N-heterocyclic carbene catalyzed hydrophosphonylation of aldehydes

Article abstract of DOI:10.1055/s-0030-1260045

N-Heterocyclic carbene catalyzed Pudovik-type reaction of dimethyl trimethylsilyl phosphite and aldehydes for the construction of carbon-phosphorus bonds have been developed, providing -hydroxyphosphonates in moderate to excellent yield. Georg Thieme Verl

Full text of DOI:10.1055/s-0030-1260045

PAPER
2073
N-Heterocyclic Carbene Catalyzed Hydrophosphonylation of Aldehydes
N
-Heterocyclic
h
C
arbene
C
at
i
a
lyzed
-
Hydroph
H
osphonylation of
u
A
ldehydes a Cai, Guang-Fen Du, Lin He,* Cheng-Zhi Gu, Bin Dai
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan and School of Chemistry and Chemical Engineering,
Shi He Zi University, Xin Jiang 832000, P. R. of China
Fax +86(993)2057270; E-mail: helin@shzu.edu.cn
Received 21 February 2011; revised 5 April 2011
for us to explore the carbon–phosphorus bond-formation
Abstract: N-Heterocyclic carbene catalyzed Pudovik-type reaction
reactions promoted by NHCs.
of dimethyl trimethylsilyl phosphite and aldehydes for the construc-
tion of carbon–phosphorus bonds have been developed, providing
a-hydroxyphosphonates in moderate to excellent yield.
a-Hydroxyphosphonates and phosphonic acids have been
used widely in pharmaceutical chemistry14 due to their
Key words: N-heterocyclic carbene, Pudovik-type reaction, a-hy- important biological activities as antibiotics,15 antivi-
rals,16 antitumour agents,17 herbicides,18 and insecti-
droxyphosphonates, aldehydes, C–P bond
cides.19 Under base or transition-metal catalysis, dialkyl
phosphonate coupled with carbonyl compounds to con-
struct a C–P bond; this reaction, which is also known as a
Pudovik-type reaction, is the most general and straightfor-
ward method for the synthesis of this type of important
compound.20 However, in contrast to the study of tradi-
tional Pudovik reactions using dialkyl phosphonate, the
catalytic synthesis of this type of compound from com-
mercially available dialkyl trimethylsilyl phosphites were
far less explored.21 Herein, we wish to report our prelimi-
nary results on NHC-catalyzed Pudovik-type reaction of
dimethyl trimethylsilyl phosphites with aldehydes, pro-
viding a-hydroxyphosphonates in high yields.
N-Heterocyclic carbenes (NHCs) have attracted consider-
able attention since the first stable carbene was success-
fully isolated in 1991 by Arduengo and co-workers.1 They
are remarkable catalysts for polarity reversal or Umpol-
ung reactivity of carbonyl-containing compounds, which
generally includes the reaction of acyl anions (Breslow in-
termediate) during the formation of carbon–carbon bonds.
Typical reactions, such as the benzoin reaction,2 Stetter-
type reaction,3 and homoenolate transformations based on
the Umpolung or extended Umpolung strategy promoted
by NHCs have been investigated extensively.4 NHCs have
also served as versatile nucleophilic catalysts for transes-
terification,5 polymerization,6 cycloaddition of ketenes,7
and other reactions.8 Recently, NHCs were found to be
highly efficient catalysts for activation of silylated re-
agents, and a series of important transformations such as
trifluoromethylation of aldehydes,9 cyanation reactions,10
Mukaiyama aldol reaction,11 and other similar reactions12
were developed. Very recently, we found that NHCs can
catalyze the vinylogous Mukaiyama aldol (VMA) reac-
tion of 2-(trimethylsilyloxy)furan with aldehydes to form
carbon–carbon bonds efficiently, based on the activation
of a Si–O bond (Equation 1).13
In initial experiments, 1,3-bis(2,6-diisopropylphenyl)imi-
dazol-2-ylidene (IPr, a stable NHC)22 was examined as a
catalyst for the coupling reaction of dimethyl trimethylsi-
lyl phosphite and p-chlorobenzaldehyde in tetrahydrofu-
ran (THF; Table 1, entry 1). To our delight, the reaction
proceeded very smoothly to give the desired a-hydroxy-
phosphonate (8a) in 82% isolated yield after six hours at
room temperature. Encouraged by this result, several dif-
ferent types of NHCs, including 2b, which is the precursor
of IPr, were surveyed separately. Using cesium carbonate
as base, NHCs generated from imidazolium, thiazolium,
and triazolium salts were also found to catalyze the reac-
tion, but with low efficiency, affording the desired prod-
uct in moderate yield (Table 1, entries 2–7). Surprisingly,
when the strong base potassium tert-butoxide (t-BuOK)
or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was used
In contrast to the extensive investigation of carbon–
carbon bond-formation reactions, carbon–phosphorus
bond constructions catalyzed by NHCs have been far less
well examined. It is therefore considered to be of interest
N
N
Mes
Mes
1)
••
(1 mol%)
R
R
+
+
O
O
RCHO
O
O
OSiMe3
O
2) HCl
OH
anti (major)
OH
syn (minor)
yield up to 98%
dr up to 82:18
Equation 1 NHC-catalyzed VMA reactions
SYNTHESIS 2011, No. 13, pp 2073–2078
x
x.
x
x
.
2
0
1
1
Advanced online publication: 13.05.2011
DOI: 10.1055/s-0030-1260045; Art ID: F21411SS
© Georg Thieme Verlag Stuttgart · New York

2074
Z.-H. Cai et al.
PAPER
instead of cesium carbonate, a clear increase in the reac- Under the optimized reaction conditions (THF, r.t., 5
tion yield was observed (Table 1, entries 8–11). The reac- mol% IPr), a variety of aldehydes were tested to investi-
tion also worked well in other media, such as toluene and gate the generality of the reaction; the results are summa-
dichloromethane to give 8a in moderate yield (Table 1, rized in Table 2. Both aromatic and aliphatic aldehydes
entries 12 and 13). However, the experimental results in- were suitable substrates for the coupling reaction. For ar-
dicated that diethyl ether was not a suitable solvent omatic aldehydes, substitution of an electron-withdraw-
(Table 1, entry 14). Lowering the catalyst loading to 1 ing group on the aromatic ring resulted in higher yield
mol% led to a clear decrease in the yield (Table 1, entry than those bearing an electron-donating group (Table 2,
15). Finally, a control experiment confirmed that the reac- entries 1–4 vs. 10–11). Additionally, the unactivated alde-
tion did not occur without catalyst (Table 1, entry 16).
hydes required more catalyst loading and longer reaction
time to reach completion (Table 2, entries 9–12). Howev-
er, the position of the substituents had no obvious impacts
on the reaction (Table 2, entries 5–8). The experimental
results indicated that naphthaldehyde is very good candi-
date for the reaction, giving the final product in excellent
yield (Table 2, entry 13). It should be noted that this pro-
tocol is also suitable for heteroaromatic aldehydes such as
furan aldehyde, affording 8n in moderate yield (Table 2,
entry 14). On the other hand, with less than 10 mol% IPr
loading, aliphatic aldehydes such as 3-phenylpropional-
dehyde and butyraldehyde can also react with trimethyls-
ilyl phosphite to provide a-hydroxyphosphonates in
moderate to good yields (Table 2, entries 15 and 16).
Table 1 NHC-Catalyzed Hydrophosphonylation of Dimethyl Tri-
methylsilyl Phosphite with 4-Chlorobenzaldehydea
OH
(MeO)2POSiMe3
O
6
1) NHC, solvent, 6 h
2) HCl, 0.5 h
P
+
OMe
MeO
CHO
Cl
8a
Cl
7a
Cl
Cl
N
N
N
N
N
N
Ar
Ar
Ar
Ar
Ar
Ar
••
1
2a: Ar = 1,3,5-Me3C6H2
2b: Ar = 2,6-(i-Pr)2C6H3
3
Ar = 2,6-(i-Pr)2C6H3
Ar = 2,6-(i-Pr)2C6H3
Based on the pioneering work on NHC-catalyzed
Mukaiyama aldol reactions, we propose the following re-
action mechanism (Scheme 1). Firstly, the NHC attacks
the silylated reagent to generate hypervalent silicate inter-
mediate (I),23 thus activating the Si–O bond. This activa-
tion might trigger subsequent addition of the aldehyde,
which, after acidic workup, could give the desired a-hy-
droxyphosphonate.
N
HO
X
R
N
Ph
N
S
N
Cl
4a: R = Bn, X = Cl
4b: R = Me, X = I
5
Entry
1
NHC
Base (mol%)
Solvent
THF
Yield (%)
82
1
2
2a
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
t-BuOK (5)
t-BuOK (5)
t-BuOK (5)
DBU (5)
THF
64
N
N
Ar
P
Ar
OSiMe3
MeO
3
2b
THF
69
MeO
O
SiMe3
P
OMe
(I)
4
3
THF
61
OMe
RCHO
5
4a
THF
40
6
4b
THF
43
O
P
MeO
R
7
5
THF
43
N
N
OMe
Ar
Ar
••
8
2a
THF
80
O
SiMe3
N
9
2b
THF
83
O
P
OH
O
P
OTMS
R
Ar
Ar
10
11
12
13
14
15b
16
3
THF
67
N
MeO
MeO
HCl
MeO
MeO
R
2b
THF
81
Scheme 1 Proposed catalytic mechanism
1
Toluene
CH2Cl2
Et2O
THF
43
1
40
In conclusion, we demonstrated that an NHC-catalyzed
Pudovik-type reaction of dimethyl trimethylsilyl phos-
phite and aldehydes can be used for the construction of
carbon–phosphorus bonds. The mild reaction conditions
and simple procedure provides a valuable method for the
synthesis of a-hydroxyphosphonate. Further studies to ex-
plore the generality of this methodology are under way in
our lab.
1
26
1
54
no catalyst
THF
–
a Reaction conditions: 6 (1.3 equiv), 7a (0.25 mol·L–1, 1.0 equiv),
NHC (5 mol%).
b Using 1 mol% IPr.
Synthesis 2011, No. 13, 2073–2078 © Thieme Stuttgart · New York

PAPER
N-Heterocyclic Carbene Catalyzed Hydrophosphonylation of Aldehydes
2075
Table 2 NHC-Catalyzed Hydrophosphonylation of Dimethyl Tri-
Table 2 NHC-Catalyzed Hydrophosphonylation of Dimethyl Tri-
methylsilyl Phosphite with Aldehydesa
methylsilyl Phosphite with Aldehydesa (continued)
OH
O
OH
O
1) IPr (5 mol%), THF
1) IPr (5 mol%), THF
R
P
R
P
(MeO)2POSiMe3
RCHO
+
(MeO)2POSiMe3
RCHO
+
OMe
OMe
MeO
2) HCl, 0.5 h
MeO
2) HCl, 0.5 h
6
7
8
6
7
8
Entry Aldehyde
Time (h) Product
Yield (%)
82
Entry Aldehyde
Time (h) Product
Yield (%)
31
CHO
14b
48
8n
1
6
8
8a
8b
8c
8d
8e
8f
CHO
O
Cl
7a
7n
CHO
CHO
15b
48
24
8o
8p
77
31
2
81
F3C
7b
7o
CHO
16b
CHO
3
24
24
8
81
F
7p
7c
a Reaction conditions: 6 (1.3 equiv), 7 (0.25 mol·L–1, 1.0 equiv), IPr
CHO
(5 mol%).
4
73 (80)c
b Using 10 mol% IPr.
c From –78 °C to r.t.
O2N
7d
CHO
5
77
Unless otherwise indicated, all reactions were conducted under a ni-
trogen atmosphere in oven-dried glassware with a magnetic stirring
bar. Column chromatography was performed with silica gel (200–
300 mesh) and analytical TLC on silica gel 60-F254. 1H (300 MHz)
and 13C (75 MHz) NMR spectra were recorded with a Bruker-DMX
300 spectrometer in CDCl3, with tetramethylsilane as an internal
standard; shifts (d) are reported in ppm. Infrared spectra were re-
corded with a Nicolet FT/IR-360 spectrophotometer and are report-
ed in wavenumbers (cm–1). Dimethyl trimethylsilyl phosphite 6 was
distilled before use. Other starting materials were obtained from
commercial supplies and were used as received. Anhydrous THF,
toluene, and Et2O were distilled from sodium and benzophenone.
Imidazolium22 and triazolium24 salts were synthesized according to
literature procedures. Petroleum ether (PE), where used, had a boil-
ing range of 60–90 °C.
Cl
7e
CHO
Cl
6
8
87
Cl
7f
Br
CHO
7
24
24
48
48
36
36
48
8g
8h
8i
74
7g
O2N
CHO
8
90
7h
IPr-Catalyzed Hydrophosphonylation of Dimethyl Trimethyl-
silyl Phosphite and Aldehydes; General Procedure
CHO
9b
78
Aldehyde 7 (0.5 mmol) was dissolved in anhydrous THF (2 mL)
and cooled to 0 °C. Freshly distilled dimethyl trimethylsilyl phos-
phite 6 (0.65 mmol, 124 mL) was added by syringe under N2, then
IPr (5 mol% or 10 mol%) was subsequently added and the mixture
was stirred at r.t. until completion of the reaction (as indicated by
TLC). After completion of the reaction, aq 10% HCl (1 mL) was
added to the mixture and stirring was continued for 30 min. The
mixture was extracted with CH2Cl2 (3 × 20 mL) and the combined
organic phase was dried with anhydrous Na2SO4 and the solvent
was evaporated under vacuum. The residue was subjected to col-
umn chromatography (silica gel; PE–EtOAc, 1:2) to give the pure
product.
7i
CHO
10b
8j
76
MeO
7j
CHO
11b
8k
8l
76
7k
MeO
CHO
12b
72
Dimethyl 1-Hydroxy-1-(4-chlorophenyl)methylphosphonate
(8a)20m
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8a.
7l
CHO
13b
8m
93
Yield: 102 mg (82%); white solid.
7m
Synthesis 2011, No. 13, 2073–2078 © Thieme Stuttgart · New York

2076
Z.-H. Cai et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 7.40–7.15 (m, 4 H), 5.17 (s, 1 H,
Dimethyl 1-Hydroxy-1-(2,4-dichlorophenyl)methylphospho-
2
3
OH), 4.94 (d, JP–H = 12.0 Hz, 1 H), 3.60 (d, JP–H = 9.0 Hz, 3 H),
nate (8f)25a
3.59 (d, 3JP–H = 9.0 Hz, 3 H).
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8f.
13C NMR (75 MHz, CDCl3): d = 135.3 (d, JC–P = 1.5 Hz), 133.9 (d,
1
JC–P = 3.8 Hz), 128.5, 128.4 (d, JC–P = 3.0 Hz), 69.8 (d, JC–P
=
Yield: 124 mg (87%); white solid.
160.5 Hz), 54.1 (d, 2JC–P = 7.5 Hz), 53.7 (2JC–P = 7.5 Hz).
1H NMR (300 MHz, CDCl3): d = 7.62 (dd, J = 9.0, 3.0 Hz, 1 H),
7.38–7.13 (m, 2 H), 5.69 (t, J = 6.0 Hz, 1 H, OH), 5.46 (dd, 2JP–H
=
=
Dimethyl 1-Hydroxy-1-(4-trifluoromethylphenyl)methylphos-
phonate (8b)
Prepared according to the general procedure and purified by chro-
3
3
12.0, 6.0 Hz, 1 H), 3.67 (d, JP–H = 9.0 Hz, 3 H), 3.64 (d, JP–H
12.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 134.4 (d, JC–P = 3.8 Hz), 133.7,
133.3 (d, JC–P = 7.5 Hz), 130.3 (d, JC–P = 3.8 Hz), 128.9 (d, JC–P
matography on silica gel (PE–EtOAc, 1:2) to afford 8b.
=
Yield: 114 mg (81%); white solid; mp 68.0–69.6 °C.
1
2.3 Hz), 127.4 (d, JC–P = 3.0 Hz), 66.4 (d, JC–P = 162.8 Hz), 54.2
IR (KBr): 3247, 2958, 1616, 1417, 1210, 1162, 1121, 1061, 1021,
884, 841, 558 cm–1.
(d, 2JC–P = 7.5 Hz), 53.7 (d, 2JC–P = 7.5 Hz).
Dimethyl 1-Hydroxy-1-(3-bromophenyl)methylphosphonate
(8g)25b
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8g.
1H NMR (300 MHz, CDCl3): d = 7.60–7.42 (m, 4 H), 5.60 (s, 1 H,
2
3
OH), 5.05 (d, JP–H = 12.0 Hz, 1 H), 3.63 (d, JP–H = 3.0 Hz, 3 H),
3.60 (d, 3JP–H = 3.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 140.9, 130.3 (dq, J = 32.3, 3.0 Hz),
Yield: 109 mg (74%); white solid.
1
127.3 (d, JC–P = 5.3 Hz), 125.4–124.8 (m), 124.1 (d, JC–F
=
270.0 Hz), 69.9 (d, 1JC–P = 160.5 Hz), 54.1 (d, 2JC–P = 7.5 Hz), 53.6
(d, 2JC–P = 7.5 Hz).
1H NMR (300 MHz, CDCl3): d = 7.58 (s, 1 H), 7.40–7.25 (m, 2 H),
7.13 (t, J = 6.0 Hz, 1 H), 5.41 (s, 1 H, OH), 4.96 (d, 2JP–H = 12.0 Hz,
1 H), 3.64 (s, 3 H), 3.60 (s, 3 H).
HRMS (ESI): m/z calcd for C10H12F3NaO4P: 307.0323; found:
307.0316.
13C NMR (75 MHz, CDCl3): d = 139.2 (d, JC–P = 1.5 Hz), 131.1 (d,
JC–P = 3.0 Hz), 130.0 (d, JC–P = 6.0 Hz), 129.8 (d, JC–P = 2.3 Hz),
1
Dimethyl 1-Hydroxy-1-(4-fluorophenyl)methylphosphonate
(8c)20m
125.7 (d, JC–P = 5.3 Hz), 122.4 (d, JC–P = 3.0 Hz), 70.0 (d, JC–P
=
159.8 Hz), 54.2 (d, 2JC–P = 7.5 Hz), 53.7 (d, 2JC–P = 7.5 Hz).
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8c.
Dimethyl 1-Hydroxy-1-(3-nitrophenyl)methylphosphonate
(8h)25c
Prepared according to the general procedure and purified by chro-
Yield: 94 mg (81%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.49–7.36 (m, 2 H), 7.08–6.88 (m,
matography on silica gel (PE–EtOAc, 1:2) to afford 8h.
2
2 H), 4.97 (d, JP–H = 12.0 Hz, 1 H), 4.21 (s, 1 H, OH), 3.65 (d,
Yield: 118 mg (90%); yellow solid.
3JP–H = 9.0 Hz, 3 H), 3.62 (d, 3JP–H = 12.0 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 8.32 (s, 1 H), 8.08 (d, J = 9.0 Hz,
1 H), 7.73 (d, J = 6.0 Hz, 1 H), 7.45 (t, J = 6.0 Hz, 1 H), 5.80 (s, 1
H, OH), 5.15 (d, 2JP–H = 12.0 Hz, 1 H), 3.71 (s, 3 H), 3.68 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 162.6 (d, 1JC–F = 242.3 Hz), 132.2,
128.8 (dd, J = 7.5, 5.3 Hz), 115.36 (dd, J = 21.8, 2.3 Hz), 69.9 (d,
1JC–P = 159.8 Hz), 54.0 (d, 2JC–P = 6.8 Hz), 53.5 (d, 2JC–P = 7.5 Hz).
13C NMR (75 MHz, CDCl3): d = 148.2 (d, JC–P = 3.0 Hz), 139.2,
Dimethyl 1-Hydroxy-1-(4-nitrophenyl)methylphosphonate
(8d)20m
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8d.
131.1 (d, J = 5.3 Hz), 129.1 (d, JC–P = 2.3 Hz), 122.9 (d, JC–P =
1
3.0 Hz), 121.9 (d, J = 5.3 Hz), 69.6 (d, JC–P = 159.8 Hz), 54.4 (d,
2JC–P = 7.5 Hz), 53.8 (d, 2JC–P = 7.5 Hz).
Dimethyl 1-Hydroxy-1-phenylmethylphosphonate (8i)20m
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8i.
Yield: 94 mg (73%); yellow solid.
1H NMR (300 MHz, CDCl3): d = 8.23 (d, J = 9.0 Hz, 2 H), 7.68 (dd,
2
J = 9.0, 3.0 Hz, 2 H), 5.41 (s, 1 H, OH), 5.23 (d, JP–H = 15.0 Hz,
Yield: 84 mg (78%); white solid.
1 H), 3.78 (d, 3JP–H = 6.0 Hz, 3 H), 3.75 (d, 3JP–H = 6.0 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.47–7.33 (m, 2 H), 7.32–7.15 (m,
13C NMR (75 MHz, CDCl3): d = 147.6 (d, JC–P = 3.8 Hz), 144.0 (d,
JC–P = 2.3 Hz), 127.6 (d, JC–P = 2.3 Hz), 123.4 (d, JC–P = 2.3 Hz),
2
3 H), 4.97 (d, JP–H = 12.0 Hz, 1 H), 4.62 (s, 1 H, OH), 3.60 (d,
3JP–H = 6.0, 3 H), 3.57 (d, 3JP–H = 6.0 Hz, 3 H).
69.9 (d, 1JC–P = 158.3 Hz), 54.5 (d, 2JC–P = 6.8 Hz), 53.7 (d, 2JC–P
=
7.5 Hz).
13C NMR (75 MHz, CDCl3): d = 136.6 (d, JC–P = 1.5 Hz), 128.3 (d,
JC–P = 3.0 Hz), 128.1 (d, JC–P = 3.8 Hz), 127.1 (d, JC–P = 6.0 Hz),
Dimethyl 1-Hydroxy-1-(2-chlorophenyl)methylphosphonate
(8e)20m
70.5 (d, 1JC–P = 159.8 Hz), 53.9 (d, 2JC–P = 6.8 Hz), 53.6 (d, 2JC–P
=
7.5 Hz).
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8e.
Dimethyl 1-Hydroxy-1-(4-methoxyphenyl)methylphosphonate
(8j)20e
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8j.
Yield: 96 mg (77%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.72–7.68 (m, 1 H), 7.28–7.12 (m,
2
3
3 H), 5.54 (d, JP–H = 9.0 Hz, 1 H), 3.68 (d, JP–H = 9.0 Hz, 3 H),
Yield: 94 mg (76%); white solid.
3.60 (d, 3JP–H = 12.0 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.40 (dd, J = 9.0, 3.0 Hz, 2 H),
13C NMR (75 MHz, CDCl3): d = 134.9, 132.8 (d, JC–P = 8.3 Hz),
129.35 (d, JC–P = 4.5 Hz), 129.24 (d, JC–P = 3.8 Hz), 129.20 (d,
JC–P = 2.3 Hz), 127.0 (d, JC–P = 3.0 Hz), 66.8 (d, 1JC–P = 161.3 Hz),
54.1 (d, 2JC–P = 6.8 Hz), 53.7 (d, 2JC–P = 7.5 Hz).
6.90 (d, J = 9.0 Hz, 2 H), 5.96 (s, 1 H, OH), 5.01 (d, 2JP–H = 9.0 Hz,
3
3
1 H), 3.80 (s, 3 H), 3.73 (d, JP–H = 9.0 Hz, 3 H), 3.68 (d, JP–H
=
9.0 Hz, 3 H).
Synthesis 2011, No. 13, 2073–2078 © Thieme Stuttgart · New York

PAPER
N-Heterocyclic Carbene Catalyzed Hydrophosphonylation of Aldehydes
2077
13C NMR (75 MHz, CDCl3): d = 159.6 (d, JC–P = 2.3 Hz), 132.2,
13C NMR (75 MHz, CDCl3): d = 141.2, 128.6, 128.4, 126.0, 66.6 (d,
1
128.5 (d, JC–P = 6.0 Hz), 113.9 (d, JC–P = 2.3 Hz), 70.1 (d, JC–P
=
1JC–P = 160.5 Hz), 53.4 (d, 2JC–P = 7.5 Hz), 53.2 (d, 2JC–P = 7.5 Hz),
30.0 (d, 3JC–P = 2.3 Hz), 31.6 (d, 2JC–P = 14.3 Hz).
159.8 Hz), 55.2, 54.1 (d, 2JC–P = 7.5 Hz), 53.7 (d, 2JC–P = 7.5 Hz).
Dimethyl 1-Hydroxy-1-(4-methylphenyl)methylphosphonate
(8k)20m
Prepared according to the general procedure and purified by chro-
Dimethyl 1-Hydroxybutylphosphonate(8p)20n
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8p.
matography on silica gel (PE–EtOAc, 1:2) to afford 8k.
Yield: 28 mg (31%); white solid.
Yield: 88 mg (76%); white solid.
1H NMR (300 MHz, CDCl3): d = 3.93–3.80 (m, 1 H), 3.76 (s, 3 H),
3.72 (s, 3 H), 3.63 (s, 1 H, OH), 1.72–1.50 (m, 3 H), 1.42–1.30 (m,
1 H), 0.88 (t, J = 6.0 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.25 (t, J = 6.0 Hz, 1 H), 7.14–
2
6.96 (m, 2 H), 6.84 (d, J = 6.0 Hz, 1 H), 5.03 (d, JP–H = 12.0 Hz,
3
3
1 H), 3.79 (s, 3 H), 3.70 (d, JP–H = 9.0 Hz, 3 H), 3.66 (d, JP–H
=
13C NMR (75 MHz, CDCl3): d = 67.3 (d, 1JC–P = 159.8 Hz), 53.3 (d,
12.0 Hz, 3 H).
2
2
2JC–P = 5.3 Hz), 53.2 (d, JC–P = 5.3 Hz), 33.3, 18.8 (d, JC–P
=
13C NMR (75 MHz, CDCl3): d = 159.6 (d, JC–P = 2.3 Hz), 138.2 (d,
JC–P = 1.5 Hz), 129.3 (d, JC–P = 2.3 Hz), 119.4 (d, JC–P = 6.0 Hz),
13.5 Hz), 13.6.
1
113.8 (d, JC–P = 3.0 Hz), 112.5 (d, JC–P = 5.3 Hz), 70.4 (d, JC–P
=
159.0 Hz), 55.2, 53.9 (d, 2JC–P = 7.5 Hz), 53.6 (d, 2JC–P = 6.8 Hz).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Dimethyl 1-Hydroxy-1-(3-methoxyphenyl)methylphosphonate
(8l)25d
Prepared according to the general procedure and purified by chro-
Acknowledgment
matography on silica gel (PE–EtOAc, 1:2) to afford 8l.
This work was supported by the Start-Up Foundation for Young
Scientists of Shi He Zi University (RCZX200806).
Yield: 88 mg (72%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.33–7.23 (m, 2 H), 7.13–7.03 (m,
2
2 H), 4.92 (d, JP–H = 9.0 Hz, 1 H), 4.80 (s, 1 H, OH), 3.61 (d,
References
3JP–H = 9.0 Hz, 3 H), 3.57 (d, 3JP–H = 9.0 Hz, 3 H), 2.26 (s, 3 H).
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13C NMR (75 MHz, CDCl3): d = 137.9 (d, JC–P = 3.8 Hz), 133.6 (d,
1
JC–P = 2.3 Hz), 129.1, 129.0, 127.1, 127.0, 70.3 (d, JC–P
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159.8 Hz), 53.9 (d, 2JC–P = 6.8 Hz), 53.6 (d, 2JC–P = 7.5 Hz), 21.2.
Dimethyl 1-Hydroxy-2-naphthmethylphosphonate (8m)20m
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8m.
Yield: 123 mg (93%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.83 (s, 1 H), 7.78–7.60 (m, 3 H),
2
7.47 (d, J = 6.0 Hz, 1 H), 7.42–7.25 (m, 2 H), 5.13 (d, JP–H
=
12.0 Hz, 1 H), 5.05 (s, 1 H, OH), 3.57 (d, 3JP–H = 3.0 Hz, 3 H), 3.53
(d, 3JP–H = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 134.23 (d, JC–P = 1.5 Hz), 133.1 (d,
JC–P = 2.3 Hz), 128.1, 128.0, 127.7, 126.2, 126.1, 124.9 (d, JC–P
=
4.5 Hz), 70.7 (d, 1JC–P = 159.8 Hz), 54.0 (d, 2JC–P = 7.5 Hz), 53.7 (d,
2JC–P = 7.5 Hz).
Dimethyl 1-Hydroxy-1-furylmethylphosphonate (8n)20n
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8n.
Yield: 32 mg (31%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.37 (s, 1 H), 6.56–6.20 (m, 2 H),
4.98 (d, 2JP–H = 15.0 Hz, 1 H), 4.11 (s, 1 H, OH), 3.75 (d, 3JP–H = 9.0
Hz, 3 H), 3.67 (d, 3JP–H = 12.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 149.7, 143.0 (d, JC–P = 3.0 Hz),
110.8, 109.5 (d, J = 6.0 Hz), 64.4 (d, 1JC–P = 166.5 Hz), 54.0 (d,
2JC–P = 6.8 Hz), 53.9 (d, 2JC–P = 8.3 Hz).
Dimethyl 1-Hydroxy-3-phenylpropylphosphonate (8o)20m
Prepared according to the general procedure and purified by chro-
matography on silica gel (PE–EtOAc, 1:2) to afford 8o.
Yield: 94 mg (77%); white solid.
1H NMR (300 MHz, CDCl3): d = 7.25–7.05 (m, 5 H), 4.42 (s, 1 H,
3
OH), 3.92–3.77 (m, 1 H), 3.72 (d, JP–H = 6.0 Hz, 3 H), 3.38 (d,
3JP–H = 6.0 Hz, 3 H), 3.02–2.78 (m, 1 H), 2.75–2.55 (m, 1 H), 2.09–
1.80 (m, 2 H).
Synthesis 2011, No. 13, 2073–2078 © Thieme Stuttgart · New York

2078
Z.-H. Cai et al.
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Synthesis 2011, No. 13, 2073–2078 © Thieme Stuttgart · New York