A catalyst-free, three-component decarboxylative coupling of amino acids with aldehydes and H-dialkylphosphites for the synthesis of α- aminophosphonates

Article abstract of DOI:10.1016/j.tetlet.2013.06.129

A simple, efficient, and new method is developed for the synthesis of α-aminophosphonates via a three-component, catalyst-free decarboxylative coupling of amino acids with aldehydes and H-dialkyl phosphite. Treatment of amino acids with aldehydes and diethyl phosphite in the absence of catalyst, base, and ligand give α-aminophosphonates in moderate to good yields. This method is simple, rapid, and high-yielding.

Full text of DOI:10.1016/j.tetlet.2013.06.129

Accepted Manuscript
A catalyst-free, three-component decarboxylative coupling of amino acids with
aldehydes and H-dialkylphosphites for the synthesis of α-aminophosphonates
Babak Kaboudin, Leila Karami, Jun-ya Kato, Hiroshi Aoyama, Tsutomu
Yokomatsu
PII:
S0040-4039(13)01114-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.06.129
TETL 43182
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
23 April 2013
15 June 2013
26 June 2013
Please cite this article as: Kaboudin, B., Karami, L., Kato, J-y., Aoyama, H., Yokomatsu, T., A catalyst-free, three-
component decarboxylative coupling of amino acids with aldehydes and H-dialkylphosphites for the synthesis of
α-aminophosphonates, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.06.129
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A catalyst-free, three-component
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decarboxylative coupling of amino acids with
aldehydes and H-dialkylphosphites for the
synthesis of α-aminophosphonates
Babak Kaboudin,* Leila Karami, Jun-ya Kato, Hiroshi Aoyama, Tsutomu Yokomatsu*
O
O
O
toluene
reflux, 1-5 h
+
+
H P(OEt)2
CO2H
P(OEt)2
N
H
N
R
H
R
13 examples
up to 75% yield

1
Tetrahedron Letters
journal homepage: www.elsevier.com
A catalyst-free, three-component decarboxylative coupling of amino acids with
aldehydes and H-dialkylphosphites for the synthesis of α-aminophosphonates
Babak Kaboudin,*a,b Leila Karami,a Jun-ya Kato,b Hiroshi Aoyama,b Tsutomu Yokomatsu*b
aDepartment of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran
bSchool of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 14321-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple, efficient, and new method is developed for the synthesis of α-aminophosphonates via a
three-component, catalyst-free decarboxylative coupling of amino acids with aldehydes and H-
dialkyl phosphite. Treatment of amino acids with aldehydes and diethyl phosphite in the absence
of catalyst, base and ligand give α-aminophosphonates in moderate to good yields. This method is
simple, rapid, and high-yielding.
Available online
2013 Elsevier Ltd. All rights reserved.
Keywords:
Aminophosphonate
Aldehyde
H-Dialkyl phosphie
Coupling
Amino acids
Many investigations have been conducted in order to develop
greener processes and methods in organic synthesis.1 One-pot
multi-step and multi-component reactions are very attractive
since they have lowered significantly the cost of the synthetic
routes by reducing the number of separation and purification
steps, as well as reducing the amount of solvents and waste.2-5
However, the application of multi-component reactions to
catalytic processes is limited since the catalysts used in these
reactions have to be compatible with each other. On the other
hand, the drawbacks of the catalytic systems, such as sensitivity
to air, high costs, and toxicity, limit their application in organic
synthesis. Therefore, catalyst-free conditions are highly desirable
for organic transformations, from environmental and economical
points of views.
O
R
P(OH)2
R
CO2H
NH2
NH2
aminophosphonic acid
amino acid
Decarboxylative functionalizations of α-amino acids adjacent to
the nitrogen are of increased interest in the field of modification
of α-amino acids, since the process leads to the facile preparation
of aza-compounds by replacing the carboxyl group of natural α-
amino acids with
a
variety of functional groups.9 This
fundamental strategy has been applied to transformations of α-
amino acids into α-aminophosphonic acids under catalytic
conditions. Corcoran reported a two step conversion of α-amino
acids to α-aminophosphonic acids via oxidative decarboxylation
with lead tetraacetate, and subsequent phosphonylation with
P(OMe)3 and TiCl4.10 In addition, Li and Wang’s group have
reported the first example of copper-catalyzed decarboxylative
coupling of proline with phosphates or secondary phosphine
oxides to construct C-P bonds in the presence of a base.11,12
Phosphorus-carbon bond formation has received intense interest
in recent years because of its wide range of applications in the
synthesis of biologically and materially significant compounds.6,7
Among organophosphorus compounds, α-aminophosphonic
acids, phosphorus analogues of natural α-amino acids, are used as
component of peptidyl inhibitors against various proteolytic
enzymes, particularly metalloproteases .8
———
* Corresponding authors. Tel.: +98 241 4153220; fax: +98 241 4214949; e-mail: kaboudin@iasbs.ac.ir and Tel./fax: +81 42 676 3239; e-mail:
yokomatu@ps.toyaku.ac.jp

2
O
O
O
O
O
Ph
P(OEt)2
toluene
reflux
Ph
P(OEt)2
+
+
+
+
H P(OEt)2
CO2H
P(OEt)2
N
H
N
Ph
H
N
OH
Ph
4
1a
3
2a
Scheme 1: Reaction of proline with diethyl phosphite and benzaldehyde at reflux in toluene
With the increasing demand for environmentally friendly
methods, and as part of our efforts to introduce novel methods for
the synthesis of organophosphorus compounds,13 we examined
decarboxylative functionalizations of α-amino acids with a
phosphonate functionality under catalyst- and base-free
conditions.
Siedel and Zhang have reported one-pot, catalyst-free conditions
for decarboxylative, three-component coupling reactions of
secondary α-amino acids with aldehydes and electron rich
bearing an -NO2 group could also be used to obtain the desired
product in moderate yield (Table 1, entry 7). meta-Substituted
benzaldehydes produced the corresponding products 2f and 2g in
moderate yields (Table 1, entries 8 and 9). Whereas p-
nitrobenzaldehyde
provided
the
corresponding
1-
aminophosphonate 2e in 56% yield (Table 1, entry 7), o-
nitrobenzaldehyde gave unidentified products without formation
of the desired product (Table 1, entry 10). This method was also
applied to the decarboxylative coupling of proline with α- and β-
naphthaldehyde in the presence of diethyl phosphite. β-
Naphthaldehyde gave the corresponding aminophosphonate 2i in
70% yield, however, α-naphthaldehyde produced the
corresponding product 2h in a lower yield of 46%, which is
possibly due to steric effects (Table 1, entries 11 and 12). The
decarboxylative coupling of thiophene-2-carbaldehyde with
proline and diethyl phosphite, gave a 53% yield of the desired
product 2j (Table 1, entry 13). Finally, the reaction of pentanal,
as an aliphatic aldehyde, with proline in the presence of diethyl
phosphite, gave 2k in 43% yield (Table 1, entry 14). In all the
entries, formation of the aminophosphonate 2 was strongly
preferred over 3. Thus, the conditions reported herein tolerate the
decarboxylative coupling of diethyl phosphite and proline with a
wide variety of aldehydes.
aromatics (β-naphthol and indole)
via azomethine ylide
formation.14 This report suggested to us that the azomethine
ylides generated through the thermal conditions would react with
phosphorous nucleophiles possessing an acidic proton without
any catalyst. To the best of our knowledge, there is no report on a
detailed study of the catalyst-free decarboxylative reaction of α-
amino acids with aldehydes and dialkyl phosphites in a one-pot
manner. Therefore we decided to study the feasibility of the
catalyst-free, decarboxylative, one-pot reaction of α-amino acids
with aldehydes and dialkyl phosphites for the synthesis of α-
aminophosphonates.
Initially, the decarboxylative reaction of proline with
benzaldehyde (1a) and diethyl phosphite was chosen as a model
reaction. The simple heating of 1.0 equiv of diethyl phosphite,
1.2 equiv of benzaldehyde (1a), and 1.5 equiv of proline in
toluene at reflux for two hours led to the formation of the desired
product 2a in 56% yield (Table 1, entry 1). The 31P NMR
analysis of the reaction mixture indicated the presence of the
known compound 4, resulting from hydrophosphorylation of
benzaldehyde (1a). Additionally, trace amounts of regioisomeric
product 3a were also detected. When the reaction was carried out
for 12 hours at reflux, the yield was increased slightly to 58%
yield (Table 1, entry 2). Formation of compound 3 was
suppressed by slow addition of benzaldehyde 1a to the refluxing
mixture of proline and diethyl phosphite in toluene via a syringe
over two hours (Table 1, entry 3). In this instance, product 2a
was isolated in 75% yield. Compound 2a was obtained in 36%
yield by slow addition of diethyl phosphite to the refluxing
mixture of proline and benzaldehyde in toluene via a syringe over
two hours. When the reaction was carried out in the presence of
triethyl phosphite instead of diethyl phosphite at reflux,
compound 2a was obtained in 43% yield (31P NMR analysis
showed the presence of compound 4 in 35% yield).
Table 1. Decarboxylative coupling of proline with aldehydes and diethyl
phosphite in toluene at reflux.
O
O
O
toluene
reflux, 1-5 h
+
+
H
CO2H
P(OEt)2
P(OEt)2
N
H
N
R
H
R
2
1
Entry
R
Time (h)
Product
Yielda
(%)
1
C6H5-
C6H5-
C6H5-
2
12
2
2
3
5
4
2
2
1
5
2
2
2
2a
2a
2a
2b
2c
2d
2e
2f
56 (63)b,c
58 (67)b,c
75 (86)c
63
2
3
4
p-MeC6H4-
5
p-Me2CHC6H4-
p-FC6H4-
61
6
65
7
p-O2NC6H4-
m-MeC6H4-
m-MeOC6H4-
o-O2NC6H4-
α-naphthyl
56
8
51
It should be noted that the use of common organic solvents, such
as THF, EtOH, CHCl3 or CH2Cl2 did not afford the desired
product 2a. Compound 2a was obtained in a low yield (<10% as
estimated by 31P NMR analysis), upon conducting the reaction in
DMF at 100 oC. The solvent-free decarboxylative reaction of
proline with benzaldehyde (1a) and diethyl phosphite gave 2a in
43% isolated yield at 100 oC for two hours. With optimal
conditions established, we next examined the three-component,
catalyst-free decarboxylative coupling of proline with aldehydes
and diethyl phosphite in toluene at reflux, and the results are
summarized in Table 1.
9
2g
-
54
d
10
11
12
13
14
-
2h
2i
46
70
53
43e
β-naphthyl
2-thienyl
2j
n-C4H9-
2k
a Reported yields are the isolated yields. Aldehyde added slowly into the
reaction mixture via a syringe
b Simple heating of a three component mixture
c Yields in parentheses were based on 2a and determined by 31P NMR
spectroscopy of the reaction mixture
First, our investigations were focused on the use of various
aldehydes. As illustrated in Table 1, the use of para-substituted
araldehydes bearing electron-withdrawing and -donating groups
had no influence on the yields of the products. A benzaldehyde
d Unidentified mixture of products.
e Reaction temperature = 90 oC.

3
The coupling reaction of proline with various dialkyl
phosphites and benzaldehyde were also studied. The reaction of
proline with dimethyl phosphite and benzaldehyde in toluene at
reflux for one hour, gave aminophosphonate 5 in 78% yield
(Scheme 2).
Acknowledgements
The Japan Society for the Promotion of Science is thanked for
supporting this work. This work was also supported by Grant-in-
Aid for Scientific Research (C) grant No: 25460155 from the
Japan Society for the Promotion of Science. The authors also
wish to thank the Institute for Advanced Studies in Basic
Sciences for partial support of this work.
O
O
O
toluene
reflux,1 h
+
+
H
CO2H
P(OR)2
P(OR)2
N
H
Ph
H
N
Supplementary Material
Ph
1a
5 (R=Me): 78%
6 (R=iPr): 75%
1
Spectroscopic characterization data and copies of H NMR,
13C NMR, and 31P NMR for compounds 2a-k. Supplementary
data associated with this article can be found, in the online
version, at.
Scheme 2: Reaction of proline with various dialkyl phosphites
and benzaldehyde
It was also possible to carry out this reaction with N-benzyl
valine15 the corresponding aminophosphonate 7 being obtained in
42% yield (Scheme 3).
References and notes
1. For example, see: a) Gawande, M. B.; Bonifacio, V. D. B.; Laque, R.;
Branco, P. S.; Varma, R. S. Chem. Soc. Rev., 2013, 15, 1226-1231; b)
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3495-3524.
2. a) Slobbe, P.; Ruijter, E.; Orru, R. V. A. Med. Chem. Commun. 2012, 3,
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Int. Ed. 2011, 50, 6234-6246.
3. a) Domling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168-3210; b)
Estevez, V.; Villacampa, M.; Menendez, J. C. Chem. Soc. Rev. 2010,
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4. a) de Graaff, C.; Ruijter, E.; Orru, R. V. A. Chem. Soc. Rev. 2012, 41,
3969-4009; b) Gu, Y.; Green Chem. 2012, 14, 2091-2128; c) Climent,
M. J.; Corma, A.; Iborra, S. RSC Adv. 2012, 2, 2016-2058.
O
P(OEt)2
O
O
CO2H
toluene
reflux, 2 h
+
+
H
P(OEt)2
N
Ph
H
NH
Ph
Ph
Ph
7
1a
Scheme 3: Reaction of N-benzyl valine with diethyl phosphite
and benzaldehyde
5. a) Singh, M. S.; Chowdury, S. RSC. Adv. 2012, 2, 4547-4592; b)
Tejedor, D.; Garcia-Tellado, F. Chem. Soc. Rev. 2007, 36, 484-491; c)
Marson, C. M. Chem. Soc. Rev. 2012, 41, 7712-7722.
6. a) Toy, A.; Walsh, E. N. Phosphorus Chemistry in Everyday Living,
American Chemical Society, Washington, DC, 2nd edn., 1987. b) Quin,
L. D. A Guide to Organophosphorus Chemistry, Wiley, New York,
2000. c) Gallo, M. A.; Lawryk, N. J. Organic Phosphorus Pesticides.
The Handbook of Pesticide Toxicology, Academic Press, San Diego,
A proposed mechanism is outlined in Scheme 4 for the direct
conversion of amino acids into aminophosphonates via
decarboxylative, three-component coupling of amino acids with
aldehydes and diethyl phosphite. The present process is thought
to proceed via the condensation of proline with an aldehyde to
give oxazolidin-5-one 8, a known intermediate, followed by
decarboxylation to give the azomethine ylide 9.16 The product 2
is obtained by the addition of diethyl phosphite to this dipole
(Scheme 4). This mechanism accounts for the formation of trace
amount of regioisomer 3 via another resonance contributor of
ylide 9.
1991. c) Engel, R. Chem Rev. 1977, 77, 349-367. d) Frank, A. W.
Chem. Rev. 1961, 61, 389-424. e) Kaboudin, B. Phosphorus, Sulfur,
Silicon Relat. Elem. 2002, 177, 1749-1751. f) Montchamp, J.-L. J.
Organomet. Chem. 2005, 690, 2388-2406. g) Hilderbrand, R. L., in
“The Role of Phosphonates in Living Systems”, CRC Press: Boca Raton,
1982. h) Redmore, D. in “Topics in Phosphorus Chemistry”; Griffith, E.
J.; Grayson, M. Eds.; Vol. 8; Wiley: New York, 1976. i) Kaboudin, B.
Karimi, M. Bioorg. Med. Chem. Lett. 2006, 16, 5324-5326. g)
Afarinkia, K.; Rees, C. W. Tetrahedron 1990, 46, 7175-7196. j)
Moonen, K.; Laureyn, I.; Stevens, C. V., Chem. Rev. 2004, 104, 6177-
6215. k) Montchamp, J.-L. J. Organomet. Chem. 2005, 690, 2388-
2406.
7. a) Barrett, G. C.; Elmore, D. T. Amino Acids and Peptides, Cambridge:
Cambridge Univ. Press, 1998; b) Atherton, F. R.; Hassall, C. H.;
Lambert, R. W. J. Med. Chem. 1986, 29, 29-40; c) Allen, M. C.; Fuhrer,
W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32, 1652-
1661. d) Hassall, C. H., in “Antibiotics”; ed. Hahn, F. E. Springer
Verlag, Berlin, 1983, Vol VI, 1-11; e) Gancarz, R.; Wieczorek, J. S.
Synthesis 1978, 625, f) Seyferth, D.; Marmor, R. S.; Hilbert, P. J. Org.
Chem. 1971, 36, 1379-1386. g) Worms, K. H.; Schmidt-Dunker, M., in:
“Organic Phosphorus Compounds”, Kosolapoff, G. M.; Marier, L.,
Eds., John Wiley & Sons, New York, 1976, Vol. 7, p 1. h) Kaboudin, B.
Phosphorus, Sulfur, Silicon 2002, 177, 1749-1751.
8. a) Berlicki, L.; Bochno, M.; Grabowiecka, A.; Bialas, A.; Kosikowska,
P.; Kafarski, P. Amino Acids 2012, 42, 1937-1945. b) Palecz, B.; Grala,
A.; Kudzin, Z. J. Chem. Eng. Data 2012, 57, 1515-1519; c) Kukhar, V.
P.; Hudson, H. R., Eds. Aminophosphonic and Aminophosphinic Acids:
Chemistry and Biological Activity; John Wiley & Sons: Chichester,
2000. d) Kaboudin, B.; Sorbiun, M. Tetrahedron Lett. 2007, 48, 9015.
9. For example, see: a) Yan, Y.; Wang, Z. Chem. Commun. 2011, 47,
9513-9515; b) Mao, H.; Wang, S.; Yu, P.; Lv, H.; Xu, R.; Pan, Y. J.
Org. Chem. 2011, 76, 1167-1169.
Scheme 4: Proposed mechanism for the conversion of proline
into aminophosphonate 2
In conclusion, we have reported a simple and novel method
for the conversion of amino acids into aminophosphonates via
the catalyst-free decarboxylative coupling of amino acids with
aldehydes and dialkyl phosphites. A simple work-up, mild
reaction conditions, moderate to good yields, catalyst-free and
clean reactions should make this method an attractive and a
useful contribution to present methodologies.17
10. Corcoran, R. C.; Green, G. M. Tetrahedron Lett. 1990, 31, 6827-6830.
11. Bi, H. P.; Zhao, L.; Liang, Y. M.; Li, C. J. Angew. Chem. Int. Ed. 2009,
48, 792. b) Bi, H. P.; Chen, W. W.; Liang, Y. M.; Li, C. J. Org. Lett.
2009, 11, 3246.
12. Yang, D.; Zhao, D.; Mao, L.; Wang, L.; Wang, R. J. Org. Chem. 2011,
76, 6426-6431.

4
13. For example, see: a) Kaboudin, B.; Emadi, S.; Hadizadeh, A. Bioorg.
Chem. 2009, 37,101-105. b) Kaboudin, B.; Emadi, S.; Hadizadeh, A.
Bioorg. Chem. 2009, 37, 101-105. c) Kaboudin, B.; Haghighat, H.;
Yokomatsu, T. Tetrahedron: Asymmetry 2008, 19, 862-866. d)
Kaboudin, B.; Saadati, F. Tetrahedron Lett. 2009, 50, 1450. e)
Kaboudin, B.; Fallahi, M. Tetrahedron Lett. 2011, 52, 4346-4348. f)
Kaboudin, B.; Alaie, S.; Yokomatsu, T. Tetrahedron: Asymmetry 2011,
22, 1813-1816. g) Kaboudin, B.; Haghighat, H.; Alaie, S. Yokomatsu,
T. Synlett 2012, 23, 1965-1969.
14. Zhang, C.; Seidel, D. J. Am. Chem. Soc. 2010, 132, 1798-1799.
15. This compound was prepared according to the method reported by:
Quitt, P.; Hellerbach, J.; Vogler, K. Helv. Chim. Acta 1963, 46, 327-
333. It should be noted that the coupling reaction of unprotected amino
acids such as phenyl alanine and valine with diethyl phosphite and
benzaldehyde were also studied. The reaction of phenyl alanine or
valine with diethyl phosphite and benzaldehyde in toluene at reflux for
12 h gave only diethyl-1-hydroxyphenylmethylphosphonate 3 as the
major product
16. Grigg, R.; Idle, J.; McMeekin, P.; Vipond, D. J. Chem. Soc., Chem.
Commun. 1987, 49.
17. General procedure for the synthesis of amino acids to
aminophosphonates: The dialkyl phosphite (1 mmol) was added to a
stirred mixture of amino acid (1.5 mmol) in toluene (2 mL) at reflux.
Aldehyde (1.5 mmol) was added to the reaction mixture in small
portions over 1-5 h (Table 1). The resultant solution was diluted with
H2O (30 mL) and extracted with EtOAc (2x25 mL). The organic layer
washed with brine (30 mL) and dried over Na2SO4. The pure product
was obtained by column chromatography on silica gel with n-hexane-
EtOAc (9:1 to 6:4). Ninhydrin-positive fractions (generally solvent
fractions of n-hexane-EtOAc at a ratio of 7:3 to 6:4) were collected and
evaporation of the solvent afforded the pure aminophosphonate 2 as a
yellow oil in 43-75% yield (see Table 1). All products gave
satisfactory spectral data in accord with the assigned structures and
literature reports. Diethyl-1-benzylpyrrolidin-2-ylphosphonate (2a):
Yellow oil, 1H NMR (400 MHz, CDCl3) ꢀ: 1.33-1.38 (m, 6H), 1.76-1.85
(m, 2H), 2.04-2.17 (m, 2H), 2.12-2.28 (m, 1H), 2.92-2.96 (m, 1H), 3.01
(dd, J1 = 10.0, J2 = 4.0 Hz, 1H), 3.43 (d, J = 13.0 Hz, 1H), 4.16-4.29
(m, 4H), 4.46 (d, J = 13.0 Hz, 1H), 7.23-7.38 (m, 5H); 13C NMR
(CDCl3, 100.6 MHz): ꢀ: 16.6 (d, JP-C = 5.0 Hz), 16.7 (d, JP-C = 6.0 Hz),
24.4 (d, JP-C = 6.0 Hz), 27.0 (d, JP-C = 2.0 Hz), 54.3 (d, JP-C = 15.1 Hz),
59.4 (d, JP-C = 174.0 Hz), 60.2 (d, JPC = 3.0 Hz), 61.8 (d, JP-C = 7.0
Hz), 62.7 (d, JP-C = 7.0 Hz), 126.9, 128.2, 128.9, 139.3; 31P NMR
(CDCl3/H3PO4, 162.0 MHz): ꢀ = 27.17. HRMS calcd for C15H25NO3P
(MH+): 298.1572 Found: 298.1563. Dimethyl-1-benzylpyrrolidin-2-
1
ylphosphonate (5): Yellow oil, H NMR (400 MHz, CDCl3) ꢀ: 1.61-
1.73 (m, 2H), 1.95-2.03 (m, 2H), 2.10-2.25 (m, 1H), 2.80-2.88 (m, 1H),
2.90-2.98 (m, 1H), 3.34 (d, J = 13.0 Hz, 1H), 3.67 (d, J = 10.0 Hz, 3H),
3.73 (d, J = 10.0 Hz, 3H), 4.29 (d, J = 13.0 Hz, 1H), 7.13-7.30 (m, 5H);
13C NMR (CDCl3, 100.6 MHz): ꢀ: 21.9 (d, JP-C = 4.0 Hz), 24.5 (d, JP-C
2.0 Hz), 50.1 (d, JP-C = 7.0 Hz), 51.1 (d, JP-C = 6.0 Hz) 51.6 (d, JP-C
=
=
14.0 Hz), 56.4 (d, JP-C = 172.8 Hz), 57.6 (d, JP-C = 3.0 Hz), 124.4,
125.6, 126.8, 136.6; 31P NMR (CDCl3/H3PO4, 162.0 MHz): ꢀ = 29.08.
HRMS calcd for C13H21NO3P (MH+): 270.1259 Found: 270.1256.
1
Diisopropyl-1-benzylpyrrolidin-2-ylphosphonate (6): Yellow oil, H
NMR (400 MHz, CDCl3) ꢀ: 1.15-1.30 (m, 12H), 1.62-1.75 (m, 2H),
1.90-2.10 (m, 2H), 2.10-2.20 (m, 1H), 2.80-2.90 (m, 2H), 3.34 (d, J =
13.0 Hz, 1H), 4.45 (d, J = 13.0 Hz, 1H), 4.65-4.75 (m, 1H), 4.80-4.85
(m, 1H), 7.13-7.30 (m, 5H); 13C NMR (CDCl3, 100.6 MHz): ꢀ: 23.7-
24.4 (m), 26.9 (d, JP-C = 2.0 Hz), 54.3 (d, JP-C = 15.0 Hz), 51.1 (d, JP-C
6.0 Hz), 51.6 (d, JP-C = 14.0 Hz), 59.8 (d, JP-C = 173.6 Hz), 60.2, 69.9
(d, JP-C = 7.0 Hz), 70.9 (d, JP-C = 7.0 Hz), 126.8, 128.0, 128.9, 137.6; 31
NMR (CDCl3/H3PO4, 162.0 MHz): ꢀ = 25.40. HRMS calcd for
=
P
C17H29NO3P (MH+): 326.1885 Found: 326.1876.
Diethyl-1-
(dibenzylamino)-2-methylpropyl phosphonate (7): Yellow oil, 1H
NMR (400 MHz, CDCl3) ꢀ: 0.85 (d, J = 6.8 Hz, 3H), 0.94 (d, J = 6.8
Hz, 3H), 1.20-1.32 (m, 6H), 1.91-2.09 (m, 1H), 2.56 (dd, J =15.6 and
8.4 Hz, 1H), 3.87 (d, J = 2.8 Hz, 4H), 4.01-4.15 (m, 4H), 7.13-7.35 (m,
10H); 13C NMR (CDCl3, 100.6 MHz): ꢀ: 16.4 (d, JP-C = 5.0 Hz), 16.5
(d, JP-C = 5.0 Hz), 20.8 (d, JP-C = 3.0 Hz), 21.4 (d, JP-C = 10.0 Hz), 28.2
(d, JP-C = 8.0 Hz), 55.3 (d, JP-C = 2.0 Hz), 60.5 (d, JPC = 8.0 Hz), 60.8 (d,
JP-C = 7.0 Hz) 61.7 (d, JP-C = 125.0 Hz), 126.8, 128.0, 129.2, 139.7; 31
P
NMR (CDCl3/H3PO4, 162.0 MHz): ꢀ = 29.28. HRMS calcd for
C22H33NO3P (MH+): 390.2198 Found: 390.2191