An efficient and convenient aldol addition of acyldiazomethane with aldehydes promoted by MgI2 etherate

Article abstract of DOI:10.1515/mgmc-2017-0006

The aldol addition of acyldiazomethane with aromatic aldehydes, vinyl aldehyde and aliphatic aldehydes was carried out efficiently in the presence of MgI₂ etherate and ⁱPr₂EtN (DIPEA) using untreated reagent-grade CH₂Cl₂ under atmospheric conditions in good to excellent yields. Iodide counterion and a non-coordinating reaction media (i.e. CH₂Cl₂) are among the critical factors for the unique reactivity of this reaction system.

Full text of DOI:10.1515/mgmc-2017-0006

Main Group Met. Chem. 2017; 40(3–4): 87–91
Xiaoqiang Xie, Weipeng Qi, Xinzhe Sun and Xingxian Zhang*
An efficient and convenient aldol addition of
acyldiazomethane with aldehydes promoted by
MgI2 etherate
DOI 10.1515/mgmc-2017-0006
Received February 2, 2017; accepted April 26, 2017; previously
published online June 2, 2017
(Jiang and Wang, 2002), Mg/La mixed oxide (Kantham
et al., 2007a,b), NAP-MgO (Kantham et al., 2007a,b) and
Bu2Mg (Trost et al., 2009, 2012). Also, some Lewis and
Bronsted acids, such as Et2Zn (Cui et al., 2011), Me2Zn
(Benfatti et al., 2009), PhCOOH (Krishna et al., 2011),
Ti(OiPr)4 (Wang et al., 2009a,b), Zr(OtBu)4 (Yao and Wang,
2003) and Sc(OTf)3 (Wang et al., 2009a,b) are utilized
into this coupling as catalysts. However, some of these
methods involve the use of very strong bases, expensive
catalysts, prolonged reaction time and vigorous reaction
conditions, which afford the low yields of the products.
Moreover, the use of strong bases may not be compatible
Abstract: Thealdoladditionofacyldiazomethanewitharo-
matic aldehydes, vinyl aldehyde and aliphatic aldehydes
was carried out efficiently in the presence of MgI2 etherate
and iPr2EtN (DIPEA) using untreated reagent-grade CH2Cl2
under atmospheric conditions in good to excellent yields.
Iodide counterion and a non-coordinating reaction media
(i.e. CH2Cl2) are among the critical factors for the unique
reactivity of this reaction system.
Keywords: acyldiazomethane; aldehydes; aldol addition; with certain functional groups in the substrates. From
MgI2 etherate.
the viewpoints above, the development of less expensive,
environmentally benign, and easily handled promoters
for aldol reaction of acyldiazomethane with aldehydes to
form α-diazo-β-hydroxy esters is still highly desirable.
Magnesium is an abundant, cheap and benign
element which exists in nature, and many reactions using
magnesium salts have been developed recently in organic
synthesis (Zhang and Li, 2003). In our previous paper, we
have demonstrated that MgI2 etherate could efficiently
catalyze Mukaiyama-type aldol reaction of aldehydes with
trimethylsilyl enolates and allylation of aldehydes with
allylstannane (Li and Zhang, 2002; Zhang, 2008). We have
also found that MgI2 etherate-promoted direct aldol addi-
tion of methyl ketone with aldehydes in the presence of Et3N
under mild reaction conditions (Liu et al., 2012). Herein, we
wish to report an efficient and facile method for the syn-
thesis of α-diazo-β-hydroxy esters by the coupling of alde-
hydes with acyldiazomethane promoted by MgI2⋅(Et2O)n
in the presence of diisopropylethylamine (DIPEA) at room
temperature under atmospheric conditions.
Introduction
α-Diazo carbonyl compounds are a potential source of
amino alcohols and acids (Doyle et al., 1998). α-Diazo
carbonyl compounds are generally prepared by the azido
transfer reaction of carbonyl compounds (Moody and
Morfitt, 1998; Yao and Wang, 2003). Recently, the syn-
thesis of α-diazo carbonyl compounds has been widely
explored, such as α-diazo-β-hydroxy esters which are
involved in many reactions in organic chemistry. The
most straightforward synthesis of α-diazo carbonyl com-
pounds involves the condensation of aldehydes and acyl-
diazomethanes. This is generally carried out by using
strong bases, such as butylithium (Schöllkopf et al., 1970),
lithium diisopropylamide (Moody and Taylor, 1987),
sodium hydride (NaH) (Jiang et al., 2001), potassium
hydroxide (KOH) (Woolsey and Khalil, 1972), tert-BuOK
(Sreedhar et al., 2005), tetrabutylammonium hydroxide
(Varala et al., 2006), 1,8-diazabicyclo[5.4.0]undec-7-ene
Results and discussion
At the onset of this work, we investigated a variety of con-
ditions with a model reaction of benzaldehyde with ethyl
diazoacetate (EDA) using MgI2 etherate as promoter in
the presence of DIPEA, and the results are summarized
in Table 1. No product formation was observed by using
only MgI2⋅(Et2O)n or DIPEA, respectively. The reaction
*Corresponding author: Xingxian Zhang, College of Pharmaceutical
Sciences, Zhejiang University of Technology, Hangzhou 310032,
P.R. China, e-mail: zhangxx@zjut.edu.cn
Xiaoqiang Xie, Weipeng Qi and Xinzhe Sun: College of
Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou 310032, P.R. China
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88ꢀ ꢀX. Xie et al.: MgI2 etherate-promoted aldol addition of acyldiazomethane with aldehydes
Table 1:ꢁScreening reaction conditions for the condensation of
Table 2:ꢁMgI2⋅(OEt2)n-promoted aldol addition of acyldiazomethane
benzaldehyde with EDAa.
with various aldehydesa.
OH
O
O
OH
O
O
O
MgI2 ·(OEt2)n , DIPEA
CH2Cl2, r.t.
MgI2 ·(Et2O)n,DIPEA
solvent, r.t.
H
2
2
1
+
H
R CHO
R
1
OEt
R
H
R
OEt
+
N2
N2
N2
N2
Entryꢀ MgI2·(Et2O)n
(mol%)b
ꢀ
DIPEAꢀ Solventꢀ Time (h) ꢀ Yield (%)c Entryꢀ R1
(mol%)b
ꢀ
R2
ꢀ Time (min)ꢀ Productꢀ Yield (%)b
1
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C6H5-
4-ClC6H4-
4-FC6H4-
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
20ꢃ 1a
15ꢃ 1b
15ꢃ 1c
15ꢃ 1d
15ꢃ 1e
15ꢃ 1f
15ꢃ 1g
15ꢃ 1h
15ꢃ 1i
15ꢃ 1j
30ꢃ 1k
30ꢃ 1l
30ꢃ 1m
15ꢃ 1n
15ꢃ 1o
20ꢃ 1p
20ꢃ 1q
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
96
97
96
96
99
98
95
94
93
93
92
93
90
93
89
88
90
NRc
94
91
98
1
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
15
30
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
200ꢃ CH2Cl2
200ꢃ CH2Cl2
200ꢃ CH2Cl2
200ꢃ CH2Cl2
200ꢃ CH2Cl2
200ꢃ CH2Cl2
200ꢃ CH2Cl2
100ꢃ CH2Cl2
300ꢃ CH2Cl2
200ꢃ CHCl3
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
8
8
3
3
2
1
ꢃ 16
ꢃ 31
ꢃ 46
ꢃ 59
ꢃ 71
ꢃ 82
2
2
3
3
50
4
4-BrC6H4-
4-NO2C6H4-
4-CF3C6H4-
3,4-F2C6H3-
2-ClC6H4-
3-NO2C6H4-
3-MeOC6H4-
4-MeOC6H4-
2-MeC6H4-
3,4-Me2C6H3-
2-Thienyl-
C6H5CHꢂ=ꢂCH-
i-Pr-
4
60
5
5
70
6
6
80
7
7
100
100
100
100
100
100
100
100
100
100
100
0.35 ꢃ 96
ꢃ 85
0.25 ꢃ 94
8
8
1
9
9
10
11
12
13
14
15
16
17
18
19
20
21
10
11
12
13
14
15
16
17
5
4
7
7
ꢃ 92
ꢃ 87
ꢃ 78
ꢃ 74
200ꢃ Tolueneꢃ
200ꢃ THF
200ꢃ Et2O
200ꢃ CH3CN ꢃ
200ꢃ DMSO
200ꢃ DMF
200ꢃ MeOH
ꢃ
ꢃ
12 ꢃ 60
12 ꢃ 61
12 ꢃ NRd
12 ꢃ NR
ꢃ
ꢃ
ꢃ
t-Bu-
Cyclohexanone
60ꢃ
–
C6H5-ꢃ C6H5-
30ꢃ 1r
45ꢃ 1s
20ꢃ 1t
aTo a solution of benzaldehyde (1.0 mmol) and EDA (1.2 mmol) in
solvents was added MgI2⋅(Et2O)n and DIPEA at room temperature.
bRelative to the benzaldehyde.
C6H5-ꢃ 4-MeOC6H4-
C6H5-ꢃ 4-NO2C6H4-
cYields after silica gel column chromatography purification.
dNRꢂ=ꢂNo reaction.
aTo a solution of aldehyde (1.0 mmol) and acyldiazomethane
(1.2 mmol) in CH2Cl2 was added 1.0 mmol of MgI2⋅(Et2O)n and
2.0 mmol of DIPEA at room temperature.
bYields after silica gel column chromatography purification.
cNRꢂ=ꢂNo reaction.
stoichiometry was checked by varying the amounts of
MgI2⋅(Et2O)n. As shown in Table 1, the yields of ethyl
3-hydroxy-2-diazo-3-phenyl propionate are improved by
increasing the amount of MgI2⋅(Et2O)n (Table 1, entries etherate was almost inactive in terms of substrate con-
2–7). 1.0 equivalent of MgI2⋅(Et2O)n was sufficient. In version and yield.
addition, the amount of DIPEA has also effects on the
With these optimal conditions in hand, we explored
reaction conversion and yield. 2.0 equivalent of DIPEA the scope and limitation of this simple process by the
was enough, although good yield was also afforded with reaction of electronically and functionally diverse alde-
3.0 equivalent of DIPEA (Table 1, entries eight and nine). hydes under the same conditions. There is no need to
Of various untreated solvents screened, excellent yield exclude moisture and oxygen from the reaction system.
was obtained in non-coordinating reaction media CH2Cl2, The experimental results are summarized in Table 2. MgI2
and good yields are afforded in CHCl3 and toluene, etherate-DIPEA could promote the direct aldol coupling
respectively (Table 1, entries 10 and 11). Moderate yields of acyldiazomethane with various aldehydes in good to
of the product were isolated in tetrahydrofuran (THF) excellent yields in a short period. Interestingly enough,
and Et2O (Table 1, entries 12 and 13), while low yields the nucleophilic addition of acyldiazomethane with alde-
were given in CH3CN and dimethylsulfoxide (DMSO) hydes in the presence of MgI2 etherate and DIPEA was
(Table 1, entries 14 and 15). No reactions were carried out processed efficiently without removal of diazo group.
in dimethylformamide (DMF) and MeOH (Table 1, entries Moreover, the aromatic aldehydes bearing electron-
16 and 17). To examine the halide anion effect, halogen donating and electron-withdrawing groups in the aro-
analogs of MgI2 etherate, MgBr2 etherate and MgCl2 ether- matic ring were reacted smoothly to afford the desired
ate were compared under parallel reaction conditions aldol adducts in good to excellent yields (Table 2, entries
(1.0 equivalent of promoters). MgCl2 etherate and MgBr2 2–14). Furthermore, we have observed the following
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X. Xie et al.: MgI2 etherate-promoted aldol addition of acyldiazomethane with aldehydesꢁ
ꢁ89
delicate electronic effects: (1) Aromatic aldehydes with Typical procedure of MgI2 etherate-promoted aldol
an electron-withdrawing substituent (i.e. Cl, F and NO2) reaction of aldehyde with acyldiazomethane
reacted faster than benzaldehyde and provided the corre-
sponding adducts in excellent yields (Table 2, entries 2–9). To a stirred mixture solution of benzaldehyde (105 mg, 1.0 mmol) and
EDA (137 mg, 1.2 mmol) in CH2Cl2 (10 mL) was added a freshly pre-
(2) Aromatic aldehydes with an electron-donating substit-
pared MgI2 etherate (Arkley et al., 1962) (1.0 mmol) at room tempera-
uent (i.e. OMe, Me) afforded the corresponding adducts in
ture, followed by addition of DIPEA (258 mg, 2.0 mmol). The resulting
reaction mixture was stirred at room temperature for 20 min and
lower yields than benzaldehyde (Table 2, entries 10–13).
Seemingly, this reactivity of aromatic aldehydes is prin-
cipally dependent on the inherent electrophilicity of the
carbonyl group. Heteroaromatic aldehyde, such as 2-thio-
phenealdehyde, was a good substrate as well (Table 2,
entry 14). Acid-sensitive aldehyde, such as cinnamalde-
hyde, reacted with EDA to afford the 1,2-adduct in good
yield without any decomposition or polymerization under
the present reaction conditions (Table 2, entry 15). Also,
the aliphatic aldehydes with the bulkier substituents
such as isopropyl and tert-butyl groups gave good yields
(Table 2, entries 16 and 17). Gratifyingly, the reactivity
of benzoyldiazomethane (Rꢀ=ꢀPh) toward the aromatic
aldehydes bearing electron-withdrawing groups and
electron-donating groups is similar compared to that of
EDA under the identical condition (Table 2, entries 19–21),
which afforded the desired products in excellent yields. In
general, aromatic, heteroaromatic, and α,β-unsaturated
aldehydes underwent the conversion efficiently in a short
period, whereas aliphatic and aromatic ketones, such as
cyclohexanone and acetophenone, with EDA did not yield
any product even prolonging the reaction time in the pres-
ence of MgI2 etherate and DIPEA.
In summary, we have demonstrated the unique reac-
tivity of MgI2 etherate in aldol coupling of aldehydes with
acyldiazomethane. This magnesium-promoted aldol addi-
tion is mild, efficient and operationally simple. Iodide
counterion and a non-coordinating reaction medium
are critical factors for the unique reactivity of this reac-
tion system. Further investigation on the reactivity of
MgI2 etherate in other C-C bond constructing reactions is
ongoing in our laboratory.
quenched with saturated aqueous Na2SO3. Extractive workup with
ether and chromatographic purification of the crude product on sil-
ica gel gave the desired aldol adduct in 96% yield.
Ethyl 2-diazo-3-hydroxy-3-phenylpropanoate (Varala et al., 2006):
Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.31 (t, Jꢀ=ꢀ7.2 Hz, 3H), 3.26 (br s, 1H),
4.29 (q, Jꢀ=ꢀ7.2 Hz, 2H), 5.93 (s, 1H), 7.28–7.45 (m, 5H).
Ethyl 3-(4-chlorophenyl)-2-diazo-3-hydroxypropanoate (Varala
et al., 2006): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.69 (br s, 1H), 4.25 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.87 (s, 1H), 7.34–7.38 (m, 4 H).
Ethyl 2-diazo-3-(4-fluorophenyl)-3-hydroxypropanoate (Varala
et al., 2006): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.52 (br s, 1H), 4.26 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.89 (s, 1H), 7.06–7.09 (m, 2H),
7.40–7.43 (m, 2H).
Ethyl 3-(4-bromophenyl)-2-diazo-3-hydroxypropanoate (Varala
et al., 2006): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.30 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.40 (br s, 1 H), 4.27 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.87 (s, 1H), 7.32 (d, Jꢀ=ꢀ8.4 Hz,
2H), 7.50–7.53 (m, 2H).
Ethyl 2-diazo-3-hydroxy-3-(4-nitrophenyl)propanoate (Varala
et al., 2006): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.28 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.90 (br s, 1H), 4.26 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.99 (s, 1H), 7.63 (d, Jꢀ=ꢀ8.6 Hz,
2H), 8.21–8.24 (m, 2H).
Ethyl 2-diazo-3-hydroxy-3-(4-(trifluoromethyl)phenyl) pro-
1
panoate (Hasegawa et al., 2006): Yellow solid. m.p. 52.3–53.1°C; H
NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.2 Hz, 3H), 3.65 (br s, 1H), 4.27 (q, Jꢀ=ꢀ7.2 Hz,
2H), 5.96 (s, 1H), 7.56 (d, Jꢀ=ꢀ8.2 Hz, 2H), 7.65 (d, Jꢀ=ꢀ8.2 Hz, 2H).
Ethyl 2-diazo-3-(3,4-difluorophenyl)-3-hydroxypropanoate: Yel-
−1
low liquid. FT-IR (KBr) (cm ): 3439, 2101, 1671, 1613, 1520, 1474, 1433,
1
1343, 1285, 1110, 1037, 787; H NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.70 (br s, 1H), 4.27 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.87 (s, 1H), 7.15–7.18 (m, 2H),
7.28–7.32 (m, 1H); 13C NMR (CDCl3): δꢀ=ꢀ166.1, 151.3 (dd, Jꢀ=ꢀ12.7 Hz,
Jꢀ=ꢀ25.4 Hz), 149.3 (dd, Jꢀ=ꢀ12.7 Hz, Jꢀ=ꢀ25.3 Hz), 136.3, 121.8 (dd, Jꢀ=ꢀ3.6,
6.4 Hz), 117.6 (d, Jꢀ=ꢀ17.4 Hz), 115.1 (d, Jꢀ=ꢀ18.4), 67.7, 61.4, 14.4; HRMS
+
(ESI): calcd. for C11H10F2N2NaO3 [Mꢀ+ꢀNa] 279.0552; found 279.0552.
Experimental section
General methods
Ethyl 3-(2-chlorophenyl)-2-diazo-3-hydroxypropanoate (Trost
1
et al., 2012): Yellow solid. H NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.2 Hz, 3H),
3.89 (br s, 1H), 4.27 (q, Jꢀ=ꢀ7.2 Hz, 2H), 6.13 (d, Jꢀ=ꢀ3.7 Hz, 1H), 7.25–7.28
(m, 1H), 7.31–7.33 (m, 1H), 7.34–7.39 (m, 1H), 7.70–7.72 (m, 1H).
For product purification by flash column chromatography, silica
gel (200ꢀ~ꢀ300 mesh) and light petroleum ether (b.p. 60ꢀ~ꢀ90°C)
were used. 1H NMR and 13C NMR were recorded with Bruker
AVANCE III instrument at 500 MHz and trimethylsilyl was used
as internal standard. High resolution mass spectrometry (electro-
spray ionization) [HRMS (ESI)] were determined on a Therm LCQ
TM Deca XP plus spectrometer.
Ethyl 2-diazo-3-hydroxy-3-(3-nitrophenyl)propanoate (Kantham
1
et al., 2007a,b): Yellow liquid. H NMR (CDCl3): δꢀ=ꢀ1.29 (t, Jꢀ=ꢀ7.1 Hz,
3H), 3.90 (br s, 1H), 4.27 (q, Jꢀ=ꢀ7.1 Hz, 2H), 6.00 (s, 1H), 7.58 (t,
Jꢀ=ꢀ8.0 Hz, 1H), 7.78 (d, Jꢀ=ꢀ7.8 Hz, 1H), 8.17 (dd, Jꢀ=ꢀ1.6, 8.1 Hz, 1H), 8.33
(s, 1H).
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ꢀX. Xie et al.: MgI2 etherate-promoted aldol addition of acyldiazomethane with aldehydes
90ꢀ
Ethyl 2-diazo-3-hydroxy-3-(3-methoxyphenyl)propanoate (Trost
et al., 2012): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.28 (t, Jꢀ=ꢀ7.1 Hz, 3H),
3.65 (br s, 1H), 4.25 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.87 (s, 1H), 6.83–6.85 (m, 1H),
6.98 (s, 1H), 6.99 (s, 1H), 7.28 (dd, Jꢀ=ꢀ7.5, 12.4 Hz, 1H); 13C NMR (CDCl3):
δꢀ=ꢀ166.5, 159.9, 140.9, 129.8, 117.9, 113.8, 111.1, 68.4, 61.2, 55.2, 14.4.
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Ethyl 2-diazo-3-(3,4-dimethylphenyl)-3-hydroxypropanoate: Yel-
−1
low liquid. FT-IR (KBr) (cm ): 3444, 2097, 1671, 1503, 1450, 1398, 1373,
1341, 1291, 1108, 1026, 780; 1H NMR (CDCl3): δꢀ=ꢀ1.31 (t, Jꢀ=ꢀ7.1 Hz, 3H),
2.27 (s, 3H), 2.28 (s, 3H), 4.29 (q, Jꢀ=ꢀ7.1 Hz, 2H), 5.86 (s, 1H), 7.15 (s, 2H),
7.20 (s, 1H); 13C NMR (CDCl3): δꢀ=ꢀ166.4, 136.9, 136.6, 136.5, 129.9, 126.9,
123.0, 68.5, 61.0, 19.7, 19.3, 14.4; HRMS (ESI): calcd. for C13H16N2NaO3
+
[Mꢀ+ꢀNa] 271.1053; found 271.1054.
Jiang, N.; Wang, J. DBU-promoted condensation of acyldiazometh-
anes with aldehydes and imines under catalytic conditions.
Tetrahedron Lett. 2002, 43, 1285–1287.
Jiang, N.; Qu, Z.; Wang, J. 1,2-aryl and 1,2-hydride migration in
transition metal complex catalyzed diazo decomposition: a
novel approach to α-aryl-β-enamino esters. Org. Lett. 2001, 3,
2989–2992.
Ethyl 2-diazo-3-hydroxy-3-(thiophen-2-yl)propanoate (Kanemasa
et al., 1999): Yellow liquid. 1H NMR (CDCl3): δꢀ=ꢀ1.31 (t, Jꢀ=ꢀ7.2 Hz, 3H),
3.39 (br s, 1H), 4.29 (q, Jꢀ=ꢀ7.2 Hz, 2H), 6.12 (s, 1H), 7.02 (dd, Jꢀ=ꢀ3.5,
5.0 Hz, 1H), 7.03–7.07 (m, 1H), 7.31 (dd, Jꢀ=ꢀ1.2, 5.0 Hz, 1H).
(E)-Ethyl 2-diazo-3-hydroxy-5-phenylpent-4-enoate (Varala et al.,
1
2006): Yellow liquid. H NMR (CDCl3): δꢀ=ꢀ1.32 (t, Jꢀ=ꢀ7.2 Hz, 3H), 2.87
Kanemasa, S.; Araki, T.; Kanai, T.; Wada, E. Fluoride-catalyzed aldol
reaction of ethyl trimethylsilyldiazoacetate with aldehydes
leading to ethyl α-diazo-β-hydroxy esters and rhodium
catalyzed decarboxylative rearrangement of diazo urethanes
leading to β-amino acrylates. Tetrahedron Lett. 1999, 40,
5259–5262.
(br s, 1H), 4.27 (q, Jꢀ=ꢀ7.2 Hz, 2H), 5.46 (s, 1H), 6.28 (dd, Jꢀ=ꢀ5.6, 16.0 Hz,
1H), 6.82 (d, Jꢀ=ꢀ15.6 Hz, 1H), 7.29–7.42 (m, 5H).
Ethyl 2-diazo-3-hydroxy-4-methylpentanoate (Arai et al., 2004):
1H NMR (CDCl3): δꢀ=ꢀ0.94 (d, Jꢀ=ꢀ6.8 Hz, 3H), 1.07 (d, Jꢀ=ꢀ6.7 Hz, 3H), 1.28
(t, Jꢀ=ꢀ7.1 Hz, 3H), 1.85–1.92 (m, 1H), 2.79 (br s, 1H), 4.21–4.30 (m, 3H).
Kantham, M. L.; Balasubrahmanyam, V.; Kumar, K. B.; Venkanna,
G. F.; Figueras, F. Catalysis in water. Aldol-type reaction of alde-
hydes and imines with ethyl diazoacetate catalyzed by highly
basic magnesium/lanthanum mixed oxide. Adv. Synth. Catal.
2007a, 349, 1887–1890.
Kantham, M. L.; Chakrapani, L.; Ramani, T. Synthesis of α-diazo-
β-hydroxy esters using nanocrystalline MgO. Tetrahedron Lett.
2007b, 48, 6121–6123.
Krishna, P. R.; Prapurna, Y. L.; Alivelu, M. Benzoic acid catalyzed
aldol-type condensation of aldehydes with ethyl diazoacetate:
highly diastereoselective products with chiral aldehydes. Eur. J.
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Li, W. D.; Zhang, X. X. Chemoselective aldol reactions of silyl eno-
lates catalyzed by MgI2 etherate. Org. Lett. 2002, 4, 3485–3488.
Liu, Y. S.; Shen, H. Z.; Zhang, X. X. An efficient direct-aldol addition
of methyl ketones with aldehydes promoted by MgI2 etherate.
Main Group Met Chem. 2012, 35, 111–115.
Ethyl 2-diazo-3-hydroxy-4,4-dimethylpentanoate (Hasegawa
1
et al., 2006): Yellow liquid. H NMR (CDCl3): δꢀ=ꢀ0.97 (s, 9H), 1.28
(t, Jꢀ=ꢀ7.1 Hz, 3H), 2.94 (br s, 1H), 4.19–4.23 (m, 3H).
2-Diazo-3-hydroxy-1,3-diphenylpropan-1-one (Jiang and Wang,
1
2002): Yellow liquid. H NMR (CDCl3): δꢀ=ꢀ4.22 (br s, 1H), 6.22 (s, 1H),
7.33–7.36 (m, 1H), 7.40–7.44 (m, 4H), 7.49–7.53 (m, 3H), 7.62–7.63 (d,
Jꢀ=ꢀ7.3 Hz, 2H).
2-Diazo-3-hydroxy-3-(4-methoxyphenyl)-1-phenylpropan-1-one:
−1
Yellow solid. m.p. 98–99°C; FT-IR (KBr) (cm ): 3425, 2067, 1598, 1569,
1513, 1444, 1349, 1236, 1173, 1037, 772, 702; 1H NMR (CDCl3): δꢀ=ꢀ3.82 (s,
3H), 3.89 (s, 1H), 6.16 (s, 1H), 6.94 (d, Jꢀ=ꢀ8.7 Hz, 2H), 7.40–7.45 (m, 4H),
7.50–7.53 (m, 1H), 7.62–7.63 (m, 2H); 13C NMR (CDCl3): δꢀ=ꢀ189.2, 159.6,
137.3, 132.0, 131.7, 128.7, 127.3, 127.2, 114.2, 68.9, 55.3; HRMS (ESI): calcd.
+
for C16H14N2NaO3 [Mꢀ+ꢀNa] 305.0897; found 305.0902.
Miyauchi, K.; Hori, K.; Hirai, T.; Takebayashi, M.; Ibata, T. The acid-
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Moody, C. J.; Taylor, R. J. Rhodium carbenoid mediated
cyclizations. Use of ethyl lithiodiazoacetate in the preparation
2-Diazo-3-hydroxy-3-(4-nitrophenyl)-1-phenylpropan-1-one
(Miyauchi et al., 1981): Yellow solid. m.p. 113–114°C; 1H NMR (CDCl3):
δꢀ=ꢀ4.17 (s, 1H), 6.31 (s, 1H), 7.45 (m, 2H), 7.53–7.56 (m, 1H), 7.60–7.62 (m,
2H), 7.69 (d, Jꢀ=ꢀ8.7 Hz, 2H), 8.26 (d, Jꢀ=ꢀ8.8 Hz, 2H).
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