β-Cyclodextrin as an efficient catalyst for the one-pot synthesis of 1-aminophosphonic esters in water

Article abstract of DOI:10.1016/j.tetlet.2007.10.082

A simple, efficient, and general method has been developed for the one-pot synthesis of α-aminophosphonic esters in water using β-cyclodextrin as an efficient catalyst. α-Aminophosphonic esters were obtained in good yields (45-82%) and purity under mild c

Full text of DOI:10.1016/j.tetlet.2007.10.082

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Tetrahedron Letters 48 (2007) 9015–9017
b-Cyclodextrin as an efficient catalyst for the one-pot synthesis
of 1-aminophosphonic esters in water
*
Babak Kaboudin and Mina Sorbiun
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45195-1159, Iran
Received 27 August 2007; revised 7 October 2007; accepted 17 October 2007
Available online 22 October 2007
Abstract—A simple, efficient, and general method has been developed for the one-pot synthesis of a-aminophosphonic esters in
water using b-cyclodextrin as an efficient catalyst. a-Aminophosphonic esters were obtained in good yields (45–82%) and purity
under mild conditions by the reaction of diethyl phosphite with a mixture of aldehyde and amine in water at reflux.
Ó 2007 Elsevier Ltd. All rights reserved.
Phosphorus–carbon bond formation has attracted
growing attention because of its application in organic
synthesis and bioorganic chemistry. a-Functionalized
phosphonic acids are valuable intermediates for the
preparation of medicinal compounds and synthetic
phite because the amine and water present during imine
formation can decompose or deactivate the Lewis acids.
1
3
14
Recently, metal triflates and perchlorates have been
reported as efficient catalysts. However, these catalyzed
reactions are often carried out in the presence of stoichio
metric amounts of additional reagents such as molecular
sieves and MgSO4.
1
–4
intermediates.
Among a-functionalized phosphonic
acids, 1-aminophosphonic acids are an important class
of compounds that exhibit a variety of interesting and
useful properties. 1-Aminophosphonic acids are impor-
tant substitutes for the corresponding a-amino acids in
O
C
O
P
5
H
C
H
C
biological systems. Indeed a number of potent antibio-
R
OH
R
OH
OH
6
7
8
tics, enzyme inhibitors, and pharmacological agents
NH2
NH2
are 1-aminophosphonic acids or peptide analogues.
Aminophosphonic acids are also found as constituents
α-amino acid
1-aminoalkylphosphonic acid
9
of natural products. Many effective methods for the
preparation of 1-aminoalkylphosphonic acids have been
1
0
developed. Of these, the Kabachnik–Fields synthesis,
catalyzed by a base or an acid, is the most convenient.
The key step in the Kabachnik–Fields synthesis of
Organic reactions in aqueous media have attracted
much recent attention. Water is one of the most abun-
dant, cheapest, and environmentally friendly solvents.
Indeed water exhibits unique reactivity and selectivity,
which is different from that of conventional organic sol-
vents. Thus, development of novel reactivity and selec-
1
-aminoalkyl phosphonates is the nucleophilic addition
of an amine to a carbonyl compound followed by the
addition of a dialkyl or diaryl phosphite to the resulting
imine. The formation of 1-hydroxyphosphonates or a
product of rearrangement frequently accompanies the
1
5
tivity is one of the challenges of aqueous chemistry.
1
1
formation of 1-aminoalkyl phosphonates. Lewis acids
b-Cyclodextrin (b-CD) is a water-soluble cyclic oligosac-
charide possessing hydrophobic cavities, which binds
substrates selectively and catalyzes chemical reactions
with high selectivity by involving reversible formation
of host–guest complexes with noncovalent bonding as
such as SnCl , SnCl , BF ÆEt O, ZnCl , MgBr , and
2
4
3
2
2
2
1
2
InCl3 have been used as catalysts. However, these
reactions cannot be carried out in a one-step operation
with the carbonyl compound, amine and dialkyl phos-
1
6
seen in enzymes. b-CD can be recovered and reused
in subsequent reactions without loss of activity. As part
of our efforts to introduce novel methods for the synthe-
*
Corresponding author. Tel.: +98 241 4153220; fax: +98 241
249023; e-mail: kaboudin@iasbs.ac.ir
1
7
4
sis of organophosphorus compounds, in this report, a
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.082

9016
B. Kaboudin, M. Sorbiun / Tetrahedron Letters 48 (2007) 9015–9017
new method for the one-pot synthesis of 1-amino-
alkylphosphonates using b-cyclodextrin as catalyst in
water is described (Scheme 1 and Table 1).
45% yield (entry 13). The reactions were clean with no
tar formation.
1
8
No 1-hydroxyphosphonates or products of rearrange-
ment were detected during the formation of 1-amino-
alkylphosphonates. These results prompted us to
examine the conversion 1-hydroxyalkylphosphonates
to 1-aminoalkylphosphonates in the presence of amines
The three-component reaction of benzaldehyde 1a, ani-
line 2a, and diethylphosphite was selected as a model
reaction for the one-pot synthesis 1-aminophosphonates
3
a using b-cyclodextrin as catalyst (Table 1). In the
absence of any catalyst, reaction in water at reflux for
4 h gave the corresponding 1-aminophosphonate 3a
1
9
in water with b-CD as catalyst (Scheme 2). Interest-
ingly, we found that diethyl 1-hydroxyphenylmethyl
phosphonate (4a) was converted to diethyl 1-amin-
ophenylmethylphosphonate (3a) in the presence of
aniline in water and b-CD as catalyst (20% yield, reflux,
2
in 15% yield (entry 1). The reaction yield was not chan-
ged by adding 3 equiv of diethyl phosphite to the reac-
tion mixture (entry 2). A mixture of aniline (2a) and
benzaldehyde (1a) with diethyl phosphite in the presence
of b-CD in water at reflux, afforded the desired product
2
0
48 h, Scheme 2). The reaction yield was increased to
55% by adding 1 equiv of diethylphosphite to the reac-
tion mixture.
3
a in 61% yield (entry 3). Other mixtures of amines and
aldehydes also reacted with diethylphosphite in the pres-
ence of a catalytic amount of b-CD to give the desired
compounds in good yields (entries 4–12). The reaction
of cyclohexylamine with benzaldehyde (1a) in the pres-
ence of diethylphosphite gave the desired product in
In summary, a simple work-up, mild reaction condi-
tions, good yields, and relatively clean reactions with
no tar formation make this method an attractive and
useful addition to present methodologies. Indeed, a wide
range of aldehydes and amines were converted to the
corresponding a-aminophosphonic esters using this
method.
Table 1. One-pot synthesis of 1-aminoalkylphosphonic esters using b-
CD in water at reflux
0
a
Entry R 1
R 2
Reaction Yield
Acknowledgment
time (h)
(%) 3
b
1
2
3
4
5
6
7
8
9
0
1
2
3
C
C
C
6
6
6
H
H
H
5
5
5
–
–
–
C
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
–
–
–
–
–
–
–
–
–
24
24
24
24
24
24
24
24
12
24
24
24
24
15
15
61
82
63
53
73
62
55
45
72
70
45
The Institute for Advanced Studies in Basic Sciences
c
(IASBS) is thanked for supporting this work.
p-CH
p-(CH
o-MeC
m-MeOC
n-C
Ph–CH@CH–
3
C
6
H
CHC
4
–
3
)
2
6
H
4
–
–
H
4
–
References and notes
6
6
4
H –
4
H
9
–
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Scheme 2.

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1
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1
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