Hydrophosphonylation of aldimines under catalysts-free conditions

Article abstract of DOI:10.1002/cjoc.201200119

Trimethylsilyl phosphite reacted with aldimines efficiently under catalysts-free conditions, giving α-aminophosphonates in good to excellent yields. Furthermore, the reaction can be scaled-up easily and the high yield can be maintained. Copyright

Full text of DOI:10.1002/cjoc.201200119

NOTE
DOI: 10.1002/cjoc.201200119
Hydrophosphonylation of Aldimines under Catalysts-Free
Conditions
Cai, Zhihua#(蔡志华)
Fan, Yecheng#(范业成)
Du, Guangfen*(杜广芬)
He, Lin*(何林)
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and
Chemical Engineering, Shihezi University, Xinjiang 832000, China
Trimethylsilyl phosphite reacted with aldimines efficiently under catalysts-free conditions, giving α-amino-
phosphonates in good to excellent yields. Furthermore, the reaction can be scaled-up easily and the high yield can
be maintained.
Keywords trimethylsilyl phosphite, aldimines, α-aminophosphonates, catalysts-free
Introduction
coupled with dimethyl trimethylsilyl phosphite
smoothly in the presence of 2 mol% 1,3-bis(2,6-diiso-
propylphenyl)imidazol-2-ylidene (IPr, a stable NHC),[8]
affording the corresponding adduct in excellent yield
(Table 1, Entry 1). However, to our surprise, in the con-
trol experiments, we found that trimethylsilyl phosphite
can react with N-tosyl benzaldimine directly in the ab-
sence of any catalysts, giving the desired α-amino-
phosphonate in impressive yield within 5 h (Table 1,
Entry 2).[9] We then re-examined the reaction very care-
fully using freshly distilled trimethylsilyl phosphite and
recrystallized N-tosyl benzaldimine in a new, dried and
clean glassware for several times, but the same results
were obtained. A brief survey of solvents indicated that
ether, dichloromethane, toluene are all suitable reaction
media, and gave the desired product in high yield (Table
1, Entries 3—5). Interestingly, when lowered reaction
temperature to 0 ℃, no obvious effect on the reaction
was observed (Table 1, Entry 6). However, when
quenched the reaction within 2 h, the reaction was not
completed under catalysts-free conditions and relatively
low yield was obtained (Table 1, Entries 7, 8).[9] On the
other hand, when alkyl phosphites such as
(MeO)2P(O)H, (EtO)2P(O)H, (MeO)3P and (EtO)3P
were used instead of dimethyl trimethylsilyl phosphite,
no addition product was detected after long reaction
time (Table 1, Entries 9—12).
α-Aminophosphoric acids and phosphonates have
attracted considerable attention in recent years due to
their intriguing biological and pharmaceutical activi-
ties.[1] Pudovik reaction,[2] coupling of phosphites with
imines, is the most straight forward and efficient proto-
col for the synthesis of this type of important compound.
Although considerable efforts have been made re-
cently,[3] given the usefulness of Pudovik reaction in
carbon-phosphorus bond constructions, the development
of simple transformation which features in high effi-
ciency is still clearly desirable. In contrast to dialkyl
phosphites, an alternative strategy through nucleophilic
addition of readily available trialkylsilyl phosphite to
suitable electrophiles was farless examined.[4] Recently,
the group of Das[5] used trialkylsilyl phosphites as nu-
cleophilic reagents successfully in iodine molecular
catalyzed aminophosphonylation of N-tosyl aldimines,
obtained sulfonamide phosphonates in excellent yields.
And more recently, we discovered that N-heterocyclic
carbenes (NHCs)[6] can also promote the Pudovik reac-
tion of trimethylsilyl phosphite with aldehydes effi-
ciently, giving α-hydroxyphosphonates in good yields.[7b]
As part of our ongoing studies of NHCs catalysis,[7] we
evisioned that NHCs may be able to catalyze the addi-
tion of trimethylsilyl phosphites with imines. In this
paper, we describe the direct coupling of trimethylsilyl
phosphite with aldmines to produce α-aminophospho-
nates.
With the optimal reaction conditions in hand, the
scope of aldimine was then evaluated (Table 2). Tosyl
arylimines with either electron-donating or withdrawing
groups worked well to furnish α-aminophosphonates in
excellent yields (Table 2, Entries 1—7). Additionally,
the substitution at different position of the aromatic ring
had no effect on the reaction (Table 2, Entries 8—12).
Results and Discussion
In our initial experiments, N-tosyl benzaldimine
*
E-mail: duguangfen@shzu.edu.cn; helin@shzu.edu.cn
Cai and Fan contributed equally to this work.
#
Received February 10, 2012; accepted May 2, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200119 from the author.
Chin. J. Chem. 2012, XX, 1—5
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Cai et al.
Table 2 α-Aminophosphonylation of aldiminesa
NOTE
Table 1 Evaluation of reaction conditionsa
GP
R
OSiMe3
PG
NH
THF, r.t.
3 - 5 h
OMe
OMe
NHTs
N
+
NTs
P
OMe
OSiMe3
OMe
P
MeO
solvent
r.t.
P
O
R
R'
R'
+
H
OMe
P
2
O
OMe
MeO
1
3
3a
1a
2
Entry
R
R' PG Time/h Product Yieldb/%
Entry Phosphite
1c Me3SiOP(OMe)2
Solvent
Time/h
Yieldb/%
1
2
3
4
5
6
C6H5
4-MeC6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Boc
Ns
5
5
3a
3b
3c
3d
3e
3f
91
95
86
83
82
99
98
86
78
91
82
98
99
92
91
95
94
95
—
—
93
THF
THF
Et2O
DCM
Toluene
THF
THF
THF
THF
THF
THF
THF
5
5
90
91
2
3
4
5
Me3SiOP(OMe)2
Me3SiOP(OMe)2
Me3SiOP(OMe)2
Me3SiOP(OMe)2
4-MeOC6H4
4-FC6H4
5
5
82
5
5
78
4-ClC6H4
4-CF3C6H4
7c 4-NO2C6H4
5
5
88
4
6d Me3SiOP(OMe)2
Me3SiOP(OMe)2
8d Me3SiOP(OMe)2
HP(O)(OEt)2
5
87
4
3g
3h
3i
7
2
71
8
9
2-MeOC6H4
3-MeOC6H4
5
2
69
5
9
24
24
24
24
NDe
NDe
NDe
NDe
10 2-ClC6H4
11 2,4-Cl2C6H4
12 3-NO2C6H4
13 2-Furyl
14 2-Naphthyl
15 CH3CH2CH2
16 Cyclohexyl
17 C6H5
5
3j
10 HP(O)(OMe)2
11 P(OEt)3
5
3k
3l
4
12 P(OMe)3
5
3m
3n
3o
3p
3q
3r
—
—
3a
a Reaction conditions: N-tosyl benzaldimine (0.3 mmol), phos-
phite (0.45 mmol), solvent (2.0 mL), room temperature. b Isolated
5
2
c
d
yield. Using 2 mol% IPr. The reaction was performed at 0 ℃.
e the product was not detected.
5
5
Interestingly, N-tosyl-1-(2-furyl)methanimine and N-
tosyl-1-(2-naphthyl)methanimine were also very good
candidates for the reaction, and afforded the corre-
sponding products in 99% and 92% yields respectively
(Table 2, Entries 13, 14). On the other hand, N-tosyl
alkylimines such as N-tosyl-1-butanimine and N-tosyl-
1-cyclohexylmethanimine, can also couple with sily-
lated reagent very smoothly (Table 2, Entries 15, 16).
But it is worthwhile noting that the use of freshly pre-
pared imine that derived from open chain aliphatic al-
dehyde is necessary for getting high yield.[10] Aldimines
bearing different N-protecting groups other than tosyl
were also investigated for the reaction. To our delight,
N-tert-butoxycarbonyl and 4-nitrophenylsulfonyl aldi-
mines were also proved to be very good reactants and
gave the desired products in excellent yields (Table 2,
Entries 17, 18). We also attempted hydrophosphonyla-
tion of tosyl-ketimines, but no product was obtained
under catalysts-free conditions (Table 2, Entries 19, 20).
Finally, the reaction was conducted on a one-gram scale
and the α-aminophosphonate 3a could be isolated in
93% yield (1.23 g, Table 2, Entry 21).
18 C6H5
3
19 C6H5
CH3 Ts
C6H5 Ts
24
24
24
20 C6H5
21d C6H5
H
Ts
a
Reaction conditions: aldimine (0.3 mmol), phosphite (0.45
mmol), THF (2.0 mL), room temperature, 5 h. Isolated yield.
Using 5 mL THF. Using 3.6 mmol N-tosyl aldimine and 5.4
b
c
d
mmol phosphite.
Scheme 1 Proposed reaction mechanism
PG
GP
R
OSiMe3
Si
N
N
+
O
P
OMe
MeO
P
R
OMe
MeO
GP
NH
H2O
OMe
R
P
OMe
O
Conclusions
Based on the pioneering work of Lewis base pro-
moted Pudovik type reaction,[7b] we propose the fol-
lowing reaction mechanism (Scheme 1). Firstly, the
Schiff base attacks the silicon atom of trimethylsilyl
phosphite to form a possible hypervalent intermediate,
thus the Si—O bond is activated, which might trigger
the addition of aldimine and after hydrolysis, could give
the desired product.
In summary, we have demonstrated an efficient ap-
proach for hydrophosphonylation of aldimines using
commercially available dimethyl trimethylsilyl phos-
phite. The mild and catalysts-free conditions, simple
procedure, easy scale-up and impressive yield provides
a valuable method for the preparation of various
α-aminophosphonates. Further improvements and ap-
2
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—5

Hydrophosphonylation of Aldimines under Catalysts-Free Conditions
plications are on going in our laboratory.
3H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 142.7,
137.9, 133.3, 128.9, 128.3, 128.2, 127.8 (d, J＝3.0 Hz),
127.0, 54.9 (d, J＝156.7 Hz), 54.6 (d, J＝6.7 Hz), 53.9
(d, J＝6.7 Hz), 21.3.
Dimethyl (4-methylphenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3b)[5] White solid,
110 mg (95%); m.p. 187—189 ℃; 1H NMR (400 MHz,
CDCl3) δ: 7.47 (d, J＝8.2 Hz, 2H), 7.19—6.86 (m, 6H),
6.82 (br s, NH), 4.78 (dd, J＝23.9, 9.8 Hz, 1H), 3.84 (d,
J＝10.8 Hz, 3H), 3.41 (d, J＝10.6 Hz, 3H), 2.29 (s, 3H),
2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.7,
137.8 (d, J＝4.0 Hz), 130.2, 128.97, 128.94, 128.0 (d,
J＝6.0 Hz), 127.0, 54.6 (d, J＝156.0 Hz), 54.4 (d, J＝
7.0 Hz), 53.9 (d, J＝7.0 Hz), 21.3, 21.0.
Experimental
General
Unless otherwise indicated, all reactions were con-
ducted under nitrogen atmosphere in oven-dried glass-
ware with magnetic stirring bar. Column chromatograph
was performed with silica gel (200—300 mesh) and
1
analytical TLC on silica gel 60-F254. H NMR (300 or
400 MHz), 13C NMR (75 or 100 MHz) spectra were
recorded on a 400 MHz or 300 MHz spectrometer in
CDCl3 or DMSO-d6, with tetramethylsilane as an inter-
nal standard. Infrared spectra were reported as wave
－
1
Dimethyl (4-methoxyphenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3c)[5] White solid,
103 mg (86%); m.p. 160—161 ℃; 1H NMR (400 MHz,
CDCl3) δ: 7.47 (d, J＝8.3 Hz, 2H), 7.12 (dd, J＝8.6, 1.8
Hz, 2H), 7.00 (d, J＝8.0 Hz, 2H), 6.72 (br s, NH), 6.63
(d, J＝8.5 Hz, 2H), 4.77 (dd, J＝24.6, 10.1 Hz, 1H),
3.85 (d, J＝10.8 Hz, 3H), 3.73 (s, 3H), 3.42 (d, J＝10.6
Hz, 3H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
159.3 (d, J＝3.0 Hz), 142.8, 137.8 (d, J＝2.0 Hz), 129.3
(d, J＝6.0 Hz), 129.0, 127.0, 125.3, 113.7 (d, J＝2.0
Hz), 55.2, 54.4 (d, J＝7.0 Hz), 54.2 (d, J＝157.0 Hz),
53.9 (d, J＝7.0 Hz), 21.3.
number (cm ). Dimethyl trimethylsilyl phosphite 2 was
distilled before use. Other starting materials were ob-
tained from commercial supplies and used as received.
Anhydrous THF, toluene and Et2O were distilled from
sodium and imines were synthesized according to lit-
eratures. Petroleum ether (PE), where used, had a boil-
ing range of 60—90 ℃.
General procedure for preparation of α-amino-
phosphonates
Aldimine (0.3 mmol) was dissolved in 2 mL of dry
THF, then cooled to 0 ℃ and dimethyl trimethylsilyl
phosphite (0.45 mmol, 86 μL) was added via syringe
under N2. Subsequently, the reaction solution was
stirred at room temperature for 5 h, 1 mL of H2O was
added at this moment and the mixture was continued
stirring for 0.5 h, then the mixture was extracted by
CH2Cl2 (20 mL×3). The combined organic phase was
filtered after drying over anhydrous Na2SO4, and con-
centrated under vacuum. The crude product was purified
through flash column chromatography (silica gel, PE-
EtOAc, 1∶1) to give desired product.
Dimethyl (4-fluorophenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3d)[3i] White solid,
1
96 mg (83%); m.p. 209—210 ℃; H NMR (400 MHz,
CDCl3) δ: 7.48 (s, 1H), 7.46 (s, 1H), 7.23—7.16 (m,
3H), 7.00 (d, J＝8.0 Hz, 2H), 6.78 (t, J＝8.5 Hz, 2H),
4.83 (dd, J＝24.2, 9.8 Hz, 1H), 3.90 (d, J＝10.8 Hz,
3H), 3.46 (d, J＝10.7 Hz, 3H), 2.29 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 162.4 (dd, J＝246.0, 3.0 Hz),
143.1, 137.8 (d, J＝1.0 Hz), 129.9 (dd, J＝8.0, 5.0 Hz),
129.2 (d, J＝4.0 Hz), 129.0, 127.0, 115.2 (dd, J＝22.0,
2.0 Hz), 54.8 (d, J＝8.0 Hz), 54.2 (dd, J＝157.0 Hz),
53.9 (d, J＝7.0 Hz), 21.4.
Procedure for preparation of N-tosyl α-amino-
phosphonates on a one-gram scale (3a)
Dimethyl (4-chlorophenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3e)[5] White solid,
Tosylimine (3.6 mmol) was dissolved in 24 mL of
dry THF, then cooled to 0 ℃ and dimethyl trimethyl-
silyl phosphite (5.4 mmol, 1.03 mL) was added via sy-
ringe under N2. Subsequently the reaction solution was
stirred at room temperature for 24 h, 5 mL of H2O was
added at this moment and the mixture was continued
stirring for 0.5 h, then the mixture was extracted by
CH2Cl2 (60 mL×3). The combined organic phase was
filtered after drying over anhydrous Na2SO4, and con-
centrated under vacuum. The crude product was purified
through flash column chromatography (silica gel, PE-
EtOAc, 1∶1) to give desired product as a white solid,
1.23 g (93%).
Dimethyl (4-methylphenylsulfonamido) (phenyl)
methyl phosphonate (3a)[5] White solid, 101 mg
(91%); m.p. 163—164 ℃; 1H NMR (300 MHz, CDCl3)
δ: 7.53—7.38 (m, 3H), 7.32—7.18 (m, 2H), 7.17—7.02
(m, 3H), 6.94 (d, J＝7.9 Hz, 2H), 4.85 (dd, J＝24.2, 9.9
Hz, 1H), 3.89 (d, J＝10.7 Hz, 3H), 3.39 (d, J＝10.5 Hz,
1
99 mg (82%); m.p. 198—199 ℃; H NMR (400 MHz,
CDCl3) δ: 7.45 (d, J＝8.3 Hz, 2H), 7.20 (br s, NH), 7.17
—7.10 (m, 2H), 7.04 (d, J＝8.3 Hz, 2H), 6.99 (d, J＝
8.0 Hz, 2H), 4.82 (dd, J＝24.4, 9.9 Hz, 1H), 3.91 (d,
J＝10.8 Hz, 3H), 3.47 (d, J＝10.7 Hz, 3H), 2.31 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 143.2, 137.6 (d, J＝2.0
Hz), 134.0 (d, J＝4.0 Hz), 131.9, 129.5 (d, J＝5.0 Hz),
129.0, 128.4 (d, J＝2.0 Hz), 127.0, 54.3 (d, J＝157.0
Hz), 54.8 (d, J＝7.0 Hz), 53.9 (d, J＝7.0 Hz), 21.3.
Dimethyl (4-methylphenylsulfonamido) (4-trifluo-
romethylphenyl) methyl phosphonate (3f) White
solid, 139 mg (99%); m.p. 228—230 ℃; 1H NMR (400
MHz, DMSO-d6) δ: 8.91 (dd, J＝10.6, 2.4 Hz, 1H),
7.41 (s, 4H), 7.40 (s, 1H), 7.01 (d, J＝8.0 Hz, 2H), 4.98
(dd, J＝24.9, 10.6 Hz, 1H), 3.70 (d, J＝10.7 Hz, 3H),
3.49 (d, J＝10.7 Hz, 3H), 3.35 (br s, NH, 1H), 2.19 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ: 142.3, 138.6,
137.7 (d, J＝1.0 Hz), 128.9 (d, J＝5.0 Hz), 128.8, 127.7
Chin. J. Chem. 2012, XX, 1—5
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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3

Cai et al.
NOTE
(dd, J＝31.0, 3.0 Hz), 126.5, 124.4, 124.0 (d, J＝271.0
Hz), 53.9 (d, J＝7.0 Hz), 53.3 (d, J＝155.0 Hz), 53.2 (d,
J＝7.0 Hz), 20.5.
solid, 107 mg (82%); m.p. 185—187 ℃; 1H NMR (400
MHz, CDCl3) δ: 7.51 (d, J＝8.3 Hz, 2H), 7.32 (dd, J＝
8.4, 2.4 Hz, 1H), 7.22 (dd, J＝2.1, 1.1 Hz, 1H), 7.03 (d,
J＝8.4 Hz, 2H), 6.94 (dd, J＝8.5, 2.0 Hz, 1H), 6.77
(br s, 1H), 5.40 (dd, J＝24.5, 9.8 Hz, 1H), 3.93 (d, J＝
10.9 Hz, 3H), 3.51 (d, J＝10.8 Hz, 3H), 2.32 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 143.6, 137.0, 134.5 (d,
J＝3.0 Hz), 134.1 (d, J＝8.0 Hz), 130.5 (d, J＝4.0 Hz),
130.3, 129.2, 128.9 (d, J＝2.0 Hz), 127.2 (d, J＝3.0 Hz),
126.9, 54.9 (d, J＝7.0 Hz), 54.0 (d, J＝7.0 Hz), 50.1 (d,
J＝158.0 Hz), 21.4; IR (KBr) ν: 3152, 2958, 2883, 1588,
1477, 1342, 1247, 1164, 1061, 1033, 903, 871, 807, 720
Dimethyl (4-methylphenylsulfonamido) (4-nitro-
phenyl) methyl phosphonate (3g)[5] White solid, 121
1
mg (98%); m.p. 207—208 ℃; H NMR (400 MHz,
DMSO-d6) δ: 8.98 (d, J＝8.3 Hz, 1H), 7.94 (d, J＝8.7
Hz, 2H), 7.50 (dd, J＝8.8, 2.0 Hz, 2H), 7.44 (d, J＝8.3
Hz, 2H), 7.07 (d, J＝8.3 Hz, 2H), 5.09 (dd, J＝25.4,
10.3 Hz, 1H), 3.69 (d, J＝10.7 Hz, 3H), 3.49 (d, J＝
10.8 Hz, 3H), 2.19 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ: 146.7 (d, J＝3.0 Hz), 142.8, 142.2, 138.0,
129.7 (d, J＝5.0 Hz), 129.2, 126.8, 122.9, 54.2 (d, J＝
7.0 Hz), 53.6 (d, J＝7.0 Hz), 53.4 (d, J＝142.0 Hz),
20.9.
Dimethyl (2-methoxyphenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3h) White solid,
103 mg (86%); m.p. 189—190 ℃; 1H NMR (400 MHz,
CDCl3) δ: 7.48 (s, 1H), 7.46 (s, 1H), 7.25 (dt, J＝9.6,
1.9 Hz, 1H), 7.02—7.06 (m, 1H), 6.95 (d, J＝8.0 Hz,
2H), 6.70 (t, J＝7.5 Hz, 1H), 6.64 (br d, J＝7.8 Hz, 1H),
6.61 (d, J＝8.3 Hz, 1H), 5.30 (dd, J＝24.6, 10.5 Hz,
1H), 3.87 (d, J＝10.7 Hz, 3H), 3.74 (s, 3H), 3.44 (d, J＝
10.6 Hz, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 156.4 (d, J＝6.0 Hz), 142.8, 137.3 (d, J＝2.0 Hz),
129.5 (d, J＝5.0 Hz), 129.2 (d, J＝3.0 Hz), 128.8, 127.0,
121.8, 127.0 (d, J＝2.0 Hz), 110.5 (d, J＝2.0 Hz), 55.6,
54.4 (d, J＝7.0 Hz), 53.8 (d, J＝7.0 Hz), 49.0 (d, J＝
161.0 Hz), 21.3.
－
1
cm .
Dimethyl (4-methylphenylsulfonamido) (3-nitro-
phenyl) methyl phosphonate (3l) White solid, 121
1
mg (98%); m.p. 162—164 ℃; H NMR (400 MHz,
CDCl3) δ: 8.05 (d, J＝1.8 Hz, 1H), 7.92 (d, J＝8.1 Hz,
1H), 7.84 (br s, 1H), 7.54 (d, J＝7.4 Hz, 1H), 7.44 (d,
J＝8.3 Hz, 2H), 7.31 (t, J＝8.0 Hz, 1H), 6.88 (d, J＝8.3
Hz, 2H), 5.00 (dd, J＝25.0, 10.9 Hz, 1H), 4.03 (d, J＝
10.8 Hz, 3H), 3.57 (d, J＝10.8 Hz, 3H), 2.18 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 147.9, 143.2, 137.6,
135.3, 134.3 (d, J＝6.0 Hz), 129.0 (d, J＝2.0 Hz), 128.9,
126.9, 123.1 (d, J＝6.0 Hz), 122.6 (d, J＝3.0 Hz), 55.4
(d, J＝3.0 Hz), 54.4 (d, J＝148.0 Hz), 54.1 (d, J＝7.0
Hz), 21.1; IR (KBr) ν: 3105, 2954, 2883, 1532, 1465,
－
1
1358, 1334, 1243, 1168, 1085, 1057 cm ; HRMS (ESI)
calcd for C16H19N2O7PSNa (MNa+) 437.0548, found
437.0538.
Dimethyl (3-methoxyphenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3i) White solid, 92
mg (78%); m.p. 163—164 ℃; H NMR (400 MHz,
Dimethyl furan-2-yl (4-methylphenylsulfonamido)
methyl phosphonate (3m)[5] White solid, 106 mg
1
1
(99%); m.p. 163—164 ℃; H NMR (400 MHz, CDCl3)
CDCl3) δ: 7.48 (s, 1H), 7.46 (s, 1H), 7.39 (d, J＝6.4 Hz,
1H), 7.00 (t, J＝7.7 Hz, 1H), 6.95 (d, J＝8.0 Hz, 2H),
6.78 (d, J＝7.5 Hz, 1H), 6.73 (s, 1H), 6.64 (d, J＝8.2
Hz, 1H), 4.85 (dd, J＝24.5, 10.2 Hz, 1H), 3.93 (d, J＝
10.8 Hz, 3H), 3.52 (s, 3H), 3.43 (d, J＝10.6 Hz, 3H),
2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.5 (d,
J＝2.0 Hz), 142.8, 137.9, 134.5, 129.2 (d, J＝2.0 Hz),
128.8, 127.1, 120.7 (d, J＝6.0 Hz), 114.2, 113.0 (d, J＝
5.0 Hz), 55.1 (d, J＝157.0 Hz), 54.9, 54.8 (d, J＝7.0
Hz), 53.9 (d, J＝7.0 Hz), 21.3.
δ: 7.57 (d, J＝8.4 Hz, 2H), 7.19—7.07 (m, 3H), 6.32—
6.01 (m, 3H), 4.92 (dd, J＝24.1, 10.1 Hz, 1H), 3.85 (d,
J＝10.8 Hz, 3H), 3.58 (d, J＝10.8 Hz, 3H), 2.35 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 146.5, 143.1, 142.6 (d,
J＝3.0 Hz), 137.3, 129.2, 126.9, 110.6 (d, J＝2.0 Hz),
109.7 (d, J＝7.0 Hz), 54.6 (d, J＝7.0 Hz), 53.9 (d, J＝
7.0 Hz), 48.5 (d, J＝163.0 Hz), 21.4.
Dimethyl (4-methylphenylsulfonamido) (naphth)
methyl phosphonate (3n) White solid, 116 mg (92%);
m.p. 172—173 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.71
(d, J＝8.0 Hz, 1H), 7.60 (s, 1H), 7.54 (d, J＝8.5 Hz,
2H), 7.50 (d, J＝8.0 Hz, 2H), 7.46—7.34 (m, 5H), 7.29
(br s, NH), 6.69 (d, J＝8.0 Hz, 2H), 5.02 (dd, J＝24.2,
10.0 Hz, 1H), 3.96 (d, J＝10.8 Hz, 3H), 3.43 (d, J＝
10.6 Hz, 3H), 1.94 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 142.8, 137.7 (d, J＝2.0 Hz), 132.8 (d, J＝2.0 Hz),
132.7 (dd, J＝6.0, 2.0 Hz), 130.3, 128.7, 128.1 (d, J＝
1.0 Hz), 127.9, 127.8 (d, J＝8 Hz), 127.3, 126.9, 126.2,
126.0, 125.6 (d, J＝4.0 Hz), 55.3 (d, J＝157.0 Hz), 54.8
(d, J＝7.0 Hz), 54.0 (d, J＝7.0 Hz), 20.9; IR (KBr) ν:
3437, 3108, 2950, 1457, 1326, 1235, 1164, 1057, 1029
Dimethyl (2-chlorophenyl) (4-methylphenylsul-
fonamido) methyl phosphonate (3j) White solid, 110
1
mg (91%); m.p. 223—224 ℃; H NMR (400 MHz,
CDCl3) δ: 7.52 (d, J＝8.2 Hz, 2H), 7.47 (d, J＝7.8 Hz,
1H), 7.18 (d, J＝7.9 Hz, 2H), 7.05 (t, J＝7.4 Hz, 3H),
6.96 (d, J＝8.0 Hz, 2H), 5.50 (dd, J＝24.6, 10.1 Hz,
1H), 3.95 (d, J＝10.8 Hz, 3H), 3.44 (d, J＝10.7 Hz, 3H),
2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.9,
137.2, 133.3 (d, J＝7.0 Hz), 131.6, 129.6 (d, J＝4.0 Hz),
129.1 (d, J＝2.0 Hz), 129.0, 126.9, 126.8 (d, J＝3.0 Hz),
54.8 (d, J＝7.0 Hz), 54.0 (d, J＝7.0 Hz), 50.5 (d, J＝
158.0 Hz), 21.3; IR (KBr) ν: 3152, 2954, 1449, 1334,
－
＋
1
cm ; HRMS (ESI) calcd for C20H22NO5PSNa (Mna )
－
1
1239, 1156, 1065, 1033 cm ; HRMS (ESI) calcd for
C16H19ClNO5PSNa (MNa+) 426.0308, found 426.0313.
Dimethyl (2,4-dichlorophenyl) (4-methylphenyl-
sulfonamido) methyl phosphonate (3k)[7d] White
442.0854, found 442.0871.
Dimethyl 1-(4-methylphenylsulfonamido) butyl
phosphonate (3o)[5] White solid, 63 mg (63%); m.p.
1
117—118 ℃; H NMR (400 MHz, CDCl3) δ: 7.76 (d,
4
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—5

Hydrophosphonylation of Aldimines under Catalysts-Free Conditions
J＝8.2 Hz, 2H), 7.29 (d, J＝8.2 Hz, 2H), 5.40 (br s,
NH), 3.66 (d, J＝1.3 Hz, 3H), 3.63 (d, J＝1.1 Hz, 3H),
2.42 (s, 3H), 1.77—1.60 (m, 1H), 1.58—1.32 (m, 2H),
1.31—1.18 (m, 2H), 0.79 (dt, J＝7.3, 1.9 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 143.3, 138.3, 129.4, 127.0,
53.5 (d, J＝7.0 Hz), 52.9 (d, J＝7.0 Hz), 49.7 (d, J＝
157.0 Hz), 32.5 (d, J＝3.0 Hz), 21.5, 18.7 (d, J＝10.0
Hz), 13.6.
References and Notes
[1] For reviews of the biological activity of α-amino phosphonic acids,
see: (a) Kafarski, P.; Lejczak, B. Curr. Med. Chem.: Anti-Cancer
Agents 2001, 1, 301; (b) Grembecka, J.; Kafarski, P. Mini-Rev. Med.
Chem. 2001, 1, 133; For pharmaceutical application of α-amino-
phosphoric acids and their derivatives see: (c) Smith, W. W.; Bartlett,
P. A. J. Am. Chem. Soc. 1998, 120, 4622; (d) Hirschmann, R.; Smith
III, A. B.; Taylor, C. M.; Benkovic, P. A.; Taylor, S. D.; Yager, K. M.;
Sprengeler, P. A.; Venkovic, S. J. Science 1994, 265, 234; (e) Alonso,
E.; Solis, A.; del Pozo, C. Synlett 2000, 698.
[2] For reviews see: (a) Kolodiazhnyi, O. I. Tetrahedron: Asymmetry
1998, 9, 1279; (b) Ma, J.-A. Chem. Soc. Rev. 2006, 35, 630; (c) Me-
rino, P.; López, E. M.; Herrera, R. P. Adv. Synth. Catal. 2008, 350,
1195.
[3] For recent examples of aminophosphonylation reactions see: (a) Joly,
G. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102; (b) Saito,
B.; Katsuki, T. Angew. Chem., Int. Ed. 2005, 44, 4600; (c) Pettersen,
D.; Marcolini, M.; Bernardi, L.; Fini, F.; Herrera, R. P.; Sgarzani, V.;
Ricci, A. J. Org. Chem. 2006, 71, 6269; (d) Saito, B.; Egami, H.;
Katsuki, T. J. Am. Chem. Soc. 2007, 129, 1978; (e) Nakamura, S.;
Nakashima, H.; Yamamura, A.; Shibata, N.; Torua, T. Adv. Synth.
Catal. 2008, 350, 1209; (f) Akiyama, T.; Morita, H.; Bachu, P.; Mori,
K.; Yamanaka, M.; Hirata, T. Tetrahedron 2009, 65, 4950; (g)
Nakamura, S.; Hayashi, M.; Hiramatsu, Y.; Shibata, N.; Funahashi,
Y.; Toru, T. J. Am. Chem. Soc. 2009, 131, 18240; (h) Wang, L.; Cui,
S.-M.; Meng, W.; Zhang, G.-W.; Nie, N.; Ma, J.-A. Chinese Sci. Bull.
2010, 55, 1729; (i) Sudhakar, D.; Siddaiah, V.; Rao, C. V. Synth.
Commun. 2011, 41, 976.
Dimethyl cyclohexyl (4-methylphenylsulfonamido)
methyl phosphonate (3p)[7d] White solid, 108 mg
(95%); m.p. 160—161 ℃; IR (KBr) ν: 3152, 2950,
2922, 2847, 1465, 1322, 1235, 1152, 1105, 1057, 1013
－
1
1
cm ; H NMR (400 MHz, CDCl3) δ: 7.75 (d, J＝8.0
Hz, 2H), 7.39—7.18 (m, 2H), 3.59 (d, J＝10.7 Hz, 3H),
3.53 (d, J＝10.7 Hz, 3H), 2.42 (s, 3H), 1.80—1.55 (m,
6H), 1.22—1.00 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ: 143.2, 138.4, 129.3, 127.1, 54.8 (d, J＝151.0 Hz),
52.8 (d, J＝7.0 Hz), 52.7 (d, J＝6.0 Hz), 39.2 (d, J＝4.0
Hz), 30.4 (d, J＝11.0 Hz), 28.0 (d, J＝3.0 Hz), 26.1 (d,
J＝1.0 Hz), 26.0, 25.7, 21.5; IR (KBr) ν: 3152, 2950,
2922, 2847, 1465, 1322, 1235, 1152, 1105, 1057, 1013
－
1
cm ; HRMS (ESI) calcd for C16H26NO5PSNa (MNa+)
398.1167, found 398.1142.
Dimethyl (tert-butoxycarbonylationamido) (phe-
nyl)methyl phosphonate (3q)[3d] White solid, 88 mg
1
(94%); m.p. 110—113 ℃; H NMR (400 MHz, CDCl3)
[4] (a) Hammerschmidt, F. Liebtgs Ann. Chem. 1991, 469; (b) Bongini,
A.; Camerini, R.; Panunzio, M. Tetrahedron: Asymmetry 1996, 7,
1467.
[5] Das, B.; Balasubramanyam, P.; Krishnaiah, M.; Veeranjaneyulu, B.;
Reddy, G. C. J. Org. Chem. 2009, 74, 4393.
δ: 7.44—7.30 (m, 5H), 5.54 (br s, NH, 1H), 5.15 (dd,
J＝21.4, 9.9 Hz, 1H), 3.77 (d, J＝10.7 Hz, 3H), 3.50 (d,
J＝10.6 Hz, 3H), 1.43 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ: 154.8 (d, J＝9.0 Hz), 135.1, 128.7, 128.1 (d,
J＝3.0 Hz), 127.7 (d, J＝5.0 Hz), 80.5, 53.7 (d, J＝7.0
Hz), 53.6 (d, J＝7.0 Hz), 51.4 (d, J＝153.0 Hz), 28.2.
Dimethyl (4-nitrophenylsulfonamido) (phenyl)
methyl phosphonate (3r)[7d] Yellow solid, 114 mg
(95%); m.p. 240—241 ℃; 1H NMR (400 MHz, CDCl3)
δ: 8.28 (d, J＝6.4 Hz, 1H), 7.96—7.90 (m, 2H), 7.76—
7.69 (m, 2H), 7.23 (br s, NH), 7.21 (d, J＝1.7 Hz, 1H),
7.16—7.02 (m, 3H), 4.94 (dd, J＝24.4, 10.2 Hz, 1H),
4.02 (d, J＝10.9 Hz, 3H), 3.42 (d, J＝10.7 Hz, 3H);13C
NMR (100 MHz, CDCl3) δ: 149.3, 146.8 (d, J＝2.0 Hz),
132.5, 128.5 (d, J＝3.0 Hz), 128.4 (d, J＝2.0 Hz), 128.3
(d, J＝6.0 Hz), 128.2, 123.3, 55.2 (d, J＝158.0 Hz),
54.8 (d, J＝7.0 Hz), 54.3 (d, J＝8.0 Hz).
[6] For recent reviews, see: (a) Enders, D.; Balensiefer, T. Acc. Chem.
Res. 2004, 37, 534; (b) Enders, D.; Niemeier, O.; Henseler, A. Chem.
Rev. 2007, 107, 5606; (c) Moore, J. L.; Rovis, T. Top. Curr. Chem.
2010, 291, 77; For some recent examples, see: (d) Jian, T.-Y.; He, L.;
Tang, C.; Ye, S. Angew. Chem., Int. Ed. 2011, 50, 9104; (e) Sun,
L.-H.; Wang, T.; Ye, S. Chin. J. Chem. 2012, 30, 190; (f) Wu, K. J.;
Li, G. Q.; Li, Y.; Dai, L. X.; You, S. L. Chem. Commun. 2011, 47,
493; (g) Huang, X.-L.; Ye, S. Chinese Sci. Bull. 2010, 55, 1753; (h)
Wang, T.; Ye, S. Sci. Sin. Chim. 2011, 41, 1306.
[7] (a) Du, G.-F.; He, L.; Gu, C.-Z.; Dai, B. Synlett 2010, 2513; (b) Cai,
Z.-H.; Du, G.-F.; He, L.; Gu, C.-Z.; Dai, B. Synthesis 2011, 13, 2073;
(c) Zhang, J.; Du, G.-F.; Xu, Y.-K.; He, L.; Dai, B. Tetrahedron Lett.
2011, 52, 7153; (d) Cai, Z. H.; Du, G. F.; Dai, B.; He, L. Synthesis
2012, 44, 694; (e) Fan, Y.-C.; Du, G.-F.; Sun, W.-F.; Kang, W.; He, L.
Tetrahedron Lett. 2012, 53, 2231.
[8] Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R. Tetrahedron 1999,
55, 14523.
[9] In the report of das, the reaction was completed within 2.5 h under
catalysis of 20 mol% iodine molecular.
[10] If using N-tosyl-1-butanimine that had been stored in icebox for sev-
eral days instead of freshly prepared substrate, only about 63% yield
was obtained.
Acknowledgement
This work was supported by the Team Innovation
Project of Shihezi University (No. 2011ZRKXTD-
0401).
(Pan, B.; Qin, X.)
Chin. J. Chem. 2012, XX, 1—5
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www.cjc.wiley-vch.de
5