Uncatalyzed three-component synthesis of α-hydrazido phosphonates

Article abstract of DOI:10.1002/ejoc.200901337

Various α-hydrazido phosphonates have been easily prepared on the basis of the nucleophilic addition of diphenyl phosphite to reactive, preformed N-acylhydrazones and a three-component; (aldehydes, N-benzoylhydrazide and di-phenyl phosphite) coupling reac

Full text of DOI:10.1002/ejoc.200901337

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200901337
Uncatalyzed Three-Component Synthesis of α-Hydrazido Phosphonates
Raquel P. Herrera,*[a,b] David Roca-López,[a] and Gloria Navarro-Moros[a]
Keywords: Multicomponent reactions / Phosphonates / Hydrazones / Nucleophilic addition
Various α-hydrazido phosphonates have been easily pre- phenyl phosphite) coupling reaction through a non-catalyzed
pared on the basis of the nucleophilic addition of diphenyl
phosphite to reactive, preformed N-acylhydrazones and a
three-component (aldehydes, N-benzoylhydrazide and di-
process. An unprecedented and promising enantioselective
example of this reaction is also reported.
catalysts are either expensive or somewhat difficult to pre-
pare. In addition, many imines are hygroscopic and are not
sufficiently stable to be isolated, particularly, those derived
from aliphatic aldehydes. N-Acylhydrazones have been
broadly used as imine surrogates,[13] since they are versatile
electrophiles, more stable than imines, and are capable of
reacting with a great number of nucleophiles towards the
synthesis of nitrogen-containing compounds. In spite of its
interest, to the best of our knowledge, the hydrophos-
phonylation of N-acylhydrazones with dialkyl phosphites
has been overlooked in the literature,[14] and only a few ex-
amples of the synthesis of α-hydrazino phosphonic acids
have been reported.[15] For a long time, it has been known
that treatment of N-tosylhydrazones with dialkyl phos-
phites gives rise to a nucleophilic addition reaction[16] that
provides interesting α-hydrazino phosphonates (Figure 1).
Moreover, other few examples of activated N-tosylhydraz-
ones have been reported, but in all these cases, a large excess
of dialkyl phosphite or strong Brønsted acids were neces-
sary to perform the process.[17] Preparation of α-hydrazino
phosphonates has also been developed with less-reactive
N,N-dialkylhydrazones but under strong reaction condi-
tions or by adding catalysts to promote the reaction.[18] α-
Hydrazino phosphonic acids and their derivatives are of po-
tential biological importance as mentioned above.[3–9,19] We
want to present here a novel and easy procedure for the
hydrophosphonylation of hydrazones in the absence of cata-
lysts and in a multicomponent process.
Introduction
The hydrophosphonylation of aldehydes and imines (Pu-
dovik reaction)[1] is the most general, straightforward and
widely applied method for construction of P–C bonds.[2]
The main interest in phosphonyl compounds and related
derivatives resides in their important biological activity as
antibiotics,[3] herbicides,[4] insecticides,[5] fungicides,[6] anti-
viral agents[7] and in their wide range of applications with
respect to enzyme inhibition,[8] including HIV protease.[9]
In particular, the nucleophilic addition reaction of dialkyl
phosphites to imines has been used as one of the most con-
venient methods in the synthesis of α-amino phosphonic
acids as structural analogues of α-amino acids (Fig-
ure 1);[10] this has a broad scope because a large variety of
substrates can be employed.[11]
Figure 1. α-Amino phosphonic acids as analogues of α-amino ac-
ids.
For this purpose, Lewis acids have been conveniently
used as promoters of such a hydrophosphonylation;[12]
however, these methods show a few limitations since these
Results and Discussion
[a] Laboratorio de Síntesis Asimétrica, Departamento de Química
Orgánica,
Firstly, we initiated the study of reactivity by testing the
less-reactive N,N-dialkylhydrazones 1–3 against nucleo-
philic addition of dialkyl phosphite 4a by a Lewis and
Brønsted acid catalyzed process.[20] Unfortunately, the reac-
tion does not work, perhaps because of the high tendency
of these hydrazones to act as nucleophiles instead of as elec-
trophiles (Scheme 1).[21]
Instituto de Ciencia de Materiales de Aragón, Universidad de
Zaragoza-CSIC,
50009 Zaragoza, Aragón, Spain
Fax: +34-976-762075
E-mail: raquelph@unizar.es
[b] ARAID, Fundación Aragón I+D,
50004 Zaragoza, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901337.
1450
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1450–1454

Uncatalyzed Three-Component Synthesis of α-Hydrazido Phosphonates
In this sense, we firstly tested Et3N as a possible
Brønsted base catalyst for this process (Table 1, Entries
1–5).
Highly reactive hydrazone 5a with an electron-with-
drawing group was used in the test reaction to explore the
viability of this hydrophosphonylation process. Firstly, we
screened differently substituted dialkyl/diphenyl phosphites
4a–e in a Brønsted base catalyzed reaction (Entries 1–5,
Table 1). Only diphenyl phosphite (4e) showed promising
reactivity when the reaction was performed at room tem-
perature in toluene (Entry 5). This might be due to the dras-
tic variation of pKas for the differently substituted phos-
phites; diphenyl phosphite (4e) is the most acidic.[24] This
result encouraged us to perform the reaction in the absence
of the amine with the same reactive phosphite 4e; fortu-
nately, this assay afforded the final product with a very
good yield (Entry 6). The screening with hydrazone 6 fur-
nished product 9 with a very good yield but after a longer
reaction time (Entry 7), and 7 provided hydrazide 10 with
a lower yield under the same reaction conditions (Entry 8).
We further explored the scope of this hydrophosphonyl-
ation process for different compounds 5a–e, under the opti-
mized reaction conditions. The corresponding derivatives
8a–e were obtained with very high yields at room tempera-
ture in toluene (Table 2, Entries 1–5). Only 5b required a
longer reaction time (Table 2, Entry 2), perhaps because of
the sterically hindered tert-butyl group.
Scheme 1. Screening with N,N-dialkylhydrazones.
At this point, we decided to increase the reactivity of
the hydrazone by varying the N-protecting group. We tested
more-reactive N-acylhydrazones[13] 5a, 6 and 7 against dif-
ferent substituted dialkyl/diphenyl phosphites 4a–e as re-
ported in Table 1. With regard to the phosphorus nucleo-
phile, it is known that it is the phosphite and not the phos-
phonate form that is the real nucleophilic species.[22] This
equilibrium, which under neutral conditions is completely
shifted towards the unreactive phosphonate form, could be
influenced by the presence of a base (Figure 2).[23]
Table 1. Hydrophosphonylation of 5a, 6 and 7 with phosphite 4a–
e.[a]
Table 2. Uncatalyzed hydrophosphonylation of 5a–e with phos-
phite 4e.[a]
Entry Hydrazone Phosphite Et3N [%] Time [h] Product Yield [%]
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5a
5a
6
4a
4b
4c
4d
4e
4e
4e
4e
20
20
20
20
20
–
24
24
24
24
24
18
48
24
–
–
–
–
8a
8a
9
n.r.[b]
n.r.[b]
n.r.[b]
n.r.[b]
Ͼ99[c]
95[d]
Entry Hydrazone
R
Time [h] Product Yield [%][b]
1
2
3
4
5
5a
5b
5c
5d
5e
iPr
24
48
24
20
8a
8b
8c
8d
8e
95
83
90
87
95
tBu
nPr
iBu
–
–
90[d]
PhCH2CH2 20
7
10
77[d]
[a] Experimental setup: To a solution of hydrazone 5a–e (1 mmol)
in toluene (3–4 mL) was slowly added 4e (1.5 mmol). After the ap-
propriate reaction time, the products 8a–e were isolated by
chromatography on silica gel (hexane/EtOAc, 7:3). [b] Isolated
yield.
[a] Experimental setup: To a solution of hydrazone 5a, 6 or 7
(1 mmol) and Et3N (20 mol-%) in toluene (2 mL) was slowly added
dialkyl/diphenyl phosphite 4a–e (1.5 mmol). After the appropriate
reaction time, the corresponding product 8a, 9 or 10 was isolated
by chromatography on silica gel (hexane/EtOAc, 7:3). [b] No reac-
tion observed. [c] Calculated conversion by 1H NMR spectroscopy.
[d] Isolated yield.
In the last years, multicomponent strategies have at-
tracted more attention in the scientific community, which
allows the obtaining of high levels of atom efficiency.[25]
Three-component condensation reactions are interesting
and important, not only because two bonds are formed in
one pot, but also because the methodology is useful for
making a broad variety of compound libraries. Moreover,
in these multicomponent processes, only a single reaction
solvent, workup procedure and purification step is required
to obtain a product that would otherwise require more
Figure 2. Equilibrium between the unreactive phosphonate and re-
active phosphite forms.
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R. P. Herrera, D. Roca-López, G. Navarro-Moros
SHORT COMMUNICATION
steps. In this context, we focused on the development of an lost in the corresponding purification of the starting mate-
uncatalyzed one-pot reaction or a multicomponent reaction rial is taken into account. An X-ray analysis served to con-
for the synthesis of α-hydrazido phosphonates with in situ firm the structure of the final products, and single crystals
generated hydrazones. We tested different solvents at room were obtained for adducts 8b and 8c (see Supporting Infor-
temperature in the test reaction depicted in Table 3 for mation).[29]
product 8a, in order to improve the in situ formation of
It is not surprising that the absolute configuration for
hydrazone as a possible rate-determining step for further different phosphonyl compounds strongly influences their
nucleophilic attack of diphenyl phosphite (4e). Among biological properties.[30] In this context, the chiral version
them THF (49%), CHCl3 (40%) and CH2Cl2 (15%) had a of this reaction is of great interest, and, to the best of our
negative influence on the reactivity, on the other hand, the knowledge, there is no previously reported example of such
use of toluene (60%) gave a better and promising result.
a process. A very preliminary screening of different chiral
organocatalysts showed that the use of commercially avail-
able Cinchonidine provided the final product 8a with an
unprecedented and promising 56% enantioselectivity in
good yield (Scheme 2).
Table 3. Multicomponent hydrophosphonylation of 11a–h and 12–
14 with phosphite 4e.[a]
Entry Aldehyde
R
Hydrazide Time [h] Product Yield [%][b]
1
2
3
4
5
6
7
8
11a
11a
11a
11b
11c
11d
11e
11f
iPr
iPr
iPr
tBu
nPr
iBu
12
13
14
12
12
12
18
24
24
72
24
24
24
18
48
24
30
8a
9
95
70
60
62
70
62
50
89
65
71
72
Scheme 2. Enantioselective organocatalytic hydrophosphonylation
of 5a.
10
8b
8c
8d
8e
8f
8g
8h
8a
Conclusions
PhCH2CH2 12
sBu
c-hexyl
c-pentyl
iPr
12
12
12
12
The present study reveals a mild and efficient method
for the preparation of α-hydrazido phosphonate derivatives,
suitable for a variety of aliphatic aldehydes. This procedure
seems superior to other studies from an atom-economy
9
11g
11h
11a
10
11[c]
[a] Experimental setup: To a solution of 12–14 (1.1 mmol) in tolu-
ene (2 mL) was slowly added 11a–g (1 mmol). After half an hour, point of view, since neither a catalyst nor a high excess of
dialkyl phosphite 4e (1.5 mmol) and toluene (2 mL) was added, and
diphenyl phosphite is necessary, even if longer reaction
the mixture was stirred at room temperature. After the appropriate
times are required. Applications of this methodology for
reaction time, the final product was isolated by chromatography
preparing enantiomerically enriched α-hydrazido phos-
phonates by an organocatalytic procedure are currently in
progress in our laboratory.
on silica gel (hexane/EtOAc, 7:3). [b] Isolated yield. [c] Reaction
performed on a 1-g scale.
After checking the ratio of substrates, concentration and
reaction time for the formation of hydrazone, the scope of
the reaction was explored by using a variety of aliphatic
aldehydes. In all cases, the reaction proceeded smoothly at
room temperature to provide the desired products 8a–h, 9
and 10. The results are presented in Table 3. These data
indicate that the reaction is highly efficient for all types of
aliphatic substrates, and the final products are stable solids.
Aldehydes 11a–h smoothly reacted with N-acylhydraz-
ides 12–14 over 18–72 h and required only a small excess of
diphenyl phosphite (1.5 equiv.) to reach complete conver-
sion. Adducts 8a–h were formed in moderate to excellent
yields (Table 3, Entries 1 and 4–10).[26,27] The procedure is
also general for different N-acylhydrazide derivatives, al-
though lower yields are obtained with 13 and 14 (Table 3,
Entries 2 and 3).[28] When the reaction was performed on a
1-g scale, the product was successfully obtained in a 72%
yield (Table 3, Entry 11). This multicomponent strategy
leads to better results in terms of overall yields than the use
Experimental Section
General Procedure for the Synthesis of Aldehyde N,N-Dialkylhydraz-
ones 1–3 and N-Benzoylhydrazones 5a–e, 6 and 7: To a solution of
the corresponding benzohydrazide or hydrazine (12 mmol) in
CH2Cl2 (10 mL) were added Na2SO4 and the corresponding alde-
hyde 11a–e (10 mmol). The mixture was stirred at room tempera-
ture and for 1 d until total consumption of the starting material. It
was then filtered and concentrated. Starting material, yields and
spectroscopic data for compounds 1–3, 5a–e, 6 and 7 are described
in the Supporting Information.
General Procedure for the Synthesis of α-Hydrazido Phosphonates
8a–e: To a solution of preformed hydrazone 5a–e (1 mmol) in tolu-
ene (3–4 mL) was added diphenyl phosphite (4e) (290 µL,
1.5 mmol), and the reaction mixture was stirred until total con-
sumption of the starting material (20–48 h). After this reaction
time, the crude product was purified by column chromatography
on silica gel (hexane/EtOAc, 7:3) to afford products 8a–e. The
amount of reagents, yields, and spectra for adducts 8a–e are re-
of preformed hydrazones (Table 2) if the amount of product ported in the Supporting Information.
1452 Eur. J. Org. Chem. 2010, 1450–1454
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Uncatalyzed Three-Component Synthesis of α-Hydrazido Phosphonates
1992, 33, 6625–6628; c) A. Peymen, W. Stahl, K. Wagner, D.
Ruppert, K.-H. Budt, Bioorg. Med. Chem. Lett. 1994, 4, 2601–
2604.
For a review, see: V. P. Kukhar, V. A. Solodenko, Russ. Chem.
Rev. 1987, 56, 856–874.
For a recent review, see: M. Ordóñez, H. Rojas-Cabrera, C.
Cativiela, Tetrahedron 2009, 65, 17–49.
Multicomponent Synthesis of α-Hydrazido Phosphonates 8a–h, 9 and
10: To a solution of 12–14 (1.1 mmol) in toluene (2 mL) was added
11a–h (1 mmol). After 0.5 h, diphenyl phosphite (4e) (1.5 mmol)
was slowly added in toluene (2 mL). The mixture was stirred at
room temperature until total consumption of the hydrazone. After
the corresponding reaction time (see Table 3), the crude product
was directly isolated by chromatography on silica gel (hexane/
EtOAc, 7:3) to afford products 8a–h, 9 and 10. The amount of
reagents, yields, and spectra for 8a–h, 9 and 10 are reported in the
Supporting Information.
[10]
[11]
[12]
For some examples of hydrophosphonylation of imines cata-
lyzed by Lewis acids, see: a) S. Lashat, H. Kunz, Synthesis
1992, 90–95; b) B. C. Ranu, A. Hajra, J. Jana, Org. Lett. 1999,
1, 1141–1143; c) K. Manabe, S. Kobayashi, Chem. Commun.
2000, 669–670; d) B. Kaboudin, R. Nazari, Tetrahedron Lett.
2001, 42, 8211–8215; e) F. Xu, Y. Luo, M. Deng, Q. Shen, Eur.
J. Org. Chem. 2003, 4728–4730; f) S. Kudrimoti, V. R. Bom-
mena, Tetrahedron Lett. 2005, 46, 1209–1210.
For reviews about N-acylhydrazones as versatile electrophiles,
see: a) M. Sugiura, S. Kobayashi, Angew. Chem. Int. Ed. 2005,
44, 5176–5186; b) G. K. Friestad, Eur. J. Org. Chem. 2005,
3157–3172; c) S. Kobayashi, M. Sugiura, C. Ogawa, Adv.
Synth. Catal. 2004, 346, 1023–1034.
For the only reported example, see: N. Rabasso, A. Fadel, Syn-
thesis 2008, 2353–2362.
a) C. Yuan, S. Chen, R. Xie, H. Feng, L. Maier, Phosphorus
Sulfur Silicon Relat. Elem. 1995, 106, 115–123; b) C. Li, C.
Yuan, Synthesis 1996, 507–510; c) M. Kaname, K. Yoshinaga,
Y. Arakawa, S. Yoshifuji, Tetrahedron Lett. 1999, 40, 7993–
7994.
Organocatalytic Enantioselective Hydrophosphonylation of 5a: To a
solution of 5a (0.2 mmol, 47 mg) and Cinchonidine (0.04 mmol,
11.8 mg) in toluene (0.5 mL), was added 4e (0.3 mmol). The mix-
ture was stirred at room temperature. After 72 h, the crude product
was directly isolated by chromatography on silica gel (hexane/
EtOAc, 7:3) to afford product 8a in a 62% yield and 56% ee.
[α]2D2 = +54.5 (c = 0.835, CHCl3, 56% ee). HPLC setup: Daicel
Chiralpak IA column (hexane/EtOAc, 7:3, flow rate 1 mL/min, UV
254.4 nm, τminor = 16.5 min, τmajor = 20.0 min).
[13]
[14]
[15]
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization data
1
for compounds 2, 3, 5a–e, 6, 7, 8a–h, 9 and 10 and H NMR, 13C
NMR and HRMS spectra for all new compounds are presented.
[16]
[17]
S. Inokawa, Y. Nakatsukasa, M. Horisaki, M. Yamashita, H.
Yoshida, T. Ogata, Synthesis 1977, 179–180.
a) M. Yamashita, J. Takeuchi, K. Nakatani, T. Oshikawa, Bull.
Chem. Soc. Jpn. 1985, 58, 377–378; b) H. Yamamoto, T.
Hanaya, H. Kawamoto, S. Inokawa, Chem. Lett. 1989, 121–
124.
a) A. Heydari, A. Javidan, M. Schaffie, Tetrahedron Lett. 2001,
42, 8071–8073; b) A. Heydari, M. Mehrdad, M. Schaffie, M. S.
Abdolrezaie, R. Hajinassirei, Chem. Lett. 2002, 1146–1147; c)
A. Heydari, A. Arefi, Catal. Commun. 2007, 8, 1023–1026.
P. Diel, L. Maier, Eur. Pat. Appl. EP 1985, 143078; [Chem.
Abstr. 1985, 103, 215544m].
For a plausible mechanism of activation of N,N-dialkylhydra-
zones, see: E. Marqués-López, R. P. Herrera, R. Fernández,
J. M. Lassaletta, Eur. J. Org. Chem. 2008, 3457–3460.
For reviews about aldehyde N,N-dialkylhydrazones as neutral
acyl anion equivalents, see: a) R. Fernández, J. M. Lassaletta,
Synlett 2000, 1228–1240; b) R. Brehme, D. Enders, R.
Fernández, J. M. Lassaletta, Eur. J. Org. Chem. 2007, 5629–
5660, and references therein.
Acknowledgments
We thank the High Council of Scientific Investigation (CSIC) (PIE-
200880I260), the Ministry of Science and Innovation (MICINN,
Madrid, Spain) (Project CTQ2009-09028) and the Government of
Aragón (Zaragoza, Spain) (Project PI064/09) for financial support
of our research. We are also grateful to Dr. Eugenia Marqués-
López, Prof. Dr. Tomás Tejero and Prof. Dr. Pedro Merino for help
and encouragement.
[18]
[19]
[20]
[1] A. N. Pudovik, I. V. Konovalova, Synthesis 1979, 81–96.
[2] For a recent review on this topic, see: P. Merino, E. Marqués-
López, R. P. Herrera, Adv. Synth. Catal. 2008, 350, 1195–1208,
and references cited therein.
[3] For selected examples, see: a) F. R. Atherton, M. J. Hall, C. H.
Hassall, S. W. Holmes, R. W. Lambert, J. Lloyd, P. S. Ringrose,
Antimicrob. Agents Chemother. 1980, 18, 897–905; b) T. Kamet-
ani, K. Kigasawa, M. Hiiragi, K. Wakisaka, S. Haga, H. Sugi,
H. Tanigawa, Y. Suzuki, K. Fukawa, O. Irino, O. Saita, S. Yam-
abe, Heterocycles 1981, 16, 1205–1242; c) F. R. Atherton, C. H.
Hassall, R. W. Lambert, J. Med. Chem. 1986, 29, 29–40.
[4] a) I. A. Natchev, Liebigs Ann. Chem. 1988, 861–867; b) M. K.
Mao, J. E. Franz, Synthesis 1991, 920–922.
[21]
[22]
For a review, see: D. F. Wiemer, Tetrahedron 1997, 53, 16609–
16644.
[23]
[24]
B. Springs, P. Haake, J. Org. Chem. 1977, 42, 472–474.
For the pKa values of different phosphorus nucleophiles, see:
J.-N. Li, L. Liu, Y. Fu, Q.-X. Guo, Tetrahedron 2006, 62, 4453–
4462.
For reviews, see: a) L. F. Tietze, U. Beifuss, Angew. Chem. Int.
Ed. Engl. 1993, 32, 131–163; b) D. J. Ramón, M. Yus, Angew.
Chem. Int. Ed. 2005, 44, 1602–1634; c) G. Guillena, G. D. J.
Ramón, M. Yus, Tetrahedron: Asymmetry 2007, 18, 693–700.
Unfortunately, the use of benzaldehyde or cinnamaldehyde did
not afford the final products after three days of reaction and
under the same reactions conditions.
For an example of selective cleavage of the hydrazine N–N
bond by using SmI2, see the Supporting Information. For a
review about this specific reactivity with SmI2, see: K. Gopa-
laiah, H. B. Kagan, New J. Chem. 2008, 32, 607–637.
The same moderate results were obtained when Et3N (20 mol-
%) was used as catalyst; 13 (71%) and 14 (63%).
CCDC-753258 (8b) and -753259 (8c) contain the supplemen-
tary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. The
[25]
[5] J. Emsley, D. Hall, The Chemistry of Phosphorus, Harper and
Row, London, 1976, p. 494.
[6] L. Maier, H. Spörri, Phosphorus Sulfur Silicon Relat. Elem.
1991, 61, 69–75.
[26]
[27]
[7] J. Huang, R. Chen, Heteroat. Chem. 2000, 11, 480–492.
[8] For selected examples, see: a) J. Bird, R. C. De Mello, G. P.
Harper, D. J. Hunter, E. H. Karran, R. E. Markwell, A. J.
Miles-Williams, S. S. Rahman, R. W. Ward, J. Med. Chem.
1994, 37, 158–169; b) J. L. Goulet, J. F. Kinneary, P. L. Durette,
R. L. Stein, R. K. Harrison, M. Izquierdo-Martin, D. W. Kuo,
T.-Y. Lin, W. K. Hagmann, Bioorg. Med. Chem. Lett. 1994, 4,
1221–1224. For a review, see: c) P. Kafarski, B. Lejczak, Phos-
phorus Sulfur Silicon Relat. Elem. 1991, 63, 193–215.
[9] a) A. Paymen, K.-H. Budt, J. Spanig, B. Stowasser, D. Ruppert,
Tetrahedron Lett. 1992, 33, 4549–4552; b) B. Stowasser, K.-H.
Budt, L. Jian-Qi, A. Paymen, D. Ruppert, Tetrahedron Lett.
[28]
[29]
Eur. J. Org. Chem. 2010, 1450–1454
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1453

R. P. Herrera, D. Roca-López, G. Navarro-Moros
SHORT COMMUNICATION
graphic views showed in Figures S1 and S2 (Supporting Infor-
mation) were made with ORTEP3 software (Copyright by Far-
rugia, L. J. University of Glasgow, 1997–2000).
H. R. Hudso (Eds.), Aminophosponic and Aminophosphinic Ac-
ids: Chemistry and Biological Activity, Wiley, Chichester, 2000;
c) J. Huang, R. Chen, Heteroat. Chem. 2000, 11, 480–492.
Received: November 20, 2009
[30] a) D. V. Patel, K. Rielly-Gauvin, D. E. Ryono, C. A. Free, W. L.
Rogers, S. A. Smith, J. M. DeForrest, R. S. Oehl, E. W. Pe-
trillo Jr., J. Med. Chem. 1995, 38, 4557–4569; b) V. P. Kukhar,
Published Online: February 1, 2010
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Eur. J. Org. Chem. 2010, 1450–1454