Hydrophosphonylation of activated alkenes and alkynes via fluoride ion activation in ionic liquid medium

Article abstract of DOI:10.1016/j.tet.2009.06.096

A simple transition metal-free hydro/hydrothiophosphonylation of Baylis-Hillman adducts, substituted allyl bromides, allenylphosphonates and alkynes, promoted by fluoride ion in ionic liquid, is described. Clear-cut evidence for fluoride activation of the

Full text of DOI:10.1016/j.tet.2009.06.096

Tetrahedron 65 (2009) 7603–7610
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Hydrophosphonylation of activated alkenes and alkynes via fluoride ion activation
in ionic liquid medium
*
E. Balaraman, Venu Srinivas, K.C. Kumara Swamy
School of Chemistry, University of Hyderabad, Hyderabad 500046, AP, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 May 2009
Received in revised form 25 June 2009
Accepted 25 June 2009
Available online 1 July 2009
A simple transition metal-free hydro/hydrothiophosphonylation of Baylis–Hillman adducts, substituted
allyl bromides, allenylphosphonates and alkynes, promoted by fluoride ion in ionic liquid, is described.
Clear-cut evidence for fluoride activation of the phosphite via pentacoordinate phosphorus is provided
for the first time. Also, in a comparative reaction, the product obtained was different from that from the
palladium catalyzed one. Structures of key products are proven by X-ray crystallography.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Hydrophosphonylation
Baylis–Hillman adducts
Fluoride activation
Penta-coordinate phosphorus
X-ray structure
Ionic liquid medium
1. Introduction
paper, we disclose that activation of P(X)H (X¼O, S) group via
pentacoordinate phosphorus4 works efficiently for a variety of
Hydrophosphonylation of organic unsaturated systems is an
important reaction that leads to versatile organophosphonates of
great synthetic utility and diverse biological activities.1–3 This re-
action is often promoted by transition metal catalysts, radical ini-
tiators, strong bases or Lewis acid-microwave (MW) assistance.1,2
Many of these routes work well only at high temperature or with
low selectivity and (except while using MW) volatile organic sol-
vents are used as reaction media. Some recent examples wherein
better success has been achieved are shown in Scheme 1.2n–p In this
substrates at room temperature in an ionic liquid medium and
leads to stereoselective products. X-ray structures of key com-
pounds (3ba, 6ab, 8 and 18; Supplementary data) have been de-
termined. Higher reactivity of hypervalent (pentacoordinate)
silicon compared to tetracoordinate species is put to wide practical
synthesis, but similar chemistry by activation of tetra- to penta-
coordinate phosphorus as utilized here is rather scarce.5,6 This is
also one of the points we wish to highlight in the present article.
2. Results and discussion
O
P
OH
O
P
H
H3PO2
Air, Δ
DMF
(a)
OH
R
R
OH
R
Pd (dba)3
Xa2ntphos
DMF
The reaction of cyclic phosphites 1a–b with various Baylis–
Hillman adducts 2a–e in the presence of (n-Bu)4NþFꢀ (TBAF) in
[bmim]þ[PF6]ꢀ leads selectively to
g-hydroxyphosphonates 3aa–
Ph
(EtO)Ph(O)P
Pd(OAc)2
P(O)Ph(OEt)
+
+
Ph
Ph
(b)
HP(O)Ph(OEt)
3ac, 3ae and 3ba–3be (Scheme 2, Table 1). The choice of these cyclic
phosphites used here was dictated by our desire to obtain well-
defined and stable crystalline products.4g In contrast, (a) the
dppe
100 °C/ 3 h
Ph
(90: 1)
OTMS
NTMS
(BSA)
OAc
OMe
Ph
O
P
MeO
MeO
(MeO)2P(O)H
+
(c)
OMe
O
(n-Bu)4N+F–
30-50 mol%
[BMIM]+[PF6]–
RT, 6 h
O
OH
Y
EWG
Y
H
O
O
O
O
EWG
Scheme 1.
P
Ar
P
+
Ar
OH
Y = O (1a)
2a-e
S (1b)
3, Yield: >90% (isolated: 72-84%)
* Corresponding author. Fax: þ91 40 23012460.
E-mail addresses: kckssc@uohyd.ernet.in, kckssc@yahoo.com (K.C. Kumara
Swamy).
Scheme 2.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.096

7604
E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
Table 1
Details on the yields of
(n-Bu)4N+F–
g
-hydroxyphosphonates (3aa–3ac, 3ae, 3ba–be)
EWG
Br
O
O
O
EWG
O
H
O
O
30-50 mol%
P
(a)
P
+
H
Entry
Y
Baylis–Hillman adduct
Ar
Product
Yielda (%)
[BMIM]+[PF6]–
RT, 6 h
Ar
H
5a-g
Br
Ar
1a
EWG
1
2
3
4
5
6
7
8
9
O
O
O
O
S
S
S
S
S
Ph
CO2Me
CO2Me
CO2Me
CN
CO2Me
CO2Me
CO2Me
CO2Et
CN
3aa
3ab
3ac
3ae
3ba (X-ray)
3bb
3bc
3bd
3be
82
72
76
80
75
84
80
73
79
O
O
O
EWG
4-MeO-C6H4
4-O2N-C6H4
Ph
P
Ar
Ph
6aa-6ag
(Yield: 76-88%)
4-MeO-C6H4
4-O2N-C6H4
1-C4H3O (furfuryl)
Ph
(n-Bu)4N+F–
H
S
30-50 mol%
O
O
Br
CN
(b)
[BMIM]+[PF6]–
RT, 6 h
P
+
a
Isolated yields.
Ph
H
1b
corresponding reaction of 1a–b with Baylis–Hillman acetates af-
fords P-CH2 allylphosphonates with the elimination of acetic acid,7
and (b) the Pd2(dba)3 catalyzed reaction of 1b with the Baylis–
a-phenyl allylphospho-
nate 4 as a major product while 1a gave a mixture of several
S
S
O
O
CN
S
O
O
O
CN
P
P
P
+
O
Ph
7 (50%)
Ph
Hillman alcohol 2a [Ar¼Ph]8 leads to the
8 (20%; X-ray)
Scheme 4.
products in low yields (Scheme 3).
Table 3
S
O
O
CO2Me
Details on the yields of a-aryl allylphosphonates 6aa–6ag
OH
P
S
O
O
CO2Me
Pd2(dba)3
Yielda (%)
P
Entry
Baylis–Hillman adduct
Product
+
Ph
Ph
H
Dioxane
110 °C, 24 h
Ar
EWG
4 [45% (isolated 35%), see text]
2a
1
2
3
4
5
6
7
Ph
CO2Me
CO2Me
CO2Me
CO2Me
CN
6aa
6ab (X-ray)
6ac
6ad
6ae
84
85
78
88
76
78
78
4-Me–C6H4
4-Cl–C6H4
4-O2N–C6H4
Ph
Scheme 3.
Later, we treated cyclic phosphite (1a) with allyl bromide (5a) in
the presence of (n-Bu)4NþFꢀ to give
-aryl allylphosphonate 6aa.
4-Me–C6H4
4-Cl–C6H4
CN
CN
6af
6ag
a
We optimized the reaction conditions for 6aa in different solvents
(Table 2). Although DMF works slightly better, [bmim]þ[PF6]ꢀ offers
the advantage that it is readily recovered. In fact, we could use the
same medium in the synthesis of 6aa for at least two consecutive
reactions. Use of DMF required removal of solvent by distillation
which was incomplete; hence an additional subsequent water-wash
was also required. Isolation using ionic liquid as the medium was
much simpler and easier in our hands. Under optimized conditions,
we have conducted the reactions of a variety of allyl bromides (5a–
a
Isolated yields.
The above procedure is fairly general and as shown in Table 4,
reactions of cyclic phosphites 1a–b with various unsaturated sys-
tems like allenes (9–10), alkynes (11–12), and dibenzylideneace-
tone (13) lead to a diverse range of phosphonates (14–18). The
Table 4
Details on the reactions of cyclic phosphites 1a–b with unsaturated systems 9–13
leading to the phosphonates 14–18
g) with cyclic phosphites (1a–b) for the synthesis of different a-aryl
allylphosphonates 6–7 (Scheme 4, Table 3). The reaction is regio-
selective for 6aa–6ag. The crude reaction mixture corresponding to
3aa–3ba showed only one diastereomer (31P and 1H NMR); we did
not observe the other diastereomer under these reaction conditions.
It is important to note that the synthesis of these by Arbuzov rear-
rangement of phosphites (OCH2CMe2CH2O)POCH2C(EWG)]CHAr
is difficult.9 The more reactive 1b leads to double phosphonylation
product 8 also under these conditions.10
Entry
1
Substrate
Product
Yield (%)
H
O
O
H
O
O
O
O
P
H
H
P
O
89
P
Ph
Ph
O
O
9
14
Me
O
Me
O
O
O
O
O
O
Me
Me
P
H
P
2
77
P
Table 2
O
Details on the yield of 6aa under different reaction conditionsa
O
10
15
Entry
Solvent
Temp (ꢁC)
Yielda (%)
O
O
O
H
P
H
1
2
3
4
5
6
7
8
9
10
THF
65
65
70
RT
110
RT
80
RT
RT
80
78
60
66
68
60
90b
73
72
84b
d
Ph
H
85 (Single
isomer)
3
4
Acetonitrile
Dichloroethane
Dichloromethane
Toluene
E
11
Ph
16
O
O
O
H
P
H
MeO2C
H
88 (Single
isomer)
DMF
E
12
1,4-Dioxane
PEG
CO2Me
17
[bmim]þ[PF6]ꢀ
Water
O
S
S
O
O
O
O
O
P
P
a
There was no reaction in the absence of TBAF; yields were based on 1H NMR
5
88
spectra.
Ph
Ph
Ph
Ph
b
Although yields were better in DMF, work-up was much easier using the ionic
liquid.
18 (X-ray)
13

E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
7605
yields are generally very good. Among the substrates listed here,
F
only phosphonylation of phenylacetylene with other phosphites
has been investigated by others before.11 Also, synthesis of the
diphosphonate such as 18 offers an opportunity for multiple
phosphonylation in a single step.
Activation of the phosphites takes place via pentacoordinate
phosphorus as evidenced by the following:
H
O
F
P
H
O
O
P
O
O
or
O
(a) Other salts like (n-Bu)4NþXꢀ [X¼Cl, Br, I, and HPO4] did not
work, because the anions are not strong enough to lead to penta-
coordination; CsF also did not work well. However, KF (or CsF)/18-
crown-6 or (n-Bu)4NþClꢀ/KF worked although not as efficiently as
(n-Bu)4NþFꢀ. (b) In place of more reactive 1a–b, when we treated
the less reactive (steric factors) 19 or 20 with an equimolar quantity
of (n-Bu)4NþFꢀ, the 1H, 31P, and 19F NMR spectra clearly show P–F
bonded intermediate [>95% by 31P NMR; cf. Figure 1] with 1J(P–
F)¼959.5 Hz, 1J(P–H)¼652.4 Hz, and 2J(F–H)¼129.4 Hz in the re-
action using 19. The resulting species (21a or 21b) was obtained as
a gummy material in >95% purity (based on 31P NMR). The 1H NMR
and 13C NMR spectra are consistent with the 8-membered phos-
phocin ring intact. This intermediate, on treatment with the allyl
bromide H2C]C(CO2Me)CH2Br, led to the phosphonate 22 as
a single product.
21a
21b
O
X
H
O
O
O
CO2Me
P
P
O
X = O (19)
= S (20)
22 (quantitative)
Based on the above observations, we propose the pathway
shown in Scheme 5 involving pentacoordinate phosphorus in-
termediate 21a or 21b. It is interesting to note that, in the
oxidative Heck-type reaction involving cleavage of a carbon–
phosphorus bond of arylphosphonic acids 23, Inoue et al. have
proposed the involvement the pentacoordinate species 24
(Scheme 6). Thus, our results are consistent with such a propo-
sal.5c We could not detect any hexacoordinate species even at
ꢀ40 ꢁC when more than one equivalent of TBAF (solution in THF)
was used. Solid TBAF (dried under vacuum at 100 ꢁC for 2 h), also
worked well. However, with added water, the reaction did not
proceed. Under basic conditions (using Et3N or NaH), the phos-
phites 1a–b did not undergo hydrophosphonylation with 2a, or
9–11 (31P NMR evidence). The reaction of phosphite 1a with 5a
using Et3N as the base gave a lower yield of 6aa.12 For the sub-
sequent step, it is possible that fluoride ion has simply increased
the acidity of phosphorus or the reaction entails a free radical
mechanism. Rico-Lattes and co-workers have earlier described an
example wherein the stable neutral P–H pentacoordinate phos-
phorane 25 is utilized in the synthesis of aminophosphonic acid
27 via the P–C bonded phosphorane 26 (Scheme 7), but the de-
tails on the mode of P–H addition are not available, perhaps
because the addition reaction was too fast.13 Similar work done
much earlier by Grechkin and Gubanova as well as Burgada and
co-workers on the addition of the vinyl ether CH2]CH(OEt) to P–
H phosphoranes had suggested a radical pathway.14 We have
Figure 1. (a) 1H [400 MHz], (b) 31P [proton coupled, 160 MHz] and (c) 19F [377 MHz]
NMR spectra of 1:1 (molar) mixture of 19 and [n-Bu]4NþFꢀleading to 21a or 21b in the
appropriate region in CDCl3. J1¼2J(F–H)¼129.4 Hz; J2¼1J(P–H)¼652.4 Hz; J3¼1J(P–F)
¼959.5 Hz. Peaks marked by ‘*’ and ‘**’ in the 1H NMR are due to CHCl3 and H(Ar)
protons, respectively.
F
P
O
F
P
O
O
H
O
Y
H
O
O
Y
(n-Bu)4N
F
Y
or
+
P
H
Y = O, S
21b (Y = O)
21a (Y = O)
Cation: (n-Bu)4N
R
F
P
EWG
R'
R
Y
O
O
O
F
fast
H
Y
R
P
R'
O
EWG
H
H
[activation
R'
via pentacoordination
or a radical pathway]
EWG
Y = O, S
Scheme 5.
O
P
F
24
F
OH
OH
O
P
Ar
OH
OH
Ar
23
Scheme 6.
conducted the reaction of 1a with (4-MeO–C6H4)CH(OH)C(CO2
-
Me)]CH2 (2b) in the presence of 1,4-benzoquinone. At 10 and
20 mol % of the quinone, no significant reduction in the product
3ab (yield 60–80%) was noticed; however, with 50 mol % of the
quinone, there was a drastic reduction. Since we expect the
radical quencher to work at low concentrations also, in our
opinion, the result is inconclusive as regards the involvement of
a radical mechanism at the later stage of phosphonylation.
However, since we are able to establish that 21a or 21b leads to

7606
E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
O
50 mol % of TBAF (1 M THF solution) was added via syringe over
O
Ph
H
a period of 2 min at room temperature. The progress of the re-
action was monitored by TLC (3–6 h). After the disappearance of
the starting material (1a or 1b), ethyl acetate (8 mL) was added
and stirring continued for 15 min. The upper layer was separated
and concentrated in vacuo to give the crude product, which was
purified by column chromatography using 70–80% ethyl acetate–/
hexanes as eluent. Only a single diastereomer was observed in the
reaction mixture (31P and 1H NMR). The [bmim]þ[PF6]ꢀ was col-
lected and reused for the next reaction. When we used 30 mol % of
the TBAF, it took w2 h more for the completion of the reaction but
the yields were essentially the same.
O
O
N
*
Ph
C18H37
O
O
*
*
P
H
P
C
NH-C18H37
O
> 95%
O
H
*
O
O
25
26
O
O
δ(P): -42 and -45
Two diastereomers
Ph
O
(From ref. 13)
*
NH-C18H37
(HO)2P
C
H
27
Pure enantiomers
[α]D20-18 and +18
4.2.1. 3aa
Scheme 7.
Isolated yield: 0.28 g (82%); Rf¼0.3 (EtOAc/hexane 4:1); white
solid; mp 112–114 ꢁC; [Found: C, 56.04; H, 6.74. C16H23O6P requires
C, 56.14; H, 6.77%]; vmax (KBr) 3399, 2924, 1734, 1454, 1240, 1134,
the phosphonate product 22, it is very likely that pentacoordi-
nate phosphorus is involved in these reactions. Finally, we note
that species such as 21a–b are still mechanistically very impor-
tant,4a and hence efforts are underway to obtain them as crys-
talline solids.
1009, 868 cmꢀ1
; dH (400 MHz, CDCl3) 7.37–7.30 (5H, m, Ar-H), 4.91
(1H, br s, CH(Ar)), 4.33–4.30 (2H, m, OCH2), 3.73–3.70 (2H, m,
OCH2), 3.64 (3H, s, OCH3), 3.38–3.36 (1H, m, CH(CO2Me)), 3.00 (1H,
br s, OH), 2.56 (1H, dt, J 12.0, 16.0, 16.0 Hz, CH2(B)), 2.22 (1H, wdt, J
4.0, 16.0, 16.0 Hz, CH2(A)), 1.14 and 0.91 (6H, 2 s, 2CH3); dC
(100 MHz, CDCl3) 173.8, 140.8, 128.8, 128.4, 126.3, 75.2, 74.1, 74.0,
52.2, 47.4, 33.4 (d, J 14.5 Hz), 32.2 (d, J(P–C) 104.2 Hz), 22.5, 21.5; dP
(160 MHz, CDCl3) 24.3.
3. Conclusion
A novel and convenient protocol for regio-/stereo-selective
hydrophosphonylation in ionic liquid medium is presented. Many
of these compounds cannot be prepared stereoselectively from
the existing methods. Clear-cut evidence for the new P–F bonded
intermediate is given for the first time. Efforts to make TBAF
essentially catalytic at 2–3 mol % are in progress. As exemplified
by the reactions using 1b palladium-catalyzed and fluoride-
mediated phosphonylation reactions to lead to different types of
products. Although conjugate addition of P(X)–H (X¼O, S) com-
pounds is very well known, the present work adds on a new
route with selectivity different from many of the existing
methodologies.
4.2.2. 3ab
Isolated yield: 0.27 g (72%); Rf¼0.25 (EtOAc/hexane 4:1); white
solid; mp 120–122 ꢁC; [Found C, 54.95; H, 6.72. C17H25O7P requires
C, 54.84; H, 6.77%]; vmax (KBr) 3474, 2957, 1744, 1613, 1518, 1260,
1211, 1049, 997 cmꢀ1
; dH (400 MHz, CDCl3) 7.26 and 6.89 (4H, 2d, J
8.8 Hz, Ar-H), 4.87 (1H, dd/t, J 5.6 Hz, CH(Anis)), 4.35–4.33 (2H,
m, OCH2), 3.80 (3H, s, OCH3), 3.73–3.70 (2H, m, OCH2), 3.68 (3H, s,
OCH3), 3.38–3.36 (1H, m, CH(CO2Me)), 2.65 (1H, d, J 5.6 Hz, OH
(The OH peak disappeared on D2O exchange)), 2.56 (1H, wdt, J 4.0,
16.0, 16.0 Hz, CH2(B)), 2.19 (1H, ddd, J 4.0, 15.2, 16.0 Hz, CH2(A)),
1.16 and 0.92 (6H, 2 s, 2CH3); dC (100 MHz, CDCl3) 173.5, 159.7,
132.8, 127.7, 114.2, 75.1 (d, J 17.0 Hz), 74.0, 73.9, 55.4, 52.1, 47.5,
33.2, 32.3 (d, J(P–C) 104.3 Hz), 22.5, 21.5; dP (160 MHz, CDCl3) 25.2;
LC–MS m/z 371 [Mꢀ1]þ.
4. Experimental
4.1. General
General experimental details are given in the Supplementary
4.2.3. 3ac
data. Compounds 1a [
using the methods previously reported from our laboratory.15a,b For
compounds (OCH2CMe2CH2O)P(S)H [1b: (P) 65.2] and [CH2{6-t-
Bu-4-Me-C6H4O}2P(S)H] [20: (P) 64.9], a modified version of the
d(P) 2.3] and 19 [d(P) 0.1] were prepared by
Isolated yield 0.29 g (76%); Rf¼0.20 (EtOAc/hexane 4:1); pale
yellow solid; mp 140–142 ꢁC; [Found: C, 49.48; H, 5.75; N, 3.46.
C16H22NO8P requires C, 49.62; H, 5.73; N, 3.62%]; vmax (KBr) 3299,
d
2965, 1728, 1522, 1348, 1260, 1055, 1005, 837 cmꢀ1
; dH (400 MHz,
d
literature procedure was followed.15b,c Dry H2S gas [prepared from
w4.0 g of FeS with w800 mL of 30% HCl] was bubbled for 0.5 h into
a solution of respective chlorophosphite (1.84 mmol) in toluene
(40 mL). Et3N (1.88 mmol) was added drop-wise (15 min); H2S gas
was passed further for 1 h, and the mixture stirred overnight at
room temperature. It was then filtered, the precipitate washed with
toluene, and the washings added to the filtrate. Concentration of
the filtrate afforded the desired product as a crystalline solid. This
reaction was very clean and no side product (dithiaphosphoric salt)
was observed.
CDCl3) 8.23 and 7.54 (4H, 2d, J 8.6 Hz, Ar-H), 5.25 (1H, br s, OH),
4.19–4.16 (3H, m, OCH2þCH(Ar)), 3.91–3.89 (2H, m, OCH2), 3.64
(3H, s, OCH3), 3.45–3.42 (1H, m, CH(CO2Me)), 2.31–2.25 (2H, m,
PCH2), 1.09 and 1.08 (6H, 2 s, 2CH3); dC (100 MHz, CDCl3) 172.6 (d, J
10.4 Hz), 148.2, 147.6, 127.0, 123.6, 75.7 and 75.6 (2d, J 6.3 Hz), 73.3
(d, J 10.2 Hz), 52.3, 46.4 (d, J 2.6 Hz), 33.2 (d, J 6.1 Hz), 22.7 (d, J(P–C)
137.5 Hz), 21.5, 21.4; dP (160 MHz, CDCl3) 25.5.
4.2.4. 3ae
Isolated yield 0.25 g (80%); Rf¼0.30 (EtOAc/hexane 4:1); white
solid; mp 138–140 ꢁC; [Found: C, 58.50; H, 6.50; N, 4.35.
C15H20NO4P requires C, 58.25; H, 6.52; N, 4.53%]; vmax (KBr) 3447,
Baylis–Hillman adducts 2a–e and allyl bromides 5a–g were
synthesized according to the standard procedures.16 Allenes 9–10
and the ionic liquid [bmim]þ[PF6]ꢀ were prepared by known
procedures.17,18
2973, 2259, 1456, 1221, 1044, 995 cmꢀ1
; dH (400 MHz, CDCl3) 7.48–
7.36 (5H, m, Ar-H), 5.12 (1H, ddwt, J 7.3 Hz, CH(Ar)), 4.43–4.40 (2H,
m, OCH2), 3.82–3.79 (2H, m, OCH2), 3.54–3.51 (1H, m, CH(CN)),
2.68–2.63 and 2.56–2.51 (2H, 2m, PCHAHB), 2.46 (1H, d, J 7.3 Hz,
OH), 1.22 and 0.95 (6H, 2s, 2CH3); dC (100 MHz, CDCl3) 139.6, 128.9,
126.0, 118.3 (d, J 14.6 Hz), 74.3 and 74.2 (2d, Jw2.0 Hz), 72.8 (d, J
8.5 Hz), 36.1, 33.4 (d, J 6.1 Hz), 32.5 (d, J(P–C) 106.7 Hz), 22.5, 21.3; dP
(160 MHz, CDCl3) 24.9.
4.2. Synthesis of g-hydroxy phosphonates 3aa–3be:
representative procedure
To phosphite (1a) or thiophosphite (1b) (1.0 mmol) and Baylis–
Hillman adduct (one of 2a–e) (1.0 mmol) in 1 mL of [bmim]þPF6ꢀ,

E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
7607
4.2.5. 3ba
3.58–3.55 (1H, m, CH(CN)), 2.68–2.64 and 2.59–2.55 (2H, 2m,
PCHAHB), 2.46 (1H, br s, OH), 1.23 and 0.97 (6H, 2s, 2CH3); dC
(100 MHz, CDCl3) 139.5, 128.9, 128.8, 125.9, 118.2 (d, J 14.5 Hz),
74.2 and 74.1 (2d, J 6.1 Hz), 72.8 (d, J 8.8 Hz), 36.1, 33.4 (d, J
5.7 Hz), 32.4 (d, J(P–C) 105.8 Hz), 22.5, 21.3; dP (160 MHz, CDCl3)
94.1.
Isolated yield 0.27 g (75%). Rf¼0.30 (EtOAc/hexane 3:2); white
solid; mp 132–134 ꢁC; [Found: C, 53.65; H, 6.45; S, 9.09. C16H23O5PS
requires C, 53.62; H, 6.47; S, 8.95%]; vmax (KBr) 3522, 2953, 1742,
1456, 1364, 1269, 1208, 1046, 995 cmꢀ1
; dH (400 MHz, CDCl3) 7.39–
7.31 (5H, m, Ar-H), 4.95 (1H, ddwt, J 7.6 Hz, CH(Ar)), 4.36–4.33 (2H,
m, OCH2), 3.76–3.73 (2H, m, OCH2), 3.67 (3H, s, OCH3), 3.42–3.39
(1H, m, CH(CO2Me)), 2.81 (1H, d, J 7.6 Hz, OH, exchanges with D2O),
2.58 (1H, dt, J 9.6, 17.2, 17.2 Hz, CH2(B)) and 2.24 (1H, ddd/dt, J 4.0,
17.2, 17.2 Hz, CH2(A)), 1.16 and 0.92 (6H, 2s, 2CH3); dC (100 MHz,
CDCl3) 173.4 (d, J 3.0 Hz), 140.6, 128.7, 128.4, 126.3, 75.2 (d, J
15.6 Hz), 74.0 and 73.9 (2d, J 6.2 Hz), 52.1, 47.3 (d, J 1.6 Hz), 33.2 (d, J
5.7 Hz), 32.2 (d, J(P–C) 104.8 Hz), 22.4, 21.4; dP (160 MHz, CDCl3)
96.3; This compound was crystallized from dichloromethane:hex-
ane (1:1) mixture at room temperature over a period of 2 d (X-ray
structure in Fig. S2; Supplementary data).
4.3. Reaction using Pd2(dba)3 catalyst: synthesis of 4
To thiophosphite (1b) (1.0 mmol), Baylis–Hillman adduct (2a)
(1.0 mmol) and Pd2(dba)3 (10 mol %) in 4 mL of dioxane was heated
at 110 ꢁC for about 24 h. The reaction mixture was quenched by
adding 3 mL of distilled water and the compound extracted using
(2ꢂ8 mL) ethyl acetate, dried over Na2SO4, and concentrated in
vacuo to get the crude material. The reaction mixture showed many
peaks in the expected phosphonate region in which compound 4
was present to an extent of 35–45% [31P NMR]. From this, 4 was
isolated using silica gel column chromatography (70% EtOAc/hex-
ane). Under identical conditions, the phosphite (1a) did not give
any appreciable amount of product/s (31P NMR).
4.2.6. 3bb
Isolated yield 0.33 g (84%); Rf¼0.42 (EtOAc/hexane 4:1); white
solid; mp 144–146 ꢁC; [Found: C, 52.32; H, 6.53; S, 8.21. C17H25O6PS
requires C, 52.57; H, 6.49; S, 8.25%]; vmax (KBr) 3522, 2958, 1758,
Isolated yield 0.12 g (35%); white solid; Rf¼0.40 (EtOAc/hexane
3:2); mp 138–140 ꢁC; [Found: C, 56.22; H, 6.24. C16H21O4PS requires
C, 56.46; H, 6.22%]; vmax (KBr) 2955, 1713, 1443, 1263, 1057,
1454, 1368, 1268, 1200, 1041, 995 cmꢀ1
; dH (400 MHz, CDCl3) 7.27
and 6.91 (4H, 2d, J 8.6 Hz, Ar-H), 4.95 (1H, dd/t, J 6.2 Hz, CH(Anis)),
4.36–4.34 (2H, m, OCH2), 3.81 (3H, s, OCH3), 3.74–3.66 (2H, m,
OCH2), 3.67 (3H, s, OCH3), 3.41–3.38 (1H, m, CH(CO2Me)), 2.73 (1H,
d, J 6.2 Hz, OH), 2.57 (1H, dt, J 9.6, 17.2, 17.2 Hz, CH2(B)) and 2.19 (1H,
ddd/dt, J 4.0, 17.2, 17.2 Hz, CH2(A)), 1.18 and 0.93 (6H, 2s, 2CH3); dC
(100 MHz, CDCl3) 173.5 (d, J 5.5 Hz), 159.6, 132.6, 127.6, 114.1, 75.0
(d, J 16.7 Hz), 74.0 and 73.9 (2d, J 6.2 Hz), 55.3, 52.1, 47.4, 33.2 (d, J
5.7 Hz), 32.3 (d, J(P–C) 104.8 Hz), 22.4, 21.4; dP (160 MHz, CDCl3)
96.7.
1009 cmꢀ1
; dH (400 MHz, CDCl3) 7.48–7.29 (5H, m, Ar-H), 6.59 and
6.48 (2H, 2d, J 2.9 Hz, C(C]CH2)), 4.79 (1H, d, J 23.4 Hz, PCH(Ar)),
4.10–3.76 (4H, m, 2OCH2), 3.73 (3H, s, OCH3), 1.06 and 0.86 (6H, 2s,
2CH3); dC (100 MHz, CDCl3) 166.0, 135.2, 134.5, 130.0, 129.9, 129.6,
129.5,128.7,127.7, 76.1 (d, J 8.4 Hz), 52.4, 42.7 (d, J 136.0 Hz), 32.5 (d,
J 5.0 Hz), 21.6, 21.1; dP (160 MHz, CDCl3) 95.7.
4.4. Reaction of allyl bromides 5a–g with 1a–b: synthesis
4.2.7. 3bc
of a-aryl substituted allylphosphonates (6aa–6ag and 7–8),
Isolated yield 0.32 g (80%); Rf¼0.32 (EtOAc/hexane 4:1); yellow
solid; mp 156–158 ꢁC; [Found: C, 47.48; H, 5.30; N, 3.41.
C16H22NO7PS requires C, 47.64; H, 5.50; N, 3.47%]; vmax (KBr) 3545,
and other phosphonates (14–18)
To a stirred solution of 1a or 1b (1.0 mmol) and substituted
allyl bromide 5a–g (1.0 mmol) in 1 mL [bmim]þPF6ꢀ, 30 mol % of
1.0 M THF solution of TBAF was added via syringe over a period of
2 min at room temperature. After disappearance of the starting
material (TLC, 1a or 1b), ethyl acetate (10 mL) was added and
stirring continued for 15 min. The upper layer was separated and
the solvent removed in vacuo to get the crude product. This
material showed only a single component in TLC (in the case of
1a), but was passed through silica gel column (hexane/ethyl ac-
etate) to remove traces of impurities, if any. The used ionic liquid
was recovered in the reaction leading to 6aa and reused without
any significant loss in yield. In the case of 1b, both the mono- and
bis-phosphonylated products (7 and 8) were observed in the re-
action mixture.
2961, 1738, 1516, 1271, 1211, 1169, 1049, 995 cmꢀ1
; dH (400 MHz,
CDCl3) 8.20 and 7.51 (4H, 2d, J 8.6 Hz, Ar-H), 5.22 (1H, d, J 4.4 Hz,
CH(Ar)), 4.15–4.12 (2H, m, OCH2), 3.86–3.83 (2H, m, OCH2), 3.62
(3H, s, OCH3), 3.37–3.34 (1H, m, CH(CO2Me)), 2.21–2.18 (3H, m,
PCH2þOH), 1.07 and 1.05 (6H, 2s, 2CH3); dC (100 MHz, CDCl3) 172.6
(d, J 10.4 Hz), 148.2, 147.6, 127.0, 123.6, 75.7 and 75.6 (2d, J 6.3 Hz),
73.3 (d, J 10.2 Hz), 52.3, 46.4 (d, J 2.6 Hz), 33.2 (d, J 6.1 Hz), 22.7 (d,
J(P–C) 107.5 Hz), 21.5, 21.4; dP (160 MHz, CDCl3) 94.6.
4.2.8. 3bd
Isolated yield 0.26 g (73%); Rf¼0.33 (EtOAc/hexane 3:2); light
brown solid; mp 126–128 ꢁC; [Found: C, 47.68; H, 6.50. C15H23O6PS
requires C, 49.72; H, 6.40%]; vmax (KBr) 3526, 2959, 1742, 1613, 1518,
1260, 1211, 1175, 1053, 999 cmꢀ1
; dH (400 MHz, CDCl3) 7.38 and 7.26
(3H, 2br s, furfuryl-H), 5.25 (1H, br s, CH(CO2Et)), 4.39–4.36 (2H, m,
OCH2), 4.20–4.17 (2H, m, OCH2), 3.73 (2H, q, J 7.1 Hz, CO2CH2CH3),
3.55–3.52 (1H, m, CH(Ar)), 2.95 (1H, d, J 8.0 Hz, OH, disappears on
D2O exchange), 2.70–2.60 and 2.41–2.33 (2H, 2m, PCHACHB), 1.22
(3H, t, J 7.1 Hz, CO2CH2CH3), 1.18 and 0.93 (6H, 2s, 2CH3); dC
(100 MHz, CDCl3) 172.6, 153.4, 142.6, 110.3, 107.6, 102.5, 73.9, 73.8,
69.1 (d, J 15.0 Hz), 61.4, 45.0, 33.2 (d, J 6.0 Hz), 32.1 (d, J(P–C)
105.0 Hz, PCH2), 22.5, 21.4, 14.0; dP (160 MHz, CDCl3) 96.3.
4.4.1. Reaction using solid TBAF
The above reaction using 1a and 5a was performed using solid
TBAF in place of 1.0 M solution in THF; in this case also, we could
isolate the product with essentially the same yield, although solid
TBAF could contain traces of moisture.
4.4.2. 6aa
Isolated yield 0.27 g (84%); Rf¼0.36 (EtOAc/hexane 3:2); white
solid; mp 138–140 ꢁC; [Found: C, 59.17; H, 6.52. C16H21O5P requires C,
59.26; H, 6.53%]; vmax (KBr) 2957, 1719, 1626, 1491, 1263, 1246, 1057,
4.2.9. 3be
Isolated yield 0.26 g (79%); Rf¼0.35 (EtOAc/hexane 3:2); white
solid; mp 150–152 ꢁC; [Found: C, 55.59; H, 6.19; N, 4.42; S, 9.88.
C15H20NO3PS requires C, 55.37; H, 6.20; N, 4.30; S, 9.85%]; vmax
1009, 835 cmꢀ1
; dH (400 MHz, CDCl3) 7.49–7.28 (5H, m, Ar-H), 6.60
and 6.50 (2H, 2d, J 2.7 Hz, C(C]CH2)), 4.80 (1H, d, J 22.7 Hz, PCH(Ar)),
4.13–3.80 (4H, m, 2OCH2), 3.75 (3H, s, OCH3), 1.08 and 0.87 (6H, 2s,
2CH3); dC (100 MHz, CDCl3) 166.6 (d, J 13.0 Hz), 135.2, 134.5, 130.0,
129.9,129.6,129.5,128.7,127.7,127.6, 76.0 (d, J 6.0 Hz), 52.4, 42.6 (d, J
135.0 Hz), 32.5 (d, J 7.0 Hz), 21.6, 21.1; dP (160 MHz, CDCl3) 19.7.
(KBr) 3445, 2973, 2254, 1467, 1402, 1228, 1044, 998 cmꢀ1
; dH
(400 MHz, CDCl3) 7.49–7.38 (5H, m, Ar-H), 5.12 (1H, d, J 7.6 Hz,
CH(Ar)), 4.46–4.42 (2H, m, OCH2), 3.85–3.81 (2H, m, OCH2),

7608
E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
4.4.3. 6ab
7.28 (4H, m, Ar-H), 6.35 and 6.22 (2H, 2d, Jw4.0 Hz, C(C]CH2)),
Isolated yield 0.30 g (85%); Rf¼0.34 (EtOAc/hexane 3:2); white
4.28–3.78 (5H, m, PCH(Ar)þ2OCH2), 1.04 and 1.00 (6H, 2s, 2CH3); dC
(100 MHz, CDCl3) 135.3, 130.9, 129.4, 118.5, 76.1, 47.2 (d, J(P–C)
137.9 Hz), 32.6 (d, J 6.3 Hz), 21.5, 21.4; dP (160 MHz, CDCl3) 15.7.
solid; mp 150–152 ꢁC; [Found: C, 60.41; H, 6.88. C17H23O5P re-
quires C, 60.35; H, 6.85%]; vmax (KBr) 2922, 1734, 1267, 1059, 1003,
835 cmꢀ1
; dH (400 MHz, CDCl3) 7.39–7.15 (4H, m, Ar-H), 6.59 and
6.49 (2H, 2d, J 4.0 Hz, C(C]CH2)), 4.78 (1H, d, J 22.7 Hz, PCH(Ar)),
4.12–3.81 (4H, m, 2OCH2), 3.75 (3H, s, OCH3), 2.34 (3H, s, CH3),
1.09 and 0.91 (6H, 2s, 2CH3); dC (100 MHz, CDCl3) 166.0, 137.4,
135.3, 131.5, 131.3, 129.8, 129.7, 129.4, 129.3, 52.4, 42.1 (d, J
135.2 Hz), 32.6 (d, J 6.3 Hz), 21.6, 21.2, 21.1; dP (160 MHz, CDCl3)
19.3; This compound was crystallized from dichloromethane/
hexane mixture (2:1) at room temperature 1 d (X-ray structure in
Fig. S2; Supplementary data).
4.4.9. 7
Isolated yield 0.15 g (50%); Rf¼0.36 (EtOAc/hexane 1:1); white
solid; mp 188–190 ꢁC; [Found: C, 58.55; H, 5.93; N, 4.65. C15H18NO2PS
requires C, 58.62; H, 5.90; N, 4.56%]; vmax (KBr) 2971, 2226,1472,1267,
1059, 1003, 835 cmꢀ1
; dH (400 MHz, CDCl3) 7.47–7.26 (5H, m, Ar-H),
6.35 and 6.20 (2H, 2d, J 2.8 Hz, C(C]CH2)), 4.18–3.75 (5H, m,
PCH(Ar)þ2OCH2), 1.04 and 0.93 (6H, 2 s, 2CH3); dC (100 MHz, CDCl3)
135.1, 135.0, 129.6, 129.5, 129.2, 128.7, 118.7, 76.3 (d, J 8.4 Hz), 47.4 (d,
J(P–C) 138.0 Hz), 32.6 (d, J 6.2 Hz), 21.5, 21.4; dP (160 MHz, CDCl3) 92.1.
4.4.4. 6ac
Isolated yield 0.28 g (78%); Rf¼0.33 (EtOAc/hexane 3:2); white
solid; mp 172–174 ꢁC; [Found: C, 53.50; H, 5.53. C16H20ClO5P re-
quires C, 53.57; H, 5.62%]; vmax (KBr) 2955, 1719, 1491, 1246, 1206,
4.4.10. 8
Isolated yield 0.95 g (20%); Rf¼0.42 (EtOAc/hexane 1:1); white
solid; mp 224–226 ꢁC; [Found: C, 50.82; H, 6.29; N, 2.97.
C20H29NO4P2S2 requires C, 50.73; H, 6.17; N, 2.96%]; vmax (KBr) 2971,
1055, 1009 cmꢀ1 1H NMR (400 MHz, CDCl3) 7.42–7.26 (4H, m, Ar-
;
H), 6.59 and 6.47 (2H, 2d, J 3.2 Hz, C(C]CH2)), 4.74 (1H, d, J 22.7 Hz,
PCH(Ar)), 4.10–3.76 (4H, m, 2OCH2), 3.73 (3H, s, OCH3), 1.05 and
0.90 (6H, 2s, 2CH3); dC (100 MHz, CDCl3) 166.5, 134.9, 130.9, 130.8,
130.1, 130.0, 128.9, 76.1, 76.0, 75.9, 52.5, 42.0 (d, J(P–C) 136.1 Hz),
32.6 (d, J 6.3 Hz), 21.6, 21.2; dp (160 MHz, CDCl3) 18.8.
2241, 1474, 1277, 1221, 1051, 1007 cmꢀ1
; dH (400 MHz, CDCl3) 7.61–
7.41 (5H, m, Ar-H), 4.48–4.41 (5H, m, PCH(Ar)þ2OCH2), 3.85–3.69
(5H, m, CH(CN)þ2OCH2), 2.48–2.37 (2H, m, PCH2), 1.23, 0.94, 0.91
and 0.86 (12H, 4s, 4CH3); dC (100 MHz, CDCl3) 130.7, 130.6, 128.9,
119.0, 74.2 and 74.1 (4d, J 5.8 Hz), 73.9, 73.8, 51.3 (dd, J(P–C)
102.5 Hz and J 7.5 Hz), 34.8 (dd, J(P–C) 105.5 Hz and J 11.9 Hz), 33.4,
33.3, 28.0, 22.6, 22.1, 21.3; dP (160 MHz, CDCl3) 92.2 and 91.2; This
compound was crystallized from dichloromethane/hexane mixture
(1:1) at room temperature (2 d). X-ray structure was determined on
this sample (Fig. S3; Supplementary data).
4.4.5. 6ad
Isolated yield 0.32 g (88%); Rf¼0.30 (EtOAc/hexane 4:1); yellow
solid; mp 144–146 ꢁC; [Found: C, 52.13; H, 5.42; N, 3.85.
C16H20NO7P requires C, 52.04; H, 5.46; N, 3.79%]; vmax (KBr) 2963,
1719, 1630, 1597, 1522, 1437, 1246, 1132, 1059 cmꢀ1
; dH (400 MHz,
CDCl3) 8.19 and 7.66 (4H, 2d, J 8.3 Hz, Ar-H), 6.68 and 6.57 (2H, 2d, J
2.8 Hz, C(C]CH2)), 4.85 (1H, d, J 22.7 Hz, PCH(Ar)), 4.20–4.10 and
3.94–3.83 (4H, 2m, 2OCH2), 3.76 (3H, s, OCH3),1.06 and 0.93 (6H, 2s,
2CH3); dC (100 MHz, CDCl3) 166.2 (d, J 13.1 Hz), 147.4, 142.3, 142.1,
134.2, 130.8, 130.7, 130.6, 130.4, 123.7, 76.2, 76.1, 76.0, 52.7, 42.6 (d,
J(P–C) 135.3 Hz), 32.6 (d, J 6.3 Hz), 21.5, 21.2; dP (160 MHz, CDCl3)
17.7.
4.4.11. 14
Isolated yield 0.37 g (89%); Rf¼0.32 (EtOAc/hexane 9:1); white
solid; mp 124–126 ꢁC; [Found: C, 55.11; H, 6.80. C19H28O6P2 requires
C, 55.07; H, 6.81%]; vmax (KBr) 2971, 1634, 1476, 1273, 1059,
1009 cmꢀ1
; dH (400 MHz, CDCl3) 7.37–7.13 (5H, m, Ar-H), 6.75 (1H,
dd, J 48.2 Hz, Jw3.0 Hz, PC]CHA (trans)), 6.28 (1H, dd, J 12.0 Hz,
Jw3.0 Hz, PC]CHA (cis)), 4.51 (dd, J 16.0, 20.0 Hz respectively,
PCH(Ar)), 4.07–3.72 (8H, m, 4OCH2),1.02, 0.94, 0.79 and 0.76 (4s,12H,
4CH3); dC (100 MHz, CDCl3) 132.6, 129.5, 129.4, 128.6, 127.8, 76.1 and
75.5 (2d, Jw8.0 Hz), 42.4 (dd, J 20.0,140.0 Hz), 32.5 (d, J 6.0 Hz), 21.8,
21.7, 21.6, 21.0; dP (160 MHz, CDCl3) 22.1 and 14.2 (2d, J 27.9 Hz each).
4.4.6. 6ae
Isolated yield 0.22 g (76%); Rf¼0.34 (EtOAc/hexane 3:2); white
solid; mp 180–182 ꢁC; [Found: C, 61.80; H, 6.22; N, 4.72.
C15H18NO3P requires C, 61.85; H, 6.23; N, 4.81%]; vmax (KBr) 2971,
2224, 1478, 1267, 1055, 1001, 845 cmꢀ1
;
dH (400 MHz, CDCl3) 7.48–
4.4.12. 15
7.29 (5H, m, Ar-H), 6.38 and 6.23 (2H, 2d, J 2.8 Hz, C(C]CH2)),
4.26–3.78 (5H, m, PCH(Ar)þ2OCH2), 1.06 and 0.95 (6H, 2s, 2CH3);
dC (100 MHz, CDCl3) 138.3, 134.6, 129.8, 129.6, 129.5, 129.2, 128.5,
118.8, 118.7, 117.7, 117.6, 75.9 and 74.2 (d each, J 8.0 Hz), 47.4 (d,
J(P–C) 138.0 Hz), 32.5 (d, J 6.0 Hz), 21.3, 21.2; dp (160 MHz, CDCl3)
15.8 [lit. 14.6 (ref. 7)].
Isolated yield 0.28 g (77%); Rf¼0.34 (EtOAc/hexane 9:1); white
solid; mp 164–166 ꢁC; [Found: C, 49.23; H, 7.78. C15H28O6P2 re-
quires C, 49.18; H, 7.70%]; vmax (KBr) 2961, 1624, 1474, 1217, 1051,
997 cmꢀ1
; dH (400 MHz, CDCl3) 4.30–3.62 (8H, m, 4OCH2), 2.98 (2H,
ddwt, J 20.7 and 18.6 Hz, PCH2), 2.12 (3H, dd, J 6.0 and 3.2 Hz, CH3),
1.86 (3H, dd, J 4.4 and 2.4 Hz, CH3), 1.02, 0.99, 0.95 and 0.92 (12H, 4s,
4CH3); dC (100 MHz, CDCl3) 155.1 (ddwt, J 22.0 and 10.0 Hz), 118.1
(dd, J(P–C) 147.0 and 11.0 Hz), 75.1 and 74.0 (2d, J 7.0 Hz), 32.6 and
33.1 (2d, J 6.0 Hz), 26.4 (dd, J(P–C) 139.0 and 14.0 Hz), 24.7 and 24.6
(2dd, J 8.0 and 3.0 Hz), 24.2 and 24.1 (2dd, J 18.0 and 3.0 Hz), 22.5,
21.6, 21.5; dp (160 MHz, CDCl3) 22.2 and 14.3 (2d, J 27.5 Hz each).
4.4.7. 6af
Isolated yield 0.24 g (78%); Rf¼0.32 (EtOAc/hexane 3:2); white
solid; mp 194–196 ꢁC; [Found: C, 62.85; H, 6.57; N, 4.62.
C16H20NO3P requires C, 62.94; H, 6.60; N, 4.59%]; vmax (KBr) 2971,
2226, 1498, 1267, 1059, 1003, 835 cmꢀ1
; dH (400 MHz, CDCl3) 7.38–
7.17 (4H, m, Ar-H), 6.32 and 6.17 (2H, 2d, Jw3.1 Hz, C(C]CH2)),
4.24–3.77 (5H, m, PCH(Ar)þ2OCH2), 2.37 (s, 3H, CH3), 1.06 and 0.98
(6H, 2s, 2CH3); dC (100 MHz, CDCl3) 138.5, 134.8, 134.6, 129.8, 129.5,
129.3, 128.8, 128.7, 119.0, 76.5 and 76.1 (2d, each, J 8.0 Hz), 47.4 (d, J
137.1 Hz), 32.6 (d, J 6.2 Hz), 21.5, 21.4, 21.1; dP (160 MHz, CDCl3) 16.0.
4.4.13. 16
Only the trans isomer (w99%) was observed in the reaction
mixture (31P and 1H NMR). Isolated yield 0.21 g (85%); Rf¼0.32
(EtOAc/hexane 4:1); pale yellow solid; mp 112–114 ꢁC; [Found: C,
61.84; H, 6.89. C13H17O3P requires C, 61.90; H, 6.79%]; vmax (KBr)
2965, 1478, 1262, 1057, 1001 cmꢀ1
; dH (400 MHz, CDCl3) 7.59–7.40
4.4.8. 6ag
(6H, m, Ar-HþPCH]CH), 6.30 (1H, dd/t, J 36.0 Hz and Jtrans
18.0 Hz, PCH), 3.92–3.86 and 4.29–4.22 (4H, 2m, 2OCH2), 1.15 and
1.07 (6H, 2s, 2CH3); dC (100 MHz, CDCl3) 150.3 (d, J 7.0 Hz), 134.5,
130.6, 128.9, 127.9, 111.8 (d, J(P–C) 192.0 Hz), 76.7, 75.5, 75.4, 32.5,
21.7, 21.4; dp (160 MHz, CDCl3) 14.9.
Isolated yield 0.25 g (78%); Rf¼0.38 (EtOAc/hexane 4:1); white
solid; mp 166–168 ꢁC; [Found: C, 55.36; H, 5.32; N, 4.36.
C15H17NO3PCl requires C, 55.31; H, 5.26; N, 4.30%]; vmax (KBr) 2976,
2224, 1491, 1261, 1055, 1007, 833 cmꢀ1
; dH (400 MHz, CDCl3) 7.43–

E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
7609
2
4.4.14. 17
1006 Hz and J(F–H)¼104 Hz)] are given as Figure S1 in Supple-
Only the trans isomer (w99%) was observed in the reaction
mentary data.
mixture (31P and 1H NMR). Isolated yield 0.21 g (88%); Rf¼0.36
(EtOAc/hexane 9:1); white solid; mp 134–136 ꢁC; [Found: C, 46.22;
H, 6.43. C9H15O5P requires C, 46.16; H, 6.46%]; vmax 2976, 1721, 1277,
4.7. X-ray crystallography
1055, 1007 cmꢀ1
; dH (400 MHz, CDCl3) 6.83 and 6.78 (2H, dd, J
X-ray data were collected on a Bruker AXS SMART diffractom-
20.0 Hz and Jtrans 17.4 Hz, PCH]CH(CO2Me)), 4.01–3.75 (4H, m,
2OCH2), 3.65 (3H, s, OCH3), 0.99 and 0.87 (6H, 2s, 2CH3); dC
(100 MHz, CDCl3) 162.1 (d, J 28.0 Hz), 135.1 (d, J 7.0 Hz), 127.6 (d, J
180.0 Hz), 74.0, 73.9, 49.9, 29.9 (d, J 6.0 Hz), 18.9, 18.6; dp (160 MHz,
CDCl3) 8.0.
eter using Mo-K
a
(
l
¼0.71073 Å) radiation. The structures were
solved and refined by standard methods.19
4.7.1. Crystal data
3ba: C16H23O5PS, M¼358.37, Orthorhombic, Space group
Pna2(1), a¼17.675(4), b¼17.125(4), c¼6.0166(15) Å, V¼1821.2(8) Å3,
Z¼4,
m
¼0.286 mmꢀ1, data/restraints/parameters: 3102/1/215, Flack
4.4.15. 18
The reaction was performed by using 2.0 mmol of thio-
phosphite 1b, 1.0 mmol of dba and 0.6 mmol of TBAF in 2 mL of
[bmim]þPFꢀ6 at room temperature. Isolated yield 0.45 g (88%);
Rf¼0.33 (EtOAc/hexane 1:1); pale yellow solid; mp 190–192 ꢁC;
[Found: C, 57.31; H, 6.48. C27H36O5P2S2 (after drying in vacuum for
2 h) requires C, 57.23; H, 6.40%]; vmax (KBr) 2967, 1723, 1454, 1266,
parameter: 0.06 (10), R indices (I>2
data)¼0.0989. CCDC no. 67227.
s
(I)): R1¼0.0415, wR2 (all
6ab: C17H23O5P, M¼338.32, Monoclinic, Space group P2(1)/n,
a¼9.7504(15), b¼9.9681(15), c¼18.162(3) Å,
b
¼92.213(2)ꢁ, V¼1763.9
(5) Å3, Z¼4,
indices (I>2
m
¼0.177 mmꢀ1, data/restraints/parameters: 3107/0/212, R
s(I)): R1¼0.0594, wR2 (all data)¼0.1378. CCDC no. 67228.
1046, 993 cmꢀ1
; dH (400 MHz, CDCl3) 7.30–7.28 (10H, m, Ar-H),
8: C20H29NO4P2S2, M¼473.50, Monoclinic, Space group P2(1)/c,
a¼15.6676(17), b¼15.1513(16), c¼10.6775(11) Å,
b
¼105.949(2)ꢁ,
4.35–4.27 (4H, m, 2OCH2), 4.02–3.96 (2H, m, PCH), 3.69–3.56 (4H,
m, 2OCH2), 3.38–3.32 (4H, m, 2CHC(O)), 0.85 and 0.84 (12H, 2s,
4CH3); dC (100 MHz, CDCl3) 202.2, 134.3, 134.2, 129.5, 129.3, 128.4,
128.2, 127.6, 127.5, 73.8, 44.9 and 44.7 (2d, J(P–C) 101.0 Hz), 43.0
(d, J 23.0 Hz), 33.2 (d, J 5.0 Hz), 22.0, 21.9, 21.3; dp (160 MHz,
CDCl3) 96.8 and 96.7; This compound was crystallized from ethyl
acetate/hexane mixture (1:1) at room temperature (w3 days). X-
ray structure was determined on this sample (Fig. S3; Supple-
mentary data).
V¼2437.1(4) Å3, Z¼4,
m
¼0.374 mmꢀ1, data/restraints/parameters:
4282/0/266, R indices (I>2
s
(I)): R1¼0.0508, wR2 (all data)¼0.1257.
CCDC no. 67229.
18: C29H36O6P2S2, M¼606.64, Triclinic, Space group P-1, a¼6.285(2),
b¼13.461(4), c¼19.169(5) Å,
a
¼88.868(4)ꢁ,
b
¼89.164(4)ꢁ,
g
¼87.965
(4)ꢁ, V¼1620.2(8) Å3, Z¼2,
m
¼0.301 mmꢀ1, data/restraints/parameters:
5655/0/356, R indices (I>2
s
(I)): R1¼0.0607, wR2 (all data)¼0.1729.
There was disorder in the solvent molecule, and hence it could not be
modelled properly. However, the main molecule is perfectly fine. CCDC
no. 67230.
4.5. Synthesis of 22
To phosphite (19) (0.5 mmol) and allyl bromide (0.5 mmol) in
5 mL dry THF, 50 mol % of TBAF (1.0 M THF solution) was added
via syringe over a period of 2 min at room temperature. After the
disappearance of starting material (allyl bromide; by TLC), the
solvent was removed in vacuo and distilled water (5 mL) was
added. The compound was extracted with ethyl acetate
(2ꢂ10 mL). The upper layer was separated and concentrated in
vacuo to give the crude product. Pure compound 22 was obtained
as white solid from toluene (5 mL) at room temperature after
12 h. Isolated yield 0.20 g (84%); Rf¼0.34 (EtOAc/hexane 3:2);
white solid; mp 124–126 ꢁC; [Found: C, 69.46; H, 7.74. C28H37O5P
requires C, 69.40; H, 7.70%]; vmax (KBr) 2922, 1734, 1267, 1059,
Acknowledgements
We acknowledge Department of Science and Technology and
University Grants Commission (both in New Delhi) for funding and
equipment. We also thank CSIR (New Delhi) for a fellowship (E.B.
and V.S.).
Supplementary data
General experimental procedure, spectra related to the identi-
fication of pentacoordinate product from 20þTBAF, PLATON and
ORTEP drawings, CIF files and 1H and 13C NMR spectra. Supple-
mentary data associated with this article can be found in the online
version, at doi:10.1016/j.tet.2009.06.096.
1003, 835 cmꢀ1
; dH (400 MHz, CDCl3) 7.04 (4H, br s, Ar-H), 6.56
and 6.22 (2H, 2d, J 4.8 Hz, C(C]CH2)), 4.20 (2H, d, J 11.4 Hz,
ArCH2), 3.82 (3H, s, OCH3), 3.53 (2H, d, J 22.4 Hz, PCH2), 2.28 (6H,
s, 2CH3), 1.41 (18H, s, 6ꢂCH3); dC (100 MHz, CDCl3) 166.5 (d, J
7.0 Hz), 144.9, 141.0, 134.7, 132.9, 130.8, 130.2, 130.1, 129.0, 127.6,
52.5, 34.9, 34.4, 31.1, 29.7 (d, J(P–C) 149.0 Hz), 21.0; dP (160 MHz,
CDCl3) 18.5.
References and notes
1. Some recent reviews on P(O)H addition to C]C or C^C bonds: (a) Baillie,
C.; Xiao, J. Curr. Org. Chem. 2003, 7, 477; (b) Tanaka, M. Top. Curr. Chem.
2004, 232, 25; (c) Montchamp, J.-L. J. Organomet. Chem. 2005, 690, 2388;
(d) Enders, D.; Saint-Dizier, A.; Lannou, M.-I.; Lenzen, A. Eur. J. Org. Chem.
2006, 29; (e) Troev, K. D. Chemistry and Application of H-Phosphonates;
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Rev. 2004, 104, 3079; (g) Beletskaya, I. P.; Kazankova, M. A. Russ. J. Org.
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4.6. Identification of intermediate 21a (or 21b) (see Fig. 1 in
the main text)
To phosphite (19) (1.0 mmol) in 5 mL of dry THF, 1.0 mmol of
TBAF (1.0 M THF solution) was added via syringe over a period of
2 min at room temperature under nitrogen atmosphere. After
2 h, the solvent was removed under reduced pressure to get 21a
(or 21b) as gummy material. The spectra are shown in the main
text, Figure 1. The spectra related to the reaction using thio-
1
2
phosphite 20 [(a) 1H NMR:
d
¼8.28 (dd, J(P–H)¼606 Hz and J(F–
¼104 Hz); (b) 31P NMR [proton decoupled, 160 MHz]:
d
¼59.0
H)
and 52.8 (d, J(P–F)¼1006 Hz); (c) 31P NMR [proton coupled,
1
1
160 MHz]:
d
¼59.1 and 52.9 (1J(P–F)¼1006 Hz and J(P–H)¼606 Hz);
(d) 19F NMR [376.8 MHz]:
d
¼ꢀ32.9 and ꢀ33.1 (dd, J(P–F)
¼
1

7610
E. Balaraman et al. / Tetrahedron 65 (2009) 7603–7610
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O
O
..
O
P
CH2O P
NC
H
H
H
O
O
Ph
CN
Ph
H
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(P) 121.7
(P, 80 MHz) 14.6; yield 7%
10. Compound 1b reacted with Baylis–Hillman acetates nearly three times faster
than 1a.
11. (a)Han, L.-B.;Tanaka, M. J. Am. Chem. Soc.1996,118,1571; (b) Jessop, C. M.; Parsons,
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´
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K.; Vittal, J. J.; Kumara Swamy, K. C. Synlett 2002, 1787.
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9. This statement refers to the following reaction (cf. ref. 7).