New and efficient synthesis of 1,3-dienylphosphonates by palladium-catalyzed substitution of propargylic esters to diethyl phosphite

Article abstract of DOI:10.1080/00397911.2012.725795

An efficient route to the synthesis of 1,3-dienylphosphonates (1) has been developed for the first time by the substitution of propargylic esters (2) to the diethyl phosphite (3) nucleophile in the presence of Pd₂ (dba) ₃ · CHCl₃ (2 mol %) and 2,2′- bis(diphenylphosphino)-1,1′-binaphthyl (4 mol%). Both the alkyl and aryl 1,3-dienylphosphonates can be prepared from this transformation. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.

Full text of DOI:10.1080/00397911.2012.725795

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New and Efficient Synthesis of 1,3-
Dienylphosphonates by Palladium-
Catalyzed Substitution of Propargylic
Esters to Diethyl Phosphite
Xiao-Ning Liu a , Wei-Lei Guo a b , Chuan-Jin Hou a & Xiang-Ping Hu b
a School of Light Industry and Chemical Enginerring, Dalian
Polytechnic University , Dalian , China
b Dalian Institute of Chemical Physics, Chinese Academy of
Sciences , Dalian , China
Published online: 26 Jun 2013.
To cite this article: Xiao-Ning Liu , Wei-Lei Guo , Chuan-Jin Hou & Xiang-Ping Hu (2013)
New and Efficient Synthesis of 1,3-Dienylphosphonates by Palladium-Catalyzed Substitution
of Propargylic Esters to Diethyl Phosphite, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:19, 2622-2626, DOI:
10.1080/00397911.2012.725795
To link to this article: http://dx.doi.org/10.1080/00397911.2012.725795
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Synthetic Communications1, 43: 2622–2626, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.725795
NEW AND EFFICIENT SYNTHESIS OF
1,3-DIENYLPHOSPHONATES BY
PALLADIUM-CATALYZED SUBSTITUTION OF
PROPARGYLIC ESTERS TO DIETHYL PHOSPHITE
Xiao-Ning Liu,1 Wei-Lei Guo,1,2 Chuan-Jin Hou,1 and
Xiang-Ping Hu2
1School of Light Industry and Chemical Enginerring, Dalian Polytechnic
University, Dalian, China
2Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
Dalian, China
GRAPHICAL ABSTRACT
Abstract An efficient route to the synthesis of 1,3-dienylphosphonates (1) has been developed
for the first time by the substitution of propargylic esters (2) to the diethyl phosphite (3)
nucleophile in the presence of Pd2(dba)3 ꢀ CHCl3 (2 mol %) and 2,20-bis(diphenyl
phosphino)-1,10-binaphthyl (4 mol%). Both the alkyl and aryl 1,3-dienylphosphonates can
be prepared from this transformation.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords 1,3-Dienylphosphonates; diethyl phosphite; Pd-catalyzed; propargylic
substitution
INTRODUCTION
Phosphonates are important natural and synthetic compounds because of their
biological and medical properties.[1] A special class of phosphonates containing con-
jugate ene moiety, 1,3-dienylphosphonates have received much consideration in
recent decades because of their widespread usefulness in organic synthesis and have
been employed in [2 þ 2] cycloaddition,[2] [4 þ 2] cycloaddition,[3] 1,3-dipolar
cycloaddition,[4] 1,4-addition,[5] and enolate alkylation[6] reactions. They have also
Received April 5, 2012.
Address correspondence to Chuan-Jin Hou, School of Light Industry and Chemical Engineering,
Dalian Polytechnic UniversityDalian, 116034, China. E-mail: houcj@dlpu.edu.cn; Xiang-Ping Hu, Dalian
Institute of Chemical Physics, China Academy of Sciences, Dalian 116023, China. E-mail: xiangping@
dicp.ac.cn
2622

SYNTHESIS OF 1,3-DIENYLPHOSPHONATES
2623
Scheme 1. Pd-catalyzed synthesis of 1,3-dienylphosphonates and allenylphosphonates.
been reported in the synthesis of biologically active products such as AP6 analogs[7]
and Fusarium toxin equisetin.[8] However, methods for the synthesis of 1,3-dienyl-
phosphonates are still rare. The need for the development of an efficient method
for the synthesis of 1,3-dienylphosphonates is, therefore, of great interest.
There are several reported methods for the synthesis of 1,3-dienylphosphonates
including the reaction of unsaturated phosphonates with N-tolsylsufonylimines,[9]
the titanium-mediated Knoevenagel condensation of conjugated aldehydes with
diethyl malonate,[2] the Pd-catalyzed coupling reaction of unsaturated phosphonates
with alkenes,[10] the Ni-catalyzed addition of P(O)-H bonds to propargyl alcohols,[11]
and the alkyne insertion into zirocoacyclopropenes.[12] Notably, Ma et al.[13] and
Azab et al.[14] reported the Pd-catalyzed isomerization of alkynylphosphonate to
1,3-dienylphosphonates [Scheme 1, Eq. (1)]. However, the catalyst was less efficient
and high catalyst loading was required (10–20 mol%). Recently, Kalek et al.[15]
reported the Pd-catalyzed propargylic substitution with phosphorus nucleophiles
to the synthesis of allenylphosphonates [Scheme 1, Eq. (2)]. Inspired by the isomer-
ization of alkynylphosphonates to allenylphosphonates,[16] we report the first
synthesis of 1,3-dienylphosphonates (1) by direct Pd-catalyzed propargylic substi-
tution of propargylic esters (2) to diethyl phosphite (3) nucleophile (Scheme 2). Both
the alkyl and aryl 1,3-dienylphosphonates can be prepared from this transformation.
To the best of our knowledge, it is the first time that the 1,3-dienylphosphonates
were synthesized by direct propargylic substitution.
RESULTS AND DISCUSSION
First, the propargylic ester substrates were synthesized from related commer-
cially available aldehydes (Scheme 3). Thus the aldehydes (4) were allowed to react
with ethynyl magnesium chloride (5) in diethyl ether to give the corresponding
propargylic alcohol (6), which can be used without further purification. Esterifi-
cation of the resultant propargylic alcohol (6) with acetic anhydride in the presence
Scheme 2. Pd-catalyzed propargylic substitution to the synthesis of 1,3-dienylphosphonates.

2624
X.-N. LIU ET AL.
Scheme 3. Synthesis of propargylic ester substrates.
Table 1. Pd-catalyzed propargylic substitution of a variety of propargylic
esters
Entry
Substrate
Product
Isolated yield (%)
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
1a
1b
1c
1d
1e
1f
87
74
75
72
82
71
of triethylamine (TEA) and 4-dimethylaminopyridine (DMAP) gave the required
propargylic esters 2a–2f.
We then examined the propargylic substitution of hex-1-yn-3-yl acetate (2b)
with diethyl phosphite (3) using palladium catalyst generated in situ from
Pd2(dba)3 ꢀ CHCl3 (2 mol%) and 2,20-bis(diphenylphosphino)-1,10-binaphthyl
(BINAP) (4 mol %) in reflux toluene. Fortunately, the reaction proceed smoothly
and the related diethyl (1E,3E)-hexa-1,3-dienylphosphonate was isolated in modest
yield (Table 1, entry 2). The stereochemistry of 2b was assigned as E,E configuration
for the double bonds which was determined by NMR compared to reported
data.[12,14] Attempts to improve the reactivity by variation of solvents and ligands
seemed unsuccessful. Either no reaction occurred or a complicated reaction mixture
was obtained when other solvents or ligands used.
Encouraged by the promising result obtained in the reaction of 2b, the scope of
propargylic substitution was then investigated under the present catalytic system,
and the results are summarized in Table 1. The results suggested that a wide variety
of propargylic esters react with diethyl phosphite (3) to give the corresponding
1,3-dienylphosphonate 1a–1f in modest to good yield. Short- and long-alkyl chain
substrates proceeded in satisfactory yield (entries 1–4). Good results were also
obtained when aryl-substituted propargylic esters were tested (entries 5 and 6).
The fluoridated substrate was also tolerant (entry 6). The results indicated the
present catalytic system was efficient for the BINAP=palladium-catalyzed
propargylic substitution in the synthesis of 1,3-dienylphosphonates.
CONCLUSION
In conclusion, we have developed a new and efficient route to the synthesis of
1,3-dienylphosphonates. The propargylic esters reacted with diethyl phosphite to

SYNTHESIS OF 1,3-DIENYLPHOSPHONATES
2625
give the corresponding 1,3-dienylphosphonates in the presence of Pd2(dba)3 ꢀ CHCl3
(2 mol %) and BINAP (4 mol%). Both of the alkyl and aryl 1,3-dienylphosphonates
can be prepared in modest to good yields. To the best of our knowledge, it is the
first time the 1,3-dienylphosphonates were synthesized by the direct propargylic
substitution. Further study of the reaction mechanism is in progress.
EXPERIMENTAL
General Procedure for Synthesis of Propargylic Ester
Substrates 2a–2f
To a stirred solution of aldehyde (30 mmol) in dry THF (60 mL) under N2
atmosphere was added ethynylmagnesium chloride (50 mL, 0.6 M in THF) dropwise
at room temeperature. The mixture was stirred for 2 h and then quenched with satu-
rated aqueous ammonium chloride solution. The aqueous layer was extracted with
Et2O, washed with brine, dried over Na2SO4, and concentrated to give the crude
propargylic alcohol, which was used directly.
The crude propargylic alcohol was dissolved in dry CH2Cl2 (40 mL), and Et3N
(30 mmol) and DMAP (3 mmol) were added. Then Ac2O (30 mmol) was added drop-
wise, and the mixture was stirred for 2 h. The reaction was quenched with water, and
the aqueous layer was extracted with Et2O. The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated. The product was purified
by chromatography on silica gel.
1
Compound 2b: H NMR (400 MHz, CDCl3): d 0.95 (t, J ¼ 7.6 Hz, 3H), 1.45–
1.51 (m, 2H), 1.73–1.79 (m, 2H), 2.09 (s, 3H), 2.45 (s, 1H), 5.36 (t, J ¼ 6.8 Hz, 1H).
General Procedure for Synthesis of 1,3-Dienylphosphonates 1a–1f
Pd2(dba)3 ꢀ CHCl3 (10.4 mg, 0.010 mmol) and BINAP (12.4 mg, 0.020 mmol)
were added into an oven-dried Schlenk tube. Then, dry toluene (2 mL) added, and
the mixture was stirred for 30 min at room temperature. Propargylic ester substrates
2 (0.5 mmol), diethyl phosphine (62.1 mg, 0.55 mmol), and Et3N (80 mL, 0.5 mmol)
were added successively. The reaction was refluxed for 12 h and cooled to room tem-
perature. The solvent was removed under reduced pressure, and the product was
purified by chromatography on silica gel.
Compound 1b: 1H NMR (400 MHz, CDCl3): d 1.04 (t, J ¼ 7.6 Hz, 3H), 1.33 (t,
3
J ¼ 7.2 Hz, 6H), 2.15–2.22 (m, 2H), 4.04–4.11 (m, 4H), 5.57 (dd, JH,H ¼ 17.2 Hz,
2JH,P ¼ 19.2 Hz, 1H), 6.08–6.18 (m, 2H), 7.08 (ddd, 3JH,H ¼ 16.8 Hz, 3JH,P ¼ 20.8 Hz,
1H); 31P NMR (162 MHz, CDCl3): d 19.91.
Complete experimental and spectral details are available online in the
Supplemental Material.
ACKNOWLEDGMENTS
The authors are grateful for the financial support from the Scientific Research
Project of the Department of Education of Liaoning Province of China (L2010048)
and the Planned Science and Technology Project of Dalian (2011J21DW010).

2626
X.-N. LIU ET AL.
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