T3P-assisted esterification and amidation of phosphinic acids

Article abstract of DOI:10.1016/j.tet.2014.09.021

A few phosphinic acids, such as phenylphosphinic acids, 1-hydroxy-3-phospholene 1-oxides and 1-hydroxyphospholane oxides are esterified with simple alcohols in the presence of propylphosphonic anhydride (T3P). If 1.1 equiv of the T3P reagent is used, the esterifications are fast and efficient at 25° C. In the case of more reactive models it was enough to apply 0.66 equiv of T3P at 85°C under microwave conditions. The amidation of 1-hydroxy-3-methyl-3-phospholene oxide could also be accomplished under similar conditions.

Full text of DOI:10.1016/j.tet.2014.09.021

Tetrahedron 70 (2014) 8280e8285
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
T3PÒ-assisted esterification and amidation of phosphinic acidsq
a
a
a
b
a,
*
ꢀ
ꢀ
ꢀ ꢀ
ꢀ
ꢀ
€
Erzsebet Jablonkai , Reka Henyecz , Matyas Milen , Janos Koti , Gyorgy Keglevich
a Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary
b API Research and Development, Spectroscopic Research, Gedeon Richter Plc., 1475 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 June 2014
Received in revised form 27 August 2014
Accepted 8 September 2014
Available online 17 September 2014
A few phosphinic acids, such as phenylphosphinic acids, 1-hydroxy-3-phospholene 1-oxides and 1-
hydroxyphospholane oxides are esterified with simple alcohols in the presence of propylphosphonic
anhydride (T3PÒ). If 1.1 equiv of the T3PÒ reagent is used, the esterifications are fast and efficient at 25ꢀ C.
In the case of more reactive models it was enough to apply 0.66 equiv of T3PÒ at 85ꢀ C under microwave
conditions. The amidation of 1-hydroxy-3-methyl-3-phospholene oxide could also be accomplished
under similar conditions.
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Phosphinic acid
Phosphinic amide
P-Heterocycles
Phosphinate
T3PÒ reagent
Green synthesis
1. Introduction
2. Results and discussion
Phosphinic derivatives are most often prepared by the reaction
of phosphinic chlorides with the corresponding nucleophiles, such
as alcohols or amines.2e4 Regarding phosphinates, we have found
that phosphinic acids may undergo direct esterification with alco-
hols under microwave (MW) conditions.5e8 However, thioester-
ification and amidation of phosphinic acids took place only partially
on MW irradiation.9,10 According to another method, phosphinates
may also be obtained by the alkylating esterification of phosphinic
acids; it was found that the combined use of phase transfer catalysis
and the MW technique is advantageous.8,11 In the last decade,
a powerful condensing agent, the trimeric propylphosphonic acid
anhydride (the T3PÒ reagent) emerged that could be used well in
many reactions, such as the coupling of amino acids, acylations,
esterifications and condensations.12 The three-component
KabachnikeFields reaction could also be performed under mild
conditions utilizing the T3PÒ reagent.13
2.1. Esterification of phosphinic acids
2.1.1. Optimization of the esterification. At first, two model com-
pounds, phenyl-H-phosphinic acid (1) and 1-hydroxy-3-methyl-3-
phospholene 1-oxide (2) were chosen to find the most suitable
conditions for the T3PÒ-mediated esterification with 3 equiv of
butanol (Table 1). As was shown in the preliminary communica-
tion,1 the esterification of phosphinic acids is practically quantita-
tive in the presence of 1.1 equiv of the T3PÒ reagent at room
temperature. After a reaction time of 30 min, phosphinates 3e and 4
were obtained in yields of 95% and 82%, respectively (Table 1, en-
tries 1 and 6). The use of only 0.66 equiv of the T3PÒ reagent under
the same conditions was almost as efficient for the 1/3e trans-
formation, as the application of 1.1 equiv (91%, Table 1, entry 2);
however, the esterification of hydroxy-phospholene oxide 2 was, in
this case, less efficient, as phosphinate 4 was obtained in only 42%
(Table 1, entry 7). Carrying out the 2/4 esterification at 85 ꢀC, the
yield was somewhat increased, but 56% is still far from quantitative
(Table 1, entry 8). The latter variation (85 ꢀC and 0.66 equiv of the
reagent) was also performed under MW conditions affording
product 4 in a yield of 79% (Table 1, entry 9). In the case of the more
reactive phenyl-H-phosphinic acid (1), the esterification was also
tried out using 0.44 equiv of the T3PÒ reagent. In this instance,
phosphinate 3e was obtained in 79% yield (Table 1, entry 3). Ele-
vating the temperature to 85 ꢀC did not help, but MW irradiation at
We have found that phosphinic acids may also be esterified by
alcohols in the presence of the T3PÒ reagent. Our preliminary re-
sults were reported in a communication.1
In this article, we show the general applicability of the T3PÒ
reagent in the esterification and amidation of different cyclic
phosphinic acids.
q
See Ref. 1.
* Corresponding author. Tel.: þ36 1 463 1111/5883; fax: þ36 1 463 3648; e-mail
address: gkeglevich@mail.bme.hu (G. Keglevich).
http://dx.doi.org/10.1016/j.tet.2014.09.021
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

E. Jablonkai et al. / Tetrahedron 70 (2014) 8280e8285
8281
Table 1
Table 2
Optimization of the esterification of phosphinic acids (1 and 2) with butanol in the
Esterification of phenyl-H-phosphinic acid (1) and diphenylphosphinic acid (5) with
presence of the T3PÒ reagent
a series of alcohols in the presence of T3PÒ
Entry
Y
ROH
T3PÒ (equiv)
Temp (ꢀC)
Time (h)
Yield (%)
Entry
Y1
Y2
T3PÒ (equiv)
Temp (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
MeOH
EtOH
PrOH
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1 (0.66)
1.1
25
25
25
25
25
25
25
25
85 (MW)
85 (MW)
85 (MW)
85 (MW)
0.5
0.5
0.5
1
0.5
1
1
1
1
1
82 (80) (3a)
89 (83) (3b)
96 (91) (3c)
81 (78) (3d)
95 (91) (3e)
91 (86) (3f)
83 (81) (3g)a
82 (78) (3h)
45 (6a)
1
2
3
4
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
1.1
25
25
25
0.5
0.5
0.5
95 (3e)
91 (3e)
79 (3e)
78 (3e)
89 (3e)
82 (4)
0.66
0.44
0.44
0.44
1.1
iPrOH
BuOH
iBuOH
sBuOH
tBuOH
MeOH
EtOH
85 (D
)
0.25a
0.25b
0.5
5
85 (MW)
25
61
7
8
9
0.66
0.66
0.66
25
0.5
42 (4)
56 (4)
79 (4)
9
85 (D
)
0.5
85 (MW)
0.5b
10
11
12
1.1
1.1
1.1
45 (6b)
47 (6c)
49 (6e)
PrOH
BuOH
1
1
a
No change on further heating.
No change on further irradiation.
b
a
As a 54e46% mixture of two isomers.
Table 3
Esterification of 1-hydroxy-3,4-dimethyl-3-phospholene 1-oxide (7)
the same temperature was quite efficient and led to a yield of 89%
(Table 1, entries 4 and 5, respectively).
It can be seen that from among the three ‘nPrP(O)O’ units of the
T3PÒ reagent, one fragment can be used without any problem. The
utilization of the second unit of ‘nPrP(O)O’ is possible with reactive
phosphinic acids, such as phenyl-H-phosphinic acid (1). With less
reactive phosphinic acids, like 1-hydroxy-3-phospholene oxide 2,
MW irradiation at 85 ꢀC was necessary to attain a yield of 79%,
when 0.66 equiv of the T3PÒ reagent was used. The esterification
using 0.44 equiv of the T3PÒ reagent was beneficial only with the
more reactive phenyl-H-phosphinic acid (1) under MW
conditions.
Entry
ROH
T3PÒ (equiv)
Temp (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
MeOH
MeOH
EtOH
EtOH
PrOH
1.1
0.66
1.1
0.66
1.1
0.66
1.1
1.1
0.66
1.1
0.66
1.1
1.1
25
85 (MW)
25
85 (MW)
25
1
1
1
1
1
84 (8a)
83 (8a)
82 (8b)
80 (8b)
79 (8c)
80 (8c)
59 (8d)
79 (8d)
62 (8d)
85 (8e)
79 (8e)
72 (8f)
81 (8f)
75 (8f)
61 (8g)
71 (8g)
57 (8g)
2.1.2. Esterification of acyclic phenylphosphinic acids (1 and 5). In
the next stage, phenyl-H-phosphinic acid (1) was esterified with
other simple (C1eC4) alcohols using 1.1 or 0.66 equiv of the T3PÒ
reagent at 25 ꢀC (Table 2). In the second variation, applying only
0.66 equiv of the T3PÒ reagent, the yields were 2e6% lower, than
using 1.1 equiv of the T3PÒ reagent. The yields of phosphinates
3aeh, regarding both series of experiments, fall in the range of
80e95% after flash column chromatography (Table 2, entries 1e8).
It is worthy of mention that the sterically hindered tert-butyl al-
cohol could be used almost as efficiently as the other alcohols
(Table 2, entry 8). The esterification with sec-butanol resulted in
product 3g as a 54e46% mixture of two diastereomers. The ester-
ification of the sterically more crowded, and hence not too reactive
diphenylphosphinic acid (5) was performed in the presence of
1.1 equiv of the T3PÒ reagent at 85 ꢀC for 1 h under MW irradiation
to afford the products in lower yields of 45e49% (Table 2, entries
9e12). The products 3aeh, 6aec and 6e, which, with the exception
of 3g, were described earlier, were identified on the basis of 31P
PrOH
85 (MW)
25
1
iPrOH
iPrOH
iPrOH
BuOH
BuOH
iBuOH
iBuOH
iBuOH
sBuOH
sBuOH
sBuOH
2a
1c
1
85b
(D)
9
85 (MW)
25
10
11
12
13
14
15
16
17
1
1
85 (MW)
25
1
85b
(D
)
1c
1
0.66
1.1
1.1
85 (MW)
25
2a
1c
1
85b
(D)
0.66
85 (MW)
a
No change on further stirring.
Temperature of the oil bath.
No change on further heating.
b
c
reactions were incomplete at 25 ꢀC after ꢁ2 h (Table 3, entries
7, 12, 15).
NMR and HRMS. Compound 3g was fully characterized also by 13
C
Eventually, the phosphinates 8aeg could be obtained in yields of
71e85% after flash column chromatography. Carrying out the es-
terifications with n-alcohols using only 0.66 equiv of the T3PÒ re-
agent at 85 ꢀC under MW, the yields of phosphinates 8aec and 8e
were 1e6% lower (Table 3, entries 2, 4, 6, 11), while with branched
alcohols as the reactant, the yields of esters 8d, 8f and 8g were
6e17% lower (Table 3, entries 9, 14, 17). It can be concluded that in
the case of n-alcohols as the partners, the use of only 0.66 equiv of
the T3PÒ reagent may be enough, but 85 ꢀC and MW irradiation are
necessary.
and 1H NMR data.
2.1.3. Esterification of cyclic phosphinic acids (7, 9 and 11). The
T3PÒ-mediated esterifications were then carried out with 1-
hydroxy-3,4-dimethyl-3-phospholene 1-oxide (7) (Table 3).
Using 1.1 equiv of the T3PÒ reagent, the reactions with n-al-
cohols were complete at 25 ꢀC after 1 h (Table 3, entries 1, 3, 5,
10), but the esterification with branched alcohols required
heating at 85 ꢀC for 1 h (Table 3, entries 8, 13, 16), as the latter

8282
E. Jablonkai et al. / Tetrahedron 70 (2014) 8280e8285
Table 5
With the exception of phosphinate 8g, the other compounds
Esterification of 1-hydroxy-3,4-dimethylphospholane 1-oxide (11)a
(8aef) were described earlier in the literature. The known species
were identified on the basis of 31P NMR and HRMS.
Then, 1-hydroxy-3-methylphospholane oxide (9) was esterified
in a similar manner using 1.1 equiv of the T3PÒ reagent (Table 4).
Reaction of the cyclic phosphinic acid (9) with alcohols at 25 ꢀC
furnished the phosphinates (10aeg) in yields of 54e81% after flash
column chromatography (Table 4, entries 1, 3, 5, 7, 9, 11, 12). The
lowest yields (55/54%) were obtained in the esterifications with
isopropyl alcohol, and sec-butyl alcohol (Table 4, entries 7, 12).
Performing the esterification with isopropyl alcohol at 85 ꢀC did not
help much (57%, Table 4, entry 8). Products 10aef consisted of ca.
1:1 mixtures of two diastereomers, while the sec-butyl ester (10g)
comprised four isomers. Carrying out the esterifications with only
0.66 equiv of the T3PÒ reagent at 85 ꢀC under MW, the yields of the
n-alkyl esters (10aec and 10e) were 10e14% lower (Table 4, entries
2, 4, 6, 10), suggesting that in the case of hydroxy-
methylphospholane oxide 9, that is of lower reactivity, it is better
to use 1.1 equiv of the T3PÒ reagent to obtain the phosphinates (10)
in higher yields.
Entry ROH
T3PÒ (equiv) Temp (ꢀC) Time (h) Yield (%) Composition
1
2
MeOH 1.1
MeOH 0.66
25
85 (MW)
25
85 (MW)
25
1
1
1
1
1
69 (12a) 91:3:6
57 (12a)
72 (12b) 92:3:5
65 (12b)
67 (12c) 94:3:3
d
3
4
5
6
EtOH
EtOH
PrOH
PrOH
1.1
0.66
1.1
d
0.66
85 (MW)
25
1
55 (12c)
35 (12d)
45 (12d) 95:3:2
75 (12e) 92:5:3
63 (12e)
54 (12f) 94:3:3
d
7
8
9
10
11
12
iPrOH 1.1
iPrOH 1.1
BuOH 1.1
BuOH 0.66
iBuOH 1.1
sBuOH 1.1
2b
d
85c
25
(D
)
1.5
1
1
2
2
85 (MW)
25
d
85c
(D
)
45 (12g) 47:45:3:5
a
The starting phosphinic acid comprised a 7:3 mixture of two isomers.
No change on further reaction.
Temperature of the oil bath.
b
c
Table 4
Esterification of 1-hydroxy-3-methylphospholane 1-oxide (9)
One can see, that in most cases, phosphinic acids may be es-
terified efficiently with alcohols under mild conditions using
1.1 equiv of the T3PÒ reagent. With more reactive phosphinic acids,
it is enough to apply the T3PÒ reagent in a quantity of 0.66 equiv,
but more forcing conditions are necessary.
Entry
ROH
T3PÒ (equiv)
Temp (ꢀC)
Time (h)
Yielda (%)
2.1.4. Amidation of 1-hydroxy-3-methyl-3-phospholene 1-oxide
(2). We wished to extend the sphere of T3PÒ-promoted de-
rivatizations of phosphinic acids. For this, 1-hydroxy-3-methyl-3-
phospholene oxide 2 was reacted with a series of primary amines
(propyl-, butyl-, hexyl- and benzyl-amines) and secondary amines
(diethyl-, di-n-propyl- and di-n-butyl-amine) at 25 ꢀC applying the
T3PÒ reagent in a quantity of 1.1 equiv (Table 6). Depending on the
reactivity of the amine, the completion required a reaction time of
1
2
3
4
5
6
7
8
MeOH
MeOH
EtOH
1.1
0.66
1.1
0.66
1.1
0.66
1.1
1.1
1.1
0.66
1.1
1.1
25
85 (MW)
25
85 (MW)
25
1
1
1
1
1
81 (10a)
67 (10a)
71 (10b)
60 (10b)
67 (10c)
57 (10c)
55 (10d)
57 (10d)
75 (10e)
61 (10e)
66 (10f)
54 (10g)d
EtOH
PrOH
PrOH
iPrOH
iPrOH
BuOH
BuOH
iBuOH
sBuOH
85 (MW)
25
1
2b
1.5b
1
85c
25
(D)
9
10
11
12
85 (MW)
25
25
1
2
2b
Table 6
a
As an w1:1 mixture of two diastereomers.
No change on further stirring.
Temperature of the oil bath.
Amidation of 1-hydroxy-3-methyl-3-phospholene 1-oxide (2)
b
c
d
As a 23:23:32;22% mixture of four diastereomers (determined on the basis of
the relative 13C NMR intensities of the C5 signals).
1-Hydroxy-dimethylphospholane oxide 11 was also subjected to
esterifications (Table 5). The experiences were similar to those
observed for the monomethyl derivatives (9), however, in this in-
stance, the esterification with isopropyl alcohol and sec-butyl al-
cohol was more efficient at 85 ꢀC for 1.5/2 h (Table 5, entries 7, 8,
12). The phosphinates (12aeg), formed in this case as a mixture of
three isomers, were obtained in yields of 45e75% after flash column
chromatography (Table 5, entries 1, 3, 5, 8, 9, 11, 12). It can be seen
from the data of Table 5 (entries 2, 4, 6, 10) that the use of only
0.66 equiv of the T3PÒ reagent led to ca. 11% lower yields of the
corresponding phosphinates 12.
The experience is that the lower reactivity of these saturated
derivatives (9 and 11) did not justify attempts at the esterification
with less T3PÒ.
The phosphinates 10aed, 10f and 10g, as well as 12aed, 12f, and
12g are new compounds and were fully characterized by 31P, 13C
and 1H NMR, as well as HRMS spectroscopy.
Entry
R1
R2
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Pr
H
H
H
H
H
H
H
H
0.5
2
0.5
0.5
2
0.5
2
0.5
2
61 (13a)
60 (13b)
65 (13c)
68 (13d)
62 (13e)a
86 (13f)
82 (13g)
87 (13h)
65 (13i)
61 (13j)
70 (13k)
iPr
Bu
iBu
sBu
Hex
cHex
Bn
Et
9
10
11
Et
Pr
Bu
Pr
Bu
2
2
a
As a 1:1 mixture of two diastereomers.

E. Jablonkai et al. / Tetrahedron 70 (2014) 8280e8285
8283
0.5 h or 2 h, and the phosphinic amides (13aek) were obtained in
a yield of 60e87% after column chromatography (Table 6, entries
1e11). The amide with the sec-butyl substituent (13e) was obtained
as a 1:1 mixture of two diastereomers. The majority of the ami-
nophospholene oxides (13) have been described earlier,21,22 only
species 13a,13b,13e,13j and 13k are new and were characterized in
detail by us.
in a 0.50 mmol and a 0.33 mmol (0.33 mL and 0.22 mL, respectively)
quantity (see the appropriate parts of Tables 1e5).
The following new compounds were thus prepared:
4.2.1. 1-Methylpropyl phenyl-H-phosphinate (3g). 31P NMR: (CDCl3)
d
: 22.2 (54%) and 23.6 (46%); 13C NMR (CDCl3)
d: 9.6 and 9.8 (CH2CH3),
21.3 and 21.9 (d, J 3.2 and 3.4, CHCH3), 30.7 and 30.8 (d, J 4.7, CHCH2),
76.0 and 76.6 (d, J 6.8, OCH),128.8 (d, J 13.9, C2 or C3),130.6 (d, J 132.5,
It can be seen that the T3PÒ reagent is also suitable to promote
efficient amidation of phosphinic acids under mild conditions. This
is the first case that a phosphinic acid is converted to amides using
the T3PÒ reagent.
C1),131.0 (d, J 11.8, C3 or C2),133.1 (d, J 2.0, C4); 1H NMR (CDCl3)
d: 0.88
and 0.96 (t, J 7.4, 3H, CH2CH3), 1.30 and 1.37 (d, J 6.2, 3H, OCHCH3),
1.50e1.77 (m, 2H, CHCH2), 4.40e4.52 (m,1H, OCH), 7.60 (d, J 558.1,1H,
PH), 7.31e7.62 (m, 3H, ArH), 7.69e7.85 (m, 2H, ArH); IR (neat) 1033,
1234, 1440, 2975 cmꢂ1; ½M þ Hꢃfþound ¼ 199:0889; C10H16O2P re-
quires 199.0888.
3. Conclusions
It was shown that phosphinic acids that do not undergo direct
esterification and amidation with alcohols and amines, re-
spectively, may be derivatized using the corresponding nucleophile
in the presence of 1.1 equiv of the T3PÒ reagent. In the case of more
reactive phosphinic acids, it was enough to apply 0.66 equiv of the
condensing agent, and in certain cases, it was helpful to accomplish
the reactions at 85 ꢀC under MW conditions. The method de-
veloped represents an environmentally-friendly approach for the
preparation of phosphinic derivatives.
4.2.2. 1-(1-Methylpropoxy)-3,4-dimethyl-3-phospholene 1-oxide
(8g). 31P NMR: (CDCl3) : 68.5; 13C NMR (CDCl3)
d d: 9.6 (CH2CH3),
16.5 (d, J 15.8, C3eCH3), 21.7 (d, J 2.6, OCHCH3), 30.7 (d, J 5.0,
OCHCH2), 36.4 and 36.8 (d, J 92.1, C2), 74.3 (d, J 6.9, OCH), 127.3 and
127.5 (d, J 10.4 and 10.2, C3); 1H NMR (CDCl3)
d: 0.82 (t, J 7.4, 3H,
CH2CH3), 1.21 (d, J 6.2, 3H,OCHCH3), 1.37e1.69 (m, 2H, OCHCH2), 1.61
(s, 6H, C3eCH3, C4eCH3), 2.20e2.47 (m, 4H, PCH2), 4.27e4.44 (m, 1H,
OCH); þIR (neat) 1030, 1244, 1446, 1651, 2973 cmꢂ1
;
½M þ Hꢃfound ¼ 203:1204; C10H20O2P requires 203.1201.
4.2.3. 1-Methoxy-3-methylphospholane 1-oxide (10a). 31P NMR
(CDCl3) : isomer A: 21.1 (d, J 7.9, C3eCH3),
: 81.1; 13C NMR (CDCl3)
4. Experimental
4.1. General
d
d
24.8 (d, J 88.0, C5), 31.1 (d, J 9.8, C4 or C3), 31.7 (d, J 12.9, C3 or C4),
32.2 (d, J 89.5, C2 or), 51.0 (d, J 6.8, OCH3); isomer B: 21.3 (d, J¼7.4,
C3eCH3), 25.5 (d, J¼87.4, C5), 31.3 (d, J¼9.8, C4 or C3), 32.0 (d, J¼12.9,
C3 or C4), 32.5 (d, J¼89.0, C2), 51.0 (d, J¼6.8, OCH3); 1H NMR (CDCl3)
The MW-assisted reactions were carried out in a 300 W CEM
Discover focused reactor equipped with a pressure controller ap-
plying 30e50 W under isothermal conditions. Standard 5 mL glass
reaction vessels were used distributed by the supplier of the CEM
reactor, and the reaction mixtures were stirred magnetically. The
13C and 1H NMR spectra were obtained in CDCl3 solution on
a Bruker DRX-500 spectrometer operating at 125.7, and 500.1 MHz,
d
: 1.05 (d, J 5.3, 3H, C3eCH3), 1.15e2.31 (m, 7H, CH2, CH), 3.66 (d, J
10.8, 3þH, OCH3); IR (neat) 1034, 1228, 1458, 2956 cmꢂ1
;
½M þ Hꢃfound ¼ 149:0732; C6H14O2P requires 149.0732.
4.2.4. 1-Ethoxy-3-methylphospholane 1-oxide (10b). 31P NMR
(CDCl3) : isomer A: 16.5 (d, J 6.0, CH2CH3),
: 79.4; 13C NMR (CDCl3)
respectively. The 13C and 1H chemical shifts are referred to TMS. 31
P
d
d
NMR spectra were obtained on a Bruker AV-300 spectrometer.
Chemical shifts are downfield relative to 85% H3PO4. Mass spec-
trometry was performed on a Thermo LTQ-FT-Ultra spectrometer,
or a Waters GCT Premier instrument applying ESI and EI modes of
operation, respectively.
21.1 (d, J 8.0, C3eCH3), 25.4 (d, J 88.0, C5), 31.2 (d, J 9.8, C4 or C3), 31.8
(d, J 13.0, C3 or C4), 32.9 (d, J 89.6, C2), 60.45 (d, J 6.6, OCH2); isomer
B: 16.5 (d, J 6.0, CH2CH3), 21.3 (d, J 7.4, C3eCH3), 26.1 (d, J 87.6, C5),
31.3 (d, J 9.8, C4 or C3), 32.0 (d, J 13.0, C3 or C4), 33.1 (d, J 89.1, C2),
60.50 (d, J 6.5, OCH2); 1H NMR (CDCl3)
d: 1.04 (d, J 6.2, 3H, C3eCH3),
1.28 (t, J 6.9, 3H, CH2CH3), 1.30e2.19 (m, 7H, skeletal CH2, CH),
4.2. General procedure for esterification of phosphinic acids
3.91e4.09 (m, 2H, OCH2); IR (neat) 1036, 1228, 1458, 2957 cmꢂ1
½M þ Hꢃþfound ¼ 163:0888; C7H16O2P requires 163.0888.
;
(1, 2, 5, 7, 9 and 11) in the presence of T3PÒ
A mixture of the phosphinic acid (0.76 mmol [phenyl-H-phos-
phinic acid (1): 0.11 g, 1-hydroxy-3-methyl-3-phospholene 1-oxide
(2): 0.10 g, diphenylphosphinic acid (5): 0.15 g, 1-hydroxy-3,4-
dimethyl-3-phospholene 1-oxide (7): 0.11 g, 1-hydroxy-3-
methylphospholane 1-oxide (9): 0.10 g, 1-hydroxy-3,4-
dimethylphospholane 1-oxide (11): 0.11 g]) and the T3PÒ reagent
(0.55 mL, 0.84 mmol 50 wt % ethyl acetate solution) was stirred for
10 min. To the resulting mixture was added the alcohol (2.3 mmol
[methanol: 0.09 mL, ethanol: 0.13 mL, propanol: 0.17 mL, iso-
propanol: 0.17 mL, butanol: 0.21 mL, isobutanol: 0.21 mL, sec-bu-
tanol: 0.21 mL, tert-butanol: 0.22 mL]) and the contents of the flask
were stirred for appropriate time (see Tables 2e5). The excess of the
T3PÒ reagent was hydrolyzed with 10% NaHCO3 solution (15 mL)
and the aqueous phase was washed with ethyl acetate (30 mL). The
combined organic phase was dried (Na2SO4), and concentrated in
vacuum to provide the crude product that was passed through
a thin (ca. 3e4 cm) layer of silica gel using 3% MeOH in CH2Cl2 as the
eluent to give the products (2, 3, 6, 8, 10 and 12) in a purity >99% as
oils. For details see Tables 1e5. During the optimization procedure
and in a part of other experiments, the T3PÒ reagent was also used
4.2.5. 1-Propoxy-3-methylphospholane 1-oxide (10c). 31P NMR
(CDCl3) : isomer A: 10.0 (CH2CH3), 21.2 (d, J
: 79.4; 13C NMR (CDCl3)
d
d
15.0, C3eCH3), 23.9 (d, J 6.1, OCH2CH2), 25.3 (d, J 88.1, C5), 31.2 (d, J 9.7,
C4 or C3), 31.8 (d, J 12.9, C3 or C4), 32.8 (d, J 89.6, C2), 65.98 (d, J 6.8,
OCH2); isomer B 10.0 (CH2CH3), 21.3 (d, J 14.3, C3eCH3), 23.9 (d, J 6.1,
OCH2CH2), 26.0 (d, J 87.6, C5), 31.4 (d, J 9.8, C4 or C3), 32.0 (d, J 12.9, C3
or C4), 33.1 (d, J 89.2, C2), 66.03 (d, J 6.8, OCH2); 1H NMR (CDCl3)
d:
0.91 (t, J 7.3, 3H, CH2CH3),1.05 (d, J 5.4, 3H, C3eCH3),1.19e2.18 (m, 9H,
skeletal CH2, CH, CH2CH3), 3.80e4.00 (m, 2H, OCH2); IR (neat) 1056,
1228, 1459, 2963 cmꢂ1; ½M þ Hꢃfþound ¼ 177:1040; C8H18O2P re-
quires 177.1039.
4.2.6. 1-Isopropoxy-3-methylphospholane 1-oxide (10d). 31P NMR
(CDCl3) d d: isomer
: 77.8 (A, 54%) and 77.7 (B, 46%); 13C NMR (CDCl3)
A: 21.3 (d, J 7.7, C3eCH3), 24.3 (d, J 4.2, OCHCH3), 26.4 (d, J 88.2, C5),
31.4 (d, J 10.0, C4 or C3), 32.0 (d, J 13.2, C3 or C4), 33.9 (d, J 89.7, C2),
69.46 (d, J 6.6, OCH); isomer B: 21.5 (d, J 7.0, C3eCH3), 24.4 (d, J 4.2,
OCHCH3), 27.0 (d, J 88.0, C5), 31.5 (d, J 10.9, C4 or C3), 32.2 (d, J 14.2,
C3 or C4), 34.1 (d, J 89.5, C2), 69.50 (d, J 6.6, OCH); 1H NMR (CDCl3)
d:
1.08 (d, J¼6.2, 3H, C3eCH3), 1.31 (d, J¼6.1, 6H, CHCH3), 1.34e2.21 (m,

8284
E. Jablonkai et al. / Tetrahedron 70 (2014) 8280e8285
7H, skeletal CH2, CH), 4.55e4.74 (m, 1H, OCH); IR (neat) 1059, 1229,
1458, 2960 cmꢂ1; ½M þ Hꢃfþound ¼ 177:1039; C8H18O2P requires
177.1039.
1.29e1.75 (m, 6H, skeletal CH2, CH), 1.93e2.08 (m, 2H, CH2CH3),
3.84e3.96 (m, 2H, OCH2); IR (neat) 1064, 1243, 1456, 2965 cmꢂ1
,
½M þ Hꢃþfound ¼ 191:1197; C9H20O2P requires 191.1195.
4.2.7. 1-Isobutoxy-3-methylphospholane 1-oxide (10f). 31P NMR
4.2.12. 1-Isopropoxy-3,4-dimethylphospholane 1-oxide (12d). 31P
(CDCl3)
d
: 79.2; 13C NMR (CDCl3)
d
: isomer A: 18.7 (CHCH3), 21.2 (d, J
NMR (CDCl3)
(CDCl3) : 18.9 (d, J 14.9, C3eCH3 or C4eCH3),19.1 (d, J 14.1, C4eCH3 or
d
: 70.9 (A, 95%), 77.4 (B, 3%) and 76.9 (C, 2%); 13C NMR
7.0, C3eCH3), 25.2 (d, J 88.2, C5), 29.2 (d, J 6.3, OCH2CH), 31.2 (d, J 9.7,
C4 or C3), 31.8 (d, J 13.0, C3 or C4), 32.7 (d, J 89.8, C2), 70.46 (d, J 6.9,
OCH2); isomer B: 18.7 (CHCH3), 21.4 (d, J 6.2, C3eCH3), 25.9 (d, J 87.7,
C5), 29.2 (d, J 6.3, OCH2CH), 31.4 (d, J 9.8, C4 or C3), 32.0 (d, J 13.1, C3
d
C3eCH3), 24.2 and 24.3 (d, J 4.0 and J 3.7, OCHCH3), 35.3 (d, J 88.6, C5
or C2), 35.6 (d, J 88.4, C2 or C5), 38.7 (d, J 10.8, C3 and C4), 69.3 (d, J 6.6,
OCH); 1H NMR (CDCl3)
d: 1.06 (br d, Jw4.8) and 1.07 (br d, Jw4.8, total
or C4), 33.0 (d, J 89.3, C2), 70.51 (d, J 6.9, OCH2); 1H NMR (CDCl3)
d:
intensity 6H, C3eCH3/C4eCH3), 1.31 (br d, J 6.2, 6H, CHCH3),
1.31e2.09 (m, 6H, skeletal CH2, CH), 4.60e4.71 (m, 1H, OCH); IR
(neat) 1065, 1244, 1457, 2961 cmꢂ1; ½M þ Hꢃfþound ¼ 191:1197;
C9H20O2P requires 191.1195.
0.79 (d, J 6.6) and 0.80 (d, J 6.6) total intensity 6H, CHCH3, 0.96 (d, J
5.0, 3H, C3eCH3), 1.08e2.04 (m, 8H, skeletal CH2, CH, CH2CH),
3.52e3.72 (m, 2H, OCH2); IR (neat) 1023, 1228, 1458, 2959 cmꢂ1
½M þ Hꢃþfound ¼ 191:1195; C9H20O2P requires 191.1195.
;
4.2.13. 1-Isobutoxy-3,4-dimethylphospholane 1-oxide (12f). 31P NMR
4.2.8. 1-(1-Methylpropoxy)-3-methylphospholane 1-oxide (10g). 31P
NMR (CDCl3)
: 77.8 (A and B, 46% [on the basis of the relative 13C
NMR intensities of the signals of the C5 atom, the ratio of A and B is
1:1]), 78.0 (C, 32%) and 77.9 (D, 22%); 13C NMR (CDCl3)
: isomer A:
(CDCl3)
(CDCl3) d: 18.9 (CHCH3), 19.0 (d, J 17.1, C3eCH3 or C4eCH3), 19.2 (d, J
d
: 72.7 (A, 94%), 79.3 (B, 3%) and 78.5 (C, 3%); 13C NMR
d
14.8, C4eCH3 or C3eCH3), 29.3 (d, J 6.3, OCH2CH), 34.3 (d, J 88.6, C5 or
C2), 34.7 (d, J 88.3, C2 or C5), 38.8 (d, J 10.8, C3 and C4), 70.6 (d, J 6.9,
d
9.7 (CH2CH3), 21.3 (d, J 15.1, C3eCH3), 21.74 (d, J 7.9, CHCH3), 26.1 (d,
J 88.3, C5), 30.69 (d, J 5.2, CHCH2), 31.3 (d, J 9.7, C4 or C3), 31.9 (d, J
13.4, C3 or C4), 33.6 (d, J 89.9, C2), 74.06 (d, J 7.1, OCH); isomer B: 9.7
(CH2CH3), 21.3 (d, J 15.1, C3eCH3), 21.74 (d, J 7.9, CHCH3), 26.6 (d, J
88.3, C5), 30.69 (d, J 5.2, CHCH2), 31.4 (d, J 9.1, C4 or C3), 31.94 (d, J
13.4, C3 or C4), 33.9 (d, J 89.5, C2), 74.08 (d, J 6.8, OCH); isomer C: 9.7
(CH2CH3), 21.4 (d, J 14.4, C3eCH3), 21.77 (d, J 8.0, CHCH3), 26.8 (d, J
88.1, C5), 30.71 (d, Jw5, CHCH2), 31.5 (d, J 9.3, C4 or C3), 32.04 (d, J
13.0, C3 or C4), 34.0 (d, J 89.9, C2), 74.2 (d, J¼7.1, OCH); isomer D: 9.7
(CH2CH3), 21.4 (d, J 14.4, C3eCH3), 21.71 (d, J 8.0, CHCH3), 27.3 (d, J
88.0, C5), 30.8 (d, Jw5, CHCH2), 31.6 (d, J 9.7, C4 or C3), 32.12 (d, J
13.6, C3 or C4), 34.4 (d, J 89.5, C2), 74.3 (d, J 6.9, OCH); 1H NMR
OCH2); 1H NMR (CDCl3)
d: 0.88 (d, J 6.7, 6H, CHCH3),1.03 (br d, Jw5.0,
6H, C3eCH3/C4eCH3), 1.26e2.08 (m, 7H, skeletal CH2, CH, OCH2CH),
3.60e3.77 (m, 2H, OCH2); IR (neat) 1024, 1244, 1456, 2961 cmꢂ1
½M þ Hꢃþfound ¼ 205:1355; C10H22O2P requires 205.1352.
;
4.2.14. 1-(1-Methylpropoxy)-3,4-dimethylphospholane 1-oxide
(12g). 31P NMR (CDCl3)
: 71.2 (A, 49%), 71.3 (B, 47%), 77.3 (C, 2%)
and 77.8 (D, 2%); 13C NMR (CDCl3)
: isomer A: 9.6 (CH2CH3), 18.8 (d, J
d
d
15.3, C3eCH3 or C4eCH3), 19.1 (d, J 14.5, C4eCH3 or C3eCH3), 21.6 (d, J
2.8, OCHCH3), 30.6 (d, J 5.3, CHCH2), 35.0 (d, J 88.8, C5 or C2), 35.4 (d, J
88.7, C2 or C5), 38.6 (d, J 10.9, C4 or C3), 38.66 (d, J 10.8, C3 or C4), 74.0
(d, J 7.0, OCH); isomer B: 9.6 (CH2CH3), 18.8 (d, J 15.3, C3eCH3 or
C4eCH3), 19.1 (d, J 14.5, C4eCH3 or C3eCH3), 21.8 (d, J 2.4, OCHCH3),
30.7 (d, J 5.1, CHCH2), 35.3 (d, J 88.5, C5 or C2), 35.8 (d, J 88.6, C2 or C5),
38.66 (d, J 10.8, C4 or C3), 38.71 (d, J 10.6, C3 or C4), 74.2 (d, J 7.0, OCH);
(CDCl3) d: 0.88 (t, J 7.3, 3H, CH2CH3), 1.05 (d, J 4.7, 3H, C3eCH3), 1.26
(d, J 6.1, 3H, CHCH3), 1.10e141 (m, 2H, CHCH2), 1.45e2.15 (m, 7H,
skeletal CH2, CH), 4.27e4.48 (m, 1H, OCH); IR (neat) 1030, 1228,
1458, 2967 cmꢂ1; ½M þ Hꢃfþound ¼ 191:1196; C9H20O2P requires
191.1195.
1H NMR (CDCl3)
d: 0.90 (t, J 7.4, 3H, CH2CH3), 1.05 (br d, Jw4.8) and
1.06 (br d, Jw4.8, total intensity 6H, C3eCH3/C4eCH3), 1.28 (d, J 6.2,
3H, CHCH3), 1.37e2.04 (m, 8H, skeletal CH2, CH, CHCH2), 4.30e4.45
4.2.9. 1-Methoxy-3,4-dimethylphospholane 1-oxide (12a). 31P NMR
(m, 1H, OCH); IR (neat) 1031, 1239, 1457, 2966 cmꢂ1; ½M þ Hꢃfþound
¼
(CDCl3)
(CDCl3)
d
: 74.7 (A, 91%), 81.3 (B, 6%) and 80.6 (C, 3%); 13C NMR
205:1352; C10H22O2P requires 205.1352.
d: 18.9 (d, J 15.7, C3eCH3 or C4eCH3), 19.1 (d, J 14.7, C4eCH3
The identification of the known compounds (3aef, 3h, 6aec, 6e,
8aef, 10e and 12e) is given in Table 7.
or C3eCH3), 33.8 (d, J 88.4, C5 or C2), 34.1 (d, J 87.9, C2 or C5), 38.6 (d,
J 10.8, C4 or C3), 38.7 (d, J 10.8, C3 or C4), 51.1 (d, J 6.7, OCH3); 1H NMR
Table 7
(CDCl3) d: 1.05 (br d, J 4.7, total intensity 6H, C3eCH3/C4eCH3),
Selected spectral data for the known esters (3aef, 3h, 6aec, 6e, 8aef, 10e and 12e)
1.24e2.10 (m, 6H, skeletal CH2, CH), 3.65 (d, J 10.8, 3H, OCH3); IR
(neat) 1033, 1242, 1456, 2961 cmꢂ1; ½M þ Hꢃfþound ¼ 163:0886;
C7H16O2P requires 163.0888.
Product
31P NMR (CDCl3)
dP (lit.)
½M þ Hꢃþfound
½M þ Hꢃþrequires
3a
3b
3c
3d
3e
3f
3h
6a
6b
6c
6e
8a
8b
8c
8d
8e
8f
27.2
25.7
25.0
22.3
25.7
25.2
15.2
33.4
31.4
31.2
31.2
70.5
68.5
68.6
66.8
68.5
67.6
79.4
27.6 [14]
24.7 [15]
24.9 [15]
22.3 [15]
24.9 [15]
25.0 [15]
15.3 [16]
34.5 [17]
30.8 [18]
33.5 [19]
31.2 [15]
70.1 [20]
68.3 [11]
68.5 [15]
66.8 [11]
68.4 [15]
68.5 [15]
79.40 (50%)
79.38 (50%) [8]
72.5 (60%)
78.4 (20%)
79.0 (20%) [8]
157.0423
171.0575
185.0733
185.0733
199.0888
199.0887
199.0888
233.0737
247.0888
261.1040
275.1196
161.0730
175.0887
188.0955a
188.0959a
203.1203
203.1204
191.1204
157.0413
171.0575
185.0731
185.0731
199.0888
199.0888
199.0888
233.0737
247.0888
261.1039
275.1195
161.0731
175.0888
188.0966a
188.0966a
203.1201
203.1201
191.1201
4.2.10. 1-Ethoxy-3,4-dimethylphospholane 1-oxide (12b). 31P NMR
(CDCl3)
(CDCl3)
d
: 72.6 (A, 92%), 79.1 (B, 5%) and 78.5 (C, 3%); 13C NMR
d
: 16.4 (d, J 6.0, CH2CH3), 18.7 (d, J 15.1, C3eCH3 or C4eCH3),
18.9 (d, J 14.2, C4eCH3 or C3eCH3), 34.3 (d, J 88.5, C5 or C2), 34.6 (d, J
88.1, C2 or C5), 38.50 (d, J 10.8, C4 or C3), 38.54 (d, J 10.9, C3 or C4),
60.4 (d, J 6.5, OCH2); 1H NMR (CDCl3)
d: 1.01 (br d, Jw4.4, total in-
tensity 6H, C3eCH3/C4eCH3), 1.24 (t, J 7.0) and 1.25 (t, J 7.0), total
intensity 3H, CH2CH3, 1.15e2.02 (m, 6H, skeletal CH2, CH),
3.89e4.10 (m, 2H, OCH2); IR (neat) 1035, 1242, 1455, 2963 cmꢂ1
½M þ Hꢃþfound ¼ 177:1042; C8H18O2P requires 177.1039.
;
4.2.11. 1-Propoxy-3,4-dimethylphospholane 1-oxide (12c). 31P NMR
(CDCl3)
(CDCl3)
d
: 72.6 (A, 94%), 78.5 (B, 3%) and 79.2 (C, 3%); 13C NMR
: 10.0 (CH2CH3), 18.7 (d, J 15.3, C3eCH3 or C4eCH3), 19.0 (d,
10e
d
12e
72.4 (92%)
78.3 (3%)
79.0 (5%)
205.1350
205.1357
J 14.4, C4eCH3 or C3eCH3), 23.8 (d, J 6.2, OCH2CH2), 33.8 (d, J 88.5, C5
or C2), 35.0 (d, J 88.2, C2 or C5), 38.5 (d, J 10.8, C4 or C3), 38.6 (d, J 10.9,
C
3 or C4), 65.9 (d, J 6.7, OCH2); 1H NMR (CDCl3)
d: 0.91 (t, J 7.4, 3H,
a
For the unprotonated M.
CH2CH3), 1.05 (br d, Jw4.7, total intensity 6H, C3eCH3/C4eCH3),

E. Jablonkai et al. / Tetrahedron 70 (2014) 8280e8285
8285
4.3. General procedure for the amidation of 1-hydroxy-3-
methyl-3-phospholene 1-oxide (2) in the presence of T3PÒ
(CH2CH3), 20.6 (d, J 12.1, C3eCH3), 30.7 (d, J 2.8, NCH2CH2), 32.0 (d, J
80.8, C5), 34.7 (d, J 84.1, C2), 44.1 (d, J 3.3, NCH2), 121.2 (d, J 9.7, C4),
137.0 (d, J 15.2, C3); 1H NMR (CDCl3)
d: 0.89 (t, J 7.3, 6H, CH2CH3),
A mixture of 1-hydroxy-3-methyl-3-phospholene 1-oxide (2)
(0.76 mmol, 0.10 g) and the T3PÒ reagent (0.55 mL, 0.84 mmol
50 wt % ethyl acetate solution) was stirred for 10 min. The amine
(1.52 mmol [propylamine: 0.12 mL, isopropylamine: 0.13 mL,
butylamine: 0.15 mL, isobutylamine: 0.15 mL, sec-butylamine:
0.15 mL, hexylamine: 0.20 mL, cyclohexylamine: 0.17 mL, benzyl-
amine: 0.17 mL, diethylamine: 0.17 mL, dipropylamine: 0.21 mL,
dibutylamine: 0.26 mL]) was added to the resulting mixture and
the contents of the flask were stirred for the appropriate time (see
Table 6). The excess of T3PÒ reagent was hydrolyzed with 10%
NaHCO3 solution (7 mL) and the aqueous phase was washed with of
ethyl acetate (30 mL). The combined organic phase was dried
(Na2SO4), filtered and concentrated in vacuum to provide the crude
product that was passed through a thin (ca. 3e4 cm) layer of silica
gel using 3% MeOH in CH2Cl2 as the eluent to give the products (13)
in a purity >99% as oils. For details, see Table 6.
1.15e1.32 (m, 4H, CH2CH3), 1.34e1.55 (m, 4H, NCH2CH2), 1.76 (s, 3H,
C3eCH3), 2.26e2.50 (m, 4H, CH2), 2.79e2.98 (m, 4H, NCH2), 5.51 (d,
J 32.4, 1H, C4eH); IR (neat) 776, 1186, 1466, 1647, 2959 cmꢂ1
½M þ Hꢃþfound¼244.1838, C13H27NOP requires 244.1825.
;
The identification of the known compounds (13c,13d and 13fei)
is given in Table 8.
Table 8
Selected spectral data for the known amides (13c, 13d and 13fei)
Product
31P NMR (CDCl3)
dP (lit.)
½M þ Hꢃþfound
½M þ Hꢃþrequires
13c
13d
13f
13g
13h
13i
63.4
63.3
63.7
60.9
63.9
65.8
63.2 [22]
63.6 [22]
63.1 [22]
60.7 [22]
63.5 [22]
65.5 [23]
188.1207
188.1207
216.1518
214.1359
222.1046
188.1204
188.1204
188.1204
216.1517
214.1361
222.1048
188.1204
The following new compounds were thus prepared:
4.3.1. 1-Propylamino-3-methyl-3-phospholene 1-oxide (13a). 31P
NMR: (CDCl3) d d: 11.2 (CH2CH3), 20.6 (d, J 12.1,
: 63.2; 13C NMR (CDCl3)
Acknowledgements
C3eCH3), 25.2 (d, J 6.3, CH2CH3), 32.1 (d, J 82.1, C5), 35.0 (d, J 85.6, C2),
42.4 (d, J 1.7, NCH2), 120.7 (d, J 9.7, C4), 136.6 (d, J 15.2, C3); 1H NMR
This project was supported by the Hungarian Scientific Research
Fund (OTKA K83118).
(CDCl3)d:0.90(t, J7.4, 3H,CH2CH3),1.42e1.64(m, 2H, CH2),1.77(s, 3H,
C3eCH3), 2.19e2.61 (m, 5H, CH2, NH), 2.78e2.98(m, 2H,NHCH2), 5.49
(d, J 33.8, 1H, C4eH); IR (neat) 773, 1173, 1457, 1649, 2962 cmꢂ1
½M þ Hꢃþfound¼174.1049, C8H17NOP requires 174.1043.
;
References and notes
1. Preliminary Communication: Jablonkai, E.; Milen, M.; Drahos, L.; Keglevich, G.
Tetrahedron Lett. 2013, 54, 5873e5875.
2. Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley: New York, NY, 2000;
pp 138e141.
3. Houben-Weyl, Methoden der Organischen Chemie, Organische Phos-
phorverbindungen II, Band E2; Regitz, M., Ed.; Georg Thieme: Stuttgart, Ger-
many, 1982; pp 213e214; 230e233.
4. Crofts, P. C. In Organic Phosphorus Compounds; Kosolapoff, G. M., Maier, L.,
Eds.; J. Wiley & Sons: New York, NY, 1973; Vol. 6, pp 39e42; Ch. 14, SubCh.
XXIe.
4.3.2. 1-Isopropylamino-3-methyl-3-phospholene 1-oxide (13b). 31P
NMR: (CDCl3) : 20.8 (d, J 12.1, C3eCH3),
: 61.0; 13C NMR (CDCl3)
26.0 (CHCH3), 33.3 (d, J 82.3, C5), 36.1 (d, J 85.8, C2), 43.4 (d, J 2.0,
NHCH), 120.8 (d, J 9.7, C4), 136.8 (d, J 15.2, C3); 1H NMR (CDCl3)
d
d
d:
1.20 (d, J 6.4, 6H, CHCH3), 1.79 (s, 3H, C3eCH3), 2.10e2.65 (m, 5H,
CH2, NH), 3.30e3.59 (m, 1H, NHCH), 5.51 (d, J 32.6, 1H, C4eH); IR
(neat) 776, 1173, 1467, 1650, 2966 cmꢂ1; ½M þ Hꢃfþound¼174.1054,
C8H17NOP requires 174.1043.
€
ꢀ
5. Keglevich, G.; Kiss, N. Z.; Mucsi, Z.; Kortvelyesi, T. Org. Biomol. Chem. 2012, 10,
2011e2018.
ꢀ
€
6. Kiss, N. Z.; Bottger, E.; Drahos, L.; Keglevich, G. Heteroat. Chem. 2013, 24,
283e288.
4.3.3. 1-(1-Methylpropylamino)-3-methyl-3-phospholene 1-oxide
(13e). 31P NMR: (CDCl3) : 61.3; 13C NMR (CDCl3)
d d: isomers A
7. Mucsi, Z.; Kiss, N. Z.; Keglevich, G. RSC Adv. 2014, 4, 11948e11954.
ꢀ
}
€
8. Keglevich, G.; Balint, E.; Kiss, N. Z.; Jablonkai, E.; Hegedus, L.; Grun, A.; Greiner,
and B 10.4 (CH2CH3), 20.7 (d, J 12.1, C3eCH3), 23.4 (d, J 2.1, CHCH3),
32.2 (d, J 4.7, CH2CH3), 33.1 and 33.2 (d, J 82.7 and 82.2, C5), 35.9 and
36.1 (d, J 86.3 and 85.2, C2), 48.7 (d, J 1.8, CH), 120.7 (d, J 9.7, C4),
I. Curr. Org. Chem. 2011, 15, 1802e1810.
9. Keglevich, G.; Kiss, N. Z.; Drahos, L.; Kortvelyesi, T. Tetrahedron Lett. 2013, 54,
466e469.
€
ꢀ
€
ꢀ
ꢀ
10. Keglevich, G.; Kiss, N. Z.; Kortvelyesi, T. Heteroat. Chem. 2013, 24, 91e99.
136.7 (d, J 15.3, C3); 1H NMR (CDCl3)
d: 0.92 (t, J 7.4, 3H, CH2CH3),
ꢀ
11. Balint, E.; Jablonkai, E.; Balint, M.; Keglevich, G. Heteroat. Chem. 2010, 21,
1.19 (d, J 6.4, 3H, CHCH3), 1.40e1.55 (m, 2H, CH2CH3), 1.79 (s, 3H,
C3eCH3), 2.17e2.62 (m, 5H, CH2, NH), 3.06e3.28 (m, 1H, NHCH),
5.52 (d, J 33.2, 1H, C4eH); IR (neat) 778, 1173, 1467, 1652,
2966 cmꢂ1; ½M þ Hꢃþfound¼188.1206, C9H19NOP requires 188.1204.
211e214.
12. Basavaprabhu; Vishwanatha, T. M.; Panguluri, N. R.; Sureshbabu, V. V. Synthesis
2013, 1569e1601.
13. Milen, M.; Abranyi-Balogh, P.; Dancso, A.; Frigyes, D.; Pongo, L.; Keglevich, G.
Tetrahedron Lett. 2013, 54, 5430e5433.
14. Dumond, Y. R.; Baker, R. L.; Montchamp, J.-L. Org. Lett. 2000, 2,
3341e3344.
15. Kiss, N. Z.; Ludanyi, K.; Drahos, L.; Keglevich, G. Synth. Commun. 2009, 39,
ꢀ
ꢀ
ꢀ
ꢀ
4.3.4. 1-Dipropylamino-3-methyl-3-phospholene 1-oxide (13j). 31P
ꢀ
NMR: (CDCl3) d d: 11.2 (CH2CH3), 20.6 (d, J
: 66.3; 13C NMR (CDCl3)
2392e2404.
16. Storer, R.; Dousson, C.; Alexandre, F. -R.; Roland, A. U.S. Patent 74054, 2006;
Chem. Abstr. 2006, 144, 370242.
17. Schuman, M.; Lopez, X.; Karplus, M.; Gouverneur, V. Tetrahedron 2001, 57,
12.1, C3eCH3), 21.6 (d, J 2.8, CH2CH3), 32.0 (d, J 80.9, C5), 34.7 (d, J
84.1, C2), 46.1 (d, J 3.3, NCH2), 121.2 (d, J 9.7, C4), 137.0 (d, J 15.2, C3);
1H NMR (CDCl3)
d: 0.86 (t, J 7.4, 6H, CH2CH3), 1.40e1.61 (m, 4H,
10299e10307.
18. Olszewski, T. K.; Boduszek, B. Tetrahedron 2010, 66, 8661e8666.
19. Keglevich, G.; Jablonkai, E.; Balazs, L. B. RSC Adv. 2014, 4, 22808e22816.
CH2CH3), 1.78 (s, 3H, C3eCH3), 2.18e2.52 (m, 4H, CH2), 2.71e2.96
(m, 4H, NCH2), 5.53 (d, J 33.7, 1H, C4eH); IR (neat) 768, 1195, 1465,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
}
20. Keglevich, G.; Petnehazy, I.; Miklos, P.; Almasy, A.; Toth, G.; Toke, L. J. Org. Chem.
1987, 52, 3983e3986.
1647, 2963 cmꢂ1
216.1517.
;
½M þ Hꢃþfound¼216.1517, C11H23NOP requires
21. Arbuzov, B. A.; Vizel, A. O.; Zvereva, M. A.; Studentsova, I. A.; Garaev, R. S. Izv.
Akad. Nauk SSSR, Ser. Khim. 1966, 1848e1850.
22. Kiss, N. Z.; Simon, A.; Drahos, L.; Huben, K.; Jankowski, S.; Keglevich;, G. Syn-
thesis 2013, 45, 199e204.
23. Szewczyk, J.; Lloyd, J. R.; Quin, L. D. Phosphorus Sulfur 1984, 21, 155e160.
4.3.5. 1-Dibutylamino-3-methyl-3-phospholene 1-oxide (13k).21 31P
NMR: (CDCl3) : 13.8 (CH2CH3), 20.1
: 66.3; 13C NMR (CDCl3)
d
d