Very simple one-step synthesis of vinylphosphonates and enamine phosphonates by direct addition of organolithium reagents to 1-alkynylphosphonates

Article abstract of DOI:10.1080/10426507.2012.655814

Direct addition of organolithium to 1-alkynylphosphonates (1) afforded vinylphosphonates and enamine phosphonates (2) in good to excellent yields. The reaction was carried out in dry THF at low temperature and proved to be completely stereoselective (syn

Full text of DOI:10.1080/10426507.2012.655814

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Phosphorus, Sulfur, and Silicon and the
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Very Simple One-Step Synthesis of
Vinylphosphonates and Enamine
Phosphonates by Direct Addition
of Organolithium Reagents to 1-
Alkynylphosphonates
Abdullatif Azab a , Dorit Moradov a , Abed Al-Aziz Al-Quntar a b
Morris Srebnik a
&
a Institute of Drug Research, School of Pharmacy, Hebrew University
of Jerusalem, Jerusalem, 91120, Israel
b Department of Material Engineering, Faculty of Engineering, Al-
Quds University, Jerusalem, Palestinian Authority
Accepted author version posted online: 09 Mar 2012.Published
online: 07 Jun 2012.
To cite this article: Abdullatif Azab , Dorit Moradov , Abed Al-Aziz Al-Quntar & Morris Srebnik (2012)
Very Simple One-Step Synthesis of Vinylphosphonates and Enamine Phosphonates by Direct Addition
of Organolithium Reagents to 1-Alkynylphosphonates, Phosphorus, Sulfur, and Silicon and the Related
Elements, 187:8, 937-943, DOI: 10.1080/10426507.2012.655814
To link to this article: http://dx.doi.org/10.1080/10426507.2012.655814
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Phosphorus, Sulfur, and Silicon, 187:937–943, 2012
Copyright ꢀC Hebrew University
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.655814
VERY SIMPLE ONE-STEP SYNTHESIS OF
VINYLPHOSPHONATES AND ENAMINE PHOSPHONATES
BY DIRECT ADDITION OF ORGANOLITHIUM REAGENTS
TO 1-ALKYNYLPHOSPHONATES
Abdullatif Azab,1 Dorit Moradov,1 Abed Al-Aziz Al-Quntar,1,2
and Morris Srebnik1
1Institute of Drug Research, School of Pharmacy, Hebrew University of Jerusalem,
Jerusalem 91120, Israel
2Department of Material Engineering, Faculty of Engineering, Al-Quds University,
Jerusalem, Palestinian Authority
GRAPHICAL ABSTRACT
Abstract Direct addition of organolithium to 1-alkynylphosphonates (1) afforded vinylphos-
phonates and enamine phosphonates (2) in good to excellent yields. The reaction was carried
out in dry THF at low temperature and proved to be completely stereoselective (syn addition).
Alkyl, aryl, and haloalkyl groups were attached to the alkynyl entity, so the resulting vinylphos-
phonates contained various functional groups. The stereochemistry of the products as well as
mechanism of the reaction were determined based on 1H and 13C NMR. The synthesis of enam-
ine phosphonates in the absence of complicated, highly expensive organometallic catalysis has
not been previously reported.
Keywords 1-Alkynylphosphonates; vinylphosphonates; direct addition; organolithium
reagents; stereoselectivity; enamines
INTRODUCTION
Vinylphosphonates have been prepared by various synthetic methods and have a wide
range of application. They can be flame-retardants,1 intermediates for drug synthesis,2 and
This article is dedicated to the memory of Prof. Morris Srebnik, who passed away on December 2, 2011.
Received 10 November 2011; accepted 24 December 2011.
We thank the School of Pharmacy of the Hebrew University and the Horowitz Fund for supporting this
research.
Address correspondence to Abdullatif Azab, Institute of Drug Research, School of Pharmacy, Hebrew
University of Jerusalem, Jerusalem, 91120, Israel. E-mail: abedazab@gmail.com
937

938
A. AZAB ET AL.
agrochemicals.3 When a nitrogen atom is present in these compounds, especially if attached
to the vinyl group as an enamine, chances are higher for biological activity. Among the
numerous studies that prove the last statement, these compounds were found to possess
antibiotic4 and herbicidal,5 antifungal activities6 and act as enzyme inhibitors.7
Enamine phosphonates can serve as successful starting materials for synthesis of
biologically active compounds.8 Enamines in general are widely investigated recently for
pharmaceutically possible activities, and as early as in 1975, Coscia et al.9 reported CNS
depression activity of enamines, in chlorpromazine-like fashion.9 Enamine derivatives of
lapachol were found to be active against Aedes aegypti, Artemia salino, and human breast
tumor cells.10 Antidyslipidemic and antioxidative activities were studied by Sashidhara
et al. for the enamine derivatives of 8-hydroxyquinoline.11 On the theoretical level, Xue
et al.12 published a study on structure–activity relationship of enamines as potential an-
tibacterial agents.
Several methods of preparing vinylphosphonates were reported in the literature but
the synthesis of enamine phosphonates by direct addition of organolithium reagents was
not reported. Cristau et al.13 added organolithium reagents to 1-alkynylphosphonates using
Cu(I) salts as catalysts. They reported that the reactions temperature ranged between −30
◦
◦C and −70 C, in Et2O as the solvent in high stereoselectivity. Contrary to the previ-
ous report, Wei and Taylor14 worked with the same solvent at room temperature without
organometallic catalysis while adding alkyllithium reagents to enyne compounds. In most
cases, stereoselectivity of the reactions was poor and no vinyl products were obtained. Ma-
jor products were obtained from the addition of alkyllithium to the carbon–carbon double
bond, while the alkyne entity isomerized to allene.
When Gil and Oh15 performed the reaction at −78 ◦C in THF and CuI as a catalyst,
they succeeded in adding alkyllithium reagents to 1-alkynylphosphonates in relatively high
yields but with no stereoselectivity.
Three studies of vinylphosphonates synthesis were done in our group prior to this
work. Baum et al.16 synthesized these compounds with very high stereo◦selectivity using
zirconocene chloride as organometallic catalyst, and using THF in −78 C. A year later,
Ben-Valid et al.17 reported the synthesis of vinylphosphonates and vinylboronates using
the previous method. Unlike the works of Baum and Ben-Valid, as well as cited references
(13–17), Al-Quntar et al.18 synthesized vinylphosphonates with high stereoselectivity, in
a two-steps reaction, using titanium tetraisopropoxide as an organometallic catalyst, and
their products contained nitrogen, even though it is not attached to the vinyl group, hence,
not enamines.
Finally, enamines are produced by organometallic catalyzed hydroamination of non-
terminal alkynes, and so did lately Hesp and Stradiotto19 in a very complex method that
proved to be stereoselective but involved multi-step reactions with very expensive catal-
ysis. Summarized comparison between reported methods of synthesis on non-terminal
vinylphosphonates and/or enamines is shown in Table 1.
RESULTS AND DISCUSSION
We added organolithium reagents to 1-alkynylphosphonates to obtain vinylphos-
phonates and enamine phosphonates in high yields and complete stereoselectivity. No
organometallic catalysis was used in our work. In case of n-butyllithium and s-butyllithium,

DIRECT ADDITION OF ORGANOLITHIUM REAGENTS TO 1-ALKYNYLPHOSPHONATES 939
Table 1 Comparison between our method and other reported methods for synthesis of vinylphosphonates and/or
enamines
Organometallic
catalysis
Nitrogen in
products
Method
Steps
Stereoselectivity
Cristau et al.
Wei & Taylor
Gil & Oh
Al-Quntar et al.
Baum et al.
Ben-Valid et al.
Hesp & Stradiotto
Azab et al.
1
1
1
2
2
2
1
1
All reactions
None
No
No
No
Yes∗
No
No
Yes
Yes
Yes
No
No
Yes
Mostly
Yes
Yes
Yes
All reactions
All reactions
All reactions
All reactions
All reactions
None
∗Not enamines.
these were used as commercially available solutions. For lithium amides, we added n-
butyllithium to the appropriate amine in THF at −78 ◦C, then allowing the temperature to
◦
◦
rise to −30 C for 15–20 min. At this point, we cooled again to −78 C and added the
1-alkynylphosphonate. In both cases, alkyllithium and lithium amides, the reaction mixture
was maintained at −78 ◦C for 4 h and then allowed to rise to room temperature. We think
that keeping the reaction mixture at low temperature for several hours determined the stere-
oselectivity of the reactions since the kinetically preferred product was completely formed
without any competition.
The general scope of the reactions is shown in Scheme 1.
Scheme 1
The suggested mechanism of the reaction is quite simple: nucleophillic addition of R2
to C2 (where C1 is the carbon attached to the phosphonate group) gives a vinyl carbanion
on C1. When reactions were worked up, a vinylic hydrogen was attached to C1 and could
be easily detected by 1H NMR due to its very high 2JPH (10.5–25.5 Hz) and relatively high
chemical shifts (5.33–7.51 ppm). When working up the reaction mixture with DCl/D2O
instead of aqueous HCl, deuterium atom binds to C1 and the typical doublet of hydrogen
attached to C1 disappeared. Moreover, the 13C-NMR of this product (2d, see Table 2)
showed a clear triplet due to the C–D coupling, which was split to a broad doublet by the
phosphorus atom.
Products were purified on a silica gel column in high to excellent yields as shown in
Table 2.
The stereochemistry of 2a–2i was determined by 13C NMR and found consistent with
reported works.13 For instance, in case of entry 2f, C3 cis to phosphorus, that is, the allylic
CH2 of n-butyl group appeared as a doublet with 3JPC = 7.4 Hz and δ = 33.7 ppm. At the

940
A. AZAB ET AL.
Table 2 Products and yields of the addition of organolithium reagents to 1-alkynylphosphonates
Entry
R1
Phenyl
R2
Isolated yield (%)
2a1
2b
2c
n-Butyl
92
86
86
79
61
80
85
76
69
Phenyl
sec-Butyl
n-Butyl
n-Butyl
3-Chloropropyl
n-Butyl
Phenyl
n-Butyl
n-Butyl
n-Butyl
2d2
2e
2f
sec-Butyl
2g
2h
2i
Diisopropylamino
Dipropylamino
Pyrazolyl
Phenyl
Phenyl
1Previously reported compound.
2With deuterium on C1.
same time, C3 trans to phosphorus, that is, the allylic CH of s-butyl group also appear as a
doublet but with 3JPC = 20.7 Hz and δ = 42.5 ppm. For product 2c, it is even more obvious:
CH2 cis to phosphorus has 3JPC = 6.9 Hz and δ = 33.4 ppm while CH2 trans to phosphorus
3
has JPC = 22.5 Hz and δ = 37.7 ppm. Product 2b shows very clear E-stereochemistry
of the added n-butyl group to the phosphorus atom: while C1 of the aromatic ring shows
3JPC = 3.1 Hz and δ = 136.0 ppm, the allylic CH2 of n-butyl group shows 3JPC = 10.1 Hz
and δ = 35.3 ppm.
Finally, when we tried to use this method for the synthesis of enamines where an
aromatic ring is attached to nitrogen atom (N-Methylaniline, for example), the presence of
products in reaction mixtures was indicated by GCMS and 31P NMR, but after work up
of the reaction mixtures and purified by silica gel, the products hydrolyzed to give β-keto
phosphonates (∼80%).
CONCLUSIONS
In this paper, we reported the direct one-step addition of organolithium reagents to
1-alkynylphosphonates that yielded vinylphosphonates and enamine phosphonates in good
to excellent yields. Our work has three advantages over previous methods: stereoselectivity
is completely E isomers, which we expect to be kinetically preferred; addition is direct
with no organometallic catalysis or multi-step reactions; and, we obtained a very simple
method for synthesis of enamine phosphonates. Stereochemistry was in high agreement
with reported works.
EXPERIMENTAL
Typical synthesis of 2a–2f: In a 10 mL vial, 1 mmol of 1-alkynylphosphonate
(0.238 g of diethyl-2-phenylethynyl phosphonate in case of entry 2a, for example) was

DIRECT ADDITION OF ORGANOLITHIUM REAGENTS TO 1-ALKYNYLPHOSPHONATES 941
dissolved in dry THF (5 mL). The vial was capped with a rubber septum and the solution
was magnetically stirred under nitrogen and cooled to −78 ◦C. Then, 1 mmol of RLi (0.63
mL of 1.6 M solution of n-BuLi, for example) was added dropwise. The reaction mixture
was kept in −78 ◦C for 4 h and allowed to warm up to room temperature for 5 min. Then, 1
M aqueous HCl (2 mL or 0.2 mL of DCl/D2O for product 2d) was added. Reaction mixture
was transferred to 100 mL separatory funnel and water (25 mL) and dichloromethane
(25 mL) was added. After phase separation, the organic layer was concentrated in vacuo
and the products were purified by silica gel column chromatography with 5%–50% ethyl
acetate/petroleum ether.
Typical synthesis of 2g–2i: In a 10 mL vial, 1 mmol of amine (0.101 g of freshly
distilled over calcium hydride diisopropylamine, in case of 2g, for example) was added.
The vial◦was capped with rubber septum, magnetically stirred under nitrogen, and cooled
to −78 C. Then, 1 mmol of n-BuLi was added dropwise and the reaction mixture was
allowed to warm up to −30 ◦C for 15–20 min. Then, it was cooled again to −78 ◦C and 1
mmol of 1-alkynylphosphonate was added. The procedure continued as for 2a except that
product purification was by silica gel column chromatography performed with 0.1%–3.5%
MeOH/CH2Cl2 as mobile phase.
Products were analyzed by GCMS, elemental analysis, and 31P-, 13C-, and 1H NMR.
The Supplemental Materials contain selected 31P, 1H, and 13C NMR spectra for 2d, 2f, and
2g (Figures S 1–S 9; posted online only).
For proton NMR, about 10 mg of the tested compound was dissolved in CDCl3
(0.8 mL) and for 13C- and 31P NMR, 50–60 mg of the tested compound was dissolved in
the same volume of solvent.
1
(Z)-Diethyl-2-phenylhex-1-enylphosphonate (2a). H NMR (500 MHz, CDCl3,
Me4Si): δ 0.93 (3H, CH3CH2CH2, t, JHH = 7.0 Hz), 1.38 (6H, CH3–CH2O, t, JHH = 7.0
Hz), 1.61 (4H, CH3CH2CH2CH2, m), 2.48 (2H, CH3CH2CH2CH2, t, JHH = 8.0 Hz), 4.17
(4H, OCH2, q, JHH = 7.5 Hz), 7.34–7.42 (5H, C6H5, overlap), 7.48 (1H, CH–P, d, 2JPH
=
25.5 Hz); 31P NMR (202.4 MHz, CDCl3, Me4Si): δ 19.81; 13C NMR (125.7 MHz, CDCl3,
Me4Si): δ 13.7, 16.3 (d, 3JPC = 6.5 Hz), 22.8, 27.9 (d, 3JPC = 9.3 Hz), 30.9, 61.7 (d, 2JPC
=
5.5 Hz), 128.3, 128.4, 129.0, 131.3 (d, 1JPC = 174.1 Hz), 135.7 (d, 3JPC = 23.4 Hz), 142.8
2
(d, JPC = 11.9 Hz); MS (EI): m/z (%) 296 (12), 197 (11), 158 (18), 129 (33), 128 (15),
117 (25), 116 (16), 114 (57), 91 (20), 32 (35), 28 (100), 18 (84), 17 (20); Anal. Calcd. For
C16H25O3P: C, 64.85; H, 8.50; P, 10.45. Found: C, 64.78; H, 8.46; P, 10.40.
(Z)-Diethyl-3-methyl-2-phenylpent-1-enylphosphonate (2b). 1H NMR (500 MHz,
CDCl3, Me4Si): δ 0.81 (3H, CHCH2CH3, t, JHH = 7.5 Hz), 1.21 (3H, CH3–CH, d, JHH
=
7.0 Hz), 1.36 (6H, CH3–CH2O, t, JHH = 7.5 Hz), 1.53 (1H, CH3–CH2CH, dq, JHH = 7.5
Hz), 1.66 (1H, CH3–CH2CH, dt, JHH = 7.0 Hz), 2.88 (1H, CH3–CH, tq, JHH = 7.0 Hz),
4.15 (4H, OCH2, q, JHH = 4.0 Hz), 7.23–7.35 (5H, C6H5, m), 7.51 (1H, CH–P, d, 2JPH
=
24.5 Hz); 31P NMR (202.4 MHz, CDCl3, Me4Si): δ 22.84; 13C NMR (125.7 MHz, CDCl3,
3
3
Me4Si): δ 12.1, 16.1 (d, JPC = 6.4 Hz), 19.3, 28.1, 35.3 (d, JPC = 10.1 Hz), 61.2 (d,
2JPC = 9.0 Hz), 127.5, 128.0, 128.2, 136.0 (d, 3JPC = 3.1 Hz), 136.5 (d, 1JPC = 193.8 Hz),
143.0 (d, 2JPC = 11.6 Hz); MS (EI): m/z (%) 296 (27), 295 (16), 281 (15), 159 (47), 158
(43), 143 (48), 131 (24), 130 (18), 129 (100), 128 (46), 117 (28), 115 (27), 91 (19); Anal.
Calcd. For C16H25O3P: C, 64.85; H, 8.50; P, 10.45. Found: C, 64.77; H, 8.46; P, 10.40.
Diethyl-2-butylhex-1-enylphosphonate (2c). 1H NMR (500 MHz, CDCl3, Me4Si):
δ 0.93 (6H, CH3CH2CH2, t, JHH = 7.0 Hz), 1.35 (6H, CH3–CH2O, t, JHH = 7.0 Hz),
1.38–1.48 (8H, CH3CH2CH2CH2, m), 2.17 (2H, CH2C=CH, cis to P, t, JHH = 8.0 Hz),
2.51 (2H, CH2C=CH, trans to P, t, JHH = 7.5 Hz), 4.07 (4H, OCH2, q, JHH = 7.5 Hz), 5.36

942
A. AZAB ET AL.
(1H, CH–P, d, 2JPH = 18.5 Hz); 31P NMR (202.4 MHz, CDCl3, Me4Si): δ 19.87; 13C NMR
(125.7 MHz, CDCl3, Me4Si): δ 13.7 (cis to P), 13.8 (trans to P), 16.1 (d, 3JPC = 6.9 Hz),
22.2 (cis to P), 22.7 (trans to P), 29.5 (cis to P), 30.5 (trans to P), 33.4 (d, 3JPC = 6.9 Hz,
3
2
1
cis to P), 37.7 (d, JPC = 22.5 Hz, trans to P), 61.0 (d, JPC = 5.5 Hz), 110.5 (d, JPC
=
189.7 Hz), 167.8 (d, 2JPC = 6.4 Hz); MS (EI): m/z (%) 276 (12), 247 (61), 192 (27), 191
(27), 151 (31), 137 (51), 81 (7), 41 (16), 32 (30), 28 (100), 18 (70), 17 (17); Anal. Calcd.
For C14H29O3P: C, 60.85; H, 10.58; P, 11.21. Found: C, 60.79; H, 10.51; P, 11.17.
Diethyl-2-butylhex-1-enylphosphonate (C1-D) (2d). 1H NMR (500 MHz, CDCl3,
Me4Si): δ 0.93 (6H, CH3CH2CH2, t, JHH = 7.0 Hz), 1.35 (6H, CH3–CH2O, t, JHH = 7.0
Hz), 1.38–1.48 (8H, CH3CH2CH2CH2, m), 2.18 (2H, CH2C=CH, cis to P, t, JHH = 8.0
Hz), 2.51 (2H, CH2C=CH, trans to P, t, JHH = 7.5 Hz), 4.07 (4H, OCH2, q, JHH = 7.5 Hz);
31P NMR (202.4 MHz, CDCl3, Me4Si): δ 19.89; 13C NMR (125.7 MHz, CDCl3, Me4Si): δ
13.6 (cis to P), 13.7 (trans to P), 16.1 (d, 3JPC = 6.4 Hz), 22.1 (cis to P), 22.6 (trans to P),
29.4 (cis to P), 30.5 (trans to P), 33.2 (d, 3JPC = 7.4 Hz, cis to P), 37.5 (d, 3JPC = 22.5 Hz,
2
1
1
trans to P), 60.8 (d, JPC = 6.0 Hz), 110.5 (d, JPC = 189.7 Hz), 110.2 (dt, JDC = 23.8
2
Hz), 167.4 (d, JPC = 6.4 Hz); MS (EI): m/z (%) 277 (28), 248 (78), 235 (32), 234 (26),
220 (27), 193 (73), 192 (100), 153 (26), 138 (49), 111 (37), 97 (33), 96 (37), 82 (49); Anal.
Calcd. For C14H28DO3P: C, 60.63; H, 10.90; P, 11.17. Found: C, 60.58; H, 10.49; P, 11.12.
(Z)-Diethyl-2-(3-chloropropyl)hex-1-enylphosphonate (2e). 1H NMR (500 MHz,
CDCl3, Me4Si): 0.94 (3H, CH3CH2, t, JHH = 7.5 Hz), 1.33 (6H, CH3–CH2O, t, JHH = 6.0
Hz), 1.39–1.50 (4H, CH3CH2CH2CH2, m), 1.98 (2H, ClCH2CH2, t, JHH = 7.5 Hz), 2.19
(2H, ClCH2CH2CH2, t, JHH = 7.5 Hz), 2.51 (2H, CH3CH2CH2CH2, t, JHH = 8.0 Hz), 3.59
(2H, ClCH2, t, JHH = 7.0 Hz), 4.10 (4H, OCH2, q, JHH = 7.0 Hz), 5.42 (1H, CH–P, d,
2JPH = 17.5 Hz); 31P NMR (202.4 MHz, CDCl3, Me4Si): δ 19.10; 13C NMR (125.7 MHz,
CDCl3, Me4Si): δ 13.6, 16.1 (d, 3JPC = 6.4 Hz), 22.0, 29.4, 31.0 (d, 3JPC = 6.9 Hz), 31.4,
37.8 (d, 3JPC = 22.1 Hz), 44.4, 61.0 (d, 2JPC = 5.5 Hz), 111.9 (d, 1JPC = 188.7 Hz), 165.4
2
(d, JPC = 6.0 Hz); MS (EI): m/z (%) 296 (12), 247 (47), 219 (55), 218 (56), 192 (92),
191 (74), 138 (60), 121 (44), 93 (59), 81 (100), 80 (48), 79 (80), 65 (52); Anal. Calcd. For
C13H26ClO3P: C, 52.61; H, 8.83; Cl, 11.95; P, 10.44. Found: C, 52.56; H, 8.80; Cl, 11.89;
P, 10.40.
(E)-Diethyl-2-sec-butylhex-1-enylphosphonate (2f). 1H NMR (500 MHz, CDCl3,
Me4Si): δ 0.87 (3H, CH3CH2CH2, t, JHH = 7.5 Hz), 0.94 (3H, CH3–CH2CH, t, JHH = 7.5
Hz), 1.05 (3H, CH3CH, d, JHH = 6.5 Hz), 1.32–1.40 (12H, CH3–CH2O, CH3CH2CH2,
CH3–CH2CH, overlap), 2.06 (2H, CH2C=CH, t, JHH = 7.0 Hz), 2.24 (1H, CH3CH, m),
4.07 (4H, OCH2, q, JHH = 7.0 Hz), 5.33 (1H, CH–P, d, 2JPH = 18.0 Hz); 31P NMR (202.4
MHz, CDCl3, Me4Si): δ 20.83; 13C NMR (125.7 MHz, CDCl3, Me4Si): δ 11.6, 13.7, 16.2
3
3
3
(d, JPC = 6.5 Hz), 19.7, 22.9, 28.6, 31.0, 33.7 (d, JPC = 7.4 Hz), 42.5 (d, JPC = 20.7
2
1
2
Hz), 60.9 (d, JPC = 5.5 Hz), 108.4 (d, JPC = 190.6 Hz), 172.7 (d, JPC = 5.5 Hz); MS
(EI): m/z (%) 276 (37), 247 (100), 233 (23), 219 (43), 191 (72), 152 (53), 138 (37), 111
(38), 109 (47), 83 (25), 82 (24), 81 (60), 65 (25); Anal. Calcd. For C14H29O3P: C, 60.85;
H, 10.58; P, 11.21. Found: C, 60.78; H, 10.49; P, 11.11.
(E)-Diethyl-2-(diisopropylamino)-2-phenylvinylphosphonate (2g). 1H NMR (300
MHz, CDCl3, Me4Si): δ 1.04 (12H, CHCH3, d, JHH = 6.6 Hz), 1.21 (6H, CH3–CH2O, t,
JHH = 7.5 Hz), 3.46 (2H, CH3–CH, q, JHH = 6.6 Hz), 3.97 (4H, OCH2, q, JHH = 7.05
Hz), 7.16 (1H, CH–P, d, 2JPH = 18.9 Hz), 7.24–7.27 (5H, C6H5, m); 31P NMR (125 MHz,
CDCl3, Me4Si): δ 27.98; 13C NMR (75.5 MHz, CDCl3, Me4Si): δ 16.1 (d, 3JPC = 7.2 Hz),
21.5, 46.6, 60.2 (d, 2JPC = 5.1 Hz), 89.2 (d, 1JPC = 200.6 Hz), 126.2, 128.1, 130.7, 137.2
(d, 3JPC = 6.6 Hz), 143.4 (d, 2JPC = 23.8 Hz); MS (EI): m/z (%) 339 (14), 324 (28), 296

DIRECT ADDITION OF ORGANOLITHIUM REAGENTS TO 1-ALKYNYLPHOSPHONATES 943
(100), 202 (62), 160 (22), 158 (27), 144 (23), 117 (26), 103 (18), 10 (11); Anal. Calcd. For
C18H30NO3P: C, 63.70; H, 8.91; N, 4.13; P, 9.13. Found: C, 63.58; H, 8.87; N, 4.07; P,
9.07.
1
(E)-Diethyl-2-(dipropylamino)-2-phenylvinylphosphonate (2h). H NMR (500
MHz, CDCl3, Me4Si): δ 1.02 (6H, CH2CH2CH3, t, JHH = 7.5 Hz), 1.24 (6H, CH3–CH2O,
t, JHH = 7.0 Hz), 1.40 (4H, CH3–CH2CH2, m, JHH = 7.5 Hz), 2.85 (4H, CH3–CH2CH2,
2
t, JHH = 7.5 Hz), 3.99 (4H, OCH2, q, JHH = 4.5 Hz), 7.09 (1H, CH–P, d, JPH = 18.0
Hz), 7.24–7.28 (5H, C6H5, m); 31P NMR (202.4 MHz, CDCl3, Me4Si): δ 27.93; 13C NMR
(125.7 MHz, CDCl3, Me4Si): δ 10.5, 16.1 (d, 3JPC = 6.9 Hz), 21.3, 53.0, 60.7 (d, 2JPC
=
3
5.2 Hz), 89.2 (d, 1JPC = 199.4 Hz), 126.2, 127.5, 131.4, 135.8 (d, JPC = 6.5 Hz), 148.6
(d, 2JPC = 23.5 Hz); MS (EI): m/z (%) 339 (25), 310 (45), 296 (33), 228 (36), 202 (100),
172 (53), 160 (23), 130 (46), 118 (20), 112 (99), 103 (24); Anal. Calcd. For C18H30NO3P:
C, 63.70; H, 8.91; N, 4.13; P, 9.13. Found: C, 63.57; H, 8.87; N, 4.09; P, 9.07.
1
(E)-Diethyl-2-phenyl-2-(1H-pyrazol-1-yl)vinylphosphonate (2i). H NMR (300
MHz, CDCl3, Me4Si): δ 1.17 (6H, CH3–CH2O, t, JHH = 6.9 Hz), 3.89 (4H, OCH2, q,
JHH = 7.2 Hz), 6.31 (1H, N=CH–CH=CH, dd, JHH = 2.0 Hz), 6.57 (1H, CH–P, d, 2JPH
=
10.5 Hz), 7.21–7.54 (7H, C6H5, N=CH–CH=CH, overlap); 31P NMR (125 MHz, CDCl3,
3
Me4Si): δ 17.62; 13C NMR (75.5 MHz, CDCl3, Me4Si): δ 16.0 (d, JPC = 7.2 Hz), 61.5
(d, 2JPC = 10.1 Hz), 102.7 (d, 1JPC = 203.2 Hz), 107.9, 128.2, 128.5, 128.6, 128.8, 130.0,
130.1 (d, 3JPC = 13.1 Hz), 142.5 (d, 2JPC = 23.5 Hz); MS (EI): m/z (%) 306 (12), 261 (14),
233 (26), 170 (35), 169 (100), 157 (63), 143 (28), 131 (21), 103 (27), 102 (65), 81 (26), 28
(46), 18 (62); Anal. Calcd. For C15H19N2O3P: C, 58.82; H, 6.25; N, 9.15; P, 10.11. Found:
C, 58.77; H, 6.20; N, 9.11; P, 10.09.
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