Nucleophilic carbene-mediated hydrophosphonylation of aldimines

Article abstract of DOI:10.1055/s-0031-1289690

Aldimines undergo efficient hydrophosphonylation reactions with dimethyl phosphite in the presence of nucleophilic heterocyclic- carbenes (NHCs) as organocatalysts to give the corresponding (α-aminoalkyl)phosphonates in moderate-to-excellent yields. Georg

Full text of DOI:10.1055/s-0031-1289690

694
PAPER
Nucleophilic Carbene-Mediated Hydrophosphonylation of Aldimines
H
ydrophosphon
h
ylation of
A
i
ldimine
-
s
Hua Cai, Guang-Fen Du,* Bin Dai, Lin He*
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan and School of Chemistry and Chemical Engineering,
Shihezi University, Xin Jiang 832000, P. R. of China
Fax +86(993)2057270; E-mail: helin@shzu.edu.cn; E-mail: duguangfen@shzu.edu.cn
Received 26 October 2011; revised 31 December 2011
Initially, we examined the addition of dimethyl phosphite
Abstract: Aldimines undergo efficient hydrophosphonylation re-
(7) to N-tosylbenzaldimine [6a; 4-methyl-N-(phenyl-
actions with dimethyl phosphite in the presence of nucleophilic
methylene)benzenesulfonamide] in the presence of the
heterocyclic carbenes (NHCs) as organocatalysts to give the corre-
stable NHC 1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidene (IPr, 1).18 The reaction proceeded smoothly to
give the desired (a-aminomethyl)phosphonate 8a in 91%
isolated yield (Table 1, entry 1). Inspired by this result, we
screened several different types of NHC generated in situ
from the corresponding precursor and a base. Interesting-
ly, all the NHCs investigated for the reaction promoted the
addition reaction efficiently, giving the desired adduct in
good-to-excellent yield (entries 2–9). A brief survey of
other solvents showed that toluene, dichloromethane, and
diethyl ether are all suitable media for the reaction (entries
10–12). Reducing the catalyst loading to 5 mol% led to a
small decrease in the yield (entry 13). Finally, a control
experiment (entry 14) showed that the hydrophosphonyl-
ation does not occur in the absence of the NHC catalyst.
sponding (a-aminoalkyl)phosphonates in moderate-to-excellent
yields.
Key words: catalysis, carbenes, imines, phosphonylations, phos-
phonates
a-Aminophosphoric acids and their esters have recently
attracted considerable attention because of their intriguing
biological activities.1 These compounds have been suc-
cessfully used in the pharmaceutical field as inhibitors of
enzymes,2 as catalytic antibodies,3 as antibacterial
agents,4 as peptide mimetics,5 and as anti-HIV agents.6
The addition of a phosphite to an imine, known as the
Pudovik reaction,7 is the most versatile and atom-economic
protocol for the preparation of a-aminophosphoric acids
and their derivatives. Owing to the significance of the
Pudovik reaction in the construction of C–P bonds, con-
siderable efforts have been made to develop catalytic
methods for these reactions.8 In the last decade, several or-
ganocatalysts, such as chiral thioureas,9 cyclic phosphoric
acids,10 and cinchona alkaloids,11 have been successfully
used in the asymmetric hydrophosphonylation of imines.
Because of the commercial availability and stability of
NHC 1, we proceeded to evaluate the scope of the reaction
with respect to the aldimine under the optimized reaction
conditions (10 mol% 1, THF, r.t.) and the results are sum-
marized in Table 2.
Tosyl arylimines bearing both electron-donating and elec-
tron-withdrawing groups worked well to give the corre-
sponding hydrophosphonylation adducts in high yields
(entries 1–9). N-Tosyl-1-(2-furyl)methanimine (6j) and
N-tosyl-1-(2-naphthyl)methanimine (6k) were also suit-
able substrates for the reaction (entries 10 and 11). How-
ever, because of the instability of alkylimines under the
reaction conditions, the linear substrate 6l gave only a low
yield of the corresponding alkyl-substituted a-amino-
phosphonate (entry 12). To our delight, however, the
branched alkylimine 6m proved to be very good reactant,
affording the desired product in excellent yield (entry 13).
Aldimines bearing N-protecting groups other than tosyl
were also examined as substrates for the reaction. 4-Nitro-
phenylsulfonyl, N-tert-butoxycarbonyl, and benzyl ald-
imines coupled smoothly with dimethyl phosphite in the
presence of 10 mol% 1 as the catalyst, but gave relatively
low yields of the corresponding products (entries 14–16).
As an important group of organocatalysts for umpolung
reactions, N-heterocyclic carbenes (NHCs) have been
widely used to construct C–C bond in unusual ways by
means of the benzoin reaction, the Stetter reaction, or oth-
er transformations.12 NHCs have also been found to be
highly efficient nucleophilic catalysts for promoting a va-
riety of 1,2-addition reactions, such as the trifluorometh-
ylation of aldehydes,13 cyanation reactions,14 and
Mukaiyama aldol reactions,15 as well as several other re-
actions.16 However, NHCs-promoted C–P bond-forma-
tion reactions have been far less intensively studied. We
recently reported that NHCs can be used to promote hy-
drophosphonylation of aldehydes to give a-hydroxyphos-
phonates in high yields.17 Encouraged by this finding, we
applied NHCs catalysts to the addition reaction of alkyl
phosphites with imines to give the corresponding (a-ami-
noalkyl)phosphonates directly in high yield. Here, we de-
scribe our latest research findings with regard to C–P
bond-forming reactions.
We also attempted an asymmetric hydrophosphonylation
of N-tosylbenzaldimine (6a) in the presence of the chiral
NHC generated from the imidazolium salt 9, but unfortu-
nately the reaction showed no enantioselectivity
(Scheme 1).
SYNTHESIS 2012, 44, 694–698
x
x
.x
x
.2
0
1
1
Advanced online publication: 03.02.2012
DOI: 10.1055/s-0031-1289690; Art ID: H101011SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Hydrophosphonylation of Aldimines
695
Table 2 NHC-Catalyzed a-Aminophosphonylation of Aldimines
On the basis of pioneering work on NHC-catalyzed 1,2-
addition reactions,19,20 two hypothetical mechanisms for
our hydrophosphonylation reaction are outlined in
Scheme 2. In path I, the NHC functions as a carbon-cen-
tered Brønsted base.19 The phosphite anion/imidazolium
ion pair A is formed after deprotonation of dimethyl phos-
phite by the NHC, possibly triggering subsequent addition
of the imine and giving, after proton transfer, the desired
(a-aminoalkyl)phosphonate. In the second mechanism,
the NHC attacks the imine to form adduct C;20 subsequent
proton transfer from the phosphite to C leads to the forma-
tion of intermediate D, which undergoes nucleophilic sub-
R2
R2
H
O
P
NH
N
IPr (10 mol%), THF, r.t.
OMe
OMe
+
OMe
R1
P
H
R1
OMe
O
6
7
8
Entrya
R1
R2
Time
(h)
Product Yield
(%)b
1
2
Ph
Ts
24
24
70
24
24
24
24
24
70
48
24
40
24
48
48
48
8a
8b
8c
8d
8e
8f
91
74
95
77
99
96
91
66
76
74
79
48
93
42
51
40
4-Tol
Ts
3
4-MeOC6H4
4-ClC6H4
4-O2NC6H4
2-ClC6H4
2,4-Cl2C6H3
3-BrC6H4
3-O2NC6H4
2-furyl
Ts
Table 1 NHC-Catalyzed Hydrophosphonylation of N-Tosylbenz-
aldimine
4
Ts
5c
6
Ts
NHTs
NTs
O
P
NHC, solvent, 24 h
OMe
OMe
+
Ts
P
H
H
OMe
O
OMe
7
Ts
8g
8h
8i
6a
7
8a
8
Ts
Cl
Ar
Cl
Ar
9
Ts
N
N
N
N
N
N
Ar
Ar
Ar
Ar
1
3
10
11
12
13
14
15
16
Ts
8j
2a Ar = 1,3,5-Me3C6H2
2b Ar = 2,6-(i-Pr)2C6H3
Ar = 2,6-(i-Pr)2C6H3
Ar = 2,6-(i-Pr)2C6H3
2-naphthyl
Pr
Ts
8k
8l
Ts
N
HO
Cy
Ts
8m
8n
8o
8p
X
R
N
Ph
N
S
N
Cl
Ph
4-Nsd
Boc
Bn
5
4a R = Bn, X = Cl
4b R = Me, X = I
Ph
Entrya
NHC
Solvent
Yield (%)b
Ph
1
2
1
THF
THF
THF
THF
THF
THF
THF
THF
THF
toluene
CH2Cl2
Et2Oc
THF
THF
91
72
82
85
80
51
90
84
83
85
83
76
78
–
a Reaction conditions: aldimine (0.3 mmol), phosphite (0.45 mmol),
THF (2.0 mL), r.t.
2a, Cs2CO3 (10 mol%)
b Isolated yield.
c THF (4 mL), –78 °C to r.t.
3
2b, Cs2CO3 (10 mol%)
d 4-Nitrophenylsulfonyl.
4
3, Cs2CO3 (10 mol%)
5
4a, Cs2CO3 (10 mol%)
NHTs
NTs
6
4b, Cs2CO3 (10 mol%)
O
P
OMe
OMe
9, t-BuOK, THF
P
+
H
H
7
5, Cs2CO3 (10 mol%)
OMe
O
0 °C, 36 h
OMe
8
2b, t-BuOK (10 mol%)
6a
7
8a
88%, 0% ee
9
2b, DBU (10 mol%)
10
11
12
13
14
1
N
N
Cl
1
9
1
Scheme 1 Attempted asymmetric hydrophosphonylation catalyzed
by a chiral NHC
1d
no catalyst
stitution to afford the final product with release of the
NHC.
a Reaction conditions: 6a (1.0 equiv, 0.15 M), 7 (1.5 equiv), NHC (10
mol%), r.t., 24 h.
b Isolated yield.
c Et2O (4 mL).
d 1 (5 mol%).
In summary, we have demonstrated an efficient protocol
for the hydrophosphonylation of aldimines. The environ-
mentally friendly organocatalysts, the mild reaction con-
© Thieme Stuttgart · New York
Synthesis 2012, 44, 694–698

696
Z.-H. Cai et al.
PAPER
Dimethyl[(4-Methoxyphenyl)(tosylamino)methyl]phosphonate
(8c)21
White solid; yield: 103 mg (95%); mp 160–161 °C.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.3 Hz, 2 H), 7.12 (dd,
J = 8.6, 1.8 Hz, 2 H), 7.00 (d, J = 8.0 Hz, 2 H), 6.72 (br s, 1 H, NH),
6.63 (d, J = 8.5 Hz, 2 H), 4.77 (dd, J = 24.6, 10.1 Hz, 1 H), 3.85 (d,
J = 10.8 Hz, 3 H), 3.73 (s, 3 H), 3.42 (d, J = 10.6 Hz, 3 H), 2.29 (s,
3 H).
O
NTs
Ar
Ar
O
H
P(OMe)2
N
R
O
N
N
TsN
R
P(OMe)2
A
(MeO)2P
H
N
C
Ar
Ar
NTs
Ar
I
N
N
II
Ar
Ar
Ar
R
N
TsHN
N
H
PO(OMe)2
N
13C NMR (100 MHz, CDCl3): d = 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.
R
N
O
NHTS
TsN
D
Ar
R
Ar
OMe
B
2
R
P
OMe
O
Dimethyl [(4-Chlorophenyl)(tosylamino)methyl]phosphonate
(8d)21
White solid; yield: 99 mg (77%); mp 198–199 °C.
Scheme 2 Two possible mechanisms for the hydrophosphonylation
reaction
1H NMR (400 MHz, CDCl3): d = 7.45 (d, J = 8.3 Hz, 2 H), 7.20 (br
s, 1 H, NH), 7.17–7.10 (m, 2 H), 7.04 (d, J = 8.3 Hz, 2 H), 6.99 (d,
J = 8.0 Hz, 2 H), 4.82 (dd, J = 24.4, 9.9 Hz, 1 H), 3.91 (d, J = 10.8
Hz, 3 H), 3.47 (d, J = 10.7 Hz, 3 H), 2.31 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 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.
ditions, and the simple procedure provide a valuable
approach for the synthesis of (a-aminoalkyl)phospho-
nates. Further exploration and development of this cata-
lytic strategy are currently underway in our laboratory.
Unless otherwise indicated, all reactions were conducted under N2
in oven- dried glassware with a magnetic stirring bar. Column chro-
matograph was performed with silica gel (200–300 mesh) and ana-
1
Dimethyl [(4-Nitrophenyl)(tosylamino)methyl]phosphonate
(8e)21
White solid; yield: 121 mg (99%); mp 207–208 °C.
lytical TLC was performed on silica gel 60-F254. H NMR (400
MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker
DMX 400 spectrometer in CDCl3 or DMSO-d6, with TMS as an in-
ternal standard. IR spectra were recorded on a Nicolet FT/IR-360
spectrophotometer. Anhyd THF, toluene, and Et2O were distilled
from sodium, and the imines were synthesized according to the lit-
erature procedures. Other starting materials were obtained from
commercial suppliers and used as received. PE, where used, had a
boiling range of 60–90 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.98 (d, J = 8.3 Hz, 1 H), 7.94
(d, J = 8.7 Hz, 2 H), 7.50 (dd, J = 8.8, 2.0 Hz, 2 H), 7.44 (d, J = 8.3
Hz, 2 H), 7.07 (d, J = 8.3 Hz, 2 H), 5.09 (dd, J = 25.4, 10.3 Hz, 1
H), 3.69 (d, J = 10.7 Hz, 3 H), 3.49 (d, J = 10.8 Hz, 3 H), 2.19 (s, 3
H).
13C NMR (100 MHz, DMSO-d6): d = 146.7 (d, J = 4.0 Hz), 142.8,
142.2, 138.0, 129.6 (d, J = 5.0 Hz), 129.2, 126.8, 122.9 (d, J = 1.0
Hz), 54.2 (d, J = 7.0 Hz), 53.6 (d, J = 7.0 Hz), 53.4 (d, J = 154.0
Hz), 20.9.
Dimethyl (a-Aminoalkyl)phosphonates: General Procedure
N-Sulfonylimine (0.3 mmol) was dissolved in anhyd THF (2 mL)
and the soln was cooled to 0 °C. Dimethyl phosphite (0.45 mmol,
42 mL) was added from a syringe under N2 and then IPr (1; 10
mol%) was subsequently added and the soln was stirred at r.t. until
the reaction was complete (TLC). The crude product was then puri-
fied by flash column chromatography [silica gel, PE–EtOAc (1:1)].
Dimethyl [(2-Chlorophenyl)(tosylamino)methyl]phosphonate
(8f)
White solid; yield: 110 mg (96%); mp 223–224 °C.
IR (KBr): 3152, 2954, 1449, 1334, 1239, 1156, 1065, 1033 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.52 (d, J = 8.2 Hz, 2 H), 7.47 (d,
J = 7.8 Hz, 1 H), 7.18 (d, J = 7.9 Hz, 2 H), 7.05 (t, J = 7.4 Hz, 1 H),
6.96 (d, J = 8.0 Hz, 3 H), 5.50 (dd, J = 24.6, 10.1 Hz, 1 H), 3.95 (d,
J = 10.8 Hz, 3 H), 3.44 (d, J = 10.7 Hz, 3 H), 2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 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.
Dimethyl [(Tosylamino)(phenyl)methyl]phosphonate (8a)21
White solid; yield: 101 mg (91%); mp 163–164 °C.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.3 Hz, 2 H), 7.26–
7.19 (m, 3 H), 7.16–7.05 (m, 3 H), 6.95 (d, J = 8.0 Hz, 2 H), 4.85
(dd, J = 24.2, 9.9 Hz, 1 H), 3.88 (d, J = 10.8 Hz, 3 H), 3.40 (d,
J = 10.6 Hz, 3 H), 2.26 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 142.7, 137.9, 133.3, 128.9, 128.2,
128.2, 127.8 (d, J = 2.0 Hz), 127.0, 54.9 (d, J = 157.0 Hz), 54.6 (d,
J = 8.0 Hz), 53.9 (d, J = 7.0 Hz), 21.3.
HRMS (ESI): m/z calcd for C16H19ClNNaO5PS [M + Na]+:
426.0308; found 426.0313.
Dimethyl [(4-Tolyl)(tosylamino)methyl]phosphonate (8b)21
White solid; yield: 110 mg (74%); mp 187–189 °C.
Dimethyl [(2,4-Dichlorophenyl)(tosylamino)methyl]phospho-
nate (8g)
White solid; yield: 120 mg (91%); mp 185–187 °C.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.2 Hz, 2 H), 7.19–
6.86 (m, 6 H), 6.82 (br s, 1 H, NH), 4.78 (dd, J = 23.9, 9.8 Hz, 1 H),
3.84 (d, J = 10.8 Hz, 3 H), 3.41 (d, J = 10.6 Hz, 3 H), 2.29 (s, 3 H),
2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 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.
IR (KBr): 3152, 2958, 2883, 1588, 1477, 1342, 1247, 1164, 1061,
1033, 903, 871, 807, 720 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.51 (d, J = 8.3 Hz, 2 H), 7.32 (dd,
J = 8.4, 2.4 Hz, 1 H), 7.22 (dd, J = 2.1, 1.1 Hz, 1 H), 7.03 (d, J = 8.4
Hz, 2 H), 6.94 (dd, J = 8.5, 2.0 Hz, 1 H), 6.77 (br s, 1 H), 5.40 (dd,
J = 24.5, 9.8 Hz, 1 H), 3.93 (d, J = 10.9 Hz, 3 H), 3.51 (d, J = 10.8
Hz, 3 H), 2.32 (s, 3 H).
Synthesis 2012, 44, 694–698
© Thieme Stuttgart · New York

PAPER
Hydrophosphonylation of Aldimines
697
13C NMR (100 MHz, CDCl3): d = 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.
HRMS (ESI): m/z [M + Na]+ calcd for C16H18Cl2NNaO5PS:
459.9918; found 459.9917.
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
HRMS (ESI): m/z [M + Na]+ calcd for C20H22NNaO5PS: 442.0854;
found 442.0871.
Dimethyl [1-(Tosylamino)butyl]phosphonate (8l)21
White solid; yield: 63 mg (48%); mp 117–118 °C.
Dimethyl [(3-Bromophenyl)(tosylamino)methyl]phosphonate
(8h)
White solid; yield: 89 mg (66%); mp 129–131 °C.
1H NMR (400 MHz, CDCl3): d = 7.76 (d, J = 8.2 Hz, 2 H), 7.29 (d,
J = 8.2 Hz, 2 H), 5.40 (br s, 1 H, NH), 3.66 (d, J = 1.3 Hz, 3 H), 3.63
(d, J = 1.1 Hz, 3 H), 2.42 (s, 3 H), 1.77–1.60 (m, 1 H), 1.58–1.32
(m, 2 H), 1.31–1.18 (m, 2 H), 0.79 (dt, J = 7.3, 1.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 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.
IR (KBr): 3108, 2950, 2879, 1600, 1465, 1338, 1239, 1168, 1025,
918, 804, 724.
1H NMR (400 MHz, CDCl3): d = 7.46 (d, J = 8.3 Hz, 2 H), 7.41 (d,
J = 6.1 Hz, 1 H, NH), 7.27–7.16 (m, 3 H), 7.01–6.95 (m, 3 H), 4.81
(dd, J = 24.6, 10.1 Hz, 1 H), 3.96 (d, J = 10.8 Hz, 3 H), 3.48 (d,
J = 10.7 Hz, 3 H), 2.28 (s, 3 H).
Dimethyl [(Cyclohexyl)(tosylamino)methyl]phosphonate (8m)
White solid; yield: 108 mg (93%); mp 160–161 °C.
13C NMR (100 MHz, CDCl3): d = 143.1, 137.5 (d, J = 2.0 Hz),
135.3, 131.1 (d, J = 6.0 Hz), 130.8 (d, J = 2.0 Hz), 129.8 (d, J = 2.0
Hz), 129.0, 126.9, 122.5 (d, J = 2.0 Hz), 55.0 (d, J = 7.0 Hz), 54.6
(d, J = 157.0 Hz), 54.1 (d, J = 7.0 Hz), 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C16H19BrNNaO5PS:
471.9782; found 471.9767.
IR (KBr): 3152, 2950, 2922, 2847, 1465, 1322, 1235, 1152, 1105,
1057, 1013 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.75 (d, J = 8.0 Hz, 2 H), 7.39–
7.18 (m, 2 H), 5.18 (dd, J = 9.5, 4.1 Hz, 1 H), 3.59 (d, J = 10.7 Hz,
3 H), 3.53 (d, J = 10.7 Hz, 3 H), 2.42 (s, 3 H), 1.80–1.55 (m, 6 H),
1.22–1.00 (m, 5 H).
Dimethyl [(3-Nitrophenyl)(tosylamino)methyl]phosphonate
(8i)
White solid; yield: 121 mg (76%); mp 162–164 °C.
13C NMR (100 MHz, CDCl3): d = 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.
HRMS (ESI): m/z [M + Na]+ calcd for C16H26NNaO5PS: 398.1167;
found 398.1142.
IR (KBr): 3105, 2954, 2883, 1532, 1465, 1358, 1334, 1243, 1168,
1085, 1057 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.05 (d, J = 1.8 Hz, 1 H), 7.92 (d,
J = 8.1 Hz, 1 H), 7.84 (br s, 1 H), 7.54 (d, J = 7.4 Hz, 1 H), 7.44 (d,
J = 8.3 Hz, 2 H), 7.31 (t, J = 7.9 Hz, 1 H), 6.88 (d, J = 8.3 Hz, 2 H),
5.00 (dd, J = 25.0, 10.9 Hz, 1 H), 4.03 (d, J = 10.8 Hz, 3 H), 3.57
(d, J = 10.8 Hz, 3 H), 2.18 (s, 3 H).
Dimethyl [{[(4-Nitrophenyl)sulfonyl]amino}(phenyl)meth-
yl]phosphonate (8n)
Yellow solid; yield: 50 mg (42%).
13C NMR (100 MHz, CDCl3): d = 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.
1H NMR (400 MHz, CDCl3): d = 8.28 (d, J = 6.4 Hz, 1 H), 7.96–
7.90 (m, 2 H), 7.76–7.69 (m, 2 H), 7.23 (br s, 1 H, NH), 7.21 (d,
J = 1.7 Hz, 1 H), 7.16–7.02 (m, 3 H), 4.94 (dd, J = 24.4, 10.2 Hz, 1
H), 4.02 (d, J = 10.9 Hz, 3 H), 3.42 (d, J = 10.7 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C16H19N2NaO7PS: 437.0548;
found 437.0538.
13C NMR (100 MHz, CDCl3): d = 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).
Dimethyl [(2-Furyl)(tosylamino)methyl]phosphonate (8j)21
White solid; yield: 106 mg (74%); mp 163–164 °C.
Dimethyl {[(tert-Butoxycarbonyl)amino](phenyl)methyl}phos-
phonate (8o)8f
White solid; yield: 48 mg (51%); mp 110.5–113.0 °C.
1H NMR (400 MHz, CDCl3): d = 7.44–7.30 (m, 5 H), 5.54 (br s, 1
H, NH), 5.15 (dd, J = 21.4, 9.9 Hz, 1 H), 3.77 (d, J = 10.7 Hz, 3 H),
3.50 (d, J = 10.6 Hz, 3 H), 1.43 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 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.
1H NMR (400 MHz, CDCl3): d = 7.57 (d, J = 8.4 Hz, 2 H), 7.19–
7.07 (m, 3 H), 6.32–6.01 (m, 3 H), 4.92 (dd, J = 24.1, 10.1 Hz, 1 H),
3.85 (d, J = 10.8 Hz, 3 H), 3.58 (d, J = 10.8 Hz, 3 H), 2.35 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 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 [(2-Naphthyl)(tosylamino)methyl]phosphonate (8k)
White solid; yield: 116 mg (79%); mp 172–173 °C.
Dimethyl [(Benzylamino)(phenyl)methyl]phosphonate (8p)8f
Oil; yield: 36 mg (40%).
IR (KBr): 3437, 3108, 2950, 1457, 1326, 1235, 1164, 1057, 1029
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46–7.26 (m, 9 H), 7.25 (s, 1 H),
4.05 (d, J = 20.2 Hz, 1 H), 3.81 (d, J = 13.2 Hz, 1 H), 3.73 (d,
J = 10.6 Hz, 3 H), 3.56 (s, 1 H), 3.54 (d, J = 10.5 Hz, 3 H), 2.67 (s,
1 H).
13C NMR (100 MHz, CDCl3): d = 139.1, 135.3 (d, J = 4.0 Hz),
128.63, 128.61, 128.5, 128.4, 128.3, 128.0 (d, J = 3.0 Hz), 127.2,
59.2 (d, J = 154.0 Hz), 53.8 (d, J = 7.0 Hz), 53.4 (d, J = 6.0 Hz),
51.1 (d, J = 17.0 Hz).
1H NMR (400 MHz, CDCl3): d = 7.71 (d, J = 8.0 Hz, 1 H), 7.60 (s,
1 H), 7.54 (d, J = 8.5 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 1 H), 7.46–7.34
(m, 5 H), 7.29 (br s, 1 H, NH), 6.69 (d, J = 8.0 Hz, 2 H), 5.02 (dd,
J = 24.2, 10.0 Hz, 1 H), 3.96 (d, J = 10.8 Hz, 3 H), 3.43 (d, J = 10.6
Hz, 3 H), 1.94 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 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,
© Thieme Stuttgart · New York
Synthesis 2012, 44, 694–698

698
Z.-H. Cai et al.
PAPER
Attempted Asymmetric Hydrophosphonylation of N-Tosyl-
benzaldimine (6a)
aminophosphonylation reactions see: (c) Gröger, H.; Saida,
Y.; Arai, S.; Martens, J.; Sasai, Hiroaki.; Shibasaki, M.
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Sasai, H.; Yamaguchi, K.; Martens, J.; Shibasaki, M. J. Am.
Chem. Soc. 1998, 120, 3089. (e) Saito, B.; Katsuki, T.
Angew. Chem. Int. Ed. 2005, 44, 4600. (f) Saito, B.; Egami,
H.; Katsuki, T. J. Am. Chem. Soc. 2007, 129, 1978.
(g) Palacios, F.; Olszewski, T. K.; Vicario, J. Org. Biomol.
Chem. 2010, 8, 4255.
The chiral NHC precursor 9 (12% mol) and t-BuOK (10% mol)
were dissolved in THF (2 mL) and the soln was stirred for 30 min
at r.t. then cooled to 0 °C. N-Tosylbenzaldimine (6a; 0.3 mmol) and
dimethyl phosphite (7; 0.45 mmol, 42 mL) were added and the mix-
ture was kept at r.t. until the reaction was complete (TLC). The
crude product was then purified by flash column chromatography
[silica gel, PE–EtOAc (1:1)] to give 8a as a white solid; yield: 97
mg (88%); mp 163–164 °C; 0% ee [HPCL: Daicel Chiralpak OJ-H,
0.50 mL/min; i-PrOH–hexane (10:90); retention times: 22.5 and
49.2 min].
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.3 Hz, 2 H), 7.26–
7.19 (m, 3 H), 7.16–7.05 (m, 3 H), 6.95 (d, J = 8.0 Hz, 2 H), 4.85
(dd, J = 24.2, 9.9 Hz, 1 H), 3.88 (d, J = 10.8 Hz, 3 H), 3.40 (d,
J = 10.6 Hz, 3 H), 2.26 (s, 3 H).
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13C NMR (100 MHz, CDCl3): d = 142.7, 137.9, 133.3, 128.9, 128.2,
128.2, 127.8 (d, J = 2.0 Hz), 127.0, 54.9 (d, J = 157.0 Hz), 54.6 (d,
J = 8.0 Hz), 53.9 (d, J = 7.0 Hz), 21.3.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
This work was supported by Shihezi University.
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Synthesis 2012, 44, 694–698
© Thieme Stuttgart · New York