Nucleophilic Addition to Nitrones Using a Flow Microreactor

Article abstract of DOI:10.1055/s-0039-1691601

Nucleophilic addition reactions of soft carbon nucleophiles to nitrones in a flow microreactor are reported for the first time. Under microflow conditions at 30 to 0 °C, a range of nitrones can be efficiently transformed into the corresponding oxyiminium ions by reaction with either acyl halides or trialkylsilyl triflates. These can subsequently undergo the addition of nucleophiles including allyltributylstannane, ketene methyl tert-butyldimethylsilyl acetal, and N-silyl ketene imines to afford the corresponding adducts in high yields; such reactions at a similar temperature under batch conditions resulted in lower yields because of undesired side reactions.

Full text of DOI:10.1055/s-0039-1691601

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© Georg Thieme Verlag Stuttgart · New York
2020, 31, A–E
letter
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Y. Arakawa et al.
Letter
Synlett
Nucleophilic Addition to Nitrones Using a Flow Microreactor
Yukihiro Arakawaa
Shun Uetaa
Takuma Okamotoa
Keiji Minagawaa,b
Yasushi Imada*a
a Department of Applied Chemistry, Tokushima University,
Minamijosanjima, Tokushima 770-8506, Japan
b Institute of Liberal Arts and Sciences, Tokushima University,
Minamijosanjima, Tokushima 770-8502, Japan
imada@tokushima-u.ac.jp
Received: 16.01.2020
Accepted after revision: 30.01.2020
Published online: 18.02.2020
temperature such as –78 °C; otherwise, Im(OBz)-1 readily
undergoes undesired rearrangement to amides 3 because of
its lability.5
DOI: 10.1055/s-0039-1691601; Art ID: st-2020-u0035-l
R1
Abstract Nucleophilic addition reactions of soft carbon nucleophiles
to nitrones in a flow microreactor are reported for the first time. Under
microflow conditions at 30 to 0 °C, a range of nitrones can be efficiently
transformed into the corresponding oxyiminium ions by reaction with
either acyl halides or trialkylsilyl triflates. These can subsequently un-
dergo the addition of nucleophiles including allyltributylstannane, ke-
tene methyl tert-butyldimethylsilyl acetal, and N-silyl ketene imines to
afford the corresponding adducts in high yields; such reactions at a sim-
ilar temperature under batch conditions resulted in lower yields be-
cause of undesired side reactions.
N
R2
Cl
PhCOCl
Nu = enolates etc.
− 78 °C
OCOPh
− 78 °C
Im(OBz)-1
Nu
O
R1
competed
at higher temp.
R1
N
H
3
N
O
R2
R1
N
R2
R2
OR'
1
2
− 30 °C
− 30 °C
Nu = N-silyl ketene imines
R1
Key words nitrones, flow, microreactor, nucleophilic addition, nitro-
gen-containing compounds
N
R2
OSiEt3
Im(OSiEt3)-1
OTf
Et3SiOTf
Nitrones 1 (Figure 1) can be attractive intermediates for
the synthesis of nitrogen-containing compounds,1 but their
use as electrophiles in nucleophilic addition reactions typi-
cally requires the strong activation of the -carbon atom
because of its comparatively low electrophilicity. Early
studies, indeed, demonstrated that 1 could be electrophilic
enough to react with ‘reactive’ nucleophiles such as organo-
magnesium and organolithium reagents, whereas ‘less re-
active’ nucleophiles such as O-silylated enolates could be in-
active.2 To enhance the reactivity and control selectivities,
the use of Lewis acid catalysts has proven to be effective.3
On the other hand, Murahashi and co-workers established a
stoichiometric activation of 1 with acyl halides, in which
the resulting N-oxyiminium ions Im(OBz)-1 are highly
electrophilic to undergo rapid addition of soft carbon nuc-
leophiles Nu, such as enolates, to give the corresponding
adduct 2 (Figure 1, upper route).4 However, the nitrone acti-
vation as well as subsequent addition reactions with use of
a batch reactor have to be carefully carried out at a very low
Figure 1 Previous strategies for utilizing nitrones as electrophiles via
their N-oxyiminium ions formed in a batch system4,6
More recently, Yoshimura and co-workers introduced
the nucleophilic addition reactions of in situ generated N-
silyl ketene imines to 1 involving activation of substrates
with triethylsilyl triflate, which also required –30 °C to fully
suppress an undesired amide formation from the corre-
sponding N-oxyiminium ions Im(OSiEt3)-1 (Figure 1, lower
route).6 As a result, the application of these synthetic meth-
ods especially in industry may be significantly limited de-
spite their high generality and reliability under carefully
controlled conditions.
Flow microreactor systems allow for efficient reactant
mixing, efficient heat and mass transfer, and precise control
of reaction times and have therefore been successfully uti-
lized for molecular transformations involving highly labile
intermediates that are difficult to control in batch systems.7
Within this manuscript, we wish to expand the utility of
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Arakawa et al.
Letter
Synlett
the flow microreactor system by adopting it to the nucleo-
philic addition to 1 through the formation of unstable N-
oxyiminium intermediates.
further run for 234 seconds (tR2) at 20 °C in a micro tube of
500 cm length prior to being poured into water to quench
the reaction (Figure 3).
A general and simple flow setup was used in this study,
which comprises of syringe pumps and helical channel mi-
cromixers connected with each other through polytetrafluo-
roethylene (PTFE) micro tubes as required (Figure 2, photo-
graph).
0.063 mL min−1
1a
0.84 M in DCM
50 cm
200 cm
187 sec
O
R2 cm
R2 sec
0.063 mL min−1
50 cm
SnBu3
Ph
Cl
t
0.94 M in DCM
0.126 mL min−1
O
Bn
Bn
N
Ph
Bn
N
O
Ph
1a
Cl
Bn
Ph
N
50 cm
V mL min–1
50 cm
N
Ph
A
OCOPh
H
20 °C T2 °C
0.51 M in DCM
OBz
2aA
Im(OBz)-1a
3a (undesired)
0.84 M in DCM
PhCO2
Bn
O
tR2
(s)
T2
V mL min–1
50 cm
N
R
R1 cm
t
R2
(cm)
NMR yield (%)
R1 sec
20 °C
(°C)
Ph
Cl
by-products
2aA
R = H or COPh
(desired)
0.94 M in DCM
H2O
234
468
468
500
1000
1000
20
20
30
16
11
1
84
89
tR1
(sec)
V
R1
(cm)
Conv. 3a
(mL min–1
)
99
(%)
70
75
84
94
95
94
(%)
syringe pump
2.95
5.89
23.6
94.2
187
1.0
50
50
0
Figure 3 Optimization of flow system conditions for the addition of A
to 1a through the formation of Im(OBz)-1a
0.5
0
0.5
200
200
200
500
0
helix-type mixer
0.125
0.063
0.125
1
product
Although the desired adduct 2aA was obtained in 84%
yield, a total of 16% by-products including the hydrolyzed
form of Im(OBz)-1a (2%) and its benzoylated form (11%),
1
syringe pump
236
2
micro tube (PTFE)
1
desired in Figure 2, and 3a (3%) was observed by H NMR
Figure 2 Determination of the optimal residence time for the genera-
tion of Im(OBz)-1a in a flow reactor
spectroscopy. The amount of by-products was reduced to
11% by prolonging the residence time tR2 twice (468 s) and
finally further reduced to only 1% by performing the nucle-
ophilic addition step at 30 °C (T2) to give 2aA in 99% NMR
yield (Figure 3).
We started our investigation by determining the opti-
mal residence time (tR1, given in s) for synthesizing N-ben-
zoyloxyiminium chloride [Im(OBz)-1a] from N-benzyl--
phenylnitrone (1a) and benzoyl chloride in the flow system
at 20 °C, in which tR1 was adjusted by changing either the
flow rate (V, given in mL·min–1) or the tube length between
the mixer and the exit (R1, given in cm). Solutions of 1a
(0.84 M) and benzoyl chloride (0.94 M) in dichloromethane
(DCM) were fed by the syringe pumps and mixed in the
mixer, in which Im(OBz)-1a could start to be produced. It
was run in the following microtube and the outflow was
poured into water that could quench Im(OBz)-1a to detect
it as its hydrolyzed form or further benzoylated form (Fig-
ure 2, desired products). For example, when tR1 was adjust-
ed to be 2.95 seconds, the conversion of 1a was determined
by 1H NMR spectroscopy to be 70% without any occurrence
of undesired rearrangement of Im(OBz)-1a to the corre-
sponding amide 3a. Prolonging tR1 increased the conversion,
and the highest value of 95% was attained with 187 seconds
of tR1 (V = 0.063 mL min–1, R1 = 200 cm) while the forma-
tion of 3a was still negligible (Figure 2).
Substrate generality of the present flow microreactor
system was explored (Table 1). Solutions of 1 (1.00 M), ben-
zoyl chloride (1.05 M), and Nu (0.60 M) were successively
mixed and treated under the initially optimized residence
times and temperatures. In the case of the combination of
1a and A, the outflow solution was collected for 1469 sec-
onds to afford 2aA in 84% isolated yield (461 mg) after puri-
fication (entry 1). 3,4-Dihydroisoquinoline N-oxide (1b), a
cyclic nitrone, was also efficiently allylated with A to give
the corresponding adduct 2bA in 89% isolated yield (319
mg) by collecting the outflow for 1159 seconds (entry 2).8
The use of silyl ketene acetal B instead of A as a nucleophile
for its addition to 1a and 1b allowed for synthesis of -ami-
no acid derivatives 2aB and 2bB, respectively, with accept-
able isolated yields at a similar production scale (entries 3
and 4). As expected, the rearrangement to the correspond-
ing amides 3 was successfully suppressed in all the above
cases. This was also the case when (4R)-4-(tert-butyldi-
methylsilyloxy)-1-pyrroline N-oxide (1c)9 was used as a
chiral substrate, although the desired product 2cB was ob-
tained in only 38% NMR yield despite full conversion of 1c
(entry 5). We soon became aware that a considerable
amount of N-benzoyloxypyrrole (Figure 4) was formed
through elimination of tert-butyldimethylsilanol from the
corresponding N-oxyiminium chloride followed by aroma-
We then connected the outlet of the first flow men-
tioned above to the second micromixer, in which Im(OBz)-
1a could encounter with allyltributylstannane (A) chosen
as a test nucleophile. A solution of A in DCM (0.60 M) was
fed by the third syringe pump at a flow rate of 0.126 mL
min–1 to the second mixer, and the resulting mixture was
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

C
Y. Arakawa et al.
Letter
Synlett
tization to release HCl. This observation led us to reopti-
mize the flow conditions by controlling the readily tunable
residence times tR1 and tR2. To our delight, the yield of 2cB
was dramatically enhanced when tR1 and tR2 were adjusted
to 0.2 and 3.93 seconds (entry 6), respectively, which was
even more improved by performing both steps at 0 °C to
give 2cB in the highest NMR yield of 97% (entry 7). By col-
lecting the outflow for 68 seconds under the suitable condi-
tions, 494 mg (74%) of 2cB was obtained in a cis/trans ratio
of 3.3:1 after a column chromatographic purification (entry
7), from which 290 mg (43%) of the cis isomer was isolated
by a single recrystallization. It should be noted that no de-
sired product 2cB was obtained in a batch reaction system
(Figure 4, top), indicating the obvious utility of the present
flow system. On the other hand, an even more challenging
issue regarding the addition to 1c was the use of A as a nuc-
leophile, which resulted in only 2% NMR yield of the corre-
sponding adduct 2cA under the conditions that were just
only optimized for the use of B (entry 8). To solve this prob-
lem, we attempted to use other acyl halides instead of ben-
zoyl chloride and preliminarily found that the use of benzo-
yl bromide with an increased tR2 (19.6 seconds) could be ef-
fective for providing the desired adduct 2cA in 79% NMR
yield in a cis/trans ratio of 10:1 (entry 9). Also in this case,
the reaction in a batch reactor was not efficient at the same
reaction temperature (Figure 4, bottom).
Table 1 Adapting Different Substrates to the Flow Microreactor Systema
1
R1 cm
tR1 sec
O
R2 cm
Ph
Cl
tR2 sec
2
Nu
T1 °C
T2 °C
OTBS
Bn
SnBu3
N
O
Ph
1a
N
OMe
O
A
B
1b
TBSO
MeO2C
N
Bn
N
Bn
N
OBz
N
Ph
Ph
O
(4R)-1c
OBz
2aA
H
2bA
2aB
TBSO
TBSO
CO2Me
N
N
N
OBz
OBz
OBz
cis: (2R,4R)-2cB
trans: (2S,4R)-2cB
CO2Me
2bB
cis: (2R,4R)-2cA
trans: (2S,4R)-2cA
Entry
1/Nu
tR1
(s)
tR2
(s)
T1
(°C)
T2
(°C)
2
Yield
(%)b
TBSO
TBSO
CO2Me
B (1.2 equiv)
1
2
3
4
5
6
7
1a/A
1b/A
1a/B
1b/B
1c/B
1c/B
1c/B
187
468
20
20
20
20
20
20
0
30
30
30
30
30
20
0
2aA
2bA
2aBc
2bB
2cB
2cB
2cB
84
PhCOCl (1.05 equiv)
N
N
187
187
187
187
0.20
0.20
468
468
468
468
3.93
3.93
89
2cB
major product
OBz
O
0 °C, 30 min
(4R)-1c
73
0%
N
60
A (1.2 equiv)
OCOPh
TBSO
38d
94d
74e
PhCOBr (1.05 equiv)
N-benzoyloxypyrrole
(4R)-1c
N
2cA
0 °C, 30 min
OBz
9%
(97)d
Figure 4 Inefficiency of the nucleophilic additions to (4R)-1c in a batch
8
1c/A
1c/A
0.20
0.20
3.93
19.6
0
0
0
0
2cA
2cA
2d
system
9f
79d,g
a Reaction conditions: Solutions of 1 (1.00 M), benzoyl chloride (1.05 M),
and the nucleophile (Nu, 0.60 M) dissolved in DCM were used unless other-
Next, we turned our attention to the addition of nitriles
to 1,6 for which trialkylsilyl triflate should activate both ni-
triles and 1 in situ by transforming them into N-silyl ketene
imines and Im(OSiR3)-1, respectively, in the presence of tri-
ethylamine (Et3N). Since both activated forms could be la-
bile and actually a low temperature was required in the
batch system (Figure 1, lower route),6 flow microreactor
synthesis would be useful for performing the reaction more
efficiently under mild conditions. For a start, we set up a
flow in which a solution of propionitrile (C, 0.80 M) and
Et3N (0.80 M) in dichloroethane (DCE) and a solution of
trimethylsilyl triflate (TMSOTf, 1.60 M) in DCE were mixed
in the first mixer to give the corresponding N-silyl ketene
imine C′.
wise noted.
b Isolated yield.
c Isolated through reduction with zinc/acetic acid after the reaction.
d NMR yield.
e cis/trans = 3.3:1.
f Benzoyl bromide was used instead of benzoyl chloride.
g cis/trans = 10:1.
The latter was mixed with a DCE solution of N-methyl-
-phenylnitrone (1d, 0.40 M) and Et3N (0.40 M) in the sec-
ond mixer at 0 °C (Figure 5, a). The first step’s residence
time (tR1) was varied, whereas that for the second step was
fixed to be 589 seconds. Although NMR yields of the desired
adduct 2dC were increased up to 56% by shortening tR1, the
formation of the undesired amide 3d was not negligible and
1d was not fully consumed even with a tR1 of 5.9 seconds.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

D
Y. Arakawa et al.
Letter
Synlett
This is possibly due to the short lifetime of C′ that could
quickly isomerize to the corresponding -silylnitrile.10 We
therefore attempted to minimize such a deactivation of C′
by performing the activation of 1d prior to that of C in the
stepwise flow system (Figure 5, b). However, although the
yield of 2dC was slightly improved, a small amount of 1d
still remained unreacted even with a suitable tR1.
spectively, to give 2dC in 79% yield along with only 6% of 3d.
It should be noted that, in a batch reactor, the side reaction
took place to afford 3d in 40% yield under comparable con-
ditions (Figure 6), indicating the effectiveness of the pres-
ent flow microreactor system.
O
TMSOTf (4 equiv)
Me
H
C'
Et3N (4 equiv)
Ph
N
H
a)
EtCN (C, 0.80 M)
Et3N (0.80 M)
in DCE
0.05 mL min−1
C (3.0 equiv)
+
1d
2dC
+
3d
Me
C
NTMS
DCE, 0 °C, 1 h
60%
40%
R1 cm
t
R1 sec
Figure 6 The reaction with 1d and C in a batch system
TMSOTf
1000 cm
589 sec
0.05 mL min−1
1.60 M in DCE
Me
N
0.10 mL min−1
NC
Me
Ph
Having the optimized conditions in hand, we evaluated
the substrate scope (Table 2). In the flow microreactor sys-
tem with 1d as an electrophile, various nitriles including C,
4-methoxyphenylacetonitrile (D), 1-naphthylacetonitrile
O
(1d, 0.40 M)
Me
N
Ph
Et3N (0.40 M) in DCE
0 °C
0 °C
2dC
OTMS
tR1
(s)
Conv. of 1d
R1
NMR yield (%)
(cm)
(%)
3d
2dC
59
24
50
20
5
75
90
92
10
17
21
10
31
56
Table 2 Substrate Scope of the Addition of Nitrones to 1 under the
Optimized Flow Conditions
5.9
b)
1 (0.40 M)
C−G (1.20 M) in DCE
0.05 mL min−1
0.10 mL min−1
1d
0.80 M in DCE
R1 cm
Et3N (1.60 M)
1000 cm
2
tR1 sec
589 s
TMSOTf
1.60 M in DCE
0.10 mL min−1
TMSOTf
1.60 M in DCE
1000 cm
589 sec
0.05 mL min−1
0 °C
0.10 mL min−1
EtCN (C, 0.40 M)
Et N (0.80 M)
MeO
2dC
MeO
in DCE
3
N
0 °C
0 °C
CN
MeO
O
1e
D
tR1
Conv. of 1d
R1
NMR yield (%)
(s)
(cm)
(%)
3d
2dC
CN
S
NC
R
CN
59
50
61
19
28
Me
12
10
96
16
67
N
Ph
E
F
OTMS
OMe
c)
1d (0.40 M)
EtCN (C, x M)
base (y M)
0.10 mL min−1
R =
2dD:
2dE:
in DCE
MeO
1000 cm
589 sec
2dC
N
R =
TMSOTf
MeO
MeO
OH
0.10 mL min−1
0 °C
1.60 M in DCE
CN
Conv. of 1d
NMR yield (%)
x (M)
y (M)
(%)
R =
2dF:
3d
2dC
2eD
S
0.40
0.80
100
26
62
1.20
1.60
100
6
79
Entry
1/Nu
2
NMR yield (%)a dra,b
Figure 5 Optimization of the flow system conditions for the addition
of C to 1d through the formation of Im(OTMS)-1d
1
1d/C
1d/D
1d/E
1d/F
1f/D
2dC
2dD
2dE
2dF
2eD
79
53:47
63:37
2
100
78
These results led us to explore their simultaneous acti-
vation in flow by means of only a single mixer, in which a
solution of 1d (0.40 M), C (0.40 M), and Et3N (0.80 M) in
DCE and a solution of TMSOTf (1.60 M) in DCE were mixed
(Figure 5, c). As expected, complete consumption of 1d was
finally attained, which was further optimized by increasing
the concentrations of C and Et3N to 0.80 M and 1.60 M, re-
3
72:28
54:46
100:0
4
67
5c
74d
a Determined by 1H NMR spectroscopy.
b Diastereomeric ratio.
c The collected reaction mixture was treated with aqueous HCl solution.
d Isolated yield.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

E
Y. Arakawa et al.
Letter
Synlett
(E), and 2-thiopheneacetonitrile (F) were successfully used
as nucleophiles to provide the desired addition products
2dC–2dF in high yields as diastereomeric mixtures (entries
1–4). In addition, 3,4-dihydro-6,7-dimethoxyisoquinoline
N-oxide (1e) reacted efficiently with D to the corresponding
adduct 2eD in good isolated yield as a single diastereomer
(entry 5).
In conclusion, we have demonstrated that nucleophilic
addition reactions to nitrones via their N-oxyiminium in-
termediates with soft carbon nucleophiles, such as allyl-
tributylstannane, silyl ketene acetal, and silyl ketene imine,
can be efficiently performed at milder temperatures (0 to
30 °C) by means of a flow microreactor system that has al-
lowed for minimization of serious side reactions. These re-
actions previously required relatively low reaction tem-
peratures (–30 to –78 °C) to be carried out in conventional
batch systems. The results show that suitable flow condi-
tions are quite sensitive to the nature of substrates but can
be optimized each time by altering readily tunable parame-
ters such as the residence time. We believe that this study
will open the way for more practical uses of nitrones as
electrophiles in organic synthesis.
(5) For selected papers on the nitrone-to-amide rearrangement,
see: (a) Hamer, J.; Macaluso, A. Chem. Rev. 1964, 64, 473.
(b) Barton, D. H. R.; Day, M. J.; Hesse, R. H.; Pechet, M. M.
J. Chem. Soc. D 1971, 945. (c) Zeng, Y.; Smith, B. T.; Hershberger,
J.; Aubé, J. J. Org. Chem. 2003, 68, 8065. (d) Zhang, Y.; Blackman,
M. L.; Leduc, A. B.; Jamison, T. F. Angew. Chem. Int. Ed. 2013, 52,
4251.
(6) Yoshimura, F.; Abe, T.; Tanino, K. Synlett 2014, 25, 1863.
(7) (a) Yoshida, J. Flash Chemistry. Fast Organic Synthesis in Micro-
systems; John Wiley & Sons, Ltd.: Chichester, 2008. (b) Yoshida,
J.; Takahashi, Y.; Nagaki, A. Chem. Commun. 2013, 49, 9896.
(c) Yoshida, J.; Saito, K.; Nokami, T.; Nagaki, A. Synlett 2011,
1189.
(8) (2bA) A dichloromethane solution of 1b (1.00 M) and that of
benzoyl chloride (1.05 M) were fed to the first micromixer
(YMC, Deneb, SUS316) by syringe pumps (YMC, YSP-101)
equipped with a gastight syringe through polytetrafluoroeth-
ylene microtubes (50 cm length, inside diameter Ø = 500 m) at
a flow rate of 0.063 mL min–1 at 20 °C. The resulting mixture
was delivered to the second micromixer through a microtube
(200 cm length, Ø = 500 m), while a dichloromethane solution
of A (0.60 M) was equally fed to the same mixer at a flow rate of
0.126 mL min–1. The finally resulting mixture was further run
through the microtube (1000 cm length, Ø = 500 m) at 30 °C
before coming out from an outlet. After a steady state was
reached, the outflow was collected for 1159 s onto water and
diluted with EtOAc (5 mL) and hexane (2 mL). The mixture was
washed successively with a sat. NaHCO3 aq solution (2 mL × 3)
and brine (2 mL × 3), dried with MgSO4, and concentrated under
reduced pressure. The resulting crude product was purified by
flash column chromatography on silica gel (hexane/EtOAc 95:5)
to afford 2bA as a brown oil. Yield: 0.319 g (89%). 1H NMR (400
MHz, CDCl3):  = 2.71 (t, J = 6.5 Hz, 2 H), 3.05 (t, J = 6.1 Hz, 2 H),
3.51 (dt, J = 12.5, 6.1 Hz, 1 H), 3.69 (dt, J = 12.5, 6.1 Hz, 1 H), 4.46
(t, J = 6.1 Hz, 1 H), 5.00–5.07 (m, 1 H), 5.05–5.11 (m, 1 H), 6.01
(ddt, J = 17.1, 10.2, 7.0 Hz, 1 H), 7.11–7.23 (m, 4 H), 7.35–7.44
(m, 2 H), 7.50–7.57 (m, 1 H), 7.88–7.97 (m, 2 H). 13C NMR (100
MHz, CDCl3):  = 25.5, 39.2, 49.7, 65.0, 117.0, 126.2, 126.6,
127.0, 128.5, 129.4, 129.5, 133.1, 133.4, 135.2, 135.7, 164.9.
Anal. Calcd for C19H19NO2: C, 77.79; H, 6.53; N, 4.77. Found: C,
77.68; H, 6.61; N, 4.87.
Funding Information
This work was supported by the Research Clusters program of
Tokushima University (no. 1802001).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691601.
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References and Notes
(1) Murahashi, S.-I.; Imada, Y. Chem. Rev. 2019, 119, 4684.
(2) Lombardo, M.; Trombini, C. Synthesis 2000, 759.
(3) Merino, P.; Tejero, T. Synlett 2011, 1965.
(4) Kawakami, T.; Ohtake, H.; Arakawa, H.; Okachi, T.; Imada, Y.;
Murahashi, S.-I. Bull. Chem. Soc. Jpn. 2000, 73, 2423.
(9) Ohtake, H.; Imada, Y.; Murahashi, S.-I. Bull. Chem. Soc. Jpn. 1999,
72, 2737.
(10) Denmark, S. E.; Wilson, T. W. Angew. Chem. Int. Ed. 2012, 51,
9980.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E