Unique chemoselective Mukaiyama aldol reaction of silyl enol diazoacetate with aldehydes and acetals catalyzed by MgI2 etherate

Article abstract of DOI:10.1016/j.tet.2019.130682

Functionalized diazo acetoacetates are prepared by an efficient Mukaiyama aldol reaction between 3-TBSO-2-diazo-3-butenoate with aldehydes and acetals under mild reaction conditions. A variety of substituted aldehydes and the corresponding acetals are both accessible in good to excellent yields through this methodology. MgI₂ etherate (MgI₂·(OEt₂)_n) is the preferred catalyst and, the addition proceeds without decomposition of the diazo moiety. In addition, this MgI₂·(OEt₂)_n-catalyzed Mukaiyama aldol reaction shows unique chemoselectivity towards aldehydes and acetals.

Full text of DOI:10.1016/j.tet.2019.130682

Journal Pre-proof
Unique chemoselective Mukaiyama aldol reaction of silyl enol diazoacetate with
aldehydes and acetals catalyzed by MgI etherate
2
Xiangwei Meng, Haokun Pan, Tengjiang Zhong, Xingxian Zhang
PII:
S0040-4020(19)31057-9
https://doi.org/10.1016/j.tet.2019.130682
TET 130682
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 August 2019
Revised Date: 16 September 2019
Accepted Date: 8 October 2019
Please cite this article as: Meng X, Pan H, Zhong T, Zhang X, Unique chemoselective Mukaiyama aldol
reaction of silyl enol diazoacetate with aldehydes and acetals catalyzed by MgI etherate, Tetrahedron
2
(2019), doi: https://doi.org/10.1016/j.tet.2019.130682.
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Graphical Abstract
Unique Chemoselective Mukaiyama Aldol Reaction
of Silyl Enol Diazoacetate with Aldehydes and Acetals
Catalyzed by MgI2 Etherate
Xiangwei Meng, Haokun Pan, Tengjiang Zhong, Xingxian Zhang*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, P. R. China.

Graphical Abstract
Unique Chemoselective Mukaiyama Aldol Reaction of
Silyl Enol Diazoacetate with Aldehydes and Acetals
Catalyzed by MgI2 Etherate
Xiangwei Meng, Haokun Pan, Tengjiang Zhong, Xingxian Zhang*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China.
2

Tetrahedron
journal homepage: www.elsevier.com
Unique Chemoselective Mukaiyama Aldol Reaction of Silyl Enol Diazoacetate
with Aldehydes and Acetals Catalyzed by MgI2 Etherate
Xiangwei Meng, Haokun Pan, Tengjiang Zhong, Xingxian Zhang
*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Functionalized diazo acetoacetates are prepared by an efficient Mukaiyama aldol reaction
between 3-TBSO-2-diazo-3-butenoate with aldehydes and acetals under mild reaction
conditions. A variety of substituted aldehydes and the corresponding acetals are both accessible
in good to excellent yields through this methodology. MgI2 etherate (MgI2•(OEt2)n) is the
preferred catalyst and, the addition proceeds without decomposition of the diazo moiety. In
addition, this MgI2•(OEt2)n-catalyzed Mukaiyama aldol reaction shows unique chemoselectivity
towards aldehydes and acetals.
Available online
Keywords:
Aldehyde
Acetal
Siloxyvinyldiazoacetate
Mukaiyama aldol reaction
Chemoselective
MgI2 etherate
* Corresponding authors.
E-mail address: zhangxx@zjut.edu.cn.
3

Introduction
Entry
1
RCHO
t (h)
1.5
Product
Yield (%)b
95
Diazoacetoacetates are useful intermediates in organic
synthesis due to their high stability and unique reactivity relative
to other classes of diazo compounds.1 In particular,
diazoacetoacetate derivatives have been employed in
cyclopropanation, ylide formation, and assorted X-H insertion
reactions (X = C, N, O, Si, etc.).2,3 Such diazoacetoacetate
derivatives not only provide for simpler methods than the parent
diazoacetates but also result in increased functionality in the
products.4 Traditionally, diazo compounds were prepared by
multistep synthesis involving diazo transfer as the final step.5,6
Alternative methods were developed which involve the base-
mediated condensation of diazo compounds with various
electrophiles. However these reactions generally require
stoichiometric amounts of the reagents under relatively harsh
reaction conditions.7,8 Therefore, an efficient synthesis of
structurally complex diazoacetoacetate derivatives under mild
conditions remains a challenging problem.
3a
2
3
1.5
6
3b
3c
98
90
2
3
3
3
8
94
89
87
89
73
4
5
6
3d
3e
3f
7
8
3g
3h
Although earlier studies have shown that condensation of
ethyl diazoacetate with aldehydes and ketones can occur with
retention of the diazo group, only recently few methods involving
Lewis acids have been used to couple diazoacetates with
aldehydes. Many Lewis acid catalysts have been utilized into the
CHO
O2N
condensation of diazoacetoacetate derivatives with aldehydes,
such as, TiCl4,
7
Sc(OTf)3,9 Zn(OTf)2,10 AgF11 and
9
8
3i
3j
82
[Cu(CH3CN)4]PF6.12 But stoichiometric amounts of the Lewis
acids were required to achieve full conversion, and these
reactions occurred at -78 °C. Magnesium, a naturally abundant
main group metal, has been actively investigated as a catalyst in
the field of C-C bond formation and functional group
transformation.13 In our previous papers,14 we have demonstrated
that MgI2 etherate could efficiently catalyze the direct aldol
reaction of acyldiazomethane with aldehydes in the presence of
DIPEA under mild conditions with high chemoselectivity.
Herein, we wish to report the preliminary results on the unique
catalytic reactivity of MgI2 etherate for the mild, efficient and
chemoselective Mukaiyama aldol reaction of aryl aldehydes and
acetals with ethyl 3-TBSO-2-diazo-3-butenoate (Scheme 1).
10
11
8
4
86
89
3k
3l
12
13
4
4
89
88
3m
a
To a solution of aldehyde 1 (1.0 mmol) and α-diazo silyl enolate 2 (1.2
mmol) in CH2Cl2 was added 10% mol of MgI2•(Et2O)n at room temperature
and the reaction mixture was stirred for several hours.
b Isolated yield by silica gel flash chromatography.
Scheme 1. MgI2 etherate-catalyzed Mukaiyama aldol reaction of aldehydes or
acetals with 3-TBSO-2-diazo-3-butenoate.
As shown in Table 1, Mukaiyama-aldol reaction of aryl
aldehydes with α-diazo silyl enolate 2 proceeded smoothly and
provided the desired adduct in good to excellent yields, which
diazo functionality is retained. Furthermore, we have observed
the following delicate electronic effects: (1) aldehydes bearing an
electron-donating group (i.e., OMe, Me) reacted much faster than
benzaldehyde and provided the corresponding products in
excellent yields (Table 1, entries 2-4). (2) aldehydes bearing
electron-withdrawing group (i.e., Cl, Br, F, NO2, CF3)
deactivated aryl aldehydes and afforded the corresponding
diazoacetoacetate derivatives in less yields (Table 1, entries 5-
10). Moreover, Mukaiyama-aldol condensation of heteroaromatic
aldehydes, such as furfural and 2-thienaldehyde, with α-diazo
silyl enolate 2 in the presence of 10 mol% MgI2 etherate to
provide the desired products in good yields, respectively (Table
1, entries 11 and 12). As well, α, β-unsaturated aldehyde such as
cinnamaldehyde gave good yield of 1, 2-addition product (Table
1, entry 13). Unfortunately, aliphatic aldehydes and ketones are
unreactive toward α-diazo silyl enolate 2 in the presence of MgI2
etherate.
Results and discussion
Initially, we have chosen benzaldehyde as a model substrate to
survey the reaction optimal catalyst. To examine the halide anion
effect, halogen analogs of MgI2 etherate, MgBr2 etherate, MgCl2
and Mg(ClO4)2 were compared under parallel reaction conditions,
respectively. The best result has been observed with MgI2
etherate as the catalyst in 94% yield. Good yield (85%) was also
given by using 10 mol% of MgClO4. However, MgCl2 and
MgBr2 etherate were inert to this reaction. We further explored
the scope of this simple process by reaction of electronically,
sterically and functionally diverse aldehydes catalyzed by MgI2
etherate in CH2Cl2 at room temperature (Table 1).
Table 1. Mukaiyama aldol reaction of α-diazo silyl enolate with
aldehydes catalyzed by MgI2•(Et2O)n.a
This interesting chemoselectivity was further evaluated by
crossover experiments of various aryl aldehydes with α-diazo
4

silyl enolate 2, respectively. The MgI2 etherate catalysis shows
high levels of aryl aldehydes discrimination in the competitive
reactions with α-diazo silyl enolate 2 (Table 2). The MgI2
etherate catalyst can uniquely recognize the delicate difference in
electronic effect involved in various aryl aldehydes. p-
Anisaldehyde is more reactive than benzaldehyde and the aldol
product of p-anisaldehyde was predominately afforded (Table 2,
entry 1). Interestingly enough, 4-nitrobenzaldehyde is much less
reactive than benzaldehyde and p-anisaldehyde in the MgI2
etherate-catalyzed process (Table 2, entries 2 and 3). Only the
Mukaiyama aldol condensation product of benzaldehyde and p-
anisaldehyde was provided, respectively. In crossover-reaction of
4-trifluoromethylbenzaldehyde with p-anisaldehyde, the former
is also less reactive than the latter (Table 3, entry 4). Furthermore,
in crossover reactions of 4-trifluoromethylbenzaldehyde with 4-
nitrobenzaldehyde, the reaction predominately gave the aldol
product of 4-trifluoromethylbenzaldehyde (Table 2, entry 5),
which demonstrated that the electron-withdrawing ability of nitro
group is much stronger than that of CF3 group.
Scheme 2. Proposed mechanism of Mukaiyama-aldol of aldehyde with diazo
silyl enolate catalyzed by MgI2•(Et2O)n
We investigated the chemoselectivity of Mukaiyama-aldol of
aldehydes over its parent imines in MgI2•(Et2O)n-catalyzed
process (Table 3). It is worthy to be noted that the high
chemoselectivity of imines was observed versus aldehydes.
Obviously, the reactivity of α-diazo silyl enolate 2 to imine is
higher than its parent aldehyde in this catalytic system.
Table 2. Cross Mukaiyama aldol reaction of α-diazo silyl enolate
with aromatic aldehyde.a
Table 3. Chemoselective aldol of aldehydes over its parent
imines a
Ph
O
O
O
NH
Entry
Ar
Ar’
time
(h)
ratiob
(3 / 3’)
yield
(%)c
97
OEt
OEt
Ar
Ar
Ph
H
TBSO
O
N2
OH OH
4
O
N
1) 10 mol% MgI2 (OEt2)
2) 4.0 mol/L HCl/MeOH
n ,CH2Cl2, r.t.
OEt
Ar
H
Ar
1
2
3
4
5
C6H5
4-MeOC6H4
4-NO2C6H4
4-NO2C6H4
4-CF3C6H4
4-NO2C6H4
2
2
1
1
8
10:90
> 99 / < 1
N2
94
C6H5
2
N2
> 99 / < 1
> 99 / < 1
96
4-MeOC6H4
4-MeOC6H4
4-CF3C6H4
3
96
85
85:15
Entry
Ar
C6H5
4-NO2C6H4
4-MeOC6H4
2-Thienyl
Ar
time
Ratio
Yield
(%)c
90
(h)
(4 / 3)b
a To a solution of aldehyde 1 (1.0 mmol), aldehyde 1’ (1.0 mmol) and α-diazo
silyl enolate 2 (1.0 mmol) in CH2Cl2 was added 10% mol of MgI2•(Et2O)n
and the reaction mixture was stirred for several hours.
b Ratio of 3/3’ was determined by column chromatography.
c Isolated overall yields.
1
2
3
4
C6H5
2
> 99 / < 1
> 99 / < 1
> 99 / < 1
> 99 / < 1
4-NO2C6H4
4-MeOC6H4
2-Thienyl
4
0.5
1
92
91
86
a The reaction was carried out by addition of aldehyde (0.5 mmol), imine (0.5
mmol) with silyl enol diazoacetate 2 (0.5 mmol) catalyzed by 10 mol %
MgI2•(OEt2)n in CH2Cl2 at room temperature.
Apparently, the reactivity of aldehydes is principally
dependent on the electron density of the formyl oxygen atom or
the coordinating ability of the formyl group toward Mg(II), not
the inherent electrophilicity of carbonyl,15 which implies the
formation of a coordination complex [RCH=O→MgI•(OEt2)n]+I-,
presumably responsible for the effective activation of electron-
rich aldehydic carbonyl.16 The reactivity of aromatic aldehyde is
subject to its inherent electron density of the aldehyde group,
which selectively activates the electron-rich functionality of
aromatic aldehydes. Thus, MgI2 etherate represents a novel type
of the formation of diazoacetoacetate in the presence of MgI2
etherate as a catalyst. It is also evident that the cationic
coordinate of the resultant Mg-enolate might be involved. These
facts underscore the uniqueness of Mg-catalyzed aldolization.
The proposed catalytic cycle (Scheme 2) suggests that the
transient iododimethyl(tert-butyl)silane (TBSI) may facilitate the
irreversible silylation of Mg-aldolate and regeneration of catalyst
MgI2•(Et2O)n.
b Ratio was determined by silica gel flash chromatography.
c Isolated yields by silica gel flash chromatography.
Acetals are typical carbonyl protecting groups as well as
synthetic equivalents of the carbonyl moiety. However, acetals
can act as strong electrophiles under acidic conditions by
generating an oxonium ion intermediate. Encouraged by the
excellent results obtained with aldehydes, we decided to explore
the reactivity of their parent acetals. Dimethyl acetals 5a-5j were
exposed to react with α-diazo silyl enolate 2 under the similar
conditions as previously employed the condensation of aldehydes
(Table 4). Accordingly, we observed an excellent results in the
efficiency of the reaction, and good yields were obtained in the
presence of 10 mol% MgI2•(OEt2)n. We have observed the
following delicate electronic effects: (1) aryl acetals bearing an
electron-donating group (i.e., OMe, Me) reacted much faster than
benzaldehyde and provided the corresponding products in
excellent yields (Table 4, entries 2-4). Aryl acetals bearing
electron-withdrawing group (i.e., NO2) deactivated aryl acetals
remarkably (Table 4, entry 9). (2) MgI2 etherate can differentiate
the steric difference in aryl acetals to much higher extents (Table
4, entries 2, 4 and 10). Unfortunately, aliphatic acetals are
unreactive toward α-diazo silyl enolate 2.
Moreover, the relative reactivity of aldehydes and acetals was
investigated in a competition experiment in their condensation
with 2 (Table 5). It is worthy to be noted that acetal reacted faster
than its parent aldehyde to exclusively afford the adduct 6.
5

Table 4. Mukaiyama aldol of α-diazo silyl enolate with acetals
catalyzed by MgI2•(Et2O)n
Table 5. Chemoselective aldol of aldehyde over its parent acetal
with silyl enol diazoacetate catalyzed by MgI2•(OEt2)n
a
a
Entry
1
Acetals
t (h)
1
Product
Yield (%)b
85
6a
Entry
R
Time (h)
Ratio (6 / 3)b
>99 / <1
yield (%)c
85
94
82
85
85
1
2
3
4
5
Ph
1
2
0.5
6b
95
4-MeOC6H4
>99 / <1
0.5
1.5
>99 / <1
>99 / <1
>99 / <1
3-MeOC6H4
4-MeC6H4
2-Thienyl
1
2
1.5
1.5
6c
87
84
a
3
4
To a solution of aldehyde (1.0 mmol), acetal (1.0 mmol) and α-diazo silyl
enolate 2 (1.0 mmol) in CH2Cl2 was added 10% mol MgI2•(Et2O)n and the
mixture was stirred for several hours.
b Ratio was determined by column chromatography.
c Isolated yields by silica gel flash chromatography.
6d
irreversible silylation of MeOMgI etherate by transient TBSI to
regenerate MgI2•(OEt2)n and expel TBSOMe as the
thermodynamically favored by product as shown in the proposed
catalytic cycle (Scheme 3). This reaction suggests the capability
of MgI2 etherate to serve as Lewis acid activator.
5
0.5
6e
93
6
7
8
1
1
8
6f
6g
6h
82
80
76
Scheme 3. Proposed mechanism of Mukaiyama aldol of acetal with diazo
silyl enolate catalyzed by MgI2•(Et2O)n
Conclusion
In conclusion, we have developed a mild, convenient and
efficient methodology for the synthesis of functionalized
diazoacetoacetate compounds by Mukaiyama aldol condensation
of aldehydes or acetals with α-diazo silyl enolate catalyzed by
MgI2 etherate. Moreover, we have demonstrated that the MgI2
etherate catalysis system has unique chemoselectivity to the
substrates. Exploitation of this protocol for generation of novel
multicyclic structures is actively pursued in our lab.
9
24
24
6i
6j
NA
NA
10
1. Experimental section
a
Acetal 5 (1.0 mmol) and α-diazo silyl enolate 2 (1.2 mmol) in CH2Cl2 was
1.1. Experimental section
added 10 mol % of MgI2•(Et2O)n at room temperature and the reaction
mixture was stirred for several hours.
Chemicals were purchased from commercial suppliers and
used as delivered. Deuterated solvents were purchased and used
without further purfication. NMR spectra were obtained on a
Waters GCT Premier spectrometer with TMS as the internal
standard and CDCl3 as the solvent. Chemical shifts are given in
b Isolated yields by silica gel flash chromatography.
Consequently, acetals can be considered activating groups of the
carbonyl moiety rather than
Mukaiyama-aldol condensation.
a protecting group in the
1
parts per million (ppm) and coupling constants in Hz. In the H
and 13C spectra, chemical shifts are reported relative to deuterated
solvents (CDCl3: 7.26/77.2 ppm). The following abbreviations
were used for 1H NMR to indicate the signal multiplicity: s
(singlet), d (doublet), t (triplet), m (multiplet), br s (broad
singlet). Melting points were measured on a BUCHI B-540 and
uncorrected. FT-IR were recorded on a Bruker Tensor 27
In view of the importance of acetal functioning as a carbonyl
equivalent for C–C bond cross coupling,17 we revealed here that
MgI2•(OEt2)n is a novel mild Lewis acid catalyst for effective and
chemoselective acetal activation. The preferential activation of
acetal over its parent aldehyde may be attributed to the fast and
6

1.2.5. Ethyl 2-diazo-5-hydroxy-3-oxo-5-phenylpentanoate (3a)
spectrometer. Analytical thin-layer chromatography was carried
out using commercial aluminum sheets precoated (0.2 mm layer
thickness) with silica gel GF254, and visualization was e ected
with short wavelength UV light (254 nm). HRMS (ESI) were
determined on a Therm LCQ TM Deca XP plus spectrometer.
Product purfication by flash chromatography was performed
using 200-400 mesh silica gel. Aldehydes and acetals were
commercially available and were used without further
purfication. α-Diazo silyl enolate was prepared according to the
reported literature.18
Compound 3a was prepared according to the general
procedure and was obtained in 95% yield as a yellow oil. 20 Rf =
0.33 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.32 (t, J =
7.2 Hz, 3H), 3.27-3.30 (m, 2H), 4.28 (q, J = 7.2 Hz, 2H), 5.21
(dd, J = 4.0, 8.4 Hz, 1H), 7.25-7.41 (m, 5H) ppm. IR (film) ν:
3507 (OH), 2138 (C=N=N), 1716 (C=O), 1651, 1373, 1303,
1204, 1131, 1060, 746 cm-1. HRMS (ESI): calcd for
C13H14N2NaO4 [M+Na]+ 285.0846; found285.0849.
1.2.6. Ethyl 2-diazo-5-hydroxy-5-(4-methoxyphenyl)-3-
oxopentanoate (3b)
1.2. Experimental procedures and product characterization.
1.2.1. General procedure for the synthesis of acetals.
Compound 3b was prepared according to the general
procedure and was obtained in 98% yield as a yellowish solid.21
The dimethyl acetals were prepared according to a literature
procedure.19 To a solution of aldehyde (5.0 mmol) and trimethyl
orthoformate (11.5 mmol) in methanol (10 mL) was added p-
TsOH·H2O (0.05 mmol). The reaction mixture was stirred at
room temperature for several hours. After completion, saturated
NaHCO3 aqueous was added and the resulting mixture was
extracted with ethyl acetate. The combined organic phase was
washed with brine, dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash column
chromatography on a silica gel to give the acetals 5a-5j.
1
m.p. 56-57 (lit. m.p. 57-59 ), Rf = 0.34 (PE : EA = 3 : 1), H
NMR (CDCl3, 500 MHz) δ 1.32 (t, J = 7.1 Hz, 3H), 3.26-3.28
(m,2H), 3.80 (s, 3H), 4.30 (q, J = 7.1 Hz, 2H), 5.16 (dd, J = 3.6,
8.9 Hz, 1H), 6.89 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H)
ppm. IR (film) ν: 3494 (OH), 2134 (C=N=N), 1720 (C=O), 1634,
1524, 1030, 935, 827 cm-1. HRMS (ESI): calcd for
C14H16N2NaO5 [M+Na]+ 315.0951; found 315.0956.
1.2.7. Ethyl 2-diazo-5-hydroxy-3-oxo-5-(p-tolyl) pentanoate (3c)
Compound 3c was prepared according to the general
procedure and was obtained in 90% yield as a yellowish oil, Rf =
0.35 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.31 (t, J =
7.1 Hz, 3H), 2.33 (s, 3H), 3.21-3.32 (m, 2H), 3.50 (s, 1H), 4.28
(q, J = 7.1 Hz, 2H), 5.16 (d, J = 8.9 Hz, 1H), 7.14 (d, J = 7.9 Hz,
2H), 7.28 (d, J = 7.9 Hz, 2H) ppm. 13C NMR (CDCl3, 125 MHz)
δ 191.9, 161.0, 139.9, 136.9, 128.9, 125.6, 69.9, 61.4, 48.5, 20.9,
14.1 ppm. IR (film) ν: 3505 (OH), 2138 (C=N=N), 1717 (C=O),
1651, 1374, 1303, 1203, 1132, 1063, 818, 745 cm-1. HRMS
(ESI): calcd for C14H16N2NaO4 [M+Na]+ 299.1002; found
299.1013
1.2.2. MgI2•(Et2O)n-catalyzed Mukaiyama aldol reaction of α-
diazo silyl enolate with aldehydes.
To a solution of aldehyde (1.0 mmol) and α-diazo silyl enolate
2 (1.2 mmol) in CH2Cl2 (5 mL) was added a freshly prepared
MgI2•(Et2O)n (0.1 mmol, 1.0 mol/L in PhMe/Et2O) at room
temperature. The reaction mixture was stirred for several hours at
room temperature. After completion (monitored by TLC), the
crude reaction mixture was concentrated under reduced pressure.
The crude reaction mixture was dissolved in 5 mL of MeOH and
stirred at 0oC, and then 1.0 mL of 4 mol/L HCl aqueous was
added dropwise. After 1h at 0oC the reaction was quenched by
slow addition of 15 mL of saturated sodium bicarbonate solution
until basic to pH paper. The resulting solution was extracted with
CH2Cl2, and the combined organic layer was dried over
anhydrous magnesium sulfate and then concentrated under
reduced pressure. The residue was purified by flash column
chromatography on a silica gel to give the desired adducts 3a-
3m.
1.2.8. Ethyl 5-(benzo[1,3]dioxol-5-yl)-2-diazo-5-hydroxy-3-
oxopentanoate (3d)
Compound 3d was prepared according to the general
procedure and was obtained in 94% yield as a yellowish solid,
1
m.p.77-79 , Rf = 0.24 (PE : EA = 3 : 1), H NMR (CDCl3, 500
MHz) δ 1.30 (t, J = 7.1 Hz, 3H), 3.20-3.22 (m, 2H), 3.45 (brs,
1H), 4.27 (q, J = 7.1 Hz, 2H), 5.10 (dd, J = 3.9, 8.4 Hz, 1H), 5.91
(s, 2H), 6.73-6.88 (m, 3H) ppm. 13C NMR (CDCl3, 125 MHz) δ
192.2, 161.2, 147.9, 147.0, 137.0, 119.3, 108.3, 106.6, 101.2,
70.3, 62.0, 49.0, 14.7 ppm. IR (film) ν: 3500 (OH), 2138
(C=N=N), 1714 (C=O), 1649, 1489, 1444, 1373, 1037, 931, 808,
745 cm-1. HRMS (ESI): calcd for C14H14N2NaO6 [M+Na]+
329.0744; found 329.0753.
1.2.3. MgI2•(Et2O)n-catalyzed Mukaiyama-aldol reaction of α-
diazo silyl enolate with acetals
To a solution of acetal 5 (1.0 mmol) and α-diazo silyl enolate
2 (1.2 mmol) in CH2Cl2 (5 mL) was added a freshly prepared
MgI2•(Et2O)n (0.1 mmol, 1.0 mol/L in PhMe/Et2O) at room
temperature. The reaction mixture was stirred for several hours at
room temperature. After completion (monitored by TLC), the
crude reaction mixture was concentrated under reduced pressure.
The combined organic phase was washed with brine, dried over
anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was purified by flash column
chromatography on a silica gel to give the desired adducts 6a-6h.
1.2.9. Ethyl 5-(4-chlorophenyl)-2-diazo-5-hydroxy-3-
oxopentanoate (3e)
Compound 3e was prepared according to the general
procedure and was obtained in 89% yield as a yellowish solid.21
m.p. 66-67 , (lit. m.p. 67-68 ), Rf = 0.32 (PE : EA = 3 : 1), 1H
NMR (CDCl3, 500 MHz) δ 1.32 (t, J = 7.2 Hz, 3H), 3.27-3.30
(m, 2H), 4.28 (q, J = 7.2 Hz, 2H), 5.21 (dd, J = 4.0, 8.4 Hz, 1H),
7.25-7.41 (m, 4H) ppm. IR (film) ν: 3515 (OH), 2136 (C=N=N),
1717 (C=O), 1622, 1504, 1028, 930, 835 cm-1. HRMS (ESI):
calcd for C13H13ClN2NaO4 [M+Na]+ 319.0456; found 319.0462.
1.2.4. Typical procedure for crossover reaction.
A schlenk reaction tube was charged with each aldehyde (1.0
mmol), α-diazo silyl enolate 2 (1.0 mmol) and CH2Cl2 (5 mL),
followed by addition of MgI2 etherate (0.1 mmol). The reaction
mixture was stirred at room temperature for several hours.
After work up, flash column chromatography afforded the
desired products. The ratio of each product was determined
by column chromatography isolation.
1.2.10. Ethyl 2-diazo-5-(4-fluorophenyl)-5-hydroxy-3-
oxopentanoate (3f)
Compound 3f was prepared according to the general
procedure and was obtained in 87% yield as a yellowish solid,
7

1
m.p.47-48 , Rf = 0.33 (PE : EA = 3 : 1), H NMR (CDCl3, 500
MHz) δ -62.61. HRMS (ESI): calcd for C14H13F3N2NaO4
MHz) δ 1.22 (t, J = 7.1 Hz, 3H),3.14-3.16 (m, 2H), 3.80(d, J =3.9
Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 5.07-5.10 (m, 1H), 6.90-6.93
(m, 2H), 7.26-7.29 (m, 2H) ppm. 13C NMR (CDCl3, 125 MHz) δ
191.4, 162.8, 160.8 (J C-F = 2.8 Hz), 138.8 (J C-F = 2.8 Hz), 127.2
(J C-F = 8.0 Hz), 114.9 (J C-F = 20.9 Hz), 76.3, 69.2, 61.3, 60.0,
48.4, 13.8 ppm. IR (film) ν: 3549 (OH), 2144 (C=N=N), 1715
[M+Na]+ 353.0720; found 353.0730.
1.2.15. Ethyl 2-diazo-5-(furan-2-yl)-5-hydroxy-3-oxopentanoate
(3k)
Compound 3k was prepared according to the general
procedure and was obtained in 89% yield as a yellowish oil, Rf =
0.24 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.24 (t, J =
7.2 Hz, 3H),3.23 (dd, J = 3.5, 17.3 Hz, 1H), 3.41 (dd, J = 9.1,
17.3 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 5.13-5.16 (m, 1H), 6.20-
6.24 (m, 2H), 7.28 (m, 1H) ppm. 13C NMR (CDCl3, 125 MHz) δ
190.9, 160.9, 155.1, 141.7, 109.9, 105.8, 63.7, 61.4, 45.0, 14.0
ppm. IR (film) ν: 3503 (OH), 2142 (C=N=N), 1716 (C=O), 1645,
1376, 1300, 910, 733 cm-1. HRMS (ESI): calcd for
C11H12N2NaO5 [M+Na]+ 275.0638; found 275.0653.
(C=O), 1642, 1507, 1375, 1331, 1282, 1214, 1063, 846, 746 cm-
1
.
19F NMR (CDCl3, 400 MHz) δ -115.09. HRMS (ESI): calcd for
C13H13FN2NaO4 [M+Na]+ 303.0752; found 303.0750.
1.2.11. Ethyl 5-(4-bromophenyl)-2-diazo-5-hydroxy-3-
oxopentanoate (3g)
Compound 3g was prepared according to the general
procedure and was obtained in 89% yield as a yellowish solid,
m.p.75.5-76.6 , Rf = 0.33 (PE : EA = 3 : 1), H NMR (CDCl3,
1
1.2.16. Ethyl 2-diazo-5-hydroxy-3-oxo-5-(thiophen-2-yl)
pentanoate (3l)
500 MHz) δ 1.30 (t, J = 7.2 Hz, 3H),3.21-3.22 (m, 2H), 3.64 (d, J
= 3.9 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 5.12-5.15 (m, 1H), 7.25
(d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H) ppm. 13C NMR
(CDCl3, 125 MHz) δ 191.7, 161.0, 142.0, 131.4, 127.5, 121.3,
69.5, 61.6, 48.4, 14.2 ppm. IR (film) ν: 3513 (OH), 2144
(C=N=N), 1718 (C=O), 1642, 1373, 1325, 1281, 1065, 748 cm-1.
HRMS (ESI): calcd for C13H13BrN2NaO4 [M+Na]+ 362.9951;
found 362.9965.
Compound 3l was prepared according to the general
procedure and was obtained in 89% yield as a yellowish oil, Rf =
0.30 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.32 (t, J =
7.2 Hz , 3H), 3.34-3.48 (m, 2H), 4.27-4.42 (m, 2H), 5.21 (m,
1H), 6.93-6.98 (m, 2H), 7.21-7.25 (m, 1H) ppm. 13C NMR
(CDCl3, 125 MHz) δ 191.4, 160.8, 146.4, 126.5, 124.5, 123.4,
66.6, 61.7, 48.4, 14.4 ppm. IR (film) ν: 3495 (OH), 2139
(C=N=N), 1715 (C=O), 1374, 1303, 1214, 1131, 1060, 1032, 745
cm-1. HRMS (ESI): calcd for C11H12N2NaO4S [M+Na]+
291.0410; found 291.0412.
1.2.12. Ethyl 2-diazo-5-hydroxy-5-(4-nitrophenyl)-3-
oxopentanoate (3h)
Compound 3h was prepared according to the general
procedure and was obtained in 73% yield as a yellowish solid,
m.p.109-110 , Rf = 0.20 (PE : EA = 3 : 1), H NMR (CDCl3,
1.2.17. Ethyl 2-diazo-5-hydroxy-3-oxo-7-phenylhept-6-enoate
(3m)
1
500 MHz) δ 1.32 (t, J = 8.9 Hz, 3H), 3.18-3.37 (m, 2H), 3.73 (d,
J = 4.8 Hz, 1H), 4.29 (q, J = 8.9 Hz, 2H), 5.29 (m, 1H), 7.56 (d,
J = 10.9 Hz, 2H), 8.18-8.20 (m, 2H) ppm. 13C NMR (CDCl3, 125
MHz) δ 191.5, 160.8, 149.8, 147.1, 126.4, 123.6, 69.4, 61.9,
48.2, 14.1 ppm. IR (film) ν: 3529 (OH), 2142 (C=N=N), 1715
(C=O), 1641, 1595, 1519, 1476, 1347, 1278, 864, 749 cm-1.
HRMS (ESI): calcd for C13H13N3NaO6 [M+Na]+ 330.0697; found
330.0702.
Compound 3m was prepared according to the general
procedure and was obtained in 88% yield as a yellowish oil, Rf =
0.27 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.30 (t, J =
7.2 Hz, 3H), 3.18 (m, 2H), 3.48 (s, 1H), 4.27 (q, J = 7.1 Hz, 2H),
4.81 (d, J = 5.7 Hz, 1H), 6.26 (dd, J = 6.0, 16.0 Hz, 1H), 6.65 (d,
J = 15.9 Hz, 1H), 7.20-7.37 (m, 5H) ppm. 13C NMR (CDCl3, 125
MHz) δ 191.6, 161.0, 136.5, 130.5, 130.1, 128.3, 127.4, 126.4,
68.6, 61.4, 46.7, 14.1 ppm. IR (film) ν: 3495 (OH), 2138
(C=N=N), 1716 (C=O), 1649, 1374, 1304, 745 cm-1. HRMS
(ESI): calcd for C15H16N2NaO4 [M+Na]+ 311.1002; found
311.1003.
1.2.13. Ethyl 2-diazo-5-hydroxy-5-(3-nitrophenyl)-3-
oxopentanoate (3i)
Compound 3i was prepared according to the general
procedure and was obtained in 82% yield as a yellowish solid,
m.p.109-110 , Rf = 0.20 (PE : EA = 3 : 1), H NMR (CDCl3,
1.2.18. Ethyl 2-diazo-5-methoxy-3-oxo-5-phenylpentanoate (6a)
1
500 MHz) δ 1.32 (t, J = 7.1 Hz, 3H), 3.19-3.35 (m, 2H), 3.73 (d,
J = 3.4 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 5.29 (m, 1H), 7.49-
7.73(m, 2H), 8.10-8.12(m, 1H), 8.20 (s, 1H) ppm. 13C NMR
(CDCl3, 125 MHz) δ 191.6, 160.9, 148.3, 145.1, 131.9, 129.4,
122.5, 120.8, 69.2, 61.8, 48.3, 14.2 ppm. IR (film) ν: 3530 (OH),
2140 (C=N=N), 1718 (C=O), 1645, 1594, 1518, 1477, 1347,
1278, 864 cm-1. HRMS (ESI): calcd for C13H13N3NaO6 [M+Na]+
330.0697; found 330.0702.
Compound 6a was prepared according to the general
procedure and was obtained in 85% yield as a yellowish oil. Rf =
0.30 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.30 (t, J =
7.1 Hz, 3H). 2.97 (dd, J = 16.2, 4.0 Hz, 1H), 3.20 (s, 3H), 3.54
(dd, J = 16.2, 9.2 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 4.75 (m, 1H),
7.31-7.39 (m, 5H) ppm. 13C NMR (CDCl3, 125 MHz) δ 189.7,
160.9, 140.8, 128.3, 127.7, 126.6, 79.2, 76.4, 61.3, 56.6, 47.9,
14.2 ppm. IR (film) ν: 2983, 2935, 2135 (C=N=N), 1716 (C=O),
1658, 1454, 1373, 1306, 1101, 1020 cm-1. HRMS (ESI): calcd for
C14H16N2NaO4 [M+Na]+ 299.1002; found 299.1004.
1.2.14. Ethyl 2-diazo-5-hydroxy-3-oxo-5-(4-(trifluoromethyl)
phenyl) pentanoate (3j)
1.2.19. Ethyl 2-diazo-5-methoxy-5-(4-methoxyphenyl)-3-
oxopentanoate (6b)
Compound 3j was prepared according to the general
procedure and was obtained in 86% yield as a yellowish solid,
1
m.p.80-81 , Rf = 0.47 (PE : EA = 3 : 1), H NMR (CDCl3, 500
Compound 6b was prepared according to the general
procedure and was obtained in 95% yield as a yellowish oil. Rf =
MHz) δ 1.24 (t, J = 7.1 Hz, 3H), 3.17-3.25 (m, 2H), 4.08 (brs,
1H), 4.21 (q, J = 7.1 Hz, 2H), 5.14-5.25 (m, 1H), 7.46 (d, J = 8.1
Hz, 2H), 7.52 (d, J = 8.3 Hz, 2H) ppm. 13C NMR (CDCl3, 125
1
0.32 (PE : EA = 3 : 1), H NMR (CDCl3, 500 MHz) δ 1.32 (t, J
= 7.1 Hz, 3H). 2.98 (dd, J = 16.1, 4.2 Hz, 1H), 3.18 (s, 3H), 3.53
(dd, J = 16.1, 9.1 Hz, 1H), 3.80 (s, 3H) 4.29 (q, J = 7.1 Hz, 2H),
4.70 (m, 1H), 6.89 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H)
ppm. 13C NMR (CDCl3, 125 MHz) δ 189.9, 161.1, 159.2, 132.7,
127.9, 113.7, 78.8, 76.4, 61.3, 56.4, 55.1, 47.9, 14.2 ppm. IR
MHz) δ 191.7, 160.8, 146.5, 129.5(J
= 40.1 Hz), 125.9,
C-F
125.3(J C-F = 4.3 Hz), 69.7, 61.8, 48.4, 14.4 ppm. IR (film) ν:
3515 (OH), 2145 (C=N=N), 1719 (C=O), 1642, 1616, 1480,
1327, 1281, 1127, 1066, 848, 742 cm-1. 19F NMR (CDCl3, 400
8

(film) ν: 2983, 2935, 2836, 2135 (C=N=N), 1713 (C=O), 1651,
1512, 1373, 1301, 1207, 1098, 1022, 833, 744 cm-1. HRMS
(ESI): calcd for C15H18N2NaO5 [M+Na]+ 329.1108; found
329.1111.
Compound 6g was prepared according to the general
procedure and was obtained in 80% yield as a yellowish oil. Rf =
0.35 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.34 (t, J =
7.1 Hz, 3H), 3.13 (dd, J = 16.9, 4.5 Hz, 1H), 3.28 (s, 3H), 3.71
(dd, J = 16.9, 8.8 Hz, 1H), 4.31 (q, J = 7.1 Hz, 2H), 4.84 (m, 1H),
6.34 (m, 2H), 7.41 (m, 1H) ppm. 13C NMR (CDCl3, 125 MHz) δ
189.4, 161.1, 153.1, 142.6, 110.1, 108.2, 71.8, 61.5, 56.6, 44.2,
14.3 ppm. IR (film) ν: 2954, 2923, 2850, 2136 (C=N=N), 1719
(C=O), 1376, 1100, 913, 743 cm-1. HRMS (ESI): calcd for
C12H14N2O5 [M+Na]+ 289.0795; found 289.0796.
1.2.20. Ethyl 2-diazo-5-methoxy-3-oxo-5-(p-tolyl)-pentanoate
(6c)
Compound 6c was prepared according to the general
procedure and was obtained in 87% yield as a yellowish oil. Rf =
0.35 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.31 (t, J =
7.1 Hz, 3H), 2.34 (s, 3H), 2.97 (dd, J = 16.1, 4.1 Hz, 1H), 3.19 (s,
3H), 3.54 (dd, J = 16.2, 9.1 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H),
4.73 (m, 1H), 7.16 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H)
ppm. 13C NMR (CDCl3, 125 MHz) δ 189.9, 160.9, 137.8, 137.4,
129.1, 126.6, 79.1, 76.4, 61.2, 56.5, 47.9, 20.9, 14.2 ppm. IR
(film) ν: 2983, 2929, 2822, 2134 (C=N=N), 1716 (C=O), 1659,
1373, 1304, 1100, 1021, 818, 744 cm-1. HRMS (ESI): calcd for
C15H18N2NaO4 [M+Na]+ 313.1159; found 313.1160.
1.2.25. Ethyl 5-(4-bromophenyl)-2-diazo-5-methoxy-3-
oxopentanoate (6h)
Compound 6h was prepared according to the general
procedure and was obtained in 76% yield as a yellowish oil. Rf =
0.30 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.32 (t, J =
7.1 Hz, 3H), 2.98 (dd, J = 16.3, 4.3 Hz, 1H), 3.20 (s, 3H), 3.49
(dd, J = 16.3, 8.9 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 4.72 (m, 1H),
7.24-7.27 (m, 2H), 7.46-7.49 (m, 2H) ppm. 13C NMR (CDCl3,
125 MHz) δ 189.6, 161.1, 140.1, 131.6, 128.5, 121.9, 78.8, 76.6,
61.5, 56.8, 47.9, 14.3 ppm. IR (film) ν: 2982, 2928, 2823, 2136
(C=N=N), 1716 (C=O), 1655, 1374, 1318, 1098, 1011, 824, 744
cm-1. HRMS (ESI): calcd for C14H15BrN2NaO4 [M+Na]+
377.0107; found 377.0101.
1.2.21. Ethyl 2-diazo-5-methoxy-5-(3-methoxyphenyl)-3-
oxopentanoate (6d)
Compound 6d was prepared according to the general
procedure and was obtained in 84% yield as a yellowish oil. Rf =
0.38 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.27 (t, J =
7.1 Hz, 3H), 2.94 (dd, J = 16.2, 3.9 Hz, 1H), 3.18 (s, 3H), 3.48
(dd, J = 16.2, 9.2 Hz, 1H), 3.76 (s, 3H), 4.24 (q, J = 7.1 Hz, 2H),
4.80-4.61 (m, 1H), 6.77-6.78 (m, 1H), 6.94 – 6.87 (m, 2H), 7.21
(t, J = 7.8 Hz, 1H) ppm. 13C NMR (CDCl3, 125 MHz) δ 189.6,
160.9, 159.6, 142.5, 129.3, 118.8, 113.2, 111.7, 79.1, 76.2, 61.2,
56.5, 54.9, 47.8, 14.1 ppm. IR (film) ν: 2983, 2936, 2835, 2135
(C=N=N), 1713 (C=O), 1658, 1487, 1373, 1316, 1103, 1022, 744
cm-1. HRMS (ESI): calcd for C15H18N2NaO5 [M+Na]+ 329.1108;
found 329.1109.
Acknowledgments
We thank National Natural Science Foundation of China
(21372203, 21877099) for financial support.
A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/
1.2.22. Ethyl 2-diazo-5-methoxy-3-oxo-7-phenylhept-6-enoate
(6e)
References
Compound 6e was prepared according to the general
procedure and was obtained in 93% yield as a yellowish solid,
m.p. 78-80 , Rf = 0.34 (PE : EA = 3 : 1), H NMR (CDCl3, 500
1. (a) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev.
2010, 110, 704-724. (b) Merlic, C. A.; Zechman, A. L. Synthesis-
Stuttgart 2003, 1137-1156. (c) Davies, H. M. L.; Beckwith, R. E.
J. Chem. Rev. 2003, 103, 2861-2903. (d) Hodgson, D. M.; Pierard,
F.; Stupple, P. A. Chem. Soc. Rev. 2001, 30, 50-61.
2. Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1-326.
3. (a) Calter, M. A.; Sugathapala, P. M.; Zhu, C. Tetrahedron Lett.
1997, 38, 3837-3840. (b) Calter, M. A.; Sugathapala, P. M.;
Tetrahedron Lett. 1998, 39, 8813-8816.
4. Shanahan, C. S.; Truong, P.; Mason, S. M.; Leszczynski, J. S.;
Doyle, M. P. Org. Lett. 2013, 15, 3642-3645.
5. Xiao, Q.; Zhang, Y.; Wang, J. B. Acc. Chem. Res. 2013, 46, 236-
247.
1
MHz) δ 1.32 (t, J = 7.1 Hz, 3H), 3.00 (dd, J = 16.0, 4.6 Hz, 1H),
3.33 (s, 3H), 3.42 (dd, J = 16.0, 8.3 Hz, 1H), 4.29 (q, J = 7.1 Hz,
2H), 4.36 (m, 1H), 6.14 (dd, J = 15.9, 7.9 Hz, 1H), 6.63 (d, J =
15.9 Hz, 1H), 7.23-7.04 (m, 5H) ppm. 13C NMR (CDCl3, 125
MHz) δ 189.8, 161.1, 136.2, 132.6, 128.5, 127.7, 126.5, 78.1,
76.6, 61.3, 56.4, 45.7, 14.2 ppm. IR (film) ν: 2982, 2931, 2822,
2134 (C=N=N), 1715 (C=O), 1651, 1372, 1300, 1103, 1097, 747
cm-1. HRMS (ESI): calcd for C16H18N2NaO4 [M+Na]+ 325.1159;
found 325.1156
6. Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.; See, M. M.;
Boone, W. P.; Bagheri, V.; Pearson, M. M. J. Am. Chem. Soc.
1993, 115, 958-964.
1.2.23. Ethyl 2-diazo-5-methoxy-3-oxo-5-(thiophen-2-yl)
pentanoate (6f)
7. Calter, M. A.; Zhu, C. J. Org. Chem. 1999, 64, 1415-1419.
8. Deng, G. S.; Tian, X.; Qu, Z. H.; Wang, J. B. Angew. Chem., Int.
Ed. 2002, 41, 2773-2775.
9. Doyle, M. P.; Kundu, K.; Russell, A. E. Org. Lett. 2005, 7, 5171-
5174.
10. Zhou, L.; Doyle, M. P. Org. Lett. 2010, 12, 796-799.
11. Kundu, K.; Doyle, M. P. Tetrahedron: Asymmetry. 2006, 17, 574-
577.
12. Xu, X. F.; Hu, W. H.; Doyle, M. P. Angew. Chem., Int. Ed. 2011,
50, 6392-6395.
Compound 6f was prepared according to the general
procedure and was obtained in 82% yield as a yellowish oil. Rf =
0.33 (PE : EA = 3 : 1), 1H NMR (CDCl3, 500 MHz) δ 1.33 (t, J =
7.1 Hz, 3H), 3.11 (dd, J = 16.6, 4.3 Hz, 1H), 3.27 (s, 3H), 3.67
(dd, J = 16.6, 8.8 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 5.05 (m, 1H),
6.97 (m, 1H), 7.04 (d, J = 3.1 Hz, 1H), 7.28 (d, J = 4.5 Hz, 1H)
ppm. 13C NMR (CDCl3, 125 MHz) δ 189.4, 161.1, 144.6, 126.5,
125.5, 125.2, 74.7, 61.5, 56.6, 48.1, 14.3 ppm. IR (film) ν: 2983,
2930, 2823, 2135 (C=N=N), 1713 (C=O), 1651, 1372, 1310,
1098, 744, 706 cm-1. HRMS (ESI): calcd for C12H14N2NaO4S
[M+Na]+ 305.0566; found 305.0568
13. (a) Corey, E. J.; Ishihara, K. Tetrahedron Lett. 1992, 33, 6807-
6810. (b) Corey, E. J.; Wang, Z. Tetrahedron Lett. 1993, 34, 4001-
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1185-1197
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40, 3206-3208.
1.2.24. Ethyl 2-diazo-5-(furan-2-yl)-5-methoxy-3-oxopentanoate
(6g)
9

16. (a) Denmark, S. E.; Almstead, N. G. J. Am. Chem. Soc. 1993, 115,
3133-3139. (b) Blackwell, J. M.; Piers, W. E.; Parvez, M. Org.
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McDonald, R. J. Am. Chem. Soc. 2002, 124, 1295-1306.
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10

Research Highlights:
►
MgI2 etherate could catalyze Mukaiyama aldol reaction between
3-TBSO-2-diazo-3-butenoate with aldehydes or acetals.
►This magnesium-catalyzed Mukaiyama aldol reaction is mild, efficient and highly
chemoselective.
►The unique reactivity of this catalytic system was demonstrated.
►The condensation of various aromatic aldehydes or acetals is performed in good to
excellent yields.