One-pot synthesis of α-amino phosphonates from aldehydes using lanthanide triflate as a catalyst

Full text of DOI:10.1021/jo971242t

J . Org. Chem. 1998, 63, 4125-4128
4125
Recently, it was reported that the imines were ef-
fectively activated by rare earth metal triflates such as
ytterbium triflate (Yb(OTf)3) and scandium triflate (Sc-
(OTf)3).10 These triflates are stable in water and can be
recovered after the reaction are completed and reused.11
Moreover, they have been used for the activation of
nitrogen-containing compounds, which deactivate most
Lewis acids. J udging from these unique properties of
lanthanide triflates, we planned to use them as a catalyst
in the reaction of diethyl phosphite with imines in order
to overcome the drawbacks described above.
On e-P ot Syn th esis of r-Am in o
P h osp h on a tes fr om Ald eh yd es Usin g
La n th a n id e Tr ifla te a s a Ca ta lyst
Changtao Qian* and Taisheng Huang
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai, 200032, China
Received December 22, 1997
Resu lts a n d Discu ssion s
In tr od u ction
In the recent years the synthesis of R-amino phospho-
nates has received an increasing amount of attention
because they are considered to be structural analogues
of the corresponding R-amino acids and transition state
mimics of peptide hydrolysis. In these connections, the
utilities of R-amino phosphonates as peptide mimics,1
haptens of catalytic antibodies,2 enzyme inhibitors,3 and
antibiotics and pharmacologic agents4 are well docu-
mented. A variety of synthetic approaches to R-amino
phosphonates are available.5 Of the methods, the nu-
cleophilic addition reaction of phosphites with imines is
one of the most convenient methods, which is usually
promoted by an alkali metal alkoxide or an acid.6 NaOEt
has been mainly used for this purpose since the pioneer-
ing work of Pudovik7 and Lewis acids such as SnCl2,
SnCl4, and BF3·Et2O have also been found to be effective.8
However, the reaction using these reagents and catalysts
resulted in unsatisfactory yields of R-amino phospho-
nates. Although later work by Zon demonstrated that
the reaction can be strongly promoted by ZnCl2 or MgBr2
in high yields,9 it cannot proceed a one-pot reaction from
aldehydes and has to start from imines because the
amines and water that exist during imine formation can
decompose or deactivate the Lewis acids.
First, benzylideneaniline was treated with diethyl
phosphite in the presence of 10 mol % Yb(OTf)3 in
dichloromethane at room temperature. The reaction
proceeded smoothly to afford the corresponding R-amino
phosphonate in excellent yield (93%), which showed that
Yb(OTf)3 effectively catalyzes the reaction indeed. How-
ever, to our knowledge, many imines are hygroscopic,
unstable at high temperature, and difficult to purify by
distillation or column chromatography. Thus it is desir-
able from a synthetic point of view that imines, generated
in situ from aldehydes and amines, immediately react
with phosphites and afford R-amino phosphonates in one-
pot way.
It was found that the reaction of benzaldehyde, ben-
zylamine, and diethyl phosphite took place smoothly in
the presence of 10 mol % Ln(OTf)3 and 4 Å molecular
Sieves or MgSO4. Among the lanthanide(III) triflates
screened, ytterbium(III) triflate (Yb(OTf)3) showed su-
perior catalytic activity, while the yield of the adduct was
lower in the presence of lanthanum(III) triflate (La-
(OTf)3). On the other hand, the reaction proceeded
sluggishly in the presence of MgSO4 without any catalyst,
and only a trace amount of product was produced after
12 h. Effect of solvents on the yields of R-amino phos-
phonates in the model reaction under the influence of a
catalyst amount of Yb(OTf)3 (10 mol %) are shown in
Table 1. Dichloromethane was the best solvent among
those tested, such as acetonitrile (71%), tetrahydronfuran
(67%), and toluene (30%), which is consistent with
solubilities of Yb(OTf)3 in those solvents. It is worth
mentioning that the yield of the R-amino phosphonate
was only 68% when promoted by 120 mol % SnCl4, but
was improved to 89% in the presence of 10 mol % Yb-
(OTf)3 in dichloromethane.
* Corresponding author: Changtao Qian, Professor of Chemistry,
Chairman, Academic Committee of Laboratory of Organometallic
Chemistry, Chinese Academy of Sciences. Phone: 86-21-64163300.
Fax: 86-21-64166128. E-mail: qianct@pub.sioc.ac.cn.
(1) Kafarski, P. and Lejczak, B. Phosphorus, Sulfur Silicon Relat.
Elem. 1991, 63, 1993.
(2) Hirschmann, R.; Smith III, A. B.; Taylor, C. M.; Benkovic, P. A.;
Taylor, S. D.; Yager, K. M.; Sprengler, P. A.; Venkovic, S. J . Science
1994, 265, 234.
(3) (a) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J . M. J .
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1987, 30, 1603.
(4) (a) Atherton, F. R.; Hassall, C. H.; Lambert, R. W. J . Med. Chem.,
1986, 29, 29. (b) Hassall, C. H. in Antibiotics; Halm, F. E., Ed.;
Springer-Verlag: Berlin, 1983, Vol. Vl, pp 1-11. (c) Wieczorek, P.;
Kaczanowska, M.; Lejczak, B.; Kafarski, P. Pestic. Sci. 1990, 30, 43.
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A.; Miglecz, E.; Bezetei, I. FEBS Lett. 1989, 117, 308. (e) Natchev, I.
A. Liebigs Ann. Chem. 1988, 861.
(5) (a) Redmore, D. Topics in Phosphorus Chemistry, Griffith, E. J .,
Grayson, M., Eds.; J ohn Wiley & Sons: New York, 1976; Vol. 8, p 515.
(b) Kukhar, V. P.; Solodenko, V. A. Russian Chem. Rev. 1987, 56, 859.
(c) Yokomatsu, T.; Yoshida, Y.; Shibuya, S. J . Org. Chem. 1994, 59,
7930.
(6) (a) Petrov, K. A.; Chauzov, V. A.; Erokhina, T. S. Usp. Khim.
1974. 43, 2045; Chem. Abstr. 1975, 82, 43486. (b) Kirby, A. J .; Warren,
S. G. The Organic Chemistry of Phosphorus; Elsevier: Amsterdam,
London, New York, 1967.
(7) Pudovik, A. N. Dokl. Akad. Nauk SSSR 1952, 83, 865; Chem.
Abstr. 1953, 47, 4300.
The reaction of several aldehydes, amines, and diethyl
phosphite were examined in the presence of a catalytic
amount (10 mol %) of Yb(OTf)3 and MgSO4 in dichlo-
romethane, and the results are summarized in Table 2.
In all cases, the three-component reaction proceeded
smoothly to afford the corresponding R-amino phospho-
(10) (a) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S. Chem.
Lett. 1995, 423. (b) Ishitani, H.; Nagayama, S.; Kobayashi, S. J . Org.
Chem. 1996, 61, 1902. (c) Cozzi, P. G.; Simone B. D.; Ronchi, A. U.
Tetrahedron Lett. 1996, 37, 1691. (d) Kobayashi, S.; Nagayama, S. J .
Org. Chem. 1997, 62, 232.
(11) (a) Kobayashi, S.; Hachiya, I. Tetrahedron Lett. 1992, 33, 1625.
(b) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hichiya, I.
Synlett 1995, 233. (c) Wang, R.; Lim, C.-M.; Tan, C.-H.; Lim, B.-K.;
Sim, K.-Y.; Loh, T.-P. Tetrahedron: Asymmetry 1995, 6, 1825. (d) Yu,
L.; Chen, D.; Wang, P. G. Tetrahedron Lett. 1996, 37, 2169.
(8) Laschat, S.and Kunz, H. Synthesis 1992, 90.
(9) Zon, J . Pol. J . Chem. 1981, 55, 643.
S0022-3263(97)01242-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/22/1998

4126 J . Org. Chem., Vol. 63, No. 12, 1998
Notes
Ta ble 1. Effect of Ca ta lysts a n d Solven ts on th e
Rea ction of Ben za ld eh yd e, Ben zyla m in e, a n d Dieth yl
P h osp h ite
is chelated by the nitrogen and the methoxy group. For
chiral amine 5a and 5c, it was perhaps that chelate and
rigid transition state A existed in the procedure of the
reaction, which worked to enhance the diastereoisomeric
excess; in sharp contrast, such a transition state A could
entry solvent catalyst (10 mol %)
additive
MgSO4
MgSO4
MgSO4
MgSO4
4 Å mol sieves
MgSO4
MgSO4
MgSO4
yield (%)c
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH3CN
toluene
CH2Cl2
CH2Cl2
None
trace
34
56
89
87
67
71
30
21
La(OTf)3
Sm(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
not be formed in the case of chiral amine (5b), which
resulted in the low diastereoisomeric excess.
a
9
10
SnCl4
SnCl4
MgSO4
MgSO4
In summary, lanthanide triflates were found to be
efficient catalysts both in the reaction of imines with
diethyl phosphite and in one-pot reaction of aldehydes,
amines, and phosphite to afford R-amino phosphonates
in good to excellent yields under the mild conditions.
Further application of these reactions to asymmetric
synthesis is now in progress.
b
68
a
b
Condition: SnCl4 (100 mol %). Condition: SnCl4 (120 mol
%). c Isolated yield.
Ta ble 2. On e-P ot Syn th esis of r-Am in o P h osp h on a tes
fr om Ald eh yd es Ca ta lyzed by Yb(OTf)3
Exp er im en ta l Section
Gen er a l. CH2Cl2 was distilled from P2O5 under Ar. 1H NMR
spectra were recorded at 300 MHz in CDCl3 using TMS as
internal reference. 31P NMR (121.4 MHz) was taken in CDCl3
using 85% H3PO4 as an external standard with broad-band 1H
decoupling. 13C NMR spectral measurements were performed
at 75.4 MHz using CDCl3 as an internal standard. Benzyli-
deneaniline was prepared from aniline and benzaldehyde.12
Diethyl phosphite was prepared according to the literature
method.13 Lanthanide(III) triflates were prepared by the re-
ported procedure and dried by heating at 200 °C under reduced
pressure prior to use.14
yield
product (%)a
entry
RCHO
benzaldehyde
p-anisaldehyde
p-tolualdehyde
p-nitrobenzaldehyde
2-furaldehyde
cyclohexanecarboxaldehyde aniline
benzaldehyde
benzaldehyde
trans-cinnamaldehyde
C9H19CHO
R′NH2
1
2
3
4
5
6
7
8
9
benzylamine
aniline
aniline
aniline
aniline
4 a
4 b
4 c
4 d
4 e
4 f
4 g
4 h
4 i
89
92
88
93
85
71
65
89
79
62
n-propylamine
aniline
aniline
benzylamine
Th e Rea ction of Ben zylid en ea n ilin e w ith Dieth yl P h os-
p h ite. Yb(OTf)3 (0.1 mmol), benzylideneaniline (1 mmol), and
diethyl phosphite (1.2 mmol) were mixtured in 5 mL of dichlo-
romethane at 0 °C. After the mixture was stirred for 5 h at
room temperature, water was added and the product was
extracted with EtOAc. The organic layer was dried with
anhydrous Na2SO4 and evaporated to give the crude product.
Analytically pure product 4a was then obtained by column
chromatography in 93% yield. r-Am in o P h osp h a te (4a ). 1H
NMR δ 7.45-7.24 (10 H, m), 4.11-3.53 (7 H, m), 2.95 (1 H, s),
1.27 (3 H, t, J ) 7.1 Hz), 1.12 (3 H, t, J ) 7.1 Hz); 31P NMR δ
22.9; 13C NMR δ 146.3 (s, Ph), 136.0 (s, Ph), 130.0 (s, Ph), 129.2
(s, Ph), 128.7 (s, Ph), 128.0 (s, Ph), 118.5 (s, Ph), 114.0 (s, Ph),
10
4 j
a
Isolated yield.
nates. Aromatic aldehydes provided excellent yields of
products, and aliphatic aldehydes afforded phosphonates
in moderate yields, which is expected in that aromatic
aldehydes have higher reactivity than aliphatic alde-
hydes. Another important feature of this reaction is that
the catalyst can be easily recovered from the aqueous
layer after the reaction is completed and can be reused
with no loss of yield (see, the following experimental
procedure).
1
77.5 (s, CH2Ph), 63.4 (s, OCH2CH3), 56.2 (d, CHP, J PC ) 150.8
Hz), 16.5 (s, OCH2CH3), 16.3 (s, OCH2CH3); HRMS calcd for
C18H24NO3P: 333.1494. Found: 333.1483.
Finally, asymmetric reactions using a chiral amine
were examined. According to our method a catalytic
amount of ytterbium triflate (10 mol %) and anhydrous
MgSO4 were treated at room temperature with an
aldehyde and a chiral amine, followed by addition of a
dialkyl phosphite. The commercially available (S)-1-
methoxy-2-phenylethylamine (5a ), (S)-R-methylbenzyl-
amine (5b), (S)-1-methoxy-3-methyl-2-butylamine (5c),
were chosen as chiral auxiliaries. The diastereoselec-
tivities of the reactions were determined by 31P-NMR and
are listed in Table 3. For benzaldehyde (entry 1 in Table
3), the 31P-NMR of product showed two resonances at δ
24.91 and δ 24.37 with the integral ratio of 78:22, leading
to the % de of 56. The best results were achieved using
(S)-1-methoxy-2-phenylethylamine (5a ), while (S)-R-
methylbenzylamine (5b) gave low diastereoisomeric ex-
cess. To explain the results obtained in the reaction, we
suggest the model A transition state in which Yb(OTf)3
A typical experimental procedure is described for one-pot
reaction of benzaldehyde, benzylamine, and diethyl phosphite:
to a suspension of Yb(OTf)3 (0.1 mmol) and 4 Å molecular sieves
or MgSO4 (125 mg) in CH2Cl2 (4 mL) were added an aldehyde
(1 mmol) in CH2Cl2 (0.5 mL) and an amine (1.1 mmol) in CH2-
Cl2 (0.5 mL) at room temperature. The mixture was stirred for
0.5 h at room temperature. Then diethyl phosphite (1 mmol)
was added to the sample pot. The mixture was further stirred
for 15-30 h, and then CH2Cl2 was removed under reduced
pressure. Water was added, and the product was extracted with
EtOAc. After the organic layer was dried and evaporated, the
crude product was chromatographed on silica gel to afford the
R-amino phosphate 4a (89% yield). Yb(OTf)3 can be almost
(12) Katagiri, N.; Miura, Y.; Niwa, R.; Xato, T. Chem. Pharm. Bull.
1983, 31, 538.
(13) McCombie, H.; Saunders: B. C.; Stacey, G. J . J . Chem. Soc.
1945, 380.
(14) Forsberg, J . H.; Spaziano, V. T.; Balasubramanian, T. M.; Liu,
G. K.; Kinsley, S. A.; Duckworth, C. A.; Poteruca, J . J .; Brown, P. S.;
Miller, J . L. J . Org. Chem. 1987, 52 1017.

Notes
J . Org. Chem., Vol. 63, No. 12, 1998 4127
Ta ble 3. On e-P ot Syn th esis of Op tica l Active r-Am in o P h osp h a tes Ca ta lyzed by Ytter biu m Tr ifla te
entry
R
R′NH2 (5)
6:7a
de, %
yield (%)b
1
2
3
4
5
6
Ph
Ph
Ph
(S )-1-phenyl-2-methoxyethylamine
(S)-R-methylbenzylamine
6a :7a , 78:22
6b:7b, 57:43
6c:7c, 74:26
6d :7d , 78:22
6e:7e, 57:43
6f:7f, 74:26
56
14
48
56
14
48
95
92
82
91
88
81
(S)-1-methoxyl-3-methyl-2-butylamine
(S)-1-phenyl-2-methoxyethylamine
(S)-R-methylbenzylamine
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
(S)-1-methoxyl-3-methyl-2-butylamine
a
b
The ratio was determined by 31P NMR. Isolated yields based on aldehydes.
quantitatively recovered from the aqueous layer and can be
reused (2nd use, 86% yield).
153.5 Hz), 16.4 (d, 3J PC ) 5.5 Hz, OCH2CH3), 16.2 (d, 3J PC ) 5.4
Hz, OCH2CH3).
r-Am in o P h osp h a te (4b). 1H NMR δ 7.40-6.58 (9H, m),
r-Am in o P h osp h a te (4i). 1H NMR δ 7.37-6.69 (11 H, m),
1
1
4.71 (1 H, d, J PH ) 23.8 Hz), 4.14-3.66 (4 H, m), 3.77 (3 H, s),
6.36-6.18 (1 H, m), 4.47 (1 H, dd, J PH ) 21.3 Hz, J ) 2.1 Hz),
1.28 (3 H, t, J ) 7.0 Hz), 1.14 (3 H, t, J ) 7.1 Hz); 31P NMR δ
23.5; 13C NMR δ 159.3 (s, Ph), 146.5 (s, Ph), 132.6 (s, Ph), 129.0
(s, Ph), 127.7 (s, Ph), 125.1 (s, Ph), 120.3 (s, Ph), 118.2 (s, Ph),
4.22-4.12 (4 H, m), 3.17 (1 H, s), 1.34 ∼ 1.26 (6 H, m); 31P NMR
δ 24.1; 13C NMR δ 146.6 (s, Ph), 146.5 (s, Ph), 136.4 (s, Ph), 133.1
(s, Ph), 133.0 (s, Ph), 129.3 (s, Ph), 127.9 (s, Ph), 126.6 (s, Ph),
123.5 (s, Ph), 118.6 (s, Ph), 113.9 (s, Ph), 63.5 (s, OCH2CH3),
1
114.1 (s, Ph), 63.3 (s, OCH2CH3), 55.4 (d, CHP, J PC ) 150.8
1
Hz), 55.6 (s, OMe), 16.4 (s, OCH2CH3), 16.3 (s, OCH2CH3); HRMS
calcd for C18H24NO4P: 349.1442. Found: 349.1395.
63.1 (s, OCH2CH3), 54.1 (d, CHP, J PC ) 153.4 Hz), 16.5 (s,
OCH2CH3); HRMS calcd for C19H24NO3P: 345.1494. Found:
345.1535.
r-Am in o P h osp h a te (4c). 1H NMR δ 7.36-6.58 (9H, m), 4.73
1
(1 H, d, J PH ) 24.1 Hz), 4.14-3.68 (4 H, m), 2.31 (3 H, s), 1.28
r-Am in o P h osp h a te (4j). 1H NMR δ 7.45 (5 H, m), 3.86-
4.4 (7 H, m), 1.1-1.65 (25 H, m); 31P NMR δ 24.8; 13C NMR δ
144.4 (s, Ph), 129.8 (s, Ph), 128.7 (s, Ph), 127.7 (s, Ph), 127.1 (s,
Ph), 77.5 (s, CH2Ph), 61.8 (d, OCH2CH3, 2J PC ) 9.2 Hz), 53.7 (d,
CHP, 149.1 Hz) 38.2 (s, C9H19), 32.3 (s, C9H19), 31.8 (s, C9H19),
30.5 (s, C9H19), 29.7 (s, C9H19), 29.3 (s, C9H19), 29.0 (s, C9H19),
(3 H, t, J ) 7.1 Hz), 1.13 (3 H, t, J ) 7.1 Hz); 31P NMR δ 23.5;
13C NMR δ 146.5 (s, Ph), 146.3 (s, Ph), 137.7 (s, Ph), 132.7 (s,
Ph), 129.4 (s, Ph), 127.7 (s, Ph), 118.4 (s, Ph), 113.9 (s, Ph), 63.3
2
1
(d, OCH2CH3, J PC ) 5.1 Hz), 55.8 (d, CHP, J PC ) 150.8 Hz),
3
21.2 (s, Me), 16.5 (d, OCH2CH3, J PC ) 4.3 Hz), 16.3 (d,
3
3
OCH2CH3, J PC ) 4.6 Hz); HRMS calcd for C18H24NO3P:
22.7 (s, C9H19 ), 16.7 (d,. OCH2CH3, J PC ) 4.3 Hz), 14.1 (s,
333.1494. Found: 333.1529.
C9H19); HRMS calcd for C21H38NO3P: 382.2511. Found:
382.2484.
r-Am in o P h osp h a te (4d ). 1H NMR δ 6.43-7.50 (9 H, m),
5.3 (1 H, m), 3.65-4.6 (4 H, m), 1.07-1.46 (6 H, m); 31P NMR δ
21.4; 13C NMR δ 173.8 (s, Ph), 147.7 (s, Ph), 145.6 (s, Ph), 129.4
(s, Ph), 128.9 (s, Ph), 123.8 (s, Ph), 119.6 (s, Ph), 119.3 (s, Ph),
r-Am in o P h osp h on a te (6a +7a ). 1H NMR δ 7.46-7.12 (10
H, m), 4.21-3.58 (6 H, m), 3.84 (3 H, s), 2.25 (1 H, s), 1.42-1.03
(9 H, m); 31P NMR δ 24.4, 24.9; 13C NMR δ 128.6 (s, Ph), 127.9
(s, Ph), 127.7 (s, Ph), 62.9 (s, OCH2CH3), 62.7 (s, OCH2CH3),
60.8 (s, CHCH2OCH3), 58.9 (s, CH2OCH3), 58.4 (s, CH2OCH3),
1
114.1 (s, Ph), 63.8 (s, OCH2CH3), 50.4 (d, CHP, J PC ) 159.2
Hz), 16.6 (s, OCH2CH3), 16.4 (s, OCH2CH3); HRMS calcd for
1
C
17H21N2O5P: 364.1188. Found: 364.1151.
58.2 (d, CHP, J PC ) 145.1 Hz), 16.5 (s, OCH2CH3), 16.3 (s,
r-Am in o P h osp h a te (4e). 1H NMR δ 7.39-6.33 (8 H, m),
OCH2CH3); HRMS calcd for C20H28NO4P: 377.1756. Found:
377.1715; the ratio of 6a to 7a is 78:22, de: 56%.
1
4.90 (1 H, d, J PH ) 23.4 Hz), 4.21-3.84 (4 H, m), 2.95 (1 H, s),
1.30 (3 H, t, J ) 7.0 Hz), 1.21 (3 H, t, J ) 7.0 Hz); 31P NMR δ
20.8; 13C NMR δ 149.5 (s, Ph), 146.2 (s, furan), 142.6 (s, furan),
129.3 (s, Ph), 119.1 (s, furan), 114.1 (s, Ph), 110.9 (s, Ph), 108.9
(s, furan), 63.5 (s, OCH2CH3), 50.4 (d, CHPh, J PC ) 159.2 Hz),
16.4 (s, OCH2CH3), 16.0 (s, OCH2CH3); HRMS calcd for
r-Am in o P h osp h on a te (6b+7b). 1H NMR δ 7.34-7.23 (10
1
H, m), 4.17-3.89 (5 H, m), 4.10 (1H, d, J PH ) 23.4 Hz), 2.96 (1
H, s), 1.32 (3 H, t, J ) 7.2 Hz), 1.10 (3 H, t, J ) 7.0 Hz); 31P
1
NMR δ 24.6, 25.1; 13C NMR δ 128.6 (s, Ph), 128.2 (s, Ph), 127.6
1
(s, Ph), 127.2 (s, Ph), 63.3 (s, OCH2CH3), 58.0 (d, CHP, J PC
)
C
15H20NO4P: 309.1130. Found: 309.1097.
151.8 Hz), 56.2 (s, CH(CH3)Ph), 21.8 (s, CH(CH3)Ph), 16.5 (s,
OCH2CH3), 16.3 (s, OCH2CH3); HRMS calcd for C19H26NO3P:
347.1650. Found: 347.1651; the ratio of 6b to 7b is 57:43, de:
14%.
r-Am in o P h osp h a te (4f). 1H NMR δ 7.19-6.63 (5 H, m),
1
4.14-3.97 (4 H, m), 3.63 (1 H, dd, J PH ) 19.0 Hz, J ) 2.1 Hz,),
1.89-1.11 (17 H, m); 31P NMR δ 26.1; 13C NMR δ 147.8 (s, Ph),
129.7 (s, Ph), 129.3 (s, Ph), 117.8 (s, Ph), 113.2 (s, Ph), 62.6 (s,
OCH2CH3), 56.1 (d, CHP, 1J PC ) 150.8 Hz), 39.9 (s, hexyl ), 31.0
(s, hexyl ), 29.7 (s, hexyl ), 28.3 (s, hexyl ), 27.0 (s, hexyl ), 22.0
(s, hexyl ), 16.4 (s, OCH2CH3); HRMS calcd for C17H28NO3P:
325.1807. Found: 325.1835.
r-Am in o P h osp h on a te (6c+7c). 1H NMR δ 7.44-7.26 (5
H, m), 4.34-3.85 (5 H, m), 3.30 (3 H, s), 3.38-3.14 (2 H, m),
2.33 (2 H, m), 1.70-1.66 (1 H, m), 1.32-0.79 (12 H, m); 31P NMR
δ 24.6, 25.5; 13C NMR δ 145.1 (s, Ph), 129.8 (s, Ph), 128.7 (s,
2
Ph), 127.2 (s, Ph), 127.1 (s, Ph), 62.9 (d, OCH2CH3, J PC ) 6.9
r-Am in o P h osp h a te (4g). 1H NMR δ 7.5 (5 H, s), 4.0-4.4
(4 H, m), 3.8-3.95 (3H, m), 2.5-2.8 (2 H, m), 1.1-1.7 (9 H, m);
Hz), 62.8 (d, OCH2CH3, J PC ) 7.5 Hz), 57.4 (d, CHP, J PC )
2
1
153.4 Hz), 55.3 (s, CH2OCH2), 54.8 (s, CH2OCH3), 24.7 (s, CH-
(CH3)2), 22.3 (s, CH(CH3)2), 21.8 (s, CH(CH3)2) 16.5 (d, J PC )
5.5 Hz, OCH2CH3), 16.3 (d, J PC ) 5.8 Hz, OCH2CH3); HRMS
calcd for C17H30NO4P: 343.1913. Found: 343.1932; the ratio
of 6c to 7c is 74:26, de: 48%.
31P NMR δ 24.1; 13C NMR δ 135.7 (s, Ph), 132.7 (s, Ph), 129.5
3
2
3
(s, Ph), 129.5 (s, Ph), 129.0 (s, Ph), 63.1 (d, OCH2CH3, J PC
)
1
7.2 Hz), 60.9 (d, CHP, J PC ) 152.8 Hz), 48.4 (s, CH2CH2CH3),
3
29.7 (s, CH2CH2CH3), 16.7 (d, OCH2CH3, J PC ) 5.1 Hz), 16.2
(d, OCH2CH3, 3J PC ) 5.3 Hz), 11.4 (s, CH2CH2CH3); HRMS calcd
for C14H24NO3P: 285.1494. Found: 285.1472.
r-Am in o P h osp h on a te (6d +7d ). 1H NMR δ 7.31-6.81 (9
H, m), 4.13-3.29 (8 H, m), 3.78 (3 H, s), 3.37 (1 H, s), 1.30 (3 H,
t, J ) 7.1 Hz), 1.15 (3 H, t, J ) 7.0 Hz); 31P NMR δ 24.7, 25.2;
13C NMR δ 159.3 (s, Ph), 139.6 (s, Ph), 132.2 (s, Ph), 129.0 (s,
Ph), 128.5 (s, Ph), 128.2 (s, Ph), 127.9 (s, Ph), 126.8 (s, Ph), 114.0
r-Am in o P h osp h a t e (4h ).3 1H NMR δ 7.48-6.58 (10 H,
m), 4.76 (1 H, d, 1J PH ) 24.2 Hz), 4.14-3.67 (4 H, m), 1.28 (3 H,
t, J ) 7.1 Hz), 1.11 (3 H, t, J ) 7.1 Hz); 13C NMR δ 139.0 (s,
Ph), 135.5 (s, Ph), 128.8 (s, Ph), 128.7 (s, Ph), 128.5 (s, Ph), 128.4
(s, Ph), 62.7 (d, OCH2CH3, 2J
149.4 Hz,), 59.2 (s, OCH3), 58.4 (s, CHCH2OCH3), 56.5 (s, CH2-
OCH2), 55.5 (s, CH2OCH3), 16.5 (d, J PC ) 5.4 Hz, OCH2CH3),
) 6.7 Hz), 59.8 (d, CHP, 1J PC
)
PC
2
(s, Ph), 128.0 (s, Ph), 127.2 (s, Ph), 63.0 (d, OCH2CH3, J ) 7.2
Hz), 62.9 (d, OCH2CH3, J PC ) 7.0 Hz), 59.5 (d, CHP, J PC
2
1
3
)

4128 J . Org. Chem., Vol. 63, No. 12, 1998
Notes
3
16.3 (d, J PC ) 5.8 Hz, OCH2CH3); HRMS calcd for C21H30
-
(2 H, m), 2.36-2.26 (2 H, m), 1.72 (1 H, m), 1.34-0.81 (12 H,
m); 31P NMR δ 24.6, 25.5; HRMS calcd for C18H32NO5P: 373.2018.
Found: 373.1980; the ratio of 6f to 7f is 74:26, de: 48%.
NO5P: 407.1862. Found: 407.1852; the ratio of 6d : 7d is 78:
22, de: 56%.
r-Am in o P h osp h on a te (6e+7e). 1H NMR δ 7.29-6.85 (9
H, m), 4.19-3.78 (6 H, m), 3.79 (3 H, s), 2.95 (1 H, s), 1.33 (3 H,
t, J ) 7.1 Hz), 1.32 (3 H, d, J ) 6.5 Hz), 1.12 (3 H, t, J ) 7.1
Hz); 31P NMR δ 24.9, 25.0; 13C NMR δ 145.0 (s, Ph), 136.3 (s,
Ack n ow led gm en t. We thank the National Science
Foundation of China for financial support of this
research.
Ph), 128.8 (s, Ph), 128.5 (s, Ph), 128.4 (s, Ph), 127.8 (s, Ph), 127.3
(s, Ph), 127.1 (s, Ph), 126.8 (s, Ph), 63.0 (d, OCH2CH3, J PC
2
)
Su p p or tin g In for m a tion Ava ila ble: IR and mass spectral
data and copies of carbon NMR spectra (18 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
2
1
6.8 Hz), 62.9 (d, OCH2CH3, J PC ) 7.1 Hz), 58.2 (d, CHP, J PC
) 151.7 Hz), 55.5 (s, CH(CH3)PH), 55.3 (s, OCH3), 22.3 (s, CH3),
3
3
16.5 (d, J PC ) 5.4 Hz, OCH2CH3), 16.2 (d, J PC ) 5.4 Hz,
OCH2CH3); HRMS calcd for C20H28NO4P: 377.1756. Found:
377.1773; the ratio of 6e to 7e is 57:43, de: 14%.
r-Am in o P h osp h on a te (6f+7f). 1H NMR δ 7.38-6.86 (4
H, m), 4.30-3.85 (5 H, m), 3.81 (3 H, s), 3.32 (3 H, s), 3.40-3.20
J O971242T