An efficient synthesis of 2-diazo-2-(trimethylsilyl)ethanols and their application to pyrazole synthesis

Article abstract of DOI:10.1055/s-2007-990817

Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or d

Full text of DOI:10.1055/s-2007-990817

PAPER
3371
An Efficient Synthesis of 2-Diazo-2-(trimethylsilyl)ethanols and Their
Application to Pyrazole Synthesis
S
ynthesis and Rea
o
c
tions of 2-D
s
iazo-2-(tr
h
imethylsilyl)
i
ethanol
y
s
uki Hari, Susumu Tsuchida, Ryosuke Sone, Toyohiko Aoyama*
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho, Nagoya 467-8603, Japan
Fax +81(52)8363439; E-mail: aoyama@phar.nagoya-cu.ac.jp
Received 9 July 2007; revised 24 July 2007
magnesium bromide salt of TMSCHN2 [TMSC(Mg-
Br)N2].9 In this study, we found that the reaction of
TMSC(MgBr)N2 with ethyl 4-phenyl-2-oxobutanoate at
–78 °C efficiently gave the corresponding trimethylsilyl-
ated diazoalcohol in high yield as an isolable product
while the reaction with TMSC(Li)N2 gave a complex mix-
ture (Scheme 2). From these results, we envisaged that
TMSC(MgBr)N2 would also react with simple aldehydes
and ketones to give the corresponding 2-diazo-2-(trimeth-
ylsilyl)ethanols. This paper describes our results on the
synthesis of 2-diazo-2-(trimethylsilyl)ethanols using
TMSC(MgBr)N2 and their application to the pyrazole
synthesis10 by [3+2]-cycloaddition reaction with ethyl
propiolate or dimethyl acetylenedicarboxylate (DMAD).
Abstract: Reaction of diazo(trimethylsilyl)methylmagnesium bro-
mide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)eth-
anols, which were applied to the synthesis of di- and trisubstituted
pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or
dimethyl acetylenedicarboxylate.
Key words: diazoalcohol, 2-diazo-2-(trimethylsilyl)ethanols, di-
azo(trimethylsilyl)methylmagnesium bromide, pyrazoles, trimeth-
ylsilyldiazomethane
a-Trimethylsilylated diazo compounds are very useful
and attractive building blocks in organic synthesis. For
example, trimethylsilyldiazoacetates have been reported
to be applicable to the aldol reaction with aldehydes,1 the
synthesis of a-trimethylsilyl-a-amino acids2 and a-trimeth-
ylsilyltetrahydrofurans,3 and so on.4 Furthermore, a-
trimethylsilyldiazoketones and 1-diazo-1-(trimethyl-
silyl)alkanes, involving trimethylsilyldiazomethane
(TMSCHN2), have also been used for various synthetic
processes.5–7 However, concerning 2-diazo-2-(trimethyl-
silyl)ethanols, there is only one report; in it, Schöllkopf et
al. described that 2-diazo-2-(trimethylsilyl)ethanols could
be synthesized by the reaction of carbonyl compounds
with lithium trimethylsilyldiazomethane [TMSC(Li)N2]
in moderate yield and the resulting 2-diazo-2-(trimethyl-
silyl)ethanols afforded trimethylsilyloxiranes with spon-
taneous expulsion of N2 at room temperature (Scheme 1).8
To date, the synthetic application of 2-diazo-2-(trimethyl-
silyl)ethanols is almost unexplored.
First, we examined the reaction conditions using
TMSC(Li)N2 or TMSC(MgBr)N2, 4-chlorobenzaldehyde
and DMAD as a model system (Table 1). According to
Schöllkopf’s method,8 the 2-diazo-2-(trimethylsilyl)eth-
anol (2a) (58% yield) was prepared from the aldehyde 1a
and subsequent [3+2] cycloaddition of 2a with DMAD
was carried out, but the yield of desired trisubstituted
pyrazole 3a was very low (20% yield from 1a) (Table 1,
entry 1). This low yield was presumably due to the de-
composition of 2a by a trace amount of remaining AcOH
used as a quencher.11 When H2O or aqueous saturated
NH4Cl was used as a quencher instead of AcOH, the reac-
tion gave a complex mixture and 2a was not obtained
(Table 1, entries 2 and 3). However, as expected, replace-
ment of TMSC(Li)N2 by TMSC(MgBr)N2 caused a dra-
matic improvement in both reactions, and 2a and 3a were
obtained in high yields (Table 1, entry 4).
Recently, we reported the one-pot synthesis of cis-b-tri-
methylsilyl-a,b-epoxy esters from a-keto esters using the
OH
O
O
i) TMSC(Li)N2
25 °C
(50%)
Me
Me
TMS
Me
Me
TMS
ii) AcOH
(65%)
Me
Me
N2
Scheme 1 An example of 2-diazo-2-(trimethylsilyl)ethanols
OM
OH
O
CO2Et
TMS
TMSC(M)N2 (1.2 equiv)
THF
CO2Et
TMS
H2O
(M = MgBr)
Ph
Ph
Ph
CO2Et
–78 °C, 1.5 h
(M = Li or MgBr)
N2
N2
Scheme 2 Reaction of TMSC(M)N2 (M = Li or MgBr) with ethyl 4-phenyl-2-oxobutanoate
SYNTHESIS 2007, No. 21, pp 3371–3375
x
x.
x
x
.
2
0
0
7
Advanced online publication: 10.10.2007
DOI: 10.1055/s-2007-990817; Art ID: F13007SS
© Georg Thieme Verlag Stuttgart · New York

3372
Y. Hari et al.
PAPER
Table 1 Examination of Reaction Conditions
i) TMSC(M)N2
(1.2 equiv), THF
–78 °C, 1.5 h
OTMS
OH
CHO
CO2Me
TMS
Cl
DMAD (2.0 equiv)
Cl
N2
THF
reflux, 1 d
N
ii) quencher
CO2Me
Cl
N
H
1a
2a
3a
Entry
TMSC(M)N2
TMSC(Li)N2
TMSC(Li)N2
TMSC(Li)N2
TMSC(MgBr)N2
Quencher
Yield (%) of 2aa
Yield (%) of 3ab
1
2
3
4
AcOH (1.2 equiv)
H2O
58
20
–
c
–
c
aq sat. NH4Cl
H2O
–
–
quant
80
a The purity was confirmed by 1H NMR measurement.
b Isolated yield from 1a.
c The reaction gave a complex mixture.
entry 3).12 It has already been reported that the reaction of
TMSCHN2 with methyl but-2-ynoate furnished a mixture
of regioisomers.13 The observed high regioselectivity in
the synthesis of 4a is presumably due to the steric repul-
sion between the (4-chlorophenyl)(hydroxy)methyl and
TMS groups of 2a, and the ethoxycarbonyl group of a
dipolarophile. Other 2-diazo-2-(trimethylsilyl)ethanols
2b–f regioselectively afforded the corresponding pyr-
azoles 4b–f in good to high yields in two steps (entries 4–
8 in Table 3).12
Table 2 2-Diazo-2-trimethylsilylethanols 2 Prepared
i) TMSC(MgBr)N2
OH
(1.2 equiv), THF
R1
R2
TMS
–78 °C, 1.5 h
ii) H2O
R1COR2
1
N2
2
Entry
Substrate
R1
Product
Yield (%)a
R2
1
2
3
4
5
6
4-ClC6H4
Ph
H
2a
2b
2c
2d
2e
2f
quant
quant
quant
93
In conclusion, we have found that TMSC(MgBr)N2 is a
quite useful reagent for the synthesis of 2diazo-2-(tri-
methylsilyl)ethanols from aldehydes and ketones. More-
over, the present method described above makes possible
the synthesis of polysubstituted pyrazoles from aldehydes
or ketones in two steps and will provide an added flexibil-
ity in the pyrazole synthesis.
H
4-MeOC6H4
t-Bu
H
H
Ph
Me
Me
94
PhCH2CH2
quant
a The purity was confirmed by 1H NMR measurement.
All melting points were measured on a Yanagimoto micro melting
points apparatus and are uncorrected. IR spectra were recorded on a
Shimadzu FTIR-8400S spectrophotometer. 1H and 13C NMR spec-
tra were recorded on a Jeol JNM-EX-270 spectrometer (1H, 270
MHz; 13C, 67.8 MHz). MS spectra (bp = base peak) were recorded
on a Jeol JMS-SX-102A spectrometer. A solution of MgBr2 in
Et2O–toluene (1:1) was prepared from MgBr2 etherate (Aldrich)
dried well under reduced pressure at 100 °C, and freshly distilled
Et2O (from Na/benzophenone ketyl) and toluene (from CaH2). Car-
bonyl compounds 1a–f were distilled prior to use. THF was distilled
from Na/benzophenone ketyl prior to use.
Next, under optimized conditions, generality for the syn-
thesis of 2-diazo-2-(trimethylsilyl)ethanols was examined
(Table 2). Various aldehydes 1b–d including aromatic
and aliphatic ones smoothly reacted with TMSC(Mg-
Br)N2 to give the corresponding 2-diazo-2-(trimethyl-
silyl)ethanols 2b–d in nearly quantitative yields,
respectively (Table 2, entries 2–4). Ketones such as ace-
tophenone (1e) and 4-phenylbutan-2-one (1f) also under-
went the reaction to afford 2e and 2f in high yields
(Table 2, entries 5 and 6). Finally, the pyrazole synthesis
using 2 was examined and the results were summarized in
Table 3. Analogous to 2a, the diazoalcohol 2f derived
from the ketone 1f reacted with DMAD to give the trisub-
stituted pyrazole 3f in high yield (83%) (Table 3, entries 1
and 2). Ethyl propiolate could also be used as a dipolaro-
phile. Thus, the reaction of 2a with ethyl propiolate
smoothly proceeded to give the 3,5-disubstituted pyrazole
4a in high yield with high regioselectivity and its regio-
isomer was not produced in detectable amounts (Table 3,
Dimethyl 3-[(4-Chlorophenyl)(trimethylsilyloxy)methyl]-1H-
pyrazole-4,5-dicarboxylate (3a)
Using TMSC(Li)N2
Under argon, n-BuLi (1.65 M in hexane solution, 0.73 mL, 1.20
mmol) was added to a solution of TMSCHN2 (1.73 M in hexane so-
lution, 0.70 mL, 1.20 mmol) in THF (4 mL) at –78 °C and the mix-
ture was stirred at –78 °C for 20 min. A solution of 4-
chlorobenzaldehyde (1a; 141 mg, 1.00 mmol) in THF (1 mL) was
added to the above mixture at –78 °C and the mixture was further
stirred at –78 °C for 1.5 h. After addition of a solution of AcOH (69
mL, 1.20 mmol) in THF (1 mL) and dilution with H2O at –78 °C, the
mixture was extracted with EtOAc (3 × 30 mL). The organic ex-
Synthesis 2007, No. 21, 3371–3375 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of 2-Diazo-2-(trimethylsilyl)ethanols
3373
Table 3 Pyrazoles 3 and 4 Prepared
OTMS
i) TMSC(MgBr)N2
(1.2 equiv), THF
–78 °C, 1.5 h
R1
R2
R3
OH
R3C≡CR4 (2.0 equiv)
R1
R2
TMS
R1COR2
N
R4
ii) H2O
THF
reflux, 1 d
N2
N
H
1
2
3 or 4
Entry
Substrate
R1
Alkyne
Product
Yield (%)a
R2
H
1
2
3
4
5
6
7
8
4-ClC6H4
PhCH2CH2
4-ClC6H4
Ph
R3 = R4 = CO2Me
R3 = R4 = CO2Me
3a
3f
80
83
81
65
78
66
77
92
Me
H
R3 = H, R4 = CO2Et
R3 = H, R4 = CO2Et
R3 = H, R4 = CO2Et
R3 = H, R4 = CO2Et
R3 = H, R4 = CO2Et
R3 = H, R4 = CO2Et
4a
4b
4c
4d
4e
4f
H
4-MeOC6H4
t-Bu
H
H
Ph
Me
Me
PhCH2CH2
a Isolated yield from 1.
tracts were washed successively with H2O (10 mL), aq sat. NaHCO3
(10 mL), H2O (10 mL), and brine (10 mL), and dried (Na2SO4). The
concentration of the solvent in vacuo gave 2a (148 mg, 58%), which
was dissolved in THF (5 mL), and dimethyl acetylenedicarboxylate
(0.24 mL, 2.00 mmol) was added. After refluxing for 1 day, the
mixture was concentrated in vacuo. The residue was purified by sil-
ica gel column chromatography (hexane–EtOAc, 3:1) to give 3a
(79 mg, 20% from 1a). For analytical and spectral data: see below.
HRMS (EI): m/z calcd for C11H1535ClOSi (M+ – N2): 226.0586;
found: 226.0581; m/z calcd for C11H1537ClOSi (M+ – N2): 228.0568;
found: 228.0551.
2-Diazo-1-phenyl-2-(trimethylsilyl)ethanol (2b)
Yield: >99%; orange oil.
IR (neat): 3398, 2044 cm–1.
1H NMR (CD2Cl2): d = 0.17 (9 H, s), 2.07 (1 H, s), 5.30 (1 H, s),
7.30–7.37 (5 H, m).
MS (EI): m/z = 220 (M+), 192 (M+ – N2), 73 (bp).
HRMS (EI): m/z calcd for C11H16OSi (M+ – N2): 192.0988; found:
Pyrroles 3 and 4 Using TMSC(MgBr)N2; Dimethyl 3-[(4-Chlo-
rophenyl)(trimethylsilyloxy)methyl]-1H-pyrazole-4,5-dicar-
boxylate (3a);
Typical Procedure
192.0971.
Under argon, n-BuLi (1.57 M in hexane solution, 0.37 mL, 0.58
mmol) was added to a solution of TMSCHN2 (1.80 M in hexane so-
lution, 0.32 mL, 0.58 mmol) in THF (3.5 mL) at –78 °C and the
mixture was stirred at –78 °C for 20 min. After the addition of
MgBr2 [1.43 M in toluene–Et2O (1:1) solution, 0.41 mL, 0.58
mmol], the mixture was further stirred at –78 °C for 10 min. A so-
lution of 4-chlorobenzaldehyde (1a; 68 mg, 0.49 mmol) in THF (0.5
mL) was added to the above mixture at –78 °C and the mixture was
further stirred at –78 °C for 1.5 h. After the addition of H2O at
–78 °C, the mixture was extracted with EtOAc (3 × 30 mL). The or-
ganic extracts were washed with H2O (10 mL) and brine (10 mL),
and dried (Na2SO4). The concentration of the solvent in vacuo gave
2a (124 mg, quant), which was dissolved in THF (2 mL), and di-
methyl acetylenedicarboxylate (0.114 mL, 0.93 mmol) was added.
After refluxing for 1 day, the mixture was concentrated in vacuo.
The residue was purified by silica gel column chromatography
(hexane–EtOAc, 4:1) to give 3a (153 mg, 80% from 1a).
2-Diazo-1-(4-methoxyphenyl)-2-(trimethylsilyl)ethanol (2c)
Yield: >99%; yellow oil.
IR (neat): 3481, 2042 cm–1.
1H NMR (CD2Cl2): d = 0.18 (9 H, s), 1.55 (1 H, s), 3.80 (3 H, s),
5.30 (1 H, s), 6.87–6.91 (2 H, m), 7.28–7.32 (2 H, m).
MS (EI): m/z = 222 (M+ – N2), 121 (bp).
HRMS (EI): m/z calcd for C12H18O2Si (M+ – N2): 222.1058; found:
222.1076.
1-Diazo-3,3-dimethyl-1-(trimethylsilyl)butan-2-ol (2d)
Yield: 93%; yellow oil.
IR (neat): 3454, 2042 cm–1.
1H NMR (CD2Cl2): d = 0.18 (9 H, s), 0.98 (9 H, s), 1.68 (1 H, s).
MS (EI): m/z = 127 (M+ – TMS), 73 (bp).
1-(4-Chlorophenyl)-2-diazo-2-(trimethylsilyl)ethanol (2a)
Yield: >99%; yellow oil.
IR (neat): 3408, 2046 cm–1.
1-Diazo-2-phenyl-1-(trimethylsilyl)propan-2-ol (2e)
Yield: 94%; yellow oil.
IR (neat): 3446, 2039 cm–1.
1H NMR (CD2Cl2): d = 0.07 (9 H, s), 1.73 (3 H, s), 2.04 (1 H, s),
7.25–7.37 (5 H, m).
1H NMR (DMSO-d6): d = 0.11 (9 H, s), 5.23 (1 H, d, J = 4.6 Hz),
5.88 (1 H, d, J = 4.6 Hz), 7.33–7.41 (4 H, m).
MS (EI): m/z = 228 (M+ – N2), 226 (M+ – N2), 73 (bp).
Synthesis 2007, No. 21, 3371–3375 © Thieme Stuttgart · New York

3374
Y. Hari et al.
PAPER
MS (EI): m/z = 234 (M+), 206 (M+ – N2), 73 (bp).
HRMS (EI): m/z calcd for C12H18OSi (M+ – N2): 206.1127; found:
1H NMR (CDCl3): d = 0.10 (9 H, s), 1.36 (3 H, t, J = 7.1 Hz), 4.35
(2 H, q, J = 7.1 Hz), 5.89 (1 H, s), 6.61 (1 H, s), 7.27–7.35 (5 H, m),
10.52 (1 H, br).
13C NMR (CDCl3): d = 0.1, 14.3, 61.1, 70.4, 105.9, 126.1, 127.7,
128.3, 142.2, 161.0.
206.1127.
1-Diazo-2-methyl-4-phenyl-1-(trimethylsilyl)butan-2-ol (2f)
Yield: >99%; yellow oil.
IR (neat): 3435, 2039 cm–1.
1H NMR (CD2Cl2): d = 0.25 (9 H, s), 1.47 (3 H, s), 1.62 (1 H, s),
1.91–1.98 (2 H, m), 2.69–2.77 (2 H, m), 7.18–7.28 (5 H, m).
MS (EI): m/z = 318 (M+), 303 (M+ – Me), 257 (bp).
HRMS (EI): m/z calcd for C16H22N2O3Si (M+): 318.1400; found:
318.1366.
Ethyl 3-[(4-Methoxyphenyl)(trimethylsilyloxy)methyl]-1H-
pyrazole-5-carboxylate (4c)
Yield: 78%; pale yellow oil.
IR (neat): 3281, 1717 cm–1.
MS (EI): m/z = 234 (M+ – N2), 73 (bp).
HRMS (EI): m/z calcd for C14H22OSi (M+ – N2): 234.1420; found:
234.1440.
Dimethyl 3-[(4-Chlorophenyl)(trimethylsilyloxy)methyl]-1H-
pyrazole-4,5-dicarboxylate (3a)
Yield: 80%; pale yellow oil.
1H NMR (CDCl3): d = 0.09 (9 H, s), 1.36 (3 H, t, J = 7.1 Hz), 3.79
(3 H, s), 4.35 (2 H, q, J = 7.1 Hz), 5.88 (1 H, s), 6.61 (1 H, s), 6.86
(2 H, d, J = 8.4 Hz), 7.28 (2 H, d, J = 8.4 Hz), 11.05 (1 H, br).
IR (neat): 3284, 1738, 1728 cm–1.
1H NMR (CDCl3): d = 0.08 (9 H, s), 3.78 (3 H, s), 3.92 (3 H, s), 6.58
(1 H, s), 7.28 (4 H, m), 11.21 (1 H, br).
13C NMR (CDCl3): d = 0.1, 14.3, 55.2, 61.0, 70.0, 105.7, 113.7,
127.5, 134.4, 140.2, 151.7, 159.0, 161.1.
MS (EI): m/z = 348 (M+), 333 (M+ – Me), 287 (bp).
13C NMR (CDCl3): d = –0.1, 51.8, 52.6, 58.6, 109.8, 118.2, 127.9,
128.5, 133.9, 139.3, 150.1, 162.1, 162.5.
HRMS (EI): m/z calcd for C17H24N2O4Si (M+): 348.1505; found:
348.1505.
MS (EI): m/z = 398 (M+), 396 (M+), 364 (bp).
Ethyl 3-[2,2-Dimethyl-1-(trimethylsilyloxy)propyl]-1H-pyr-
azole-5-carboxylate (4d)
Yield: 66%; colorless crystals (hexane–EtOAc); mp 133–134 °C.
IR (neat): 3177, 1730 cm–1.
HRMS (EI): m/z calcd for C17H2135ClN2O5Si (M+): 396.0879;
found: 396.0893; m/z calcd for C17H2137ClN2O5Si (M+): 398.0879;
found: 398.0895.
Dimethyl 3-[4-Phenyl-2-(trimethylsilyloxy)butan-2-yl]-1H-
pyrazole-4,5-dicarboxylate (3f)
1H NMR (CDCl3): d = 0.03 (9 H, s), 0.88 (9 H, s), 1.38 (3 H, t,
J = 7.1 Hz), 4.43 (2 H, q, J = 7.1 Hz), 6.65 (1 H, s), 10.70 (1 H, br).
Yield: 83%; pale yellow oil.
IR (neat): 3326, 1738, 1730 cm–1.
13C NMR (CDCl3) d = –0.2, 14.4, 25.6, 35.9, 61.0, 75.6, 106.3,
144.2, 145.3, 161.8.
1H NMR (CDCl3): d = 0.26 (9 H, s), 1.75 (3 H, s), 2.02–2.27 (2 H,
m), 2.45–2.63 (2 H, m), 3.85 (3 H, s), 3.93 (3 H, s), 7.06–7.26 (5 H,
m), 10.8 (1 H, br).
13C NMR (CDCl3): d = 2.5, 28.9, 30.5, 43.9, 52.2, 52.5, 109.9,
125.7, 128.1, 128.2, 141.3, 151.5, 162.1, 163.9.
MS (EI): m/z = 389 (M+ – Me), 282 (bp).
HRMS (EI): m/z calcd for C19H25N2O5Si (M+ – Me): 389.1529;
MS (EI): m/z = 298 (M+), 283 (M+ – Me), 241 (bp).
Anal. Calcd for C14H26N2O3Si: C, 56.34; H, 8.78; N, 9.39. Found:
C, 56.32; H, 8.90; N, 9.43.
Ethyl 3-[1-Phenyl-1-(trimethylsilyloxy)ethyl]-1H-pyrazole-5-
carboxylate (4e)
Yield: 77%; pale yellow oil.
IR (neat): 3274, 1724 cm–1.
1H NMR (CDCl3): d = 0.06 (9 H, s), 1.38 (3 H, t, J = 7.1 Hz), 1.99
(3 H, s), 4.37 (2 H, q, J = 7.1 Hz), 6.68 (1 H, s), 7.22–7.31 (3 H, m),
7.36–7.39 (2 H, m), 10.97 (1 H, br).
found: 389.1533.
Ethyl 3-[(4-Chlorophenyl)(trimethylsilyloxy)methyl]-1H-pyr-
azole-5-carboxylate (4a)
Yield: 81%; yellow oil.
IR (neat): 3287, 1728 cm–1.
13C NMR (CDCl3): d = 1.9, 14.3, 30.2, 61.1, 74.7, 105.8, 125.1,
127.1, 128.0, 140.8, 146.7, 154.3, 161.4.
1H NMR (CDCl3): d = 0.11 (9 H, s), 1.37 (3 H, t, J = 7.1 Hz), 4.36
(2 H, q, J = 7.1 Hz), 5.86 (1 H, s), 6.61 (1 H, s), 7.28 (4 H, m), 10.40
(1 H, br).
13C NMR (CDCl3): d = 0.1, 14.3, 61.2, 69.9, 106.0, 127.4, 127.4,
128.5, 128.5, 133.3, 141.0, 160.6.
MS (EI): m/z = 317 (M+ – Me, bp).
HRMS (EI): m/z calcd for C16H21N2O3Si (M+ – Me): 317.1324;
found: 317.1322.
Ethyl 3-[4-Phenyl-2-(trimethylsilyloxy)butan-2-yl]-1H-pyr-
azole-5-carboxylate (4f)
Yield: 92%; pale yellow oil.
IR (neat): 3291, 1728 cm–1.
1H NMR (CDCl3): d = 0.17 (9 H, s), 1.41 (3 H, t, J = 7.1 Hz), 1.69
(3 H, s), 2.09 (2 H, t, J = 8.7 Hz), 2.32–2.37 (1 H, m), 2.57–2.68 (1
H, m), 4.40 (2 H, q, J = 7.1 Hz), 6.66 (1 H, s), 7.07–7.26 (5 H, m).
13C NMR (CDCl3): d = 2.4, 14.4, 22.7, 30.5, 46.6, 61.1, 74.4, 104.2,
125.7, 128.1, 128.2, 141.6, 142.0, 153.4, 161.7.
MS (EI): m/z = 354 (M+), 352 (M+), 291 (bp).
HRMS (EI): m/z calcd for C16H2135ClN2O3Si (M+): 352.1010;
found: 352.1009; m/z calcd for C17H2137ClN2O3Si (M+): 354.0981;
found: 354.1001.
Ethyl 3-[Phenyl(trimethylsilyloxy)methyl]-1H-pyrazole-5-car-
boxylate (4b)
Yield: 65%; pale yellow oil.
IR (neat): 3277, 1725 cm–1.
MS (EI): m/z = 345 (M+ – Me), 317 (bp).
Synthesis 2007, No. 21, 3371–3375 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of 2-Diazo-2-(trimethylsilyl)ethanols
3375
HRMS (EI): m/z calcd for C18H25N2O3Si (M+ – Me): 345.1643;
found: 345.1635.
Chemistry, Vol. 1; Dondoni, A., Ed.; JAI Press Ltd.:
London, 1993, 51–101.
(7) Reactions using 1-diazo-1-trimethylsilylalkanes except for
TMSCHN2: (a) Aoyama, T.; Shioiri, T. Tetrahedron Lett.
1986, 27, 2005. (b) Aoyama, T.; Shioiri, T. Tetrahedron
Lett. 1988, 29, 6295. (c) Aoyama, T.; Shioiri, T. Chem.
Pharm. Bull. 1989, 37, 2261. (d) Han, S.; Kass, S. R. J.
Chem. Soc., Perkin Trans. 1 1999, 1553.
Acknowledgment
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research (KAKENHI).
(8) Schöllkopf, U.; Scholz, H.-U. Synthesis 1976, 271.
(9) Hari, Y.; Tsuchida, S.; Aoyama, T. Tetrahedron Lett. 2006,
47, 1977.
(10) For a review: Elguero, J. Comprehensive Heterocyclic
Chemistry II, Vol. 3; Shinkai, I., Ed.; Elsevier: Oxford, 1996,
1–75.
(11) When, during the workup of 2a, the organic extracts were
not washed with aq sat. NaHCO3, no final product 3a was
obtained after the reaction with DMAD.
(12) The position of the ethoxycarbonyl group in 4 was
determined by NOE measurement (Figure 1). For example:
References
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3%
TMSO
H
H
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Cl
N
CO2Et
N
H
4a
Figure 1 NOE data for 4
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5229.
Synthesis 2007, No. 21, 3371–3375 © Thieme Stuttgart · New York