Regioselective Oxidative C-H Phosphonation of Imidazo[1,2-a]pyridines and Related Heteroarenes Mediated by Manganese(III) Acetate

Article abstract of DOI:10.1002/ejoc.201500984

Herein, we report a Mn^III-mediated regioselective method for the direct C-H phosphonation of imidazo[1,2-a]pyridines by using dialkyl phosphites. 3-Phosphonated imidazo[1,2-a]pyridines are synthesized in good to excellent yields under the optimized reaction conditions. The present method is also applicable to the functionalization of related heteroarenes, and unlike previously reported methods, the present strategy works well with (NH)-heteroarenes. Regioselective synthesis of phosphonylated heteroarenes: A mild, direct, and regioselective C-H phosphonation of imidazo[1,2-a]pyridines and related heteroarenes has been developed. Unlike those previously reported, the present method also works with (NH)-heteroarenes.

Full text of DOI:10.1002/ejoc.201500984

FULL PAPER
DOI: 10.1002/ejoc.201500984
Regioselective Oxidative C–H Phosphonation of Imidazo[1,2-a]pyridines and
Related Heteroarenes Mediated by Manganese(III) Acetate
Mahipal Yadav,[ Saidulu Dara,
a,b]
[a,c]
Varma Saikam,
[a,c]
Mukesh Kumar,
[a]
Sravan Kumar Aithagani,[ Satya Paul, Ram A. Vishwakarma,
a,c]
[b]
[a,b]
and
Parvinder Pal Singh*[
a,c]
Keywords: Synthetic methods / C–H functionalization / Regioselectivity / Nitrogen heterocycles / Phosphorus / Manganese /
Radicals
III
Herein, we report a Mn -mediated regioselective method for
optimized reaction conditions. The present method is also ap-
plicable to the functionalization of related heteroarenes, and
the direct C–H phosphonation of imidazo[1,2-a]pyridines by
using dialkyl phosphites. 3-Phosphonated imidazo[1,2-a]pyr- unlike previously reported methods, the present strategy
idines are synthesized in good to excellent yields under the
works well with (NH)-heteroarenes.
Introduction
Imidazo[1,2-a]pyridines have attracted significant inter-
est among the medicinal chemistry community because of
[1]
their promising and diverse bioactivity, which includes
[
1e,2]
[3]
[4]
[5]
antiviral,
antiulcer, antifungal, antibacterial, anti-
[
6]
[7]
cancer, and antituberculosis properties. This class of
compounds has also been described as calcium channel
[
8]
[9]
blockers, cyclin-dependent kinase (CDK) inhibitors,
and GABAA receptor modulators.[
10]
Importantly, imid-
azo[1,2-a]pyridine is the key structural unit in many com-
mercially available drugs (some are shown in Figure 1) such
[
11]
[12]
[16]
[13]
[14]
as zolpidem,
saripidem,
alpidem,
zolimidine,
olprinone,
[
15]
[17]
GSK812397,
and minodronic acid.
Be-
cause of its importance in medicinal chemistry, significant
work has been carried out for the diversification of imid-
azo[1,2-a]pyridines (Scheme 1) through a C–H functionaliz-
Figure 1. Imidazo[1,2-a]pyridine-based drugs.
[
18–25]
ation strategy.
However, to date, no attention has been
Our continued interest in medicinal chemistry and the
[
27–29]
paid to the synthesis of its phosphonated analogues. As development of new methodologies,
motivated us to
phosphonated heteroaryls are also historically known for establish an approach for the phosphonation of imidazo-
their pharmaceutical and synthon properties,[ the synthe- [1,2-a]pyridine and related heteroarenes and explore their
26]
[
7]
sis of phosphonated imidazo[1,2-a]pyridines would, there- potential in medicinal chemistry. In view of the synthesis
fore, be of great importance.
of phosphonated heteroarenes, several groups have made
[
30]
attempts by employing transition-metal catalysis
as well
[
31]
as redox/radical-based oxidative
and iodine-mediated
[
32]
methods, but most of them are specific to particular sub-
strates. To the best of our knowledge, there is still no report
of the phosphonation of imidazo[1,2-a]pyridines. After sev-
eral attempts, we have successfully developed an effective
regioselective method for the phosphonation of imid-
azo[1,2-a]pyridines. Our optimized method gives good to
excellent yields of the coupled products and works very well
with many other heteroarenes such as (NH)- and N-pro-
tected indoles, azaindoles, and pyrroles.
[
a] Medicinal Chemistry Division, Indian Institute of Integrative
Medicine,
Canal Road, Jammu 180001, India
E-mail: ppsingh@iiim.ac.in
http://www.iiim.res.in
[
[
b] Department of Chemistry, University of Jammu,
Jammu 180006, India
c] Academy of Scientific and Innovative Research,
Canal Road, Jammu 180001, India
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500984.
6526
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Regioselective Oxidative C–H Phosphonation Reaction
Scheme 1. Functionalization of imidazo[1,2-a]pyridines (Boc = tert-butoxycarbonyl, NMP = N-methylpyrrolidone).
Results and Discussion
observed (Table 1, Entry 5). Then, employing transition-
[
30a]
[30b,31d]
metal catalysts such as palladium
and silver salts
The idea of a phosphonylation reaction was examined by afforded a somewhat positive result, however, the yield of
using 2-phenylimidazo[1,2-a]pyridine (1a) and (iPrO) P- phosphonylated product 3a was only moderate (Table 1,
2
(O)H (2a) as reaction partners under various coupling con- Entries 6–10). The use of di-tert-butyl peroxide (DTBP) was
ditions. Initially, iodine with and without tert-butyl- also unsuitable (Table 1, Entry 11). The use of manganese
hydroperoxide (TBHP) in different solvents was employed salts appeared to be comparatively significant, as Mn-
(
Table 1, Entries 1–3), but no product formation was ob- (OAc) ·2H O in acetic acid provided phosphonylated prod-
3 2
served. The use of N-chlorosuccinimide (NCS) was also un- uct 3a in a yield of 40% (Table 1, Entry 12). Surprisingly,
successful (Table 1, Entry 4). 2-Phenylimidazo[1,2-a]pyr- changing the solvent to NMP significantly increased the
idine (1a) was then treated with diisopropyl phosphoryl yield of 3a to 76% (Table 1, Entry 13). Efforts to reduce the
chloride in the presence of 1,8-diazabicyclo[5.4.0]undec-7- amount of manganese salt by conducting the reactions in
ene (DBU) for a direct phosponylation, but no reaction was the presence of external oxidants did not successfully in-
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst [equiv.]
Oxidant
Solvent
T [°C]
% Yield[b]
1
2
3
4
I
I
I
2
2
2
(0.2)
(1.0)
(1.0)
TBHP
PEG400[c]
PEG400
50
50
40
40
90
100
100
r.t.
100
r.t.
80
n.d.[c]
n.d.
n.d.
n.d.
n.d.
20
25
n.d.
10
n.d.
n.d.
40
76
34
–
–
–
–
K
K
K
–
CH
CH
DCE
2
Cl
Cl
2
NCS (1.0)
–
Pd(OAc)
PdCl (0.1)
AgNO (0.2)
AgO (1.0)
Ag(bipy)
–
Mn(OAc)
Mn(OAc)
Mn(OAc)
Mn(OAc)
Mn(OAc)
2
2
[c]
[
[
[
[
d]
e]
e]
f]
5
6
7
8
9
1
1
1
1
1
1
1
2
(0.1)
2
2
2
S
S
S
2
2
2
O
O
O
8
8
8
CH
CH
CH
3
3
2
CN
CN
2
3
Cl
2
/H
2
O
dioxane
0
1
2
3
4
5
6
2
(S
2
O
8
)[c] (1.0)
–
CH
CH
CH
3
3
3
CN
CN
COOH
DTBP
–
–
3
3
3
3
3
·2H
·2H
·2H
·2H
·2H
2
2
2
2
2
O (3.0)
O (3.0)
O (1.0)
O (1.0)
O (1.0)
80
80
80
80
NMP
NMP
NMP
dioxane
MnO
2
K
K
2
S
S
2
O
O
8
8
26
13
2
2
80
[
a] Reagents and conditions: 1a (0.5 mmol), 2a (1.25 mmol), catalyst (see above), and oxidant (3 equiv.) in anhydrous solvent (3.0 mL) at
a specified temperature (see above) for 16 h under nitrogen. [b] Yield of the isolated product. [c] PEG400 = polyethylene glycol 400, n.d.:
not determined, DCE = 1,2-dichloroethane, bipy = 2,2Ј-bipyridine. [d] Diisopropyl phosphoryl chloride was used instead of 2a with DBU
as the base. [e] 1,10-Phenanthroline (0.3 equiv.) was used as a ligand. [f] Reaction was performed in open air.
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P. P. Singh et al.
FULL PAPER
crease the yield (Table 1, Entries 14–16). Among the various different positions of pyridine ring smoothly underwent re-
reactions conditions, Mn(OAc) ·2H O in NMP at 80 °C actions with dialkyl phosphites and afforded the corre-
3
2
was found to be the best (Table 1, Entry 13).
sponding products 3f–3i in good to excellent yields. The
With these optimized conditions in hand, the scope of reactions of imidazo[1,2-a]pyridine with a methyl group in
the reaction between imidazo-[1,2-a]pyridines 1 and dialkyl the 6-position and diisopropyl phosphite and diethyl phos-
phosphites 2 was investigated (Table 2). 2-Phenylimidazo- phite gave the corresponding products 3f and 3g in excellent
[
1,2-a]pyridine (1a) smoothly underwent reactions with di- yields of 88 and 84%, respectively. Having a methyl group
ethyl phosphite (2b) and dimethyl phosphite (2c) to afford at the 7-position also gave the required product 3h in a
the desired products 3b and 3c in good yields of 72 and good yield of 80%. The 2-phenylimidazo[1,2-a]pyridine
6
6%, respectively. 2-Phenylimidazo[1,2-a]pyridine (1a) also with a methyl group in the 8-position smoothly underwent
smoothly underwent a reaction with dibenzyl phosphite the reaction, and product 3i was obtained in a good 80%
2d) to give the required product 3d in 52% isolated yield. yield. When 6-bromo- and 6-chloro-containing imidazopyr-
(
When the bulkier di-tert-butyl phosphite was employed un- idines were treated with 2a, the corresponding desired prod-
der the optimized reaction conditions, none of the expected ucts 3j and 3k were formed in good yield, 78 and 65%,
product 3e was formed. Similarly, the reaction between di- respectively. A further investigation was then carried out to
phenylphosphine oxide and 2-phenylimidazo[1,2-a]pyridine evaluate the influence of the substituents on the phenyl ring
(1a) did not provide the coupled product (entry not shown of the imidazo[1,2-a]pyridines. The presence of electron-do-
in Table 2). A wide range of substituted imidazo[1,2-a]pyr- nating groups (Me, OMe) gave the required products 3l and
idines were then subjected to the reaction conditions to de- 3m in 85 and 72% yield, respectively. The 2-phenylimid-
termine the general applicability of the present method. azo[1,2-a]pyridines that contained electron-withdrawing
Imidazo[1,2-a]pyridines substituted with a methyl group at groups (F, Cl) on the phenyl ring also underwent a smooth
conversion and gave the expected products 3n–3p in high
Table 2. Scope of phosphonylation of imidazopyridines.[a,b]
yields (71–75%). Phenyl rings that contained either an elec-
tron-donating (OMe) or electron-withdrawing (NO ) group
2
in the meta position were also subjected to the reaction con-
ditions and gave corresponding coupled products 3q and 3r
in 58 and 45% yield, respectively.
Next, the optimized reaction conditions were applied to
other heteroarenes to further expand the scope of the pres-
ent protocol. To our delight, the reactions of both substi-
tuted and unsubstituted indole 4 with dialkyl phosphites
2a–2c smoothly underwent the reaction and gave the re-
gioselective 2-phosphonated products in moderate to good
Table 3. Scope of phosphonylation of indoles, azaindoles, and pyr-
roles.[
a,b]
[
a] Reagents and conditions: 1 (0.5 mmol), 2 (1.25 mmol), and
Mn(OAc) ·2H
for 16 h under nitrogen. [b] Isolated yield.
[a] Reagents and conditions: 4 (0.5 mmol), 2 (1.25 mmol), and
3
2
O (1.5 mmol) in anhydrous NMP (3.0 mL) at 80 °C Mn(OAc)
3 2
·2H O (1.5 mmol) in anhydrous NMP (3.0 mL) at 80 °C
for 16 h under nitrogen. [b] Isolated yield.
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Eur. J. Org. Chem. 2015, 6526–6533

Regioselective Oxidative C–H Phosphonation Reaction
yields (Table 3). Upon treatment with the different dialkyl was successfully applied to the regioselective phosphonyl-
phosphites 2a–2c, N-methylindole gave the corresponding ation of other heteroarenes such as (NH)- and N-protected
coupled products 5a–5c in good to excellent yields of 82, indoles, azaindoles, and pyrroles. Biological evaluations of
73, and 52%, respectively. When (NH)-indole was treated the synthesized phosphonate analogues and other synthetic
with dialkyl phosphites 2a and 2b, the coupling reaction applications are in progress and will be reported at a later
proceeded smoothly and gave the corresponding products time.
5d and 5e in 68 and 62% yield, respectively. Furthermore,
substituted (NH)-indoles that contained 5-Cl and 5-OMe
groups gave good yields of the expected coupled products
Experimental Section
5
f (70%) and 5g (48%). Azaindole also proceeded to react
General Procedure for the Phosphonation of Imidazo[1,2-a]pyridines
and Related Heteroarenes: To an oven-dried round-bottomed flask
with diisopropyl phosphite 2a but gave a comparatively
lower yield of the respective coupled product 5h (40%). In purged with nitrogen were added the imidazo[1,2-a]pyridine, ind-
contrast, 5-bromoazaindole afforded the required product ole, azaindole, or pyrrole (0.5 mmol) and Mn(OAc) ·2H
i in good yield (55%). The successful C–H phosphonations (1.5 mmol, 3 equiv.) followed by the addition of H-phosphonate
3
2
O
5
(
1.25 mmol, 2.5 equiv.). NMP (3 mL) was then added by syringe
of (NH)-indole and (NH)-azaindole motivated us to per-
under nitrogen, and the reaction mixture was heated to 80 °C for
16 h. The reaction mixture was cooled to room temperature, and
brine solution was added to it. The resulting mixture was extracted
form the reaction with (NH)-pyrrole, which was the limita-
tion in a previously reported method.[
31c]
Interestingly,
when the present method was attempted with an unprotec-
ted pyrrole, the reaction smoothly proceeded and gave the
respective coupled product 5j in high yield (75%). Further-
more, the N-protected pyrrole (N-Boc-pyrrole) also under-
went smooth conversion into 5k in a good yield of 70%.
To verify the pathway that is involved under the present
conditions, control experiments were carried out in the
presence of a free-radical scavenger (Scheme 2). When
with Et
with Na
product was purified by flash column chromatography on silica gel
ethyl acetate/petroleum ether, 1:3) to give the pure product.
2
O (3ϫ 25 mL), and the combined organic layers were dried
2
SO and concentrated under reduced pressure. The crude
4
(
Diisopropyl (2-Phenylimidazo[1,2-a]pyridin-3-yl)phosphonate (3a):
1
Off-white solid (136 mg, 76%); m.p. 122 °C. H NMR (400 MHz,
CDCl
3
): δ = 9.28 (d, J = 7.0 Hz, 1 H), 7.93–7.91 (m, 2 H), 7.70 (d,
J = 8.8 Hz, 1 H), 7.45–7.33 (m, 4 H), 6.92 (t, J = 6.6 Hz, 1 H),
2
,2,6,6-tetramethylpiperidinyloxy (TEMPO, 1 equiv.), a 4.65–4.57 (m, 2 H), 1.32 (d, J = 6.2 Hz, 6 H), 1.00 (d, J = 6.2 Hz,
3
1
13
radical scavenger, was added to the reaction system, the 6 H) ppm. P NMR (162 MHz, CDCl
coupling process was significantly suppressed. Similarly, the (126 MHz, CDCl
reaction did not proceed in the presence 10 equiv. of
TEMPO. These results suggest that the reaction follows a
radical pathway, which is the same pathway previously pro-
posed by the Ishii group.[31b]
3
): δ = 5.77 ppm. C NMR
3
): δ = 154.56 (d, J = 17.4 Hz), 147.95 (d, J =
1
1
4.5 Hz), 133.97, 129.88, 128.69, 128.54, 127.83, 127.24, 117.32,
13.27, 108.60 (d, J = 227.6 Hz), 71.64 (d, J = 5.3 Hz), 23.97 (d,
J = 4.0 Hz), 23.37 (d, J = 5.4 Hz) ppm. HRMS (ESI): calcd. for
P [M + H]+ 359.1519; found 359.1543.
19 23 2 3
C H N O
Diethyl
(2-Phenylimidazo[1,2-a]pyridin-3-yl)phosphonate
(3b):
): δ =
1
Brownish gum (118 mg, 72%). H NMR (400 MHz, CDCl
3
9.20 (d, J = 7.0 Hz, 1 H), 7.86 (dd, J = 7.9, 1.6 Hz, 2 H), 7.73 (dd,
J = 9.0, 0.8 Hz, 1 H), 7.45–7.42 (m, 4 H), 6.96 (td, J = 6.9, 1.1 Hz,
1
6
H), 4.16–4.07 (m, 2 H), 3.97–3.87 (m, 2 H), 1.14 (t, J = 7.1 Hz,
3
1
13
H) ppm. P NMR (162 MHz, CDCl
3
): δ = 8.15 ppm. C NMR
(
101 MHz, CDCl
3
): δ = 155.04 (d, J = 18.1 Hz), 148.21 (d, J =
1
1
=
4.1 Hz), 133.70, 129.73, 128.81, 128.42, 127.88, 127.48, 117.39,
13.45, 107.32 (d, J = 227.2 Hz), 62.42 (d, J = 5.0 Hz), 15.88 (d, J
+
19 2 3
7.0 Hz) ppm. HRMS (ESI): calcd. for C17H N O P [M + H]
331.1206; found 331.1221.
Dimethyl (2-Phenylimidazo[1,2-a]pyridin-3-yl)phosphonate (3c): Off-
1
white solid (99 mg, 66%); m.p. 74 °C. H NMR (500 MHz,
CDCl
Scheme 2. Preliminary mechanistic studies. Reagents and condi-
tions: 1a (0.5 mmol), 2a (1.25 mmol), Mn(OAc)
3
·2H
2
O (1.5 mmol),
3
): δ = 9.15 (dt, J = 7.0, 1.1 Hz, 1 H), 7.84 (ddd, J = 3.8, 2.7,
1.7 Hz, 2 H), 7.72–7.71 (m, 1 H), 7.45–7.43 (m, 4 H), 6.96 (td, J =
6.9, 1.2 Hz, 1 H), 3.64 (d, J = 11.7 Hz, 6 H) ppm. P NMR
and TEMPO in anhydrous NMP (3.0 mL) at 80 °C for 16 h under
nitrogen. Isolated yields are provided.
3
1
1
3
(
162 MHz, CDCl
δ = 155.51 (d, J = 17.7 Hz), 148.43 (d, J = 14.7 Hz), 133.53, 129.56,
28.95, 128.43, 127.97, 127.67, 117.48, 113.59, 106.19 (d, J =
229.2 Hz), 52.67 (d, J = 5.1 Hz) ppm. HRMS (ESI): calcd. for
P [M + H]+ 303.0893; found 303.0894.
3 3
): δ = 11.31 ppm. C NMR (126 MHz, CDCl ):
1
Conclusions
15 15 2 3
C H N O
In summary, we have reported a C–H functionalization
by using a regioselective manganese salt promoted oxidative
phosphonation between imidazo[1,2-a]pyridines and dialkyl
phosphites. The optimized reaction conditions presented
herein do not require any additional base or acid. These
Dibenzyl (2-Phenylimidazo[1,2-a]pyridin-3-yl)phosphonate (3d):
1
Light brownish gum (118 mg, 52%). H NMR (500 MHz, CDCl
3
):
δ = 9.12 (dd, J = 7.0, 1.0 Hz, 1 H), 7.86 (dd, J = 7.9, 1.6 Hz, 2 H),
7
7
.69 (d, J = 8.9 Hz, 1 H), 7.42–7.36 (m, 4 H), 7.24–7.23 (m, 6 H),
.10 (dd, J = 7.2, 1.9 Hz, 4 H), 6.91 (td, J = 6.9, 1.2 Hz, 1 H), 5.08
reactions afforded a variety of 3-phosphonated imidazo- (dd, J = 11.5, 8.6 Hz, 2 H), 4.89 (dd, J = 11.5, 7.2 Hz, 2 H) ppm.
3
1
13
[
1,2-a]pyridines in good to excellent yields, and the strategy
P NMR (162 MHz, CDCl
3
): δ = 8.81 ppm. C NMR (126 MHz,
Eur. J. Org. Chem. 2015, 6526–6533
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P. P. Singh et al.
FULL PAPER
CDCl
3
): δ = 155.42 (d, J = 17.9 Hz), 148.24 (d, J = 14.8 Hz), 135.35 Diisopropyl
(6-Chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)phos-
1
(d, J = 7.4 Hz), 133.62, 129.84, 128.89, 128.46, 128.44, 128.06,
phonate (3k): Light yellow solid (127 mg, 65%); m.p. 112 °C. H
128.04, 127.60, 117.37, 113.45, 106.98 (d, J = 228.7 Hz), 68.07 (d,
3
NMR (500 MHz, CDCl ): δ = 9.42–9.41 (m, 1 H), 7.91–7.89 (m, 2
J = 4.9 Hz) ppm. HRMS (ESI): calcd. for C27
H] 455.1519; found 455.1509.
H
23
N
2
O
3
P [M + H), 7.65–7.63 (m, 1 H), 7.44–7.40 (m, 3 H), 7.34–7.32 (m, 1 H),
+
4.65–4.58 (m, 2 H), 1.32 (d, J = 6.2 Hz, 7 H), 1.01 (d, J = 6.2 Hz,
3
1
13
6
H) ppm. P NMR (162 MHz, CDCl
3
): δ = 5.04 ppm. C NMR
Diisopropyl
phonate (3f): Brownish gum (163 mg, 88%). H NMR (400 MHz,
CDCl ): δ = 9.09 (s, 1 H), 7.91 (dd, J = 7.9, 1.4 Hz, 2 H), 7.62 (d,
(6-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)phos-
1
(126 MHz, CDCl
3
): δ = 153.88 (d, J = 16.8 Hz), 145.22 (d, J =
1
1
4.3 Hz), 132.48, 128.72, 127.88, 127.63, 126.88, 125.45, 120.53,
16.47, 108.35 (d, J = 226.8 Hz), 70.93 (d, J = 5.4 Hz), 22.91 (d,
3
J = 9.0 Hz, 1 H), 7.45–7.38 (m, 3 H), 7.23 (dd, J = 9.1, 1.3 Hz, 1
H), 4.66–4.58 (m, 2 H), 2.40 (s, 3 H), 1.33 (d, J = 6.2 Hz, 6 H),
J = 4.0 Hz), 22.34 (d, J = 5.4 Hz) ppm. HRMS (ESI): calcd. for
C
19
H
22ClN
2 3
O
P [M + H]+ 393.1129; found 393.1118.
3
1
1
6
1
1
3
.02 (d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl ): δ =
.10 ppm. 13C NMR (126 MHz, CDCl
7.7 Hz), 146.99 (d, J = 14.6 Hz), 134.14, 130.31, 129.83, 128.57,
27.79, 126.24, 123.10, 116.57, 108.17 (d, J = 228.2 Hz), 71.58 (d,
3
): δ = 154.31 (d, J = Diisopropyl [2-(p-Tolyl)imidazo[1,2-a]pyridin-3-yl]phosphonate (3l):
1
Off-white solid (158 mg, 85%); m.p. 127 °C. H NMR (500 MHz,
CDCl ): δ = 9.26 (dd, J = 7.0, 0.9 Hz, 1 H), 7.82 (d, J = 8.1 Hz, 2
3
J = 5.2 Hz), 23.99 (d, J = 4.0 Hz), 23.37 (d, J = 5.5 Hz), 18.50 ppm.
H), 7.70 (d, J = 8.9 Hz, 1 H), 7.36–7.33 (m, 1 H), 7.23 (d, J =
+
HRMS (ESI): calcd. for C20
73.1660.
H
25
N
2
O
3
P [M + H] 373.1676; found
8.3 Hz, 2 H), 6.91 (td, J = 6.9, 1.2 Hz, 1 H), 4.60 (ddt, J = 12.4,
7.7, 6.2 Hz, 2 H), 2.39 (s, 3 H), 1.33 (d, J = 6.2 Hz, 6 H), 1.01 (d,
3
3
1
J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl
3
): δ = 5.97 ppm.
Diethyl (6-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)phosphonate
1
3
1
C NMR (126 MHz, CDCl ): δ = 154.71 (d, J = 17.6 Hz), 147.92
(
3g): Brownish gum (144 mg, 84%). H NMR (400 MHz, CDCl
3
):
3
(
d, J = 14.4 Hz), 138.60, 130.97, 129.75, 128.57, 128.54, 127.21,
δ = 8.98 (s, 1 H), 7.83 (dd, J = 7.6, 1.4 Hz, 2 H), 7.61 (d, J =
1
2
17.22, 113.18, 108.21 (d, J = 227.2 Hz), 71.59 (d, J = 5.1 Hz),
9
4
7
.0 Hz, 1 H), 7.45–7.39 (m, 3 H), 7.23 (dd, J = 9.1, 1.2 Hz, 1 H),
4.01 (d, J = 3.8 Hz), 23.40 (d, J = 5.5 Hz), 21.38 ppm. HRMS
.14–4.05 (m, 2 H), 3.94–3.84 (m, 2 H), 2.39 (s, 3 H), 1.13 (t, J =
+
.1 Hz, 6 H) ppm. 3 P NMR (162 MHz, CDCl
1
(ESI): calcd. for C H N O P [M + H] 373.1676; found 373.1679.
): δ = 8.51 ppm.
): δ = 154.75 (d, J = 17.7 Hz), 147.22
d, J = 14.5 Hz), 133.82, 130.57, 129.68, 128.71, 127.85, 126.12,
20 25
2
3
3
1
3
C NMR (126 MHz, CDCl
3
Diisopropyl [2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]phos-
(
1
phonate (3m): Yellowish gum (139 mg, 72%). H NMR (400 MHz,
1
23.35, 116.63, 106.84 (d, J = 227.3 Hz), 62.36 (d, J = 5.0 Hz),
21 2 3
5.88 (d, J = 7.4 Hz) ppm. HRMS (ESI): calcd. for C18H N O P
CDCl
3
): δ = 9.26 (dt, J = 7.0, 1.1 Hz, 1 H), 7.92–7.90 (m, 2 H),
.69 (ddt, J = 9.0, 1.9, 1.1 Hz, 1 H), 7.35 (ddd, J = 8.9, 6.8, 1.2 Hz,
H), 6.98–6.95 (m, 2 H), 6.91 (td, J = 6.9, 1.2 Hz, 1 H), 4.63 (ddt,
1
7
1
[
M + H]+ 345.1363; found 345.1389.
J = 12.4, 7.9, 6.2 Hz, 2 H), 3.86 (s, 3 H), 1.35 (d, J = 6.2 Hz, 6 H),
1.03 (d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl ): δ =
3
Diisopropyl
(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)phos-
3
1
1
phonate (3h): Colorless gum (148 mg, 80%). H NMR (400 MHz,
CDCl ): δ = 9.13 (d, J = 7.1 Hz, 1 H), 7.92–7.90 (m, 2 H), 7.47 (s,
H), 7.44–7.36 (m, 3 H), 6.77 (dd, J = 7.1, 1.5 Hz, 1 H), 4.64–4.56
m, 2 H), 2.44 (s, 3 H), 1.32 (d, J = 6.2 Hz, 6 H), 1.01 (d, J =
1
3
6
=
1
.12 ppm. C NMR (126 MHz, CDCl
17.5 Hz), 147.93 (d, J = 14.4 Hz), 131.22, 128.54, 127.22, 126.43,
17.12, 113.30, 113.12, 107.86 (d, J = 229.1 Hz), 71.60 (d, J =
5.1 Hz), 55.31, 24.04 (d, J = 3.9 Hz), 23.41 (d, J = 5.5 Hz) ppm.
3
): δ = 160.18, 154.43 (d, J
3
1
(
.2 Hz, 6 H) ppm. 3 P NMR (162 MHz, CDCl
C NMR (101 MHz, CDCl
1
6
3
): δ = 6.03 ppm.
): δ = 154.56 (d, J = 17.4 Hz), 148.39
d, J = 14.5 Hz), 138.45, 134.09, 129.84, 128.57, 127.77, 127.63,
15.82, 107.92 (d, J = 228.7 Hz), 71.52 (d, J = 5.2 Hz), 23.95 (d, J
4.0 Hz), 23.36 (d, J = 5.4 Hz), 21.28 ppm. HRMS (ESI): calcd.
+
1
3
20 25 2 4
HRMS (ESI): calcd. for C H N O P [M + H] 389.1625; found
3
389.1622.
(
1
=
Diisopropyl [2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl]phosphon-
1
ate (3n): Off-white solid (139 mg, 74%); m.p. 140 °C. H NMR
+
for C20
H
25
N
2
O
3
P [M + H] 373.1676; found 373.1657.
(
400 MHz, CDCl
3
): δ = 9.24 (d, J = 7.0 Hz, 1 H), 7.93 (dd, J =
Diisopropyl
(8-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)phos-
8.8, 5.5 Hz, 2 H), 7.70 (dd, J = 9.0, 0.6 Hz, 1 H), 7.47–7.31 (m, 1
1
phonate (3i): Off-white solid (148 mg, 80%); m.p. 108–109 °C. H H), 7.12 (t, J = 8.8 Hz, 2 H), 6.96–6.92 (m, 1 H), 4.68–4.60 (m, 2
3
1
NMR (400 MHz, CDCl
3
): δ = 9.12 (d, J = 7.0 Hz, 1 H), 7.92–7.89 H), 1.34 (d, J = 6.2 Hz, 6 H), 1.04 (d, J = 6.2 Hz, 6 H) ppm.
P
1
9
(m, 2 H), 7.42–7.39 (m, 3 H), 7.16–7.14 (m, 1 H), 6.84 (t, J =
NMR (162 MHz, CDCl
CDCl
): δ = –113.09 ppm. 13C NMR (126 MHz, CDCl
): 163.25 (d, JC,F = 248.3 Hz), 153.51 (d, J = 17.6 Hz), 147.90 (d, J
3
3
): δ = 5.66 ppm. F NMR (376 MHz,
6
6
.9 Hz, 1 H), 4.65–4.57 (m, 2 H), 2.67 (s, 3 H), 1.31 (d, J = 6.2 Hz,
H), 1.01 (d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl
3
3
): δ =
31
1
3
δ = 5.99 ppm. C NMR (126 MHz, CDCl
3
): δ = 153.07 (d, J =
7.4 Hz), 147.26 (d, J = 14.4 Hz), 133.24, 128.96, 127.48, 126.76,
26.26, 125.17, 124.93, 112.20, 107.92 (d, J = 227.6 Hz), 70.47 (d,
= 14.4 Hz), 131.73 (d, JC,F = 8.3 Hz), 130.10 (d, JC,F = 2.9 Hz),
128.50, 127.41, 117.28, 114.83 (d, JC,F = 21.5 Hz), 113.38, 108.53
(d, J = 227.3 Hz), 71.71 (d, J = 5.2 Hz), 24.00 (d, J = 3.9 Hz), 23.42
1
1
J = 5.2 Hz), 22.92 (d, J = 3.9 Hz), 22.34 (d, J = 5.4 Hz), 16.25 ppm.
2 3
(d, J = 5.3 Hz) ppm. HRMS (ESI): calcd. for C19H22FN O P [M
+
+ H]+ 377.1425; found 377.1419.
HRMS (ESI): calcd. for C20
73.1660.
25 2 3
H N O P [M + H] 373.1676; found
3
Diisopropyl [2-(4-Fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-
1
Diisopropyl
phonate (3j): Light yellow solid (170 mg, 78%); m.p. 109 °C.
NMR (400 MHz, CDCl ): δ = 9.51 (s, 1 H), 7.91 (dd, J = 7.8,
.7 Hz, 2 H), 7.60 (dd, J = 9.4, 1.6 Hz, 1 H), 7.45–7.40 (m, 4 H), H), 4.65–4.59 (m, 2 H), 2.38 (s, 3 H), 1.33 (d, J = 6.2 Hz, 7 H),
(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)phos-
phosphonate (3o): Brownish gum (146 mg, 75%). H NMR
1
H
(500 MHz, CDCl
3
): δ = 9.05 (s, 1 H), 7.92–7.89 (m, 2 H), 7.59 (d,
3
J = 9.0 Hz, 1 H), 7.22 (d, J = 9.1 Hz, 1 H), 7.11 (t, J = 8.6 Hz, 2
1
4
7
3
1
3
.67–4.59 (m, 2 H), 1.33 (d, J = 6.2 Hz, 7 H), 1.03 (d, J = 6.2 Hz, 1.03 (d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl ): δ =
H) ppm. 31P NMR (162 MHz, CDCl
): δ = 5.03 ppm. C NMR 5.98 ppm. F NMR (376 MHz, CDCl
): δ = 163.19 (d, JC,F = 248.0 Hz), 153.24
13
19
): δ = –113.31 ppm.
13
C
3
3
(126 MHz, CDCl
3
): δ = 154.77 (d, J = 16.9 Hz), 146.35 (d, J = NMR (126 MHz, CDCl
3
1
1
4.3 Hz), 133.51, 130.77, 129.79, 128.92, 128.62, 127.91, 117.82, (d, J = 17.5 Hz), 146.92 (d, J = 14.5 Hz), 131.66 (d, JC,F = 8.3 Hz),
09.32 (d, J = 226.9 Hz), 108.11, 71.98 (d, J = 5.4 Hz), 23.95 (d, 130.44, 130.29 (d, JC,F = 3.2 Hz), 126.22, 123.20, 116.52, 114.76 (d,
J = 4.0 Hz), 23.38 (d, J = 5.4 Hz) ppm. HRMS (ESI): calcd for
C H22BrN O P [M + H] 437.0624; found 437.0624.
19 2 3
J
C,F = 21.5 Hz), 108.16 (d, J = 228.1 Hz), 71.62 (d, J = 5.3 Hz),
+
24.00 (d, J = 4.0 Hz), 23.41 (d, J = 5.4 Hz), 18.47 ppm. HRMS
6530
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6526–6533

Regioselective Oxidative C–H Phosphonation Reaction
2 3
H24FN O
P [M + H]+ 391.1581; found (d, J = 8.0 Hz, 1 H), 7.40–7.34 (m, 2 H), 7.20–7.15 (m, 2 H), 3.94
(
3
ESI): calcd for C20
91.1592.
3
1
(s, 3 H), 3.81 (d, J = 11.4 Hz, 6 H) ppm. P NMR (162 MHz,
1
3
CDCl
3 3
): δ = 13.10 ppm. C NMR (126 MHz, CDCl ): δ = 140.16
Diisopropyl [2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]phosphon-
ate (3p): Off-white solid (139 mg, 71%); m.p. 91 °C. 1H NMR
(d, J = 12.4 Hz), 126.48 (d, J = 15.8 Hz), 124.73, 124.69 (d, J =
2
2
C
18.6 Hz), 122.20, 120.38, 114.55 (d, J = 17.3 Hz), 110.04 (d, J =
.0 Hz), 53.11 (d, J = 5.4 Hz), 31.82 ppm. HRMS (ESI): calcd. for
(
(
400 MHz, CDCl
3
): δ = 9.24 (dt, J = 7.0, 1.0 Hz, 1 H), 7.92–7.88
m, 2 H), 7.72–7.69 (m, 1 H), 7.43–7.36 (m, 3 H), 6.94 (td, J = 6.9,
.2 Hz, 1 H), 4.64 (ddt, J = 12.4, 7.9, 6.2 Hz, 2 H), 1.34 (d, J =
P [M + H]+ 240.0784; found 240.0763.
11
H
14NO
3
1
6
31
[33]
.2 Hz, 6 H), 1.04 (d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz,
): δ = 5.46 ppm. 13C NMR (126 MHz, CDCl
d, J = 17.3 Hz), 147.91 (d, J = 14.4 Hz), 134.84, 132.44, 131.21, (br. s, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 9.1 Hz, 1 H),
Diisopropyl (1H-Indol-2-yl)phosphonate (5d):
Brownish solid
1
CDCl
(
3
3
3
): δ = 153.24 (94 mg, 68%); m.p. 154 °C. H NMR (500 MHz, CDCl ): δ = 10.29
1
7
5
3
28.52, 128.07, 127.48, 117.34, 113.46, 108.84 (d, J = 227.2 Hz), 7.31–7.28 (m, 1 H), 7.16–7.13 (m, 1 H), 7.04–7.03 (m, 1 H), 4.72
1.80 (d, J = 5.3 Hz), 23.99 (d, J = 4.0 Hz), 23.44 (d, J = (ddt, J = 12.4, 8.0, 6.2 Hz, 2 H), 1.39 (d, J = 6.2 Hz, 6 H), 1.27 (d,
31
.3 Hz) ppm. HRMS (ESI): calcd. for C19
93.1129; found 393.1127.
H
22ClN
2
O
3
P [M + H]+
3
J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl ): δ = 8.54 ppm.
1
3
C NMR (126 MHz, CDCl ): δ = 138.21 (d, J = 12.8 Hz), 127.56
3
(
d, J = 15.5 Hz), 125.37 (d, J = 219.8 Hz), 124.27, 121.79, 120.39,
112.22 (d, J = 1.4 Hz), 111.25 (d, J = 16.9 Hz), 71.68 (d, J =
.1 Hz), 24.12 (d, J = 3.8 Hz), 23.79 (d, J = 5.1 Hz) ppm. HRMS
Diisopropyl [2-(3-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]phos-
phonate (3q): Light yellow gum (112 mg, 58%). H NMR
1
5
(
(
9
2
500 MHz, CDCl
3
): δ = 9.29 (d, J = 7.0 Hz, 1 H), 7.70 (d, J =
.0 Hz, 1 H), 7.52–7.49 (m, 2 H), 7.37–7.30 (m, 2 H), 6.95–6.91 (m,
H), 4.61 (ddt, J = 12.4, 7.6, 6.2 Hz, 2 H), 3.86 (s, 3 H), 1.31 (d,
+
ESI): calcd. for C14
H
20NO
3
P [M + H] 282.1254; found 282.1255.
Diethyl (1H-Indol-2-yl)phosphonate (5e):[ Brownish gum (77 mg,
33]
31
1
J = 6.2 Hz, 6 H), 1.02 (d, J = 6.2 Hz, 6 H) ppm. P NMR
162 MHz, CDCl ):
): δ = 5.72 ppm. 13C NMR (126 MHz, CDCl
δ = 159.21, 154.34 (d, J = 17.5 Hz), 147.87 (d, J = 14.4 Hz), 135.15,
62%). H NMR (400 MHz, CDCl ): δ = 9.81 (br. s, 1 H), 7.69 (d,
3
(
3
3
J = 8.0 Hz, 1 H), 7.50 (d, J = 8.3 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1
H), 7.16 (t, J = 7.5 Hz, 1 H), 7.07–7.06 (m, 1 H), 4.23–4.10 (m, 4
3
1
1
1
28.85, 128.56, 127.29, 122.45, 117.32, 115.14, 114.85, 113.33,
08.68 (d, J = 227.4 Hz), 71.70 (d, J = 5.2 Hz), 55.40, 23.99 (d, δ = 10.63 ppm. C NMR (126 MHz, CDCl ): δ = 137.30 (d, J =
H), 1.35 (t, J = 7.1 Hz, 6 H) ppm. P NMR (162 MHz, CDCl3):
1
3
3
J = 3.9 Hz), 23.44 (d, J = 5.4 Hz) ppm. HRMS (ESI): calcd. for 12.8 Hz), 126.40 (d, J = 15.6 Hz), 123.49, 122.54 (d, J = 219.4 Hz),
+
C
20
H
25
N
2
O
4
P [M + H] 389.1625; found 389.1644.
120.75, 119.50, 111.22 (d, J = 1.3 Hz), 110.66 (d, J = 16.9 Hz),
1.85 (d, J = 5.1 Hz), 15.24 (d, J = 6.8 Hz) ppm. HRMS (ESI):
calcd. for C H NO P [M + H] 254.0941; found 254.0947.
12 16 3
6
Diisopropyl [2-(3-Nitrophenyl)imidazo[1,2-a]pyridin-3-yl]phosphon-
+
1
ate (3r): Off-white solid (91 mg, 45%); m.p. 92 °C. H NMR
400 MHz, CDCl ): δ = 9.26 (d, J = 7.0 Hz, 1 H), 8.90–8.89 (m, 1
H), 8.32 (d, J = 7.7 Hz, 1 H), 8.28–8.26 (m, 1 H), 7.73 (d, J =
.9 Hz, 1 H), 7.62 (t, J = 8.0 Hz, 1 H), 7.44–7.40 (m, 1 H), 6.99
td, J = 6.9, 1.0 Hz, 1 H), 4.70 (qd, J = 12.4, 6.2 Hz, 2 H), 1.35 (d,
J = 6.2 Hz, 6 H), 1.08 (d, J = 6.2 Hz, 6 H) ppm. P NMR
): δ = 4.79 ppm. 13C NMR (101 MHz, CDCl
162 MHz, CDCl ):
δ = 151.68 (d, J = 17.0 Hz), 147.96 (d, J = 14.0 Hz), 147.91, 135.81,
(
3
Diisopropyl (5-Chloro-1H-indol-2-yl)phosphonate (5f): Brownish so-
1
lid (109 mg, 70%); m.p. 153 °C. H NMR (400 MHz, CDCl
0.85 (br. s, 1 H), 7.64 (d, J = 1.5 Hz, 1 H), 7.44 (d, J = 8.7 Hz, 1
H), 7.23 (dd, J = 8.7, 1.3 Hz, 1 H), 6.93 (d, J = 2.5 Hz, 1 H), 4.72
qd, J = 12.4, 6.2 Hz, 2 H), 1.38 (d, J = 6.2 Hz, 6 H), 1.27 (d, J =
3
): δ =
8
(
1
31
(
(
3
3
31
6
.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl
3
): δ = 7.77 ppm.
): δ = 135.63 (d, J = 13.2 Hz), 127.39
d, J = 15.6 Hz), 125.87 (d, J = 219.9 Hz), 124.91, 123.61, 119.85,
13
C NMR (126 MHz, CDCl
3
1
1
4
35.72, 128.86, 128.55, 127.74, 125.09, 123.33, 117.55, 113.79,
09.82 (d, J = 229.7 Hz), 72.13 (d, J = 5.5 Hz), 23.92 (d, J =
(
1
5
12.34 (d, J = 1.2 Hz), 109.24 (d, J = 16.8 Hz), 70.90 (d, J =
.3 Hz), 23.03 (d, J = 3.9 Hz), 22.71 (d, J = 5.1 Hz) ppm. HRMS
.2 Hz), 23.51 (d, J = 5.1 Hz) ppm. HRMS (ESI): calcd. for
+
C
19
H
22
N
3
O
5
P [M + H] 404.1370; found 404.1364.
P: [M + H]+ 316.0864; found
(
ESI): calcd. for C14H19ClNO
3
Diisopropyl (1-Methyl-1H-indol-2-yl)phosphonate (5a):[ Reddish 316.0889.
brown gum (120 mg, 82%). H NMR (400 MHz, CDCl
33]
1
[33]
3
): δ = 7.69–
Diisopropyl (5-Methoxy-1H-indol-2-yl)phosphonate (5g):
Light
): δ =
7
(
.66 (m, 1 H), 7.38–7.34 (m, 2 H), 7.19–7.13 (m, 2 H), 4.79–4.71
m, 2 H), 3.94 (s, 3 H), 1.39 (d, J = 6.2 Hz, 6 H), 1.27 (d, J =
.2 Hz, 6 H) ppm. 31P NMR (162 MHz, CDCl
): δ = 7.61 ppm.
): δ = 139.99 (d, J = 12.1 Hz), 127.82
d, J = 220.2 Hz), 126.56 (d, J = 15.6 Hz), 124.34, 122.16, 120.18,
1
brownish gum (74 mg, 48%). H NMR (400 MHz, CDCl
3
9.64 (br. s, 1 H), 7.37 (d, J = 8.9 Hz, 1 H), 7.08 (d, J = 2.1 Hz, 1
6
3
H), 6.96 (dd, J = 12.3, 2.8 Hz, 2 H), 4.70 (qd, J = 12.4, 6.2 Hz, 2
H), 3.85 (s, 3 H), 1.38 (d, J = 6.2 Hz, 6 H), 1.26 (d, J = 6.2 Hz, 6
13
C NMR (126 MHz, CDCl
3
(
1
5
31
13
H) ppm. P NMR (162 MHz, CDCl
3
): δ = 8.27 ppm. C NMR
13.84 (d, J = 17.6 Hz), 109.94 (d, J = 2.0 Hz), 71.42 (d, J =
.4 Hz), 31.84, 24.15 (d, J = 3.9 Hz), 23.81 (d, J = 4.9 Hz) ppm.
HRMS (ESI): calcd. for C15
96.1424.
Diethyl (1-Methyl-1H-indol-2-yl)phosphonate (5b):[33] Reddish
(
126 MHz, CDCl ): δ = 153.45, 132.51 (d, J = 12.6 Hz), 126.82 (d,
3
J = 16.1 Hz), 124.65 (d, J = 220.1 Hz), 114.69, 111.99, 109.69 (d,
J = 17.1 Hz), 100.89, 70.54 (d, J = 4.8 Hz), 54.66, 23.07 (d, J =
+
H
22NO
3
P [M + H] 296.1410; found
2
3
.4 Hz), 22.73 (d, J = 4.9 Hz) ppm. HRMS (ESI): calcd. for
P [M + H]+ 312.1359; found: 312.1388.
15 4
C H22NO
1
brown gum (96 mg, 73%). H NMR (400 MHz, CDCl
d, J = 8.0 Hz, 1 H), 7.39–7.33 (m, 2 H), 7.29–7.14 (m, 2 H), 4.23–
3
): δ = 7.68
Diisopropyl (1H-Pyrrolo[2,3-b]pyridin-2-yl)phosphonate (5h): Off-
(
4
1
white solid (56 mg, 40%); m.p. 168 °C. H NMR (500 MHz,
3
1
.11 (m, 4 H), 3.95 (s, 3 H), 1.35 (t, J = 7.1 Hz, 6 H) ppm.
): δ = 10.05 ppm. 13C NMR (101 MHz,
): δ = 140.08 (d, J = 12.3 Hz), 126.52 (d, J = 15.7 Hz), 126.20
d, J = 217.7 Hz), 124.54, 122.16 (d, J = 1.2 Hz), 120.28 (d, J =
P
CDCl
3
): δ = 13.32 (br. s, 1 H), 8.73–8.72 (m, 1 H), 8.07 (dd, J =
.9, 1.3 Hz, 1 H), 7.18 (dd, J = 7.9, 4.7 Hz, 1 H), 7.09 (d, J =
.3 Hz, 1 H), 4.80–4.74 (m, 2 H), 1.41 (d, J = 6.2 Hz, 6 H), 1.23
NMR (162 MHz, CDCl
CDCl
3
7
4
(
3
(
0
31
d, J = 6.2 Hz, 6 H) ppm. P NMR (162 MHz, CDCl
3
): δ =
.5 Hz), 114.11 (d, J = 17.4 Hz), 109.98 (d, J = 2.1 Hz), 62.66 (d,
J = 5.3 Hz), 31.82, 16.31 (d, J = 6.6 Hz) ppm. HRMS (ESI): calcd.
for C13H18NO P [M + H] 268.1097; found 268.1103.
3
Dimethyl (1-Methyl-1H-indol-2-yl)phosphonate (5c):[33] Reddish
.67 ppm. 13C NMR (126 MHz, CDCl
7
1
1
3
): δ = 149.10 (d, J =
5.0 Hz), 144.63, 129.79, 126.15 (d, J = 219.2 Hz), 119.00 (d, J =
4.4 Hz), 115.45, 109.11 (d, J = 16.5 Hz), 70.57 (d, J = 5.1 Hz),
+
23.12 (d, J = 3.9 Hz), 22.76 (d, J = 5.0 Hz) ppm. HRMS (ESI):
1
P [M + H]+ 283.1206; found 283.1227.
brown gum (61 mg, 52%). H NMR (400 MHz, CDCl
3
19 2 3
): δ = 7.69 calcd. for C13H N O
Eur. J. Org. Chem. 2015, 6526–6533
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6531

P. P. Singh et al.
FULL PAPER
Diisopropyl
(5-Bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)phosphonate
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(5i): Off-white solid (99 mg, 55%); m.p. 148 °C. H NMR
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3
H), 8.18 (d, J = 1.9 Hz, 1 H), 7.00 (dd, J = 4.9, 1.9 Hz, 1 H), 4.79
qd, J = 12.4, 6.2 Hz, 2 H), 1.41 (d, J = 6.2 Hz, 6 H), 1.25 (d, J =
.2 Hz, 6 H) ppm. 31P NMR (162 MHz, CDCl
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1
3
[
13
C NMR (126 MHz, CDCl
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4
1
1
2
31.72, 128.01 (d, J = 219.2 Hz), 120.54 (d, J = 14.5 Hz), 111.06,
08.14 (d, J = 16.4 Hz), 70.91 (d, J = 5.2 Hz), 23.07 (d, J = 3.9 Hz),
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18BrN
J
=
4.9 Hz) ppm. HRMS (ESI): calcd. for
+
C
13
H
2
O
3
P [M + H] 361.0311; found 361.0338.
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Diisopropyl (1H-Pyrrol-2-yl)phosphonate (5j): Off-white solid
1
(86 mg, 75%); m.p. 67 °C. H NMR (400 MHz, CDCl
3
): δ = 10.87
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(br. s, 1 H), 7.03 (dtd, J = 4.1, 2.6, 1.4 Hz, 1 H), 6.71 (tdd, J = 3.6,
2
1
6
.6, 1.4 Hz, 1 H), 6.28 (tt, J = 3.8, 2.4 Hz, 1 H), 4.62 (ddt, J =
2.4, 8.3, 6.2 Hz, 2 H), 1.35 (d, J = 6.2 Hz, 6 H), 1.24 (d, J =
[
[
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(
7
5
2
0.94 (d, J = 4.9 Hz), 24.03 (d, J = 3.7 Hz), 23.68 (d, J =
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54.0917; found 254.0936.
H18NO
3
P [M + Na]+
tert-Butyl
5k): Colorless gum (116 mg, 70%). H NMR (400 MHz, CDCl
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2-(Diisopropoxyphosphoryl)-1H-pyrrole-1-carboxylate
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31
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Supporting Information (see footnote on the first page of this arti-
1
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1
3
31
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of Scientific and Industrial Research (CSIR), New Delhi for the
research grants # HCP 0001 and BSC 0108. M. Y., S. D., V. S., and
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Published Online: August 26, 2015
Eur. J. Org. Chem. 2015, 6526–6533
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6533