Triflic acid mediated functionalization of α-hydroxyphosphonates: Route for sulfonamide phosphonates

Article abstract of DOI:10.1039/c3ra43823f

An operationally simple synthetic method for (±)-α-aryl/ methylsulfonamidomethylphosphonates and new (±)-γ-aryl/methyl sulfonamidomethylvinylphosphonates has been developed through straightforward reactions of (±)-α-hydroxyphosphonates with sulfonamides in the presence of triflic acid (TfOH) at room temperature in a vessel open to air. For γ-dimethylallylhydroxyphosphonate, the (E)-1,3-butadienylphosphonate was formed quantitatively using TfOH while FeCl₃ afforded the expected product in moderate yield unpredictably. The favourable sulfonoamidation of benzyl alcohol is also observed when TfOH was used for α- hydroxyphosphonates having a benzyloxy group. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra43823f

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Triflic acid mediated functionalization of
a-hydroxyphosphonates: route for sulfonamide
phosphonates†
Cite this: RSC Adv., 2013, 3, 20503
Gangaram Pallikonda and Manab Chakravarty*
An operationally simple synthetic method for (ꢀ)-a-aryl/methylsulfonamidomethylphosphonates and new
ꢀ)-g-aryl/methyl sulfonamidomethylvinylphosphonates has been developed through straightforward
reactions of (ꢀ)-a-hydroxyphosphonates with sulfonamides in the presence of triflic acid (TfOH) at
(
Received 22nd July 2013
room temperature in
a
vessel open to air. For g-dimethylallylhydroxyphosphonate, the (E)-1,3-
afforded the expected
Accepted 12th August 2013
butadienylphosphonate was formed quantitatively using TfOH while FeCl
3
DOI: 10.1039/c3ra43823f
product in moderate yield unpredictably. The favourable sulfonoamidation of benzyl alcohol is also
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observed when TfOH was used for a-hydroxyphosphonates having a benzyloxy group.
(
because of their instability) and metal salts (to activate the
Introduction
imines). Recently reported I (ref. 6a) and Amberlyst-15 (ref. 6h)
2
The sulfonamide phosphonates form a class of distinct organ- catalyzed methods explored the synthesis of sulfonamide
ophosphorus compounds where medicinally relevent sulfon-
phosphonates by reacting only N-tosylaldimines (freshly
1
amide bears the phosphonate unit. These compounds are
prepared) with expensive and moisture-sensitive dialkyl trime-
1
b
ꢁ
utilized as potential candidates for uorescent b-lactamase
thylsilylphosphites at 0 C under inert atmosphere (Scheme 1).
and matrix metalloproteinase (MMPs) inhibitors as an analogue It is again noteworthy that the syntheses of N-sulfonylimines
6
e
of known MMP inhibitors such as carboxylate and hydrox- prefer the induction of TiCl , Si(OEt) , BF etc. or multistep
4
4
3
1c,d
6
a,1d
amate.
In addition, these compounds are also well recog- transformation along with special apparatus.
The reported yields of related sulfonamide phosphonates
properties with selected lanthanides and actinides. Moreover, obtained from tosylation reaction of a-aminophosphonate is
1a
nized as ame retardant materials along with their binding
2
6f
sulfonamide phosphonates can be regarded as N-protected a- or
also inadequate. The most recent synthetic method for g-ami-
g-aminophosphonates, one of the most-desired structural
novinylphosphonates also required excess imines and Ti(II)
7
motifs in bioorganic and medicinal chemistry due to its unique
complexes at very low temperature.
The g-amino-
3
biological properties. The related desulfonations are also well vinylphosphonates, thus synthesized, are already proved to be
4
7a
explored. Thus, synthesis of protected or deprotected amino- potent anti-inammatory agents. In this regard, any simple
3,5
phosphonates has been pursued by several research groups.
synthetic method that avoids the use of imines, metals and also
The direct addition of imines with phosphites, preferably in the can be performed in open air at room temperature with water as
presence of metal salt, is the most common approach for a by-product would be attractive for medicinal/organic chemists.
5
synthesizing a-aminophosphonates but synthesizing N-sulfo-
A synthetic method performed at room temperature is always
nylimines requires special treatment due to the weak nucleo-
philicity of sulfonamides. Therefore, attempts for synthesis of
benecial as far as energy consumption is concerned. Hence,
6c
8
with our current interest on organophosphonates, specically
8a
specic a-sulfonamide phosphonates are sporadically in the umpolung reactivity of allyllic phosphonates, we
1,6
mentioned in the literature
but g-sulfonamide vinyl- present here an operationally simple, new and efficient
phosphonates described herein are completely new. Most of
these synthetic methods require freshly prepared imines
Department of Chemistry, Birla Institute of Technology and Sciences, Pilani
Hyderabad Campus, Shamirpet, Hyderabad-500078, AP, India. E-mail: manab@
hyderabad.bits-pilani.ac.in; Fax: +91-040 6630 3998; Tel: +91-040 6630 3537
†
Electronic supplementary information (ESI) available: General informations
1
13
and references for the synthesis of precursors, H and C NMR spectra. CCDC
34282 (5a). For ESI and crystallographic data in CIF or other electronic format
9
6
a,f
see DOI: 10.1039/c3ra43823f
Scheme 1 Reported recent methods for a-sulfonamide phosphonates.
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TfOH-mediated route to synthesize a-aryl/methylsulfonami- Table 1 TfOH mediated reactions of sulfonamides with a-hydroxyphosphonates
a
(
ꢀ)-1a–c
domethylphosphonates and more distinctively g-aryl/me-
thylsulfonamidomethylvinylphosphonates in moderate to high
yield using cheap and easily accessible a-hydroxyphosphonates
under mild conditions. We envisage that these new g-aryl/me-
thylsulfonamidomethylvinylphosphonates, described herein,
will enhance the potential in the eld of materials as well as
biological sciences due the presence of sulfonamide at the
g-position for a useful vinylphosphonate.
b
c
Entry
1
1/R
Product
(ꢀ)-2/Yield (%)
Results and discussion
Synthesis of (ꢀ)-a-aryl/methylsulfonamidomethyl-
phosphonates
1a/4-MeC H –
2a/94
2b/90
2c/92
2d/90
6
4
Initially, we preferred phosphonate (ꢀ)-1a and p-toluenesulfo-
2
namide (TsNH ) as model substrates to optimize the suitable
reaction conditions using different Lewis and Brønsted acids
see ESI† for details). The reported method of using FeCl for
2
3
4
6 5
1a/C H –
(
3
this type of transformation could not offer a satisfactory result
9
even under reux in nitromethane. With a possibility of
1a/4ClC
6
H
4
–
hydrolyzing the alkoxy bonds of phosphonates, we tried the
same reaction with TfOH, known to show a comparative effect
as FeCl3 in allylic amination reactions starting from allylic/
1
0
1a/4-NO
2
C
6
H
4
–
benzylic alcohols. Both FeCl
catalyst for the reaction of benzylic/allylic alcohols with TsNH
ref. 10) whereas sulfonamide phosphonate (ꢀ)-2a was isolated
effectively from the reaction of hydroxyphosphonate (ꢀ)-1a with
TsNH only in the presence of TfOH. This different effect was
observed probably due to the presence of phosphoryl group for
3
and TfOH worked very well as a
2
(
5
6
1a/4-NH C H –
2
6
4
2e/92
2f/80
2
(
ꢀ)-1a. Moreover, TfOH and its salts are extensively used for
3 6 4
1a/4-CF C H –
10,11
amination reactions of alcohols.
of TfOH in the reaction medium using triate salt, efforts of
treating Yb(OTf) and Cu(OTf) in place of TfOH were in vain.
Screening with different stoichiometry (mol%) of TfOH showed
that this reaction was mostly favoured with 60–100 mol% and it
might be due to the presence of a strong coordinating group
such as phosphonate for (ꢀ)-1a. The only known direct
approach from hydroxyphosphonates to only aminophos-
phonates with moderate yield was reported in the presence of
acidic alumina using a kitchen-type microwave oven. Using
the same approach, we could isolate the product (ꢀ)-2a with
only 25% yield whereas the g-sulfonamide phosphonate was
not formed even aer 30 min by starting with phosphonate
Considering the generation
12
3
2
0
7
8
1a/R ¼ Ph; R ¼ n-Bu–
2g/88
2h/85
13
1a/2-naphthyl–
14
9
1a/Me–
2i/91
2j/70
2k/73
(
I
ꢀ)-(E)-4a. Inspired by the report of Chan and co-workers on
1
1
0
1
6 4
1b/4-MeC H –
15
2
-catalyzed allylic alkylation of sulfonamides, our attempt to
use I2 for the synthesis of sulfonamide phosphonate failed
under the present reaction conditions. There was no difference
in the outcome even when the reaction was performed using LR
grade 1,4-dioxane without exclusion of air/moisture at room
temperature. Thus, TfOH/1,4-dioxane at room temperature
appears to be the most suitable condition for the synthesis of
sulfonamide phosphonates even in a vessel open to air.
6 4
1b/4-ClC H –
d
12
1c/4-MeC
6
H
4
–
2l/68
As the variations of substituents for sulfonamides reect the
1c,d
activity of sulfonamide phosphonates, we have explored this
reaction using different types of sulfonamides. The examples are
shown in Table 1. The yield and duration of the reaction did not
a
Reaction conditions: Phosphonate (1 mmol), sulfonamide (1 mmol) and
TfOH (1mmol) in1,4-dioxane(3mL) under openair atroom temperature.
b
0
c
d
Except for entry 7, all R ¼ H. Isolated yield. FeCl
3
/dichloroethane
differ much when the substituent (electron donating/accepting) (DCE) was used under nitrogen atmosphere at room temperature.
2
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is changed in aryl groups for arylsulfonamides. The meth-
anesulfonamide also worked very well to yield (ꢀ)-2i effectively.
The yield was also good (Table 1, entry 7) when comparatively
more electron rich N-butylsulfonamide was used. Notably, the
yield was relatively poor (Table 2, entry 10) when the phospho-
nate (ꢀ)-1b was used. Interestingly, along with the expected
compound (2j), we could also isolate the synthetically useful
sulfonamide (3a, Scheme 2) from the reaction mixture of (ꢀ)-1b
Scheme 2 TfOH catalyzed sulfonamidation of benzyl alcohol.
and TsNH
reaction of TsNH
2
. The compound 3a was formed perhaps from the
with benzyl alcohol, generated by the partial
2
Table 2 TfOH mediated reactions of sulfonamides with a-hydroxyphosphonates
a
acidic hydrolysis of phosphonate (ꢀ)-1b in the reaction mixture.
(
ꢀ)-4a–c
The known sulfonamide 3a was synthesized recently using
16
transition-metal (Ru, Mn etc.) catalyzed reactions. It is also
noteworthy that the primary benzylic alcohols did not react with
9
TsNH
2
using FeCl
3
even on prolonged heating. Inspired by
these related reports and further to verify our result, we treated
benzyl alcohol with only three sulfonamides separately in the
presence of a catalytic amount of TfOH (10 mol%) at room
temperature using 1,4-dioxane as solvent, which afforded
compounds 3a–c in moderate to good yield (Scheme 2). Even
though a similar approach was reported with allylic alcohols,
primary benzylic alcohol was not used in the literature using
b
c
Entry 4/R
Product
(E)-5/Yield (%)
10
this method. Thus, we believe that this facile metal-free
process should be added to the existing methods for the
synthesis of sulfonamides of type 3.
1
2
4a/4-MeC
6
H
4
–
5a/92
5b/90
Surprisingly, unlike (ꢀ)-1a and 1b, the phosphonate (ꢀ)-1c
2 3
reacted with TsNH in the presence of FeCl /dichloroethane
(DCE) in place of TfOH at room temperature. As expected, the
4a/C
6
H
5
–
presence of an electron donating group at the aryl part for
phosphonates is needed for this method.
Synthesis of (ꢀ)-g-aryl/methyl sulfonamidovinylphosphonates
3
4
4a/4-NO
2
C
6
H
4
–
5c/86
5d/82
Further, we have extended our studies to synthesize new
sulfonamide phosphonates regio- and stereoselectively where
the sulfonamide is attached to a g-carbon of a vinylphosphonate
by choosing the easily-accessible cheap phosphonates (ꢀ)-(E)-
0
4a/R ¼ Ph; R ¼ n-Bu–
4a–c. The newly synthesized sulfonamide phosphonates are
shown in Table 2. The reaction of (ꢀ)-(E)-4a with TsNH was not
2
3
clean in the presence of FeCl /DCE or nitromethane whereas
5
6
7
4a/Me–
5e/82
5f/88
5g/90
TfOH/1,4-dioxane gave almost quantitative yield of (ꢀ)-(E)-5a.
Indeed, compounds (ꢀ)-(E)-5a–c were isolated and puried
simply by crystallization from ethyl acetate. The phosphonate
(
ꢀ)-(E)-4b with an extra methyl group at b-C also afforded
6 4
4b/4-MeC H
expected products (ꢀ)-(E)-5e–f in high yields. There was no
evidence to account for the formation of g-aminophosphonate
from the reported reaction of (ꢀ)-(E)-4a with amines in the
14
4b/4ClC
6
H
4
–
literature. The TfOH-mediated method did not produce any
other possible isomeric products either with a (Z)-conguration
or sulfonamides attached at the a-carbon. It is important to note
that the g-aminovinylphosphonates were synthesized with
mainly E-conguration [Z-isomers: (0–33%)] by Lu et al. using
the umpolung reactivity of allylic phosphonates supported by
expensive Pd(PPh3)4 starting from a-acetoxyallylic phospho-
d
8
4c/4-MeC
6
H
4
5h/56
a
Reaction conditions: Phosphonate (1 mmol), sulfonamide (1 mmol)
17
nates and only amines under puried nitrogen.
b
and TfOH (1 mmol) in 1,4-dioxane (3 mL) in an open vessel. Except
0
c
d
Using TfOH, attempted reactions of sulfonamides
(mentioned here) with phosphonate (E)-4c led to the formation
entry 4, all R ¼ H. Isolated yield. TfOH gave the diene and hence
FeCl /DCE was used under nitrogen atmosphere.
3
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of (E)-1,3-dienylphosphonate 6 quantitatively instead of form- showed the characteristic doublet of doublet at ꢃd 4.80 (dd, J ꢃ
1
ing sulfonamide phosphonates. Unpredictably, the expected 9.6 and 24.0 Hz) for P–C(a)H in H NMR and a doublet at ꢃd
1
3
product (E)-5h was obtained with moderate yield along with 54.9 (d, J ꢃ 159.0 Hz) for P–C(a)H in C NMR spectra. The
diene 6 by the employment of FeCl /DCE at room temperature. stereochemistries for compounds (E)-(ꢀ)-5a–h including 6 are
3
3
1
3
P NMR for the reaction mixture showed that the ratio of depicted by analysing the coupling constant ( JP–C ꢃ22.0–
1
3
product (E)-5h and diene (E)-6 formed is 70/30, respectively. The 24.0 Hz) between the phosphorus and g-carbon in C NMR by
7,20
formation of dienes could not be avoided even when the reac- comparing the values that are reported in the literature.
ꢁ
tion was performed at ꢂ30 C. It is worth noting that a similar Moreover, single-crystal X-ray crystallographic studies for (ꢀ)-5a
type of observation to form an elimination product from conrmed the (E)-conguration as well as the position (g) of
18
21
2
-phenylpropan-2-ol was reported in the literature. Moreover, sulfonamide unequivocally (Fig. 1).
the synthesis of 1,3-butadienylphosphonates is well demon-
strated by Srebnik et al. via zirconation of 1-alkynylphospho- previous studies,
Thus, based on the observed experimental results and
10–13,18
we believe that the reaction proceeds via
1
9a
nates.
precursor to synthesize phosphorus based polymers, used in conjugation effect of adjacent substituents. Unlike other Lewis
This diene compound (6) could also be used as a a carbocation intermediate that will be stabilized by inductive/
19b
the biomedical eld.
acids, TfOH promotes the formation of a carbocation from
The sulfonamide phosphonates, synthesized herein, are a-hydroxyphosphonate, which is relatively hard to achieve,
1
13 31
characterized using multinuclear NMR ( H/ C/ P) spectros- without any other side reactions such as coordination with
copy. The sulfonamide phosphonates (ꢀ)-2a–l (except 2g) phosphoryl group, alkene and sulfonamide.
In case of simple a-hydroxy (aryl)phosphonates (1a–c), the
intermediate carbocation is stabilized by electron donating
substituents present in the aryl group (+I effect), followed by
nucleophilic attack of sulfonamide to yield the desired (ꢀ)-a-
aryl/methylsulfonamidomethylphosphonate (Scheme 3a). In
case of a-hydroxy allylicphosphonates (4a–b; where R
1
¼ Ph and
R
2
¼ H), it is expected that the generated carbocation at the
a-carbon (to phosphonate moiety) is stabilized by an adjacent
double bond via a resonance effect and thus generated a more
stable carbocation at a g-carbon (which is further stabilized by a
+
R effect of aryl groups), followed by nucleophilic attack of
sulfonamide (SN1 type mechanism), which selectively leads to
ꢀ)-g-aryl/methyl sulfonamidomethylvinylphosphonates in very
good yields (Scheme 3b). In case of compound 4c (where R
¼ Me), the carbocation (at g-carbon) undergoes elimination
E1 type) rather than nucleophilic substitution reaction, and
(
1
¼
R
2
(
yielded diene (E)-6 as the sole product under this condition.
Thus, we conclude that the reaction proceeds via carbocation
Fig. 1 ORTEP diagram (with 20%) probability labels for compound (E)-(ꢀ)-5a.
Scheme 3 A plausible mechanism for the formation of sulfonamide phosphonates and diene.
2
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intermediate and selectively leads to the expected products in
very good yields.
(ꢀ)-Diethyl (4-methoxyphenyl)(phenylsulfonamido)methyl-
phosphonate (2b). The reaction was stirred for 6 h at room
ꢁ
temp. Yield 0.679 g (90%); white solid; mp 132–135 C; IR (KBr,
ꢂ1
1
cm ) 3117, 1611, 1516, 1460, 1394, 1325, 1232, 1157, 1029; H
NMR (400 MHz, CDCl
Conclusions
3
) d 1.06 and 1.36 (two sets of triplets, J ¼
In conclusion, TfOH has been efficiently used to synthesize a 7.1 Hz each, 6H), 3.58–3.81 (m, 1H), 3.85 (s, 3H), 3.87–3.91 (m,
variety of sulfonamide phosphonates (specically new (ꢀ)-g- 1H), 4.23–4.28 (m, 2H), 4.56 (dd, J ¼ 9.6 and 24.1 Hz, 1H), 6.59
aryl/methylsulfonamidomethylvinylphosphonates)
from a-hydroxyphosphonates and directly sulfonamides (not
starting (d, J ¼ 8.5 Hz, 2H), 7.05–7.44 (m, 6H), 7.58 (d, J ¼ 7.2 Hz, 2H);
13
3
C NMR (101 MHz, CDCl ) d 16.2 and 16.5 (two sets of doublets,
sulfonylimines) using an operationally simple method at room J ¼ 5.5 Hz each), 54.8 (d, J ¼ 159.3 Hz), 55.2, 63.5 and 64.1 (two
temperature in a vessel open to air. Although the method sets of doublets, J ¼ 7.1 Hz each), 113.5, 125.5, 126.9, 128.2,
3
1
appears very simple and obvious, it should be a metal-free facile 129.6, 131.7, 141.2, 159.2; P NMR (162 MHz, CDCl
alternative for highly demanding sulfonamide phosphonates Anal. Calc. for C18H24NO
6
3
) d 19.7.
PS: C, 52.29; H, 5.85; N, 3.39. Found:
including sulfonamides obtained from benzyl alcohol. The C, 52.15; H, 5.92; N, 3.31%.
water as a by-product and the selectivities for (ꢀ)-g-aryl/meth-
(ꢀ)-Diethyl (4-chlorophenylsulfonamido)(4-methoxyphenyl)-
ylsulfonamidomethylvinylphosphonates are added advantages. methylphosphonate (2c). This compound is synthesized in a
A new method for the synthesis of 1,3-butadienylphosphonate manner analogous to compound 2b by starting with 1a (0.300 g,
ꢁ
is also described. Initial antibacterial and antifungal studies for 1.094 mmol). Yield 0.450 g (92%); white solid; mp 163–165 C;
ꢂ1
these sulfonamide phosphonates has already been started with IR (KBr, cm ) 3092, 2930, 1614, 1516, 1470, 1394, 1333, 1237,
1
our collaborators.
1023; H NMR (400 MHz, CDCl
3
) d 1.10 and 1.40 (two sets of
triplets, J ꢃ 7.2 Hz each, 6H), 3.57–3.81 (m, 1H), 3.84 (s, 3H),
3
.87–3.91 (m, 1H), 4.27–4.34 (m, 2H), 4.77 (dd, J ¼ 9.6 and 25.6
Experimental
Hz, 1H), 6.58 (d, J ¼ 8.4 Hz, 2H), 7.08–7.12 (m, 4H), 7.37 (d, J ¼
1
3
8
1
1
.8 Hz, 2H), 7.54–7.57 (br, m, 1H); C NMR (101 MHz, CDCl ) d
The general experimental conditions and synthesis of the
precursors are described in ESI.†
3
6.2 and 16.5 (two sets of doublets, J ¼ 5.7 Hz each), 54.9 (d, J ¼
59.2 Hz), 55.3, 63.7 and 63.9 (two sets of doublets, J ¼ 7.1 Hz
each), 113.6, 125.2, 128.4, 128.5, 129.6 (d, J ¼ 6.0 Hz), 138.1,
General procedure for the synthesis of sulfonamide
phosphonate (ꢀ)-2a
31
1
39.8 (d, J ¼ 2.1 Hz), 159.4 (d, J ¼ 2.7 Hz); P NMR (162 MHz,
+
3
CDCl ) d 19.5; LC/MS m/z 448 [M + 1] . Anal. Calc. for
To a stirred solution of (ꢀ)-1a (0.5 g, 1.824 mmol) and p-tolue- C H ClNO PS: C, 48.27; H, 5.18; N, 3.13. Found: C, 48.36; H,
1
8
23
6
nesulfonamide (0.31 g, 1.824 mmol) in 1,4-dioxane (4 mL) open 5.08; N, 3.21%.
to the air, TfOH (0.16 mL, 1.824 mmol) was added. The reaction
mixture was stirred for 5 h at room temperature. Aer methylphosphonate (2d). This compound also was synthesized
completion of the reaction as indicated by TLC, the mixture was analogously by starting with 1a (0.300 g, 1.094 mmol) by stirring
(ꢀ)-Diethyl (4-methoxyphenyl)(4-nitrophenylsulfonamido)-
quenched with ice-cold water, and the aqueous layer was the reaction mixture for 8 h.
ꢁ
extracted with ethyl acetate (3 ꢄ 20 mL). The combined organic
Yield 0.450 g (90%); light yellow solid; mp 186–188 C; IR
ꢂ1
1
layer was dried over Na SO . Aer ltration and removal of (KBr, cm ) 3101, 1611, 1525, 1344, 1236, 1026; H NMR
2
4
solvent in vacuum, the crude product was puried by column (400 MHz, CDCl ) d 1.08 and 1.45 (two sets of triplets, J ¼ 7.1 Hz
3
chromatography using 65% ethyl acetate–petroleum ether as each, 6H), 3.58–3.65 (m, 1H), 3.67 (s, 3H), 3.88–3.92 (m, 1H),
eluent to afford compound (ꢀ)-2a as a white solid. All the other 4.34–4.41 (m, 2H), 4.83 (dd, J ¼ 24.2 and 10.1 Hz, 1H), 6.53 (d,
compounds (ꢀ)-2b–k were prepared analogously unless stated J ¼ 8.4 Hz, 2H), 7.09–7.12 (m, 2H), 7.71 (d, J ¼ 9.0 Hz, 2H), 7.93
1
3
otherwise.
(d, J ¼ 8.4 Hz, 2H), 8.21 (br, dd, J ¼ 10.0, 4.0 Hz, 1H); C NMR
(
ꢀ)-Diethyl (4-methoxyphenyl)(4-methylphenylsulfonamido)- (101 MHz, CDCl ) d 16.2 and 16.5 (two sets of doublets, J ¼ 5.5
3
methylphosphonate (2a). Yield 0.733 g (94%); white solid; mp Hz each), 55.1 (d, J ¼ 160.8 Hz), 55.2, 63.8 and 64.3 (two sets of
ꢁ
ꢂ1
1
1
6
1
44–148 C; IR (KBr, cm ) 3120, 2911, 1398, 1325, 1229, 1159, doublets, J ¼ 7.3 Hz each), 113.6, 123.2, 124.8, 128.3, 129.7 (d,
1
31
094; H NMR (400 MHz, CDCl ) d 1.06 and 1.35 (t, J ¼ 7.1 Hz, J ¼ 5.9 Hz), 147.2 (d, J ¼ 2.4 Hz), 149.2, 159.6 (d, J ¼ 2.7 Hz);
P
3
+
H), 2.28 (s, 3H), 3.56–3.85 (m, 1H), 3.88 (s, 3H), 3.89–4.12 (m, NMR (162 MHz, CDCl ) d 19.2; LC/MS m/z 459 [M + 1] . Anal.
3
H), 4.22–4.27 (m, 2H), 4.78 (dd, J ¼ 9.6 and 24.0 Hz, 1H), 6.60 Calc. for C H N O PS: C, 47.16; H, 5.06; N, 6.11. Found: C,
1
8
23 2 8
(d, J ¼ 8.8 Hz, 2H), 6.95 (br, 1H), 6.98 (d, J ¼ 8.1 Hz, 2H), 7.12 (dd, 47.23; H, 5.12; N, 6.21%.
13
J ¼ 8.7, 2.0, Hz, 2H), 7.46 (d, J ¼ 8.3 Hz, 2H); C NMR (101 MHz,
CDCl
) d 16.1 and 16.4 (two sets of doublets, J ¼ 5.8 Hz each), methylphosphonate (2e). The reaction was performed in
1.3, 54.7 (d, J ¼ 158.3 Hz), 55.2, 63.5 and 64.0 (two sets of manner similar to 2d using similar molar quantities. No
doublets, J ¼ 7.1 Hz each), 113.5, 125.7, 127.1, 128.9, 129.5 (d, column chromatography was used. The product was isolated by
(ꢀ)-Diethyl (4-aminophenylsulfonamido)(4-methoxyphenyl)-
3
2
3
1
J ¼ 6.0 Hz), 138.1, 142.5, 159.2 (d, J ¼ 2.7 Hz); P NMR (162 crystallization method from ethyl acetate. Yield 0.430 g (92%);
ꢁ
ꢂ1
MHz, CDCl ) d 19.8. Anal. Calc. for C H NO PS: C, 53.39; H, white solid; mp 197–199 C; IR (KBr, cm ) 3089, 2992, 2875,
3
19 26
6
1
6
.13; N, 3.28. Found: C, 53.26; H, 6.19; N, 3.21%. This compound 1614, 1514, 1461, 1328, 1230, 1164, 1023; H NMR (400 MHz,
6
g
is known in the literature.
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DMSO-d6) d 1.01 and 1.21 (t, J ¼ 7.1 Hz, 6H), 3.62–3.66 (m, 1H), 6.0 Hz), 131.8, 134.3, 137.8 (d, J ¼ 1.9 Hz), 159.0 (d, J ¼ 2.6 Hz);
3
1
+
3
1
(
.68 (s, 3H), 3.79–3.84 (m, 1H), 4.03–4.05 (m, 2H), 4.56 (dd, J ¼
P NMR (162 MHz, CDCl ) d 19.7; LC/MS m/z 464 [M + 1] . Anal.
3
0.3 and 24.1 Hz, 1H), 5.78 (br, 2H), 6.33 (d, J ¼ 8.6 Hz, 2H), 6.68 Calc. for C H NO PS: C, 57.01; H, 5.65; N, 3.02. Found: C,
2
2
26
6
d, J ¼ 8.6 Hz, 2H), 7.14–7.16 (m, 2H), 7.18 (d, J ¼ 8.0 Hz, 2H), 57.12; H, 5.58; N, 3.07%.
1
3
8.26 (dd, J ¼ 10.3 and 1.7 Hz, 1H); C NMR (101 MHz, DMSO-
(ꢀ)-Diethyl (4-methoxyphenyl)(methylsulfonamido)methyl-
d6) d 16.0 and 16.2 (two sets of doublets, J ¼ 5.6 Hz each), 53.8 phosphonate (2i). This reaction was performed using 1a
(
1
1
d, J ¼ 158.3 Hz), 54.9, 62.2 (d, J ¼ 6.9 Hz), 62.7 (d, J ¼ 6.9 Hz), (0.400 g) and reaction time was 8 h. Yield 0.466 g (91%); white
ꢁ
ꢂ1
12.0, 113.1, 126.4, 126.6, 128.3, 129.4 (d, J ¼ 5.9 Hz), 152.0, solid; mp 146–148 C; IR (KBr, cm ) 3118, 1614, 1585, 1518,
3
1
1
58.4 (d, J ¼ 2.6 Hz); P NMR (162 MHz, DMSO-d6) d 20.6; LC/ 1464, 1322, 1255, 1039; H NMR (400 MHz, CDCl
3
) d 1.10 and
+
MS m/z 429 [M + 1] . Anal. Calc. for C H N O PS: C, 50.46; H, 1.39 (two sets of triplets, J ꢃ 7.1 Hz each, 6H), 2.59 (S, 3H), 3.64–
1
8
25 2 6
5.88; N, 6.54. Found: C, 50.61; H, 5.82; N, 6.61%.
3.90 (m, 1H), 3.91 (s, 3H), 3.92–3.96 (m, 1H), 4.23–4.31 (m, 2H),
(
ꢀ)-Diethyl (4-methoxyphenyl)(4-(triuoromethyl)phenyl- 4.82 (dd, J ¼ 9.8 and 23.8 Hz, 1H), 6.91 (d, J ¼ 8.4 Hz, 2H), 7.48
1
3
sulfonamido)methylphosphonate (2f). This reaction was per- (d, J ¼ 8.7 Hz, 2H); C NMR (101 MHz, CDCl
3
) d 16.2 and 16.4
formed using 1a (0.200 g, 0.729 mmol) and reaction time was 8 (two sets of doublets, J ¼ 5.8 Hz each), 42.1, 54.5 (d, J ¼ 163.9
ꢁ
h. Yield 0.280 g (80%); white solid; mp 154–156 C; IR (KBr, Hz), 55.3, 63.7 and 64.0 (two sets of doublets, J ¼ 7.1 Hz each),
ꢂ1
1
31
cm ) 3087, 1615, 1516, 1462, 1321, 1235, 1172, 1027; H NMR 114.3, 126.4, 129.6 (d, J ¼ 5.9 Hz), 159.8 (d, J ¼ 2.2 Hz); P NMR
+
(
400 MHz, CDCl
3
) d 1.06 and 1.43 (two sets of triplets, J ¼ 7.1 Hz (162 MHz, CDCl
3
) d 19.9; LC/MS m/z 352 [M + 1] . Anal. Calc. for
each, 6H), 3.57–3.63 (m, 1H), 3.68 (s, 3H), 3.82–3.91 (m, 1H), C H NO PS: C, 44.44; H, 6.31; N, 3.99. Found: C, 44.56; H,
1
3
22
6
4
.30–4.38 (m, 2H), 4.80 (dd, J ¼ 10.1 and 24.2 Hz, 1H), 6.52 (d, J 6.38; N, 3.91%.
8.5 Hz, 2H), 7.09 (d, J ¼ 10.4 Hz, 2H), 7.36 (d, J ¼ 8.3 Hz, 2H), (ꢀ)-Diethyl
namido)methylphosphonate (2j). This compound was synthe-
) d 16.2 and 16.5 (two sets of doublets, J ¼ sized by starting with 1b (0.300 g, 0.856 mmol) using the same
¼
(4-(benzyloxy)phenyl)(4-methylphenylsulfo-
1
3
7
.66 (d, J ¼ 8.4 Hz, 2H), 7.96 (br, dd, J ¼ 9.9, 3.7 Hz, 1H);
C
NMR (101 MHz, CDCl
3
5
.7 Hz each), 55.0, 54.9 (d, J ¼ 160.4 Hz), 63.8 and 64.2 (two sets procedure as 2g. Along with the product, compound 3a was also
of doublets, J ¼ 7.1 Hz each), 113.5, 124.8, 125.1, 125.2, 127.6, isolated from column by using 10% EtOAc in petroleum ether.
ꢁ
1
2
1
29.7 (d, J ¼ 6.0 Hz), 133.3 (q, J ¼ 32.8 Hz), 144.8, 159.4 (d, J ¼
Yield 0.300 g (70%); white solid; mp 147–149 C; IR (KBr,
3
1
ꢂ1
1
.6 Hz); P NMR (162 MHz, CDCl ) d 19.3; LC/MS m/z 482 [M + cm ) 3117, 2872, 1609, 1509, 1332, 1234, 1161, 1052; H NMR
3
+
] . Anal. Calc. for C H F NO PS: C, 47.40; H, 4.82; N, 2.91. (400 MHz, CDCl ) d 1.04 and 1.35 (two sets of triplets, J ¼ 7.2 Hz
1
9
23
3
6
3
Found: C, 47.56; H, 4.76; N, 2.98%.
each, 6H), 2.28 (s, 3H), 3.55–3.65 (m, 1H), 3.84–3.90 (m, 1H),
(
ꢀ)-Diethyl (N-butylphenylsulfonamido)(4-methoxyphenyl) 4.18–4.26 (m, 2H), 4.74 (dd, J ¼ 23.9 and 9.6 Hz, 1H), 4.97 (s,
methylphosphonate (2g). This reaction was performed using 1a 2H), 6.69 (d, J ¼ 8.5 Hz, 2H), 6.83–6.87 (m, br, 1H), 6.97 (d, J ¼
(
0.500 g) and reaction time was 12 h.
8.0 Hz, 2H), 7.12 (dd, J ¼ 8.7 and 2.0 Hz, 2H), 7.33–7.39 (m, 5H),
ꢂ1
13
Yield 0.750 g (88%), colorless gummy liquid; IR (KBr, cm
)
7.46 (d, J ¼ 8.3 Hz, 2H); C NMR (101 MHz, CDCl
3
) d 16.1 and
1
2
960, 1610, 1513, 1445, 1348, 1252, 1159, 1026; H NMR (400 16.5 (two sets of doublets, J ¼ 5.8 Hz each), 21.4, 54.7 (d, J ¼
MHz, CDCl ) d 0.79–0.82 (m, 3H), 1.06–1.09 (m, 3H), 1.15–1.18 158.2 Hz), 63.5 and 64.0 (two sets of doublets, J ¼ 7.1 Hz each),
3
(
3
2
m, 2H), 1.25–1.31 (m, 5H), 3.397–3.422 (m, 2H), 3.79 (s, 3H), 69.9, 114.5, 126.0, 127.1, 127.4, 128.0, 128.6, 128.9, 129.5 (d, J ¼
3
1
.94–4.21 (m, 4H), 5.43 (d, J ¼ 25.6 Hz, 1H), 6.80 (d, J ¼ 8.8 Hz, 8.5 Hz), 136.7, 138.1, 142.6, 158.5; P NMR (162 MHz, CDCl ) d
3
1
3
+
H), 7.40–7.78 (m, 5H), 7.79 (d, J ¼ 7.2 Hz, 2H); C NMR (101 19.8; LC/MS m/z 504 [M + 1] . Anal. Calc. for C25
) d 13.6, 16.2 and 16.4 (two sets of doublets, J ¼ 5.7 59.63; H, 6.01; N, 2.78. Found: C, 59.48; H, 6.08; N, 2.71%.
N-Benzyl-4-methylbenzenesulfonamide (3a), mp ¼ 115–
6
H30NO PS: C,
MHz, CDCl
3
Hz each), 20.2, 31.7, 46.6, 55.2, 56.8 (d, J ¼ 162.6 Hz), 62.7 and
ꢁ
ꢂ1
6
6
1
3.0 (two sets of doublets, J ¼ 7.4 Hz each), 113.8, 125.3 (d, J ¼ 117 C; yield 0.045 g (20%); white solid; IR (KBr, cm ) 3272,
1
.3Hz, 2H), 127.6, 128.7, 131.5 (d, J ¼ 8.6 Hz, 2H), 132.3, 140.7, 1598, 1496, 1319, 1167, 1089; H NMR (400 MHz, CDCl
3
) d 2.43
3
1
59.7; P NMR (162 MHz, CDCl ) d 20.4; LC/MS m/z 492 [M + (s, 3H), 4.11 (d, J ¼ 6.2 Hz, 2H), 4.87 (br t, J ¼ 6.1 Hz, 1H), 7.18–
3
+
+
Na] . Anal. Calc. for C H NO PS: C, 56.28; H, 6.87; N, 2.98. 7.31 (m, 7H), 7.75 (d, J ¼ 8.3 Hz, 2H); LC/MS m/z 262 [M + 1] .
2
2
32
6
7
Found: C, 56.15; H, 6.93; N, 2.85%.
ꢀ)-Diethyl (4-methoxyphenyl)(naphthalene-2-sulfonamido)
methylphosphonate (2h). This reaction was performed using 1a mido)methylphosphonate (2k). This compound was synthe-
This compound is known.
(
(ꢀ)-Diethyl (4-(benzyloxy)phenyl)(4-chlorophenylsulfona-
(
0.300 g) and reaction time was 8 h.
sized using similar procedure and molar quantities as 2j for 12 h.
ꢁ
ꢁ
Yield 0.430 g (85%); white solid; mp 142–144 C; IR (KBr,
Yield 0.320 g (73%); white solid; mp 138–142 C; IR (KBr,
ꢂ1
1
ꢂ1
1
cm ) 1614, 1514, 1461, 1328, 1230, 1023; H NMR (400 MHz, cm ) 3122, 1609, 1513, 1455, 1335, 1243, 1165, 1024; H NMR
CDCl ) d 1.03 and 1.35 (two sets of triplets, J ¼ 7.2 Hz each, 6H), (400 MHz, CDCl ) d 1.06 and 1.39 (two sets of triplets, J ¼ 7.1 Hz
3
3
3
2
7
.43 (s, 3H), 3.53–3.81 (m, 1H), 3.87–3.91 (m, 1H), 4.22–4.29 (m, each, 6H), 3.58–3.64 (m, 1H), 3.85–3.90 (m, 1H), 4.73–4.81 (m,
H), 4.82 (dd, J ¼ 9.7 and 23.8 Hz, 1H), 6.35 (d, J ¼ 8.4 Hz, 2H), 2H), 4.77 (dd, J ¼ 24.0 and 9.7 Hz, 1H), 4.99 (s, 2H), 6.68 (d, J ¼
.05–7.08 (m, 2H), 7.14–7.18 (br, m, 1H), 7.47–7.75 (m, 6H), 8.01 8.4 Hz, 2H), 7.11 (d, J ¼ 8.6 Hz, 4H), 7.34–7.42 (m, br, 6H), 7.48
1
3
13
(s, 1H); C NMR (101 MHz, CDCl
3
) d 16.1 and 16.4 (two sets of (d, J ¼ 8.4 Hz, 2H); C NMR (101 MHz, CDCl
3
) d 16.2 and 16.5
doublets, J ¼ 5.8 Hz each), 54.9 (d, J ¼ 158.2 Hz), 54.9, 63.7 and (two sets of doublets, J ¼ 5.7 Hz each), 54.8 (d, J ¼ 157.9 Hz),
6
1
3.9 (two sets of doublets, J ¼ 7.1 Hz each), 113.4 (d, J ¼ 2.1 Hz), 63.7 and 64.0 (two sets of doublets, J ¼ 7.1 Hz each), 70.1,
22.5, 125.1, 126.9, 127.5, 128.3, 128.4, 128.6, 129.0, 129.5 (d, J ¼ 114.6 (d, J ¼ 1.9 Hz), 125.4, 127.5, 128.1, 128.5, 128.6, 129.6
2
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(
d, J ¼ 6.0 Hz), 136.6, 138.3, 139.6 (d, J ¼ 1.9 Hz), 158.7 (d, J ¼ 2.7
N-Benzyl-4-chlorobenzenesulfonamide (3c). The reaction
3
1
+
Hz); P NMR (162 MHz, CDCl ) d 19.5; LC/MS m/z 524 [M + 1] . was stirred for 8 h at room temp. Yield 1.020 g (78%), as a white
Anal. Calc. for C H ClNO PS: C, 55.01; H, 5.19; N, 2.67. Found: solid. IR (KBr, cm ): 3248, 2643, 1916, 1575, 1475, 1331, 1177,
C, 55.16; H, 5.08; N, 2.58%.
3
ꢂ1
2
4
27
6
1
1092; H NMR (400 MHz, CDCl ) d 4.16 (d, J ¼ 6.4 Hz, 2H), 4.81
3
(
ꢀ)-Diethyl
(4-methyphenylsulfonamido)(p-tolyl)methyl- (br t, J ꢃ 6.0 Hz, 1H), 7.18–7.29 (m, 5H), 7.47 (d, J ¼ 8.4 Hz, 2H),
+
phosphonate (2l). Anhydrous FeCl
added to a stirred solution of 1c (0.3 g, 1.161 mmol) and p-tol- is known.
3
(0.188 g, 1.161 mmol) was 7.78 (d, J ¼ 8.4 Hz, 2H); LC/MS m/z 280 [M ꢂ 1] . This compound
16a
uenesolfonamide (0.19 g, 1.161 mmol) in 1,2-dichloroethane
(
3.0 mL) and then the reaction mixture was stirred at room
General procedure for the synthesis of (ꢀ)-g-
aminophosphonates 5a–g
temperature under N for 12 h. Aer completion of the reaction
as indicated by TLC, the reaction mixture was quenched with
2
saturated NH Cl solution, and the aqueous layer was extracted To a stirred solution of 4a (0.200 g, 0.740 mmol), p-toulene-
4
with ethyl acetate (2 ꢄ 15 mL). The combined organic layer was sulfonamide (0.120 g, 0.740 mmol) and 1,4-dioxane (3.0 mL), in
2 4
dried over Na SO . Aer ltration and removal of solvent in a round-bottom ask open to air at room temperature TfOH
vacuum, the crude product was puried by column chroma- (0.06 mL, 0.740 mmol) was added. The reaction mixture was
tography using 70% ethyl acetate–petroleum ether as the eluent stirred for 6–7 h. Aer completion of the reaction as indicated
to afford the product.
by TLC, the reaction mixture was quenched with ice cold water,
ꢁ
Yield 0.320 g (68%); white solid; mp 152–154 C; IR (KBr, and the aqueous layer was extracted with ethyl acetate (2 ꢄ
ꢂ1
1
cm ) 3142, 2889, 1598, 1459, 1341, 1241, 1162, 1050; H NMR 10 mL). The combined organic layer was dried over Na SO .
2
4
(
400 MHz, CDCl ) d 1.05 and 1.35 (two sets of triplets, J ¼ 7.2 Hz Aer ltration and removal of solvent in vacuum, the crude
3
each, 6H), 2.24 (s, 3H), 2.28 (s, 3H), 3.56–3.64 (m, 1H), 3.86–3.90 product was washed with ethyl acetate (2 ꢄ 5 mL). The resulting
m, 1H), 4.19–4.26 (m, 2H), 4.74 (dd, J ¼ 24.0 and 9.7 Hz, 1H), solid was recrystallized from ethyl acetate to yield compound
.89–6.97 (m, 5H), 7.08 (dd, J ¼ 8.1, 2.0 Hz, 2H), 7.45 (d, J ¼ 8.3 5a. Compounds 5b–c were prepared analogously using similar
(
6
1
3
3
Hz, 2H); C NMR (101 MHz, CDCl ) d 16.1 and 16.5 (two sets of molar quantities unless stated otherwise. In the case of 5d–g,
doublets, J ¼ 5.8 Hz each), 21.0, 21.3, 55.1 (d, J ¼ 157.5 Hz), 63.5 the crude product was puried by column chromatography
and 64.0 (two sets of doublets, J ¼ 7.0 Hz each), 127.0, 128.2 (d, using 80% ethyl acetate–petroleum ether as the eluent.
J ¼ 6.0 Hz), 128.6, 128.7 (d, J ¼ 2.1 Hz), 130.6, 137.4 (d, J ¼ 3.1
(E)-Diethyl 3-(4-methylphenylsulfonamido)-3-phenylprop-1-
3
1
Hz), 138.1 (d, J ¼ 1.8 Hz), 142.5; P NMR (162 MHz, CDCl ) enylphosphonate (5a). This compound was sparingly soluble in
3
+
ꢁ
d 19.7; LC/MS m/z 412 [M + 1] . Anal. Calc. for C19
5.46; H, 6.37; N, 3.40. Found: C, 55.38; H, 6.32; N, 3.51%.
H26NO PS: C, CDCl . Yield 0.288 g (92%); white solid; mp 155–160 C; IR (KBr,
5
3
ꢂ1
1
5
cm ) 3118, 2911, 1477, 1398, 1325, 1229, 1159, 1094; H NMR
400 MHz, CDCl ) d 1.26–1.32 (m, 6H), 2.39 (s, 3H), 3.98–4.05 (m,
(
3
4
7
H), 5.05 (br, 1H), 5.81–5.90 (m, 2H), 6.72–6.83 (m, 1H), 7.05–
General procedure for the TfOH catalyzed sulfonamidation of
benzyl alcohol
13
.20 (m, 7H), 7.62 (d, J ¼ 8.4 Hz, 2H); C NMR (101 MHz, CDCl
3
)
d 16.3 and 16.4 (d, J ¼ 6.3 Hz each), 21.5, 59.6 (d, J ¼ 23.3 Hz),
To a stirred solution of benzyl alcohol (0.500 g, 4.629 mmol), 61.9 and 62.0 (d, J ¼ 5.2 Hz), 118.5 (d, J ¼ 187.6 Hz), 127.2 (d, J ¼
p-toluenesolfonamide (0.790 g, 4.629 mmol) in 1,4-dioxane 16.4 Hz), 128.2, 128.9, 129.5, 137.6, 137.8, 137.9, 143.3, 150.1 (d,
3
1
(5.0 mL), TfOH (0.04 mL, 0.4629 mmol) was added under N
2
at J ¼ 6.2 Hz); P NMR (162 MHz, CDCl
3
) d 17.1; LC/MS m/z 424
+
room temperature and the reaction mixture was stirred for 8 h. [M + 1] . Anal. Calc. for C H NO PS: C, 56.73; H, 6.19; N, 3.31.
2
0
26
5
Aer completion of the reaction as indicated by TLC, the Found: C, 56.61; H, 6.07; N, 3.45%; X-ray structural analysis was
mixture was quenched with ice cold water, and the aqueous done on this sample to conrm the stereochemistry.
layer was extracted with ethyl acetate (2 ꢄ 100 mL). The
(E)-Diethyl
3-(phenylsulfonamido)-3-phenylprop-1-enyl-
combined organic layer was dried over Na
2
SO
4
. Aer ltration phosphonate (5b). This compound was also moderately soluble
ꢁ
and removal of solvent in vacuum, the crude product was in CDCl
3
ꢂ1
. Yield 0.274 g (90%); white solid; mp 178–184 C; IR
1
puried by column chromatogram using 30% ethyl acetate– (KBr, cm ) 3108, 2903, 1476, 1395, 1325, 1234, 1162, 1020; H
petroleum ether) as the eluent to afford the product. All the NMR (400 MHz, CDCl ) d 1.24–1.31 (m, 6H), 3.99–4.05 (m, 4H),
other compounds were prepared analogously using similar 5.07 (br, 1H), 6.71–6.82 (m, 1H), 7.03–7.04 (m, 2H), 7.15–7.18 (m,
3
1
3
molar quantities unless stated otherwise. All these compounds 3H), 7.35–7.38 (m, 2H), 7.46–7.49 (m, 1H), 7.71–7.74 (m, 2H);
are known in literature. NMR (101 MHz, CDCl
) d 16.3 and 16.4 (d, J ¼ 6.3 Hz each), 59.6
N-Benzyl-4-methylbenzenesulfonamide (3a). Yield 0.68 g (d, J ¼ 23.1 Hz), 61.9 and 62.0 (d, J ¼ 5.2 Hz), 118.6 (d, J ¼ 187.1
56%); data is given before. Hz), 126.9, 127.2, 128.3, 128.9, 132.5 (two peaks are merged),
C
3
16b
(
3
1
N-Benzylbenzenesulfonamide (3b). The reaction was stirred 137.7, 140.6, 149.9 (d, J ¼ 6.2 Hz); P NMR (162 MHz, CDCl
3
) d
+
for 9 h at room temp. Yield 0.810 g, (71%), as a white solid. IR 17.1; LC/MS m/z 410 [M + 1] . Anal. Calc. for C19
H
24NO
5
PS: C,
ꢂ1
(
1
(
(
KBr, cm ): 3332, 2926, 1967, 1895, 1447, 1325, 1221, 1157, 55.74; H, 5.91; N, 3.42. Found: C, 55.61; H, 5.98; N, 3.49%.
1
065; H NMR (400 MHz, CDCl ) d 4.14 (d, J ¼ 6.0 Hz, 2H), 4.87
(E)-Diethyl
3-(4-nitrophenylsulfonamido)-3-phenylprop-1-
3
br t, J ꢃ 6.0 Hz, 1H), 7.18–7.25 (m, 5H), 7.49–7.60 (m, 3H), 7.87 enylphosphonate (5c). Reaction was performed for 10 h at room
+
d, J ¼ 8.4 Hz, 2H); LC/MS m/z 246 [M ꢂ 1] . This compound is temperature using 4a (0.300 g). Yield 0.434 g (86%); light yellow
1
6b
ꢁ
ꢂ1
known.
solid; mp 162–164 C; IR (KBr, cm ) 3113, 1525, 1468, 1350,
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1
+
1
(
221, 1166, 1039; H NMR (400 MHz, CDCl
two sets of triplets, J ¼ 7.1 Hz each, 6H), 3.96–4.07 (m, 4H), 57.65; H, 6.45; N, 3.20. Found: C, 57.73; H, 6.41; N, 3.12%.
(E)-Diethyl 2-methyl-3-(4-chlorophenylsulfonamido)-3-phe-
3 5
) d 1.24 and 1.31 17.4; LC/MS m/z 438 [M + 1] . Anal. Calc. for C21H28NO PS: C,
5
1
5
8
6
1
1
1
5
.14–5.18 (m, br, 1H), 5.76 (ddd, J ¼ 18.8 Hz, 17.2 Hz, 1.6 Hz,
H), 6.78 (ddd, J ¼ 21.9 Hz, 17.1 Hz, 5.5 Hz, 1H), 7.05–7.78 (m, nylprop-1-enylphosphonate (5g). The reaction mixture was
H), 7.78 (d, J ¼ 8.8 Hz, 2H), 7.83–7.89 (m, 1H), 8.06 (d, J ¼ stirred for 12 h starting with 4b (0.500 g, 1.759 mmol). Yield 0.73
1
3
ꢁ
ꢂ1
.8 Hz, 2H); C NMR (101 MHz, CDCl
3
) d 16.2 and 16.3 (d, J ¼ g (90%); white solid; mp 120–125 C; IR (KBr, cm ) 3102, 2897,
1
.2 Hz each), 60.1 (d, J ¼ 23.5 Hz), 62.3 and 62.4 (d, J ¼ 5.7 Hz), 1643, 1478, 1327, 1218, 1163, 1026; H NMR (500 MHz, CDCl
3
) d
18.4 (d, J ¼ 188.0 Hz), 123.7, 127.3, 128.1, 128.3, 128.8, 137.4, 1.28–1.33 (m, 6H), 1.91 (s, 3H), 3.98–4.07 (m, 4H), 4.87 (d, J ¼ 8.0
3
1
47.1, 149.4, 149.9 (d, J ¼ 5.9 Hz); P NMR (162 MHz, CDCl
3
) d Hz, 1H), 5.79–5.83 (m, 2H), 7.01–7.02 (m, 2H), 7.19–7.24 (m,
+
13
6.6; LC/MS m/z 455 [M + 1] . Anal. Calc. for C H N O PS: C, 3H), 7.35–7.36 (m, 2H), 7.64–7.67 (m, 2H); C NMR (126 MHz,
1
9
23 2 7
0.22; H, 5.10; N, 6.16. Found: C, 50.32; H, 5.06; N, 6.23%.
E)-Diethyl 3-(N-butylphenylsulfonamido)-3-phenylprop-1- 61.8 and 61.9 (d, J ¼ 5.6 Hz), 64.7 (d, J ¼ 22.9 Hz), 114.4 (d, J ¼
enylphosphonate (5d). Reaction was performed with 4a (0.500 189.1 Hz), 127.5, 128.6, 128.7, 129.2, 129.4, 137.5, 139.1, 139.2,
CDCl ) d 16.5 and 16.6 (d, J ꢃ 5.8 Hz each), 18.2 (d, J ¼ 6.8 Hz),
3
(
3
1
g) for 12 h at room temperature. Yield 0.706 g (82%), gummy 158.3 (d, J ¼ 8.2 Hz); P NMR (162 MHz, CDCl
3
) d 17.2; LC/MS
PS: C, 52.46; H,
3
) d 0.66–0.69 (m, 3H), 0.991–1.04 (m, 5.50; N, 3.06. Found: C, 52.36; H, 5.58; N, 3.12%.
ꢂ1
+
colorless liquid; IR (KBr, cm ) 2985, 1634, 155, 1324, 1031, 974; m/z 458 [M + 1] . Anal. Calc. for C20H25NClO
5
1
H NMR (400 MHz, CDCl
3
5
7
H), 1.28–1.34 (m, 7H), 3.03–3.05 (m, 2H), 3.99–4.08 (m, 4H),
.71–5.79 (m, 2H), 6.82–6.94 (m, 1H), 7.12–7.13 (m, 2H), 7.27–
1
3
FeCl -mediated reaction of 4c with TsNH
3 2
.28 (m, 3H), 7.46–7.58 (m, 3H), 7.79–7.82 (m, 2H); C NMR
(
3
101 MHz, CDCl ) d 13.4, 16.3 and 16.4 (d, J ¼ 6.3 Hz each), 19.9, Anhydrous FeCl (0.218 g, 1.35 mmol) was added to a stirred
3
3
2.3, 45.6, 61.8 and 61.9 (d, J ¼ 5.7 Hz each), 62.9 (d, J ¼ 23.3 solution of 4c (0.300 g, 1.35 mmol) and TsNH (0.230 g, 1.35
2
Hz), 121.1 (d, J ¼ 186.7 Hz), 127.2, 128.4, 128.5, 128.7, 129.1, mmol) in 1,2-dichloroethane (4.0 mL) and the reaction mixture
3
1
1
32.5, 136.7, 140.7, 148.1 (d, J ¼ 5.9 Hz); P NMR (162 MHz, was stirred at room temperature under N for 6 h. The crude
2
CDCl
3
) d 16.9. a small peak (ꢃ8%) which appeared at d 18.7 product was puried by column chromatography using EtOAc–
+
might be due to other isomers. LC/MS m/z 466 [M + 1] . Anal. petroleum ether as the eluent to afford the diene 6 (using 20%
Calc. for C H NO PS: C, 59.34; H, 6.93; N, 3.01. Found: C, EtOAc in petroleum ether) followed by compound 5h (70%
2
3
32
5
59.42; H, 6.85; N, 3.08%.
EtOAc in petroleum ether).
(
E)-Diethyl 3-(methylsulfonamido)-3-phenylprop-1-enyl-
(E)-Diethyl 3-methyl-3-(N-butylphenylsulfonamido)-3-phe-
phosphonate (5e). This reaction was performed using 4a (0.200 nylprop-1-enylphosphonate (5h). Anhydrous FeCl (0.218 g, 1.35
3
g, 0.740 mmol), methanesulfonamide (0.14 g, 1.48 mmol) and mmol) was added to a stirred solution of 4c (0.300 g, 1.35 mmol)
TfOH (0.065 mL, 0.740 mmol) in 1,4-dioxane (3.0 mL) under air and p-toulenesolfonamide (0.230 g, 1.35 mmol) in 1,2-dichlo-
at room temperature for 14 h. Yield 0.21 g (82%), white solid; roethane (4.0 mL) and the reaction mixture was stirred at room
ꢁ
ꢂ1
mp 93–95 C; IR (KBr, cm ) 3133, 1625, 1464, 1317, 1151, 1043; temperature under N
2
for 6 h. The crude product was puried by
1
H NMR (400 MHz, CDCl ) d 1.26–1.33 (m, 6H), 2.70 (s, 3H), column chromatography using (70% ethyl acetate–petroleum
3
4
.02–4.11 (m, 4H), 5.21–5.23 (br, 1H), 5.89–5.98 (m, 1H), 6.13 (d, ether) as the eluent to afford 5h.
ꢁ
J ¼ 8.2 Hz, 1H), 6.88 (ddd, J ¼ 21.8, 17.1, 5.3 Hz, 1H), 7.32–7.38
Yield 0.285 g (56%); white solid; mp 92–95 C; IR (KBr,
1
3
ꢂ1
1
(m, 5H); C NMR (101 MHz, CDCl
3
) d 16.3 and 16.4 (d, J ¼ 6.2 cm ): 3114, 1631, 1322, 1222, 1144, 1030; H NMR (400 MHz,
Hz each), 41.9, 59.7 (d, J ¼ 23.2 Hz), 62.1 and 62.2 (d, J ¼ 5.7 Hz CDCl ) d 1.31–1.34 (m, 12H), 2.42 (m, 3H), 4.03–4.09 (m, 4H),
3
each), 118.4 (d, J ¼ 187.4 Hz), 127.4, 128.5, 129.2, 138.5, 150.4 5.06 (s, br, 1H), 5.79 (dd/t, J ¼ 17.6 Hz each, 1H), 6.69 (dd, J ¼
3
1
(
d, J ¼ 5.9 Hz); P NMR (162 MHz, CDCl ) d 16.9; LC/MS m/z 348 22.4 and 17.6 Hz, 1H), 7.28 (d, J ¼ 8.0 Hz, 2H), 7.75 (d, J ¼ 8.4
3
+
13
[M + 1] . Anal. Calc. for C14
H22NO
5
PS: C, 48.41; H, 6.38; N, 4.03. Hz, 2H); C NMR (101 MHz, CDCl
3
) d 16.4 (d, J ¼ 6.3 Hz), 21.5,
Found: C, 48.29; H, 6.31; N, 4.07%.
27.3, 57.4 (d, J ¼ 21.9 Hz), 61.9 (d, J ¼ 5.4 Hz), 114.9 (d, J ¼ 187.0
3
1
(
E)-Diethyl 2-methyl-3-(4-methylphenylsulfonamido)-3-phe- Hz), 126.9, 129.6, 140.1, 143.1, 156.6 (d, J ¼ 4.8 Hz); P NMR
+
nylprop-1-enylphosphonate (5f). This compound was synthe- (162 MHz, CDCl ) d 18.2; LC/MS m/z 376 [M + 1] . Anal. Calc. for
3
sized by using 4b (0.300 g, 1.055 mmol), p-toulenesolfonamide C H NO PS: C, 51.19; H, 6.98; N, 3.73. Found: C, 51.26; H,
1
6
26
5
(0.18 g, 1.055 mmol) and 1,4-dioxane (3.0 mL) in the open air at 6.91; N, 3.65%.
room temperature for 10 h in the presence of TfOH (0.09 mL,
(E)-Diethyl 3-methylbuta-1,3-dienylphosphonate (6). Yield
ꢁ
1
1
.055 mmol). Yield 0.410 g (88%); white solid; mp 140–142 C; 0.055 g (20%); H NMR (400 MHz, CDCl
3
) d 1.26 (t, J ¼ 7.2 Hz
ꢂ1
1
IR (KBr, cm ) 3122, 1628, 1476, 1325, 1224, 1163, 1020; H each, 6H), 1.79 (s, 3H), 3.88–4.12 (m, 4H), 5.24–5.25 (br, 2H),
1
3
NMR (500 MHz, CDCl ) d 1.29–1.33 (m, 6H), 1.90–1.91 (m, 3H), 5.55–5.64 (m, 1H), 7.09 (dd, J ꢃ 18 and 21.8 Hz, 1H); C NMR
3
2
.41 (s, 3H), 3.98–4.07 (m, 4H), 4.80 (d, J ¼ 7.0 Hz, 1H), 5.05 (d, (101 MHz, CDCl ) d 16.2 (d, J ¼ 6.3 Hz each), 17.6, 61.6 (d, J ¼ 5.6
3
J ¼ 6.9 Hz, 1H), 5.88 (d, J ¼ 17.5 Hz, 1H), 6.99 (dd, J ¼ 7.5, 1.9 Hz, Hz), 114.6 (d, J ¼ 191.6 Hz), 123.6, 140.6 (d, J ¼ 23.8 Hz), 151.0
1
3
31
2
H), 7.22–7.24 (m, 5H), 7.65 (d, J ¼ 8.3 Hz, 2H); C NMR (126 (d, J ¼ 6.1 Hz); P NMR (162 MHz, CDCl ) d 19.9; LC/MS m/z 205
3
+
19c
MHz, CDCl
3
) d 16.5 and 16.6 (d, J ꢃ 5.8 Hz each), 18.0 (d, J ¼ 6.8 [M + 1] . This compound is known in the literature. In the
Hz), 21.7, 61.6 and 61.8 (d, J ¼ 5.6 Hz), 64.7 (d, J ¼ 23.0 Hz), presence of TfOH, the phosphonate 4c gives this diene 6 with a
1
1
14.4 (d, J ¼ 188.4 Hz), 127.3, 127.4, 128.7, 129.2, 129.8, 137.4, quantitative yield at room temperature within 2 h under
31
37.8, 143.8, 158.4 (d, J ¼ 8.5 Hz); P NMR (162 MHz, CDCl
3
) d nitrogen atmosphere using 1,4-dioxane as solvent.
2
0510 | RSC Adv., 2013, 3, 20503–20511
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RSC Advances
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Acknowledgements
We thank Department of Science and Technology-FAST TRACK
for nancial support. We also thank Research Initiation grant
(BITS, Pilani) for an additional nancial support. Special thanks
go to Mr Satish, Mr Swamy, Mr Ramesh, Mr Srinivasa and Dr
Moloy Sarkar for helping in many ways. We gratefully thank Dr E.
Balaraman for a useful discussion while writing the manuscript.
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(
c) using Barbier type conditions (Zn): R. Fan, D. Pu, F. Wen, 21 Colorless block, C20
H
26NO
5
PS, M ¼ 423.45, triclinic, space
ꢀ
˚
Y. Ye and X. Wang, J. Org. Chem., 2008, 73, 3623; (d) By using
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group P1, a ¼ 10.8332(8), b ¼ 10.9777(8), c ¼ 10.9787(8) A,
3
˚
V ¼ 1078.87(14) A , Z ¼ 2, data/restraints/parameters: 3780/
0/257, R indices (I > 2s(I)): R
1
¼ 0.0472, wR (all data) ¼
2
3
Using BF : ; (e) J. Vicario, J. M. Ezpeleta and F. Palacios,
0.1290.
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 20503–20511 | 20511