of P(O)-OH compounds is in the order: R2P(O)-OH >
(R)(RO)P(O)-OH >> (RO)2P(O)-OH.
Scheme 4. Proposed mechanism.
Scheme 2. Scope of nucleophiles.
3. Conclusion
In summary, we developed an highly efficient and convenient
method for the direct esterification of P(O)-OH compounds with
phenols. The approach avoids the use of metals and air-sensitive
reagents, and the reaction can be performed under ambient
conditions, making the experimental procedure simple. The
synthetic method has high potential for the synthesis of
biologically active molecules, catalytic ligands, and
organophosphorus compounds.
We further expanded the practical application of this method,
and S-naphthalen-2-yl diphenyl phosphinothioate (6a) can be
obtained in 86% yield in the reaction of diphenyl phosphinic acid
with naphthalene-2-thiol (5a) at the optimized reaction
conditions. When 4-chloro benzenethiol (5b) was adopted, there
was not found the desired esterification product (Scheme 2, path
1). Furthermore, aliphatic thiols such as propane-1-thiol (5c) and
phenylmethanethiol (5d) were also tested for the reaction. To our
surprise, these compounds were also not tolerated in this
reaction, while yielded the corresponding 1H-imidazole-1-
carbothioates after the reaction. It was obviously that these 1H-
imidazole-1-carbothioates lack of the driving force to activate the
P(O)-OH compounds to afford the esterification products.
Interestingly, when methanol and iso-propanol were treated to
the reaction, the corresponding products were gained in 51% and
86% yields, respectively.
4. Experimental section
4.1 General information and materials.
All solvents used in reactions were freshly distilled. All other
reagents were recrystallized or distilled as necessary. All
reactions were performed under an atmosphere of dry nitrogen.
1H (400 MHz), 13C (100 MHz), and 31P (162 MHz) spectra were
recorded on a 400MHz spectrometer in CDCl3. 1H NMR
chemical shifts are reported using TMS as internal standard; 13C
NMR chemical shifts are reported relative to CDCl3 as internal
standard.
4.2 General procedure.
Scheme 3. Control experiment.
A mixture of P(O)-OH compounds (0.5 mmol), phenols (0.5
mmol), CDI (0.5 mmol) and PhNMe2 (0.75 mmol) in CH3CN
(1.0 mL) was stirred at room temperature under N2 atmosphere
for 12 h. Removal of the solvent under reduced pressure gave the
crude product; pure product was obtained by passing the crude
product through a short silica gel column using Hexane/EtOAc
(1:1 to 5:1) as eluent .
Control experiments for the reaction of diphenyl phosphinic
acid with phenol were performed under the standard reaction
conditions without the addition of CDI. As depicted in Scheme 3,
no matter the reaction conducted in room temperature or heated
o
to 100 C, there was not found the generation of the desired
product after the reaction. So, we deduced that CDI is crucial for
the present esterification reaction.
Acknowledgments

Sakakura, A.; Katsukawa, M.; Ishihara, K. Org. Lett. 2005, 7, 1999; (h)
Sakakura, A.; Katsukawa, M.; Hayashi, T.; Ishihara, K. Green Chem.
2007, 9, 1166; (i) Park, C.-H.; Givens, R. S. J. Am. Chem. Soc. 1997, 119,
2453; (j) Xiong, B.; Ye, Q.; Feng, X.; Zhu, L.; Chen, T.; Zhou, Y.; Au,
C.-T.; Yin, S.-F. Tetrahedron. 2014, 70, 9057; (k) Xiong, B.; Feng, X.;
Zhu, L.; Chen, T.; Zhou, Y.; Au, C.-T.; Yin, S.-F. ACS Catal. 2015, 5,
537.
This work was supported by National Natural Science
Foundation of China (21606080, 21676077, 21476068),
Scientific Research Fund of Hunan Provincial Education
Department (16B111).
Supplementary Material
14. (a) Twibanire, J. K.; Grindley, T. B. Org. Lett. 2011, 13, 2988; (b)
Subiros-Funosas, R.; Khattab, S. N.; Nieto-Rodriguez, L.; El-Faham, A.;
Albericio, F. Aldrichimica Acta. 2013, 46, 21.
Supplementary data associated with this article can be found in
the online version.
References and notes
Highlights
1. (a) Imamoto, T. In Handbook of Organophosphorus Chemistry, Engel, R.
Eds.; Marcel Dekker: New York, 1992; (b) Quin, L. D. In A Guide to
Organophosphorus Chemistry, Wiley-Interscience: New York, 2000.
2. (a) Bock, T.; Möhwald, H.; Mülhaupt, R. Macromol. Chem. Phys. 2007,
208, 1324; (b) Kirumakki, S.; Huang, J.; Subbiah, A.; Yao, J.; Rowland,
A.; Smith, B.; Mukherjee, A.; Samarajeewa, S.; Clearfield, A. J. Mater.
Chem. 2009, 19, 2593; (c) Kim, D.; Salman, S.; Coropceanu, V.;
Padmaperuma, A. B.; Sapochak, L. S.; Kahn, A.; Bredas, J. L. Chem.
Mater. 2010, 22, 247.
• Direct esterification reaction of P(O)-OH
compounds with phenols is achieved.
• Avoids the use of metals and air-sensitive
reagents.
3. (a) Pollack, S. J.; Jacobs, J. W.; Schultz, P. G. Science. 1986, 234, 1570;
(b) Janda, K. D.; Schloeder, D.; Benkovic, S. J.; Lerner, R. A. Science.
1988, 241, 1188.
4. (a) Baumgartner, T.; Réau, R. Chem. Rev. 2006, 106, 4681; (b) Engel, R.
Chem. Rev. 1977, 77, 349.
• Reactions can be performed under ambient
conditions.
5. (a) Williams, N. H.; Harrison, J. M.; Read, R. W.; Black, R. M. Arch.
Toxicol. 2007, 81, 627; (b) Nomura, D. K.; Hudak, C. S.; Ward, A. M.;
Burston, J. J.; Issa, R. S.; Fisher, K. J.; Abood, M. E.; Wiley, J. L.;
Lichtman, A. H.; Casida, J. E. Bioorg. Med. Chem. Lett. 2008, 18, 5875;
(c) Ashani, Y.; Gupta, R. D.; Goldsmith, M.; Silman, I.; Sussman, J. L.;
Tawfik, D. S.; Leader, H. Chem. Biol. Interact. 2010, 187, 362.
6. (a) Spangler, L. A.; Mikolajczyl, M.; Burdge, E. L.; Kielbasinski, P.;
Smith, H. C.; Lyzwa, P.; Fisher, J. D.; Omelańczuk, J. J. Agric. Food
Chem. 1999, 47, 318; (b) Kukhar, V. P.; Hudson, H. R. In
Aminophosphonic and Aminopho-sphinic Acids: Chemistry and
Biological Activity; Wiley & Sons: Chichester, U.K., 2000.
7. (a) Fukuto, T. R.; Metcalf, R. L. J. Am. Chem. Soc. 1959, 81, 372; (b)
Nowlan, C.; Li, Y.; Hermann, J. C.; Evans, T.; Carpenter, J.; Ghanem, E.;
Shoichet, B. K.; Raushel, F. M. J. Am. Chem. Soc. 2006, 128, 15892; (c)
Moon, Y.; Moon, Y.; Choi, H.; Hong, S. Green Chem, 2017, 19, 1007; (d)
Botez, L.; De Jong, G. B.; Slootweg, J. C.; Deelman, B.-J. Eur. J. Org.
Chem, 2017, 2017, 434; (e) Xia, M.; Cheng, J. Tetrahedron Lett. 2016,
57, 4702; (f) Chen, Q.; Zeng, J.; Yan, X.; Huang, Y.; Wen, C.; Liu, X.;
Zhang, K. J. Org. Chem, 2016, 81, 10043.
8. (a) Atherton, F. R.; Openshaw, H. T.; Todd, A. R. J. Chem. Soc. 1945,
660; (b) Atherton, F. R.; Todd, A. R. J. Chem. Soc. 1947, 674; (c) Wang,
G.; Shen, R. W.; Xu, Q.; Goto, M.; Zhao, Y.-F.; Han, L.-B. J. Org. Chem.
2010, 75, 3890.
9. Copper-catalyzed O-arylation of the dialkyl phosphonates with
diaryliodonium salts, see: FanÞanaìs-Mastral, M.; Feringa, B. L. J. Am.
Chem. Soc. 2014, 136, 9894.
10. (a) Xiong, B.; Zeng, K.; Zhang, S.; Zhou, Y.; Au, C.-T.; Yin, S.-F.
Tetrahedron, 2015, 71, 9293. (b) Xiong, B.; Feng, X.; Zhu, L.; Chen, T.;
Zhou, Y.; Au, C.-T.; Yin, S.-F. ACS Catal. 2015, 5, 537.
11. For the activation of P(O)-OH compounds via the P(O)-Cl intermediate,
see: (a) Pollart, K. A.; Harwood, H. J. J. Org. Chem. 1962, 27, 4444; (b)
Kasemsuknimit, A.; Satyender, A.; Chavasiri, W.; Jang, D. O. Bull.
Korean Chem. Soc. 2011, 32, 3486; (c) Swamy, K. C. K.; Kumar, N. S.
Acc. Chem. Res. 2006, 39, 324.
12. For reviews of the synthesis of phosphoric acid esters, see: (a) Hayakawa,
Y. In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I.;
Winterfeldt, E. Eds.; Pergamon, Oxford, 1991, Vol. 6; (b) Reese, C. B.
Org. Biomol. Chem. 2005, 3, 3851; (c) Keglevich, G.; Kiss, N. Z.; Mucsi,
Z.; Körtvélyesi, T. Org. Biomol. Chem. 2012, 10, 2011; (d) Dumond, Y.
R.; Baker, R. L.; Montchamp, J.-L. Org. Lett. 2000, 2, 3341; (e) Kiss, N.
Z.; Ludányi, K.; Drahos, L.; Keglevich, G. Synth. Commun. 2009, 39,
2392
13. For selected examples for the activation of P(O)-OH compounds, see: (a)
Park, Y.; Seo, J.; Park, S.; Yoo, E. J.; Lee, P. H. Chem. Eur. J. 2013, 19,
16461; (b) Unoh, Y.; Hashimoto, Y.; Takeda, D.; Hirano, K.; Satoh, T.;
Miura, M. Org. Lett. 2013, 15, 3258; (c) Park, Y.; Jeon, I.; Shin, S.; Min,
J.; Lee, P. H. J. Org. Chem. 2013, 78, 10209; (d) Peng, A.-Y.; Ding, Y.-
X. J. Am. Chem. Soc. 2003, 125, 15006; (e) Ryu, T.; Kim, J.; Park, Y.;
Kim, S.; Lee, P. H. Org. Lett. 2013, 15, 3986; (f) Sakakura, A.;
Katsukawa, M.; Ishihara, K. Angew. Chem. Int. Ed. 2007, 46, 1423; (g)