A new asymmetric activation strategy for hydrazones as acyl anion equivalents in the bimetallic catalyzed carbonyl-ene reaction

Article abstract of DOI:10.1039/d1ob00017a

A new asymmetric activation strategy for hydrazones as acyl anion equivalents is developed in the bimetallic catalyzed carbonyl-ene reaction of isatins and hydrazones. Under mild conditions, optically active functionalized 3-hydroxy-2-oxindoles were furnished in up to 98% yield with up to 97% enantioselectivity. In this process, formaldehydetert-butylhydrazone which is seldom employed in asymmetric carbonyl-ene reactions accelerated by a metallic catalyst can be activated well by a Br?nsted base. A possible catalytic cycle is proposed.

Full text of DOI:10.1039/d1ob00017a

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
A new asymmetric activation strategy for
hydrazones as acyl anion equivalents in the
bimetallic catalyzed carbonyl-ene reaction†
Cite this: Org. Biomol. Chem., 2021,
9, 2055
1
Wen-Bo Hu,
Xixi Song
and Min-Can Wang
*
A new asymmetric activation strategy for hydrazones as acyl anion equivalents is developed in the bi-
metallic catalyzed carbonyl-ene reaction of isatins and hydrazones. Under mild conditions, optically
active functionalized 3-hydroxy-2-oxindoles were furnished in up to 98% yield with up to 97% enantio-
selectivity. In this process, formaldehyde tert-butylhydrazone which is seldom employed in asymmetric
carbonyl-ene reactions accelerated by a metallic catalyst can be activated well by a Brønsted base. A
possible catalytic cycle is proposed.
Received 5th January 2021,
Accepted 8th February 2021
DOI: 10.1039/d1ob00017a
rsc.li/obc
develop a new activation strategy to overcome the sensitivity of
these reagents towards metal Lewis acids. Although the pio-
Introduction
Hydrazones as acyl anion equivalents have a great synthetic neering work by Baldwin and co-workers shows that metallated
value due to the versatility of the expected functionalized N-tert-butyl monosubstituted hydrazones as stable anionic aza-
1
8
product. Activated hydrazones employed in asymmetric trans- enolates can increase the C-nucleophilicity, to the best of our
formation, which is an important strategy to build the chiral knowledge, N-tert-butyl hydrazones activated by a chiral metal
C–C bond, have attracted much attention over the last few complex as a Brønsted base have not been reported yet in
2
years. N,N-Dialkyl hydrazones have shown reactivity in the asymmetric catalysis.
enantioselective conjugate addition reaction, ene-type reac-
During the past few years, we have applied chiral dinuclear
tions and imino aza-enamine reaction. Alternatively, Carreira zinc cooperative catalysts to a variety of asymmetric catalyses,
3
9
reported the iridium-catalyzed asymmetric allylic substitution such as asymmetric copolymerization, [3
+ 2] cyclic
4
10
11
12
reaction with N,N-dialkylhydrazones. On the other hand, addition, cascade reaction, conjugate addition, Friedel–
1
3
14
hydrazones activated by Lewis acids could participate in asym- Crafts alkylation,
metric hydrocyanation and Mannich reactions.
aza-Henry reaction,
and 1,2-carbonyl
5
15
addition. Considering that the Brønsted base site of a dinuc-
The aza-enamine (nucleophilic) character of N-monoalkyl lear zinc catalyst should offer an opportunity for the reaction
hydrazones activated by H-bond organocatalysis in the asym- with the NH group on hydrazones, affording a stable anionic
metric carbonyl-ene reaction was discovered by the Lassaletta aza-enolate as a C-nucleophile, we decided to explore the reac-
6
group using bisurea or squaramide catalysts (Fig. 1a, R = H).
After that, Zhu demonstrated the chiral phosphoric acid (CPA)-
catalyzed asymmetric aza-Mannich reaction of N-alkyl hydra-
zones via H-bond activation, generating two contiguous stereo-
tivity of N-tert-butyl hydrazones in the nucleophilic addition
7
centers with an excellent yield and ee value (Fig. 1a, R = aryl).
Due to the tendency of hydrazones to bind to acidic metals
and lead to side reactions, decomposition, or catalyst deactiva-
6
a
tion,
the development of catalytic enantioselective
approaches by hydrazone activation of chiral metal Lewis acid
catalysts is problematic. Therefore, it is highly desirable to
The College of Chemistry and Molecular Engineering, Zhengzhou University, 75
Daxue Road, Zhengzhou, Henan 450052, P. R. China.
E-mail: wangmincan@zzu.edu.cn
†
Electronic supplementary information (ESI) available: NMR spectra and HPLC
traces for the compounds. See DOI: 10.1039/d1ob00017a
Fig. 1 Different activation modes for hydrazones.
Org. Biomol. Chem., 2021, 19, 2055–2062 | 2055
This journal is © The Royal Society of Chemistry 2021

View Article Online
Paper
Organic & Biomolecular Chemistry
reaction with carbonyl compounds (Fig. 1b). Herein, we different metals. In particular, ZnMe
2
led to the formation of
report a new strategy of Brønsted base activating N-tert-butyl the desired product with high efficiency and 83% ee (Table 1,
n
hydrazones for the asymmetric metal-catalyzed carbonyl-ene entry 8). The use of Mg Bu
2
gave 3aa in a low level of enantio-
reaction of isatins and hydrazones using dinuclear zinc meric excess (Table 1, entry 9). Mixed metals were not efficient
catalysts.
in enantioselectivity (Table 1, entries 10 and 11). Therefore,
ZnEt was chosen as the optimal metal for further
2
optimization.
Results and discussion
Several parameters were explored further to improve the
reactivity and enantioselectivity, such as catalyst loading, sol-
vents, additives and temperature, on this transformation
We commenced our investigation by examining the reaction of
methyl substituted isatin and formaldehyde tert-butyl hydra-
zone in the presence of ligand L2 (10 mol%) and ZnEt2
(
Table 2). 15 mol% and 20 mol% catalyst loading amounts
showed no obvious improvement of the reaction results
Table 2, entries 2 and 3). When the catalyst loading was
(20 mol%). At 0 °C, with toluene as the solvent, the reaction
(
proceeded smoothly and gave the product (3aa) in 96% yield
with 68% ee (Table 1, entry 2). Encouraged by the good result,
a series of ligands with different substituents and structures,
reduced to 5 mol%, the yield and enantiomeric excess of 3aa
decreased (Table 2, entry 1). Screening of solvents (Table 2,
entries 4–7) showed that THF gave the highest enantio-
selectivity compared with others. Moreover, 4 Å MS proved to
be the most efficient additive in the asymmetric carbonyl-ene
reaction, leading to the product 3aa with 98% yield and 97%
ee (Table 2, entry 8). Performing the reaction at room tempera-
ture and −20 °C decreased the enantioselectivity of 3aa to 92%
and 96% ee (Table 2, entries 13 and 14). The absolute con-
figuration was confirmed as (S) based on the optical rotation
including AzePhenol ligand L
were employed (Table 1, entries 1 and 3–7). ProPhenol ligand
gave a little higher ee value than AzePhenol ligand L (63%
1 3 7
and ProPhenol ligands L –L ,
L
2
1
ee) that bears the same substituted group. To our delight,
modification of the aromatic ring of L from phenyl to thienyl
2
4
(L ) substantially improved the efficiency and enantio-
selectivity of the reaction to 98% yield and 88% ee (Table 1,
entry 4). We then evaluated the reaction outcome by using
6b
of the product 3da (see the ESI†). As a result, the optimized
conditions were isatin (0.125 mmol), hydrazone (0.25 mmol),
L (0.0125 mmol), ZnEt (0.025 mmol), 4 Å MS (25 mg) and
4
2
2
THF (2 ml) at 0 °C under a N atmosphere.
The generality of the protecting group on nitrogen of isatin
was explored under the optimal conditions obtained above.
a
Table 1 Screening conditions for the ligand and metal
a
Table 2 Optimization of reaction conditions
b
c
Entry
n
Solv.
Add.
t (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
5
Toluene
Toluene
Toluene
THF
Dioxane
2
Et O
Benzene
THF
THF
THF
THF
None
None
None
None
None
None
None
12
12
12
6
12
12
12
6
12
12
12
12
3
95
96
96
98
95
80
99
98
90
96
99
99
96
91
81
87
79
91
77
35
47
97
66
63
70
69
92
96
b
c
15
20
10
10
10
10
10
10
10
10
10
10
10
Entry
MR
2
L
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
ZnEt
ZnEt
ZnEt
ZnEt
ZnEt
ZnEt
ZnEt
2
2
2
2
2
2
2
L
1
L
2
L
3
L
4
L
5
L
6
L
7
L
4
L
4
L
4
L
4
96
96
95
98
96
85
96
95
97
97
97
63
68
73
88
70
45
37
83
10
25
65
d
4 Å MS
e
9
Et
Na
3
N
2
e
10
11
12f
13
CO
3
e
ZnMe
2
Ph
Ph
3
PS
n
e
9
0
1
Mg Bu
ZnEt + Mg Bu
ZnMe
2
THF
THF
THF
3
P
d
n
d
1
1
2
2
4 Å MSd
e
n
g
2
+ Mg Bu
2
14
4 Å MS
30
a
a
Unless otherwise noted, all reactions were conducted with 1a
Unless otherwise noted, all reactions were conducted with 1a
for a suitable period of
(10 mol%) + time. Isolated yields. Determined by HPLC using a chiral column.
b
(
0.25 mmol) and 2a (0.125 mmol) under
N
2
.
Isolated yields. (0.25 mmol) and 2a (0.125 mmol) under N
2
c
d
b
c
Determined by HPLC using a chiral column. ZnEt
2
n
e
n
d
e
f
g
Mg Bu
2
(10 mol%). ZnMe
2
(10 mol%) + Mg Bu
2
(10 mol%).
25 mg was used. 50 mol% was used. r.t. −20 °C.
2056 | Org. Biomol. Chem., 2021, 19, 2055–2062
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
a
Table 3 The generality of the reaction with various isatins
selective carbonyl-ene reaction and furnished the addition
product (3ja) in 83% yield with 82% ee (entry 10). 7-Br isatin
could be subjected into the reaction to deliver the enantio-
selective addition product (3ka) in 92% yield with 94% ee
1
6
(
entry 11). Finally, substituted N-benzyl isatins (1l and 1m)
were found to be compatible with the reaction and formed the
desired chiral oxindoles in 93% and 88% yields with 97% and
8
9% ee, respectively.
Finally, we examined the reaction of the N-methyl substrate
b
c
Entry
X
R
Product
t (h)
Yield (%)
ee (%)
(
1a) with acetaldehyde tert-butyl hydrazone (2b) under the opti-
1
2
3
4
5
6
7
8
9
1
1
1
1
H
H
H
H
Me
H
Ac
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
6
5
5
5
4
3
3
4
3
15
4
4
4
98
92
81
97
93
94
93
91
89
83
92
93
88
97
45
75
90
95
90
96
93
92
82
94
97
89
mized conditions (Scheme 1), furnishing the oxindole (3ab)
with two contiguous chiral centres in 91% yield with 2.4 : 1 dr
and low stereoselectivity. Further research in this field has
been conducted by our group. Since the product, functiona-
lized 3-hydroxy-2-oxindoles, is not stable and easy to racemize
at room temperature according to a previous study, we con-
ducted methylation of the hydroxy group to form the protected
product (4a or 4h) which is stable and can avoid further race-
mization (Scheme 2).
Bn
Me
Me
Me
Me
Me
Me
Me
Bn
Bn
5-F
5-Br
5-Me
5-MeO
5-Ph
4-Br
7-Br
5-Me
5-F
6
b
0
1
2
3
3ja
3ka
3la
3ma
1
7
According to the previous reports, a plausible mechanism
is shown in Scheme 3. Firstly, the dinuclear zinc catalyst
(ZnEt L ) containing both Brønsted base and Lewis acid sites
2 4
a
Unless otherwise noted, all reactions were conducted with
for a suitable period of
time. Isolated yields. Determined by HPLC using a chiral column.
1
(0.25 mmol) and 2a (0.125 mmol) under N
2
b
c
is produced from ZnEt2 and the ligand spontaneously.
Subsequently, hydrazone is activated by the Brønsted base site
on the catalyst, forming complex 5 through deprotonation.
The products (3aa–3da) were obtained with high efficiency Then the carbonyl group of isatin binds to the Lewis acid site
(
(
81–98% yield) and variable degrees of enantioselectivity from a less sterically hindered position, generating zinc–
45–97% ee). N-Methyl-isatin (1a) gave excellent results in both oxygen coordination, followed by the carbonyl-ene reaction to
yield and enantiomeric excess (Table 3, entry 1). A moderate give the intermediate 7. The high enantioselectivity was sup-
result was achieved for N-Ac isatin (1c), which might be due to posed to arise from the bifunctional mode of activation.
the low solubility of 1c and a competitive binding effect of the Finally, the desired product is furnished accompanied by the
acyl group. A good conversion for N-Bn (1d) isatin was regeneration of hydrazone–catalyst complex 5 to complete the
observed after several hours, enantioselectivities reaching high catalytic circle.
values, 90% ee (Table 3, entry 4). However, since isatin itself
(
1b) without a protecting group had a detrimental effect on
stereoselectivity, the product 3ba was provided with a good
yield and 45% ee (Table 3, entry 2).
In order to further explore the generality of this dinuclear
metal catalyzed carbonyl-ene reaction, we treated formal-
dehyde tert-butyl hydrazone with various N-methyl- or
N-benzyl-isatins in this asymmetric process, which are pre-
sented in Table 3 (entries 5–13). Isatins with different substi-
tuted groups (electron-withdrawing or electron-donating) were
found to be well tolerated, giving the corresponding functiona-
lized 3-hydroxy-2-oxindoles (3ea–3ka) in 83–94% yields with
excellent levels of enantioselectivity. Isatins (1e and 1f) with Scheme 1 The reaction with acetaldehyde tert-butyl hydrazone.
5
-F and 5-Br groups were compatible with the reaction con-
ditions, affording the corresponding products 3ea and 3fa in
3% and 94% yields with 95% and 90% enantioselectivities,
9
respectively. Furthermore, substrates 1g, 1h and 1i with elec-
tron-rich substituents (5-Me, 5-MeO and 5-phenyl) furnished
the corresponding chiral 3-hydroxy-2-oxindoles with 89–93%
yields and 92–96% ee, respectively (entries 7–9). Next, 4-Br
isatin (1j) was tested. 4-Br isatin is challenging since the steric
effect of Br prevents isatin from binding to the catalyst. To our
delight, 4-Br isatin was a suitable substrate for the enantio- Scheme 2 Derivatization of the product.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2055–2062 | 2057

View Article Online
Paper
Organic & Biomolecular Chemistry
2
0
2b
were synthesized according to the literature. Other
reagents were obtained from commercial sources and used as
received without further purification. Melting points were
determined using b-type tube melting point apparatus and are
uncorrected. Optical rotations were measured with
a
1
PerkinElmer model 341 Polarimeter at 20 °C in CHCl
3
. H and
1
3
C NMR spectra were measured on a Bruker DPX 400 NMR
1
13
instrument (400 MHz for H NMR and 100 MHz for C NMR).
Tetramethylsilane (TMS) served as the internal standard
1
(
0 ppm) for H NMR, and CDCl
3
served as the internal stan-
1
3
dard (77.0 ppm) for C NMR. NMR data are represented as
follows: chemical shift (δ ppm), multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet, comp =
complex), coupling constant in hertz (Hz), integration. FT-IR
spectra were recorded on a PerkinElmer Spectrum Two L600
system and are reported in terms of frequency of absorption
−
1
(
cm ). High-resolution mass spectra (HRMS) were obtained
using an Agilent LC-MSAD-Trap-XCT instrument using electro-
spray ionization time-of-flight (ESI-TOF). High performance
liquid chromatography (HPLC) was performed on an instru-
ment consisting of a JASCO model PU-1580 intelligent HPLC
pump and a JASCO model UV-1575 intelligent UV-vis detector
(
×
254 nm) using Daicel Chiralpak AS, AD, OJ or OD-H (4.6 mm
250 mm) columns.
Scheme 3 Proposed catalytic cycle.
Conclusions
General procedure for the asymmetric carbonyl-ene reaction of
hydrazones
In summary, we have developed a novel asymmetric activation
strategy for hydrazones as acyl anion equivalents in the
enantioselective carbonyl-ene reaction of N-monoalkyl hydra-
zone and isatin. The chiral dinuclear zinc catalyst as the
Brønsted base activates N-tert-butyl hydrazone, enabling the
asymmetric carbonyl-ene reaction to deliver functionalized
In a flame-dried Schlenk tube, a solution of diethylzinc (25 μL,
1
1
.0 mol L− in hexane, 0.025 mmol, 20 mol%) was added to a
solution of the chiral ligand (S,S)-L (8.3 mg, 0.0125 mmol) in
4
dry THF (1.0 mL) under nitrogen at 0 °C. The mixture was
stirred at room temperature for 30 min. Then 1 (0.125 mmol),
2
(0.25 mmol) and dry THF (1.0 mL) were added to the
3
-hydroxy-2-oxindoles in high yields with excellent enantio-
mixture. The solution was stirred at 0 °C for the necessary reac-
tion time. Upon completion, the reaction was quenched with
selectivities under mild conditions. This method demon-
strated that chiral metal catalysis, besides organocatalysis, is a
powerful method in triggering the reaction of hydrazones and
carbonyl compounds through an asymmetric pathway. Further
efforts are underway to explore this new asymmetric activation
strategy for other enantioselective transformations.
sat. NH Cl (aq., 2 mL) and the reaction mixture was extracted
4
three times with EA (3 × 2 mL). The combined organics were
washed with brine followed by drying with MgSO , filtration
4
and concentration in vacuo. The crude product was purified by
preparative TLC using the indicated solvent mixture to
afford 3.
Experimental section
Derivatization of the product
Unless otherwise noted, all reactions sensitive to air or moist-
ure were carried out under nitrogen using standard Schlenk 3aa (32.6 mg, 0.125 mmol) or 3ha was dissolved in dry MeCN
and vacuum line techniques. Diethylzinc (1.0 mol L− in (3 mL). At 0 °C, Cs
1
2
3
CO (82 mg, 0.25 mmol) and MeI (0.31 mL,
hexane) was purchased from Aldrich and used as received. 5 mmol) were added. The mixture was stirred for 12 h. After
1
3c
18
L
1
and L
2
–L
7
2
were synthesized according to the literature. completion, the reaction was quenched with H O (2 mL). The
Methyl substituted isatins were prepared by methylation of organic layer was separated. The aqueous layer was extracted
isatins using MeI and NaH. Benzyl substituted isatins were with EA (2 × 5 mL). The combined organics were washed with
furnished with BnBr and NaH. Acyl protected isatin was pre- brine followed by drying with MgSO
pared using Ac O and DMAP. Allyl protected isatin was pre- tration in vacuo. The crude product was purified by preparative
pared using allyl bromide and K CO . Hydrazones 2a and TLC using the indicated solvent mixture to afford 4a or 4h.
4
, filtration and concen-
2
1
9
2
3
2058 | Org. Biomol. Chem., 2021, 19, 2055–2062
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
(
2
S,E)-3-[(tert-Butyldiazenyl)methyl]-3-hydroxy-1-methylindolin-
-one (3aa)
(m, 6H), 7.17 (t, J = 7.6 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.67 (d,
J = 8.0 Hz, 1H), 4.97 (d, J = 15.6 Hz, 1H), 4.78 (d, J = 15.6 Hz,
1
1
H), 4.46 (d, J = 12.4 Hz, 1H), 4.14 (d, J = 12.4 Hz, 1H), 3.87 (s,
H), 0.99 (s, 9H) ppm; C NMR (100 MHz, CDCl ): δ = 177.1,
3
The crude product was purified by preparative TLC (dichloro-
1
3
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow
2
5
142.8, 135.4, 129.9, 128.8, 128.5, 127.7, 127.4, 125.0, 123.0,
109.4, 75.4, 73.6, 68.0, 44.0, 26.6 ppm; IR (neat): 3443, 3136,
2
3
oil, 32.0 mg, 98% yield; [α] = +43 (c = 0.35, in CHCl ); HPLC
D
−
1
(Chiralpak AS, hexane/i-PrOH = 95/5, flow rate = 1.0 mL min
,
−1
856, 2959, 1634, 1400, 1273, 1186, 1107, 560 cm ; MS (ESI):
λ = 254 nm): tR (major) = 16.20 min, tR (minor) = 19.63 min,
+
1
m/z = 338.1 [M + H] .
9
1
7
1
3
7% ee; H NMR (400 MHz, CDCl ): δ = 7.33 (d, J = 7.2 Hz,
H), 7.29 (t, J = 7.6 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.78 (d, J =
.2 Hz, 1H), 4.39 (d, J = 12.4 Hz, 1H), 4.19 (s, 0.8 H), 4.13 (d, J =
2.4 Hz, 1H), 3.18 (s, 3H), 0.99 (s, 9H) ppm; C NMR
(S,E)-3-[(tert-Butyldiazenyl)methyl]-5-fluoro-3-hydroxy-1-
methylindolin-2-one (3ea)
13
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow
oil, 32.4 mg, 93% yield; [α] = +25 (c = 0.12, in CHCl ); HPLC
D
3
(Chiralpak OD-H, hexane/i-PrOH = 95/5, flow rate = 1.0 mL
min , λ = 254 nm): t
1
1
(100 MHz, CDCl ): δ = 177.0, 143.6, 129.8, 128.6, 124.8, 123.0,
3
1
2
08.2, 75.4, 73.5, 67.9, 26.5, 26.2 ppm; IR (neat): 3471, 2972,
2
5
−1
957, 1789, 1714, 1467, 1273, 1186, 1107, 776, 571 cm ; MS
+
(ESI): m/z = 262.1[M + H] .
−
1
R
(major) = 9.32 min, t
R
(minor) =
1
1.43 min, 95% ee; H NMR (400 MHz, CDCl ): δ = 7.11 (m,
(S,E)-3-[(tert-Butyldiazenyl)methyl]-3-hydroxyindolin-2-one
3
H), 7.01 (m, 1H), 7.04 (m, 1H), 4.33 (d, J = 12.4 Hz, 1H), 4.13
(3ba)
1
3
(
(
(
d, J = 12.8 Hz, 1H), 3.18 (s, 3H), 1.05 (s, 9H) ppm; C NMR
100 MHz, CDCl ): δ = 176.7, 158.2 (d, 240.0 Hz), 139.5, 130.3
d, 8.0 Hz), 115.9 (d, 23.0 Hz), 113.1 (d, 25.0 Hz), 108.8 (d, 8.0
The crude product was purified by preparative TLC (dichloro-
3
methane/petroleum ether/EtOAc = 10/4/3) to afford a white
2
5
solid, 28.4 mg, 92% yield; [α] = −13 (c = 0.35, in CHCl
3
);
D
Hz), 75.6, 73.3, 68.1, 26.5, 26.4 ppm; IR (neat): 3462, 3008,
HPLC (Chiralpak AS, hexane/i-PrOH = 90/10, flow rate = 1.0 mL
2
7
925, 2855, 1744, 1647, 1493, 1460, 1232, 1104, 911, 809,
−
1
min , λ = 254 nm): t
R
(minor) = 12.78 min, t
7.38 min, 45% ee; H NMR (400 MHz, DMSO-d): δ = 10.29 (s,
H), 7.18 (d, J = 7.6 Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 6.88 (t, J =
.6 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 6.30 (s, 1 H), 4.28 (d, J = (S,E)-5-Bromo-3-[(tert-butyldiazenyl)methyl]-3-hydroxy-1-
R
(major) =
−1
+
21 cm ; MS (ESI): m/z = 280.1 [M + H] . HRMS (ESI-TOF): m/z
1
1
1
7
1
+
+
3 2
[M + H] , calcd for C14H19FN O 280.1456, found 288.1455.
1
3
0.8 Hz, 1H), 3.96 (d, J = 11.2 Hz, 1H), 0.86 (s, 9H) ppm;
C
methylindolin-2-one (3fa)
NMR (100 MHz, DMSO-d): δ = 178.6, 142.5, 130.7, 129.5, 125.3,
The crude product was purified by preparative TLC (dichloro-
1
2
21.7, 109.7, 75.0, 74.1, 67.5, 26.7 ppm; IR (neat): 3461, 2972,
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow
−1
959, 1789, 1714, 1467, 1273, 1186, 1107, 776 cm ; MS (ESI):
2
5
oil, 39.9 mg, 94% yield; [α] = −22 (c = 0.25, in CHCl
3
); HPLC
+
D
m/z = 248.3 [M + H] .
(
Chiralpak OD-H, hexane/i-PrOH = 95/5, flow rate = 1.0 mL
−
1
min , λ = 254 nm): t
R
(major) = 10.52 min, t
R
(minor) =
(
2
S,E)-1-Acetyl-3-[(tert-butyldiazenyl)methyl]-3-hydroxyindolin-
-one (3ca)
The crude product was purified by preparative TLC (dichloro-
1
1
2
1
9.17 min, 90% ee; H NMR (400 MHz, CDCl ): δ = 7.43 (m,
3
H), 6.67 (d, J = 8.4 Hz, 1H), 4.32 (d, J = 12.8 Hz, 1H), 4.25 (s,
H), 4.15 (d, J = 12.8 Hz, 1H), 3.17 (s, 3H), 1.03 (s, 9H) ppm;
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow 13
3
C NMR (100 MHz, CDCl ): δ = 176.4, 142.6, 132.5, 130.6,
2
5
oil, 29.3 mg, 81% yield; [α] = +27 (c = 0.32, in CHCl ); HPLC
D
3
128.3, 115.7, 109.7, 75.4, 73.2, 68.2, 26.5, 26.4 ppm; IR (neat):
1
(
Chiralpak AS, hexane/i-PrOH = 95/5, flow rate = 0.8 mL min−
,
3
8
440, 2968, 2926, 2858, 1714, 1639, 1613, 1484, 1464, 1107,
λ = 254 nm): t (minor) = 12.99 min, t (major) = 15.08 min,
R
R
−1
+
10, 677, 563 cm ; MS (ESI): m/z = 340.0 [M + H] ; HRMS
1
7
1
1
5% ee; H NMR (400 MHz, CDCl ): δ = 8.19 (d, J = 8.0 Hz,
+
+
3
(ESI-TOF): m/z [M + H] , calcd for C H BrN O 340.0655,
14 19 3 2
H), 7.36 (q, 2H), 7.21 (t, J = 7.6 Hz, 1H), 4.47 (d, J = 13.2 Hz,
found 340.0657.
H), 4.27 (d, J = 13.2 Hz, 1H), 2.66 (s, 3H), 0.96 (s, 9H) ppm;
1
3
C NMR (100 MHz, CDCl ): δ = 177.6, 170.6, 140.2, 130.4, (S,E)-3-[(tert-Butyldiazenyl)methyl]-3-hydroxy-1,5-
3
1
3
7
27.5, 125.6, 124.0, 116.7, 75.7, 73.7, 68.3, 26.2 ppm; IR (neat): dimethylindolin-2-one (3ga)
459, 2942, 2950, 1789, 1766, 1712, 1467, 1173, 1186, 1123,
The crude product was purified by preparative TLC (dichloro-
76, 571 cm− ; MS (ESI): m/z = 290.2 [M + H] .
1
+
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow
2
5
oil, 32 mg, 93% yield; [α] = +36 (c = 0.33, in CHCl
3
); HPLC
D
(
S,E)-1-Benzyl-3-[(tert-butyldiazenyl)methyl]-3-hydroxyindolin-
-one (3da)
The crude product was purified by preparative TLC (dichloro- 10.78 min, 96% ee; H NMR (400 MHz, CDCl
methane/petroleum ether/EtOAc = 10/6/3) to afford a colour- 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 4.30 (d, J =
(
Chiralpak OD-H, hexane/i-PrOH = 95/5, flow rate = 1.0 mL
2
−1
min , λ = 254 nm): t (major) = 8.08 min, tR (minor) =
R
1
3
): δ = 7.16 (s,
2
5
less oil, 40.9 mg, 97% yield; [α] = +41 (c = 0.14, in CHCl3); 12.4 Hz, 1H), 4.10 (d, J = 12.4 Hz, 1H), 3.17 (s, 3H), 2.31 (s,
D
1
3
3
HPLC (Chiralpak AS, hexane/i-PrOH = 95/5, flow rate = 1.0 mL 3H), 1.05 (s, 9H) ppm; C NMR (100 MHz, CDCl ): δ = 176.5,
−
1
min , λ = 254 nm): t
R
(major) = 15.83 min, t
R
(minor) = 141.2, 132.5, 130.0, 128.4, 125.6, 108.0, 75.5, 73.3, 68.0, 26.5,
1
3
1.47 min, 90% ee; H NMR (400 MHz, CDCl ): δ = 7.27–7.33 26.2, 21.0 ppm; IR (neat): 3495, 3376, 2960, 2927, 1715, 1700,
3
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2055–2062 | 2059

View Article Online
Paper
Organic & Biomolecular Chemistry
1
2
684, 1628, 1591, 1102, 806, 486, 474 cm−1; MS (ESI): m/z = (S,E)-7-Bromo-3-[(tert-butyldiazenyl)methyl]-3-hydroxy-1-
+
+
76.2 [M + H] . HRMS (ESI-TOF): m/z [M + H] , calcd for methylindolin-2-one (3ka)
+
15 22 3 2
C H N O 276.1707, found 276.1705.
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow
2
5
3
oil, 39.1 mg, 92% yield; [α] = +25 (c = 0.31, in CHCl ); HPLC
(
S,E)-3-[(tert-Butyldiazenyl)methyl]-3-hydroxy-5-methoxy-1-
D
−
1
(
Chiralpak AS, hexane/i-PrOH = 95/5, flow rate = 1.0 mL min
λ = 254 nm): t (major) = 10.82 min, tR (minor) = 15.55 min,
4% ee; H NMR (400 MHz, CDCl
H), 7.27 (d, J = 8.4 Hz, 1H), 6.91 (t, J = 8.0 Hz, 1H), 4.33 (d, J =
,
methylindolin-2-one (3ha)
R
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a light
brown oil, 33.1 mg, 91% yield; [α] = +19 (c = 0.35, in CHCl );
3
HPLC (Chiralpak OD-H, hexane/i-PrOH = 95/5, flow rate =
1
=
1
1
1
9
3
): δ = 7.40 (d, J = 8.0 Hz,
1
2
5
D
12.4 Hz, 1H), 4.10 (d, J = 12.4 Hz, 1H), 3.58 (s, 3H), 1.03 (s, 9H)
13
ppm; C NMR (100 MHz, CDCl
31.7, 126.1, 124.2, 123.8, 74.8, 73.4, 68.2, 29.9, 26.5 ppm; IR
neat): 3522, 3286, 2934, 2827, 1725, 1712, 1692, 1600, 1491,
012, 751 cm ; MS (ESI): m/z = 340.0 [M + H] . HRMS
ESI-TOF): m/z [M + H] , calcd for C H BrN O 340.0655,
14 19 3 2
3
): δ = 177.3, 141.0, 135.4,
.0 mL min− , λ = 254 nm): t
1
(major) = 11.02 min, t
): δ = 6.98 (s,
R
R
(minor)
1
1
17.36 min, 93% ee; H NMR (400 MHz, CDCl
3
(
1
(
H), 6.83 (d, J = 7.6 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 4.29 (d, J =
2.4 Hz, 1H), 4.09 (d, J = 12.4 Hz, 1H), 3.17 (s, 3H), 1.06 (s, 9H)
−1
+
+
+
1
3
ppm; C NMR (100 MHz, CDCl
3
): δ = 176.4, 156.3, 136.9,
29.7, 114.7, 111.9, 108.7, 75.7, 73.2, 68.0, 55.8, 26.5,
6.3 ppm; IR (neat): 3479, 3410, 2959, 2921, 2853, 1701, 1638,
found 340.0654.
1
2
1
−
1
486, 1224, 1030, 554, 472 cm ; MS (ESI): m/z = 292.2 [M +
+
+
+
(
S,E)-1-Benzyl-3-[(tert-butyldiazenyl)methyl]-3-hydroxy-5-
H] ; HRMS (ESI-TOF): m/z [M + H] , calcd for C H N O
22 3 3
1
5
methylindolin-2-one (3la)
2
92.1656, found 292.1658.
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a white
(
S,E)-3-[(tert-Butyldiazenyl)methyl]-3-hydroxy-5-phenyl-1-
2
5
solid, 40.9 mg, 93% yield; [α] = +13 (c = 0.22, in CHCl3);
D
methylindolin-2-one (3ia)
HPLC (Chiralpak AS, hexane/i-PrOH = 80/20, flow rate = 1.0 mL
−
1
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a colorless
oil, 37.5 mg, 89% yield; [α] = −17 (c = 0.11, in CHCl
min , λ = 254 nm): t
9
R
(major) = 5.21 min, t
R
(minor) =
1
.27 min, 97% ee; H NMR (400 MHz, CDCl ): δ = 7.26–7.30
3
2
5
3
); HPLC
(m, 5H), 7.14 (s, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.55 (d, J = 8.0
Hz, 1H), 4.94 (d, J = 16.0 Hz, 1H), 4.77 (d, J = 15.6 Hz, 1H), 4.40
D
(Chiralpak OD-H, hexane/i-PrOH = 90/10, flow rate = 1.0 mL
−
1
min , λ = 254 nm): t
R
(major) = 6.50 min, t
R
(minor) =
(
(
1
1
d, J = 12.4 Hz, 1H), 4.12 (d, J = 12.4 Hz, 1H), 3.62 (s, 1H), 2.26
1
1
3
1
1
1
0.31 min, 92% ee; H NMR (400 MHz, CDCl ): δ = 7.59 (s,
3
s, 3H), 1.03 (s, 9H) ppm; C NMR (100 MHz, CDCl
3
): δ =
76.8, 140.3, 135.4, 132.6, 130.0, 128.8, 128.4, 127.7, 127.3,
25.8, 109.4, 109.2, 75.5, 73.6, 68.0, 44.0, 26.6, 21.0 ppm; IR
H), 7.53 (m, 3H), 7.41 (m, 3H), 6.86 (d, J = 8.4 Hz), 4.24 (d, J =
2.4 Hz, 1H), 4.17 (d, J = 12.4 Hz, 1H), 3.23 (s, 3H), 1.01 (s, 9H)
1
3
ppm; C NMR (100 MHz, CDCl
3
): δ = 176.9, 142.9, 140.7,
(
6
neat): 3435, 3134, 2858, 2827, 1662, 1619, 1400, 1012, 751,
98, 618 cm− ; MS (ESI): m/z = 352.2 [M + H] . HRMS
1
+
1
6
1
=
C
36.5, 132.6, 129.1, 128.8, 128.3, 126.8, 123.9, 108.5, 75.5, 73.4,
+
+
8.0, 26.5, 26.4 ppm; IR (neat): 3481, 3381, 2924, 2854, 1717,
(
ESI-TOF): m/z [M + H] , calcd for C H N O 352.2020,
21 26 3 2
−
1
610, 1486, 1361, 1107, 808, 701, 633, 534 cm ; MS (ESI): m/z
found 352.2017.
+
+
338.2 [M + H] . HRMS (ESI-TOF): m/z [M + H] , calcd for
+
20
24 3 2
H N O 338.1863, found 338.1867.
(S,E)-1-Benzyl-3-[(tert-butyldiazenyl)methyl]-5-fluoro-3-
(S,E)-4-Bromo-3-[(tert-butyldiazenyl)methyl]-3-hydroxy-1-
hydroxyindolin-2-one (3ma)
methylindolin-2-one (3ja)
The crude product was purified by preparative TLC (dichloro-
The crude product was purified by preparative TLC (dichloro- methane/petroleum ether/EtOAc = 10/6/3) to afford a colorless
2
5
methane/petroleum ether/EtOAc = 10/6/3) to afford a yellow oil, 39.1 mg, 88% yield; [α] = +13 (c = 0.32, in CHCl
3
); HPLC
D
2
5
oil, 35.3 mg, 83% yield; [α] = −29 (c = 0.28, in CHCl
3
); HPLC (Chiralpak AS, hexane/i-PrOH = 80/20, flow rate = 1.0 mL
Chiralpak OD-H, hexane/i-PrOH = 95/5, flow rate = 1.0 mL min , λ = 254 nm): t (major) = 5.60 min, tR (minor) =
D
−
1
(
R
−
1
1
min , λ = 254 nm): t
R
(minor) = 14.36 min, t
6.74 min, 82% ee; H NMR (400 MHz, CDCl ): δ = 7.15 (t, 2H), 7.07 (q, 1H), 6.87 (m, 1H), 6.59 (t, J = 4.4 Hz, 1H), 4.95 (d, J =
.72 (q, 1H), 4.63 (d, J = 12.4 Hz, 1H), 4.51 (d, J = 12.4 Hz, 1H), 16.0 Hz, 1H), 4.78 (d, J = 15.6 Hz, 1H), 4.41 (d, J = 12.8 Hz, 1H),
R 3
(major) = 8.14 min, 89% ee; H NMR (400 MHz, CDCl ): δ = 7.29 (t, 5H),
1
1
6
3
1
2
1
3
1
3
13
.18 (s, 3H), 0.90 (s, 9H) ppm; C NMR (100 MHz, CDCl
76.1, 145.9, 131.2, 126.9, 126.4, 119.7, 107.1, 76.5, 70.6, 67.7, CDCl
6.3, 26.3 ppm; IR (neat): 3567, 3386, 2834, 2827, 1825, 1701, 127.8, 127.3, 116.1, 115.9, 113.3, 113.1, 110.1, 110.0, 75.5, 73.4,
3
): δ = 4.78 (d, J = 12.4 Hz, 1H), 1.03 (s, 9H) ppm; C NMR (100 MHz,
3
): δ = 176.8, 160.5, 158.1, 138.6, 135.0, 130.1, 128.9,
−
1
+
692, 1626, 1491, 1012 cm ; MS (ESI): m/z = 340.1 [M + H] . 68.1, 44.1, 26.5 ppm; IR (neat): 3334, 3124, 2877, 2824, 1662,
+
+
−1
HRMS (ESI-TOF): m/z [M + H] , calcd for C14
H
19BrN
3
O
2
1609, 1402, 1012, 761, 698, 618, 751 cm ; MS (ESI): m/z =
+
3
40.0655, found 340.0657.
356.1 [M + H] .
2060 | Org. Biomol. Chem., 2021, 19, 2055–2062
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
S,E)-3-[(tert-Butyldiazenyl)ethyl]-3-hydroxy-1-methylindolin-2-
Paper
(
Acknowledgements
one (3ab)
We are grateful to the National Natural Science Foundation of
China (NNSFC: 21871237).
The crude product was purified by preparative TLC (dichloro-
methane/petroleum ether/EtOAc = 10/6/3) to afford a light
yellow oil, 31.3 mg, 91% yield; HPLC (Chiralpak AS, hexane/
−
1
i-PrOH = 95/5, flow rate = 1.0 mL min , λ = 254 nm): t
R
1
(
(
minor) = 9.62 min, tR (major) = 13.95 min, 20% ee; H NMR Notes and references
400 MHz, CDCl
.33 (t, J = 8.0 Hz, 1H), 7.14 (t, J = 7.2 Hz, 0.5H), 7.08 (t, J = 7.6
Hz, 1H), 6.89 (d, J = 8.0 Hz, 0.5H), 6.82 (d, J = 8.0 Hz, 1H), 3.87
3
): δ = 7.61 (m, 1H), 7.38 (d, J = 7.2 Hz, 1H),
1
(a) R. Lazny and A. Nodzewska, Chem. Rev., 2010, 110,
386; (b) R. Brehme, D. Enders, R. Fernandez and
7
1
J. M. Lassaletta, Eur. J. Org. Chem., 2007, 5629;
(c) R. Fernandez and J. M. Lassaletta, Synlett, 2000, 1228.
For a review of hydrazones in asymmetric organocatalysis,
see: M. de Gracia Retamosa, E. Matador, D. Monge,
J. M. Lassaletta and R. Fernandez, Chem. – Eur. J., 2016, 22,
13430. For other examples, see: (a) T. Hashimoto,
H. Kimura and K. Maruoka, Angew. Chem., Int. Ed., 2010,
(
(
1
1
3
1
q, J = 6.8 Hz, 1H), 3.26 (s, 1.5H), 3.21 (s, 3H), 1.16 (s, 9H), 1.06
1
3
s, 3H) ppm; C NMR (100 MHz, CDCl ): δ = 176.3, 144.1,
3
2
38.4, 129.8, 128.1, 126.0, 125.3, 124.9, 123.9, 123.0, 109.9,
08.2, 78.1, 76.5, 75.0, 67.9, 26.7, 26.2 13.1 ppm; IR (neat):
731, 3489, 3395, 3372, 2924, 2854, 1742, 1719, 1471, 1462,
367, 1091, 753 cm−1; MS (ESI): m/z = 276.2 [M + H]+. HRMS
+
+
(ESI-TOF): m/z [M + H] , calcd for C15
H
22
N
3
O
2
276.1707,
49, 6844; (b) T. Hashimoto, M. Omote and K. Maruoka,
found 276.1709.
Angew. Chem., Int. Ed., 2011, 50, 3489; (c) H.-X. Chen, Y. Li,
X. He, Y. Zhang, W. He, H. Liang, Y. Zhang, X. Jiang,
X. Chen, R. Cao, G.-F. Liu and L. Qiu, Eur. J. Org. Chem.,
(
S,E)-3-[(tert-Butyldiazenyl)methyl]-3-methoxy-1-
methylindolin-2-one (4a)
2
018, 6733.
The crude product was purified by preparative TLC (petroleum
ether/EtOAc = 5/1) to afford a colorless oil, 31.3 mg, 91% yield;
3
(a) D. Monge, E. Martín-Zamora, J. Vázquez, M. Alcarazo,
E. Álvarez, R. Fernández and J. M. Lassaletta, Org. Lett.,
2007, 9, 2867; (b) H. Zhang, Q. Yao, W. Cao, S. Ge, J. Xu,
X. Liu and X. Feng, Chem. Commun., 2018, 54, 12511;
2
5
[
D
3
α] = +26 (c = 0.14, in CHCl ); HPLC (Chiralpak OD-H,
−
1
hexane/i-PrOH = 98/2, flow rate = 0.5 mL min , λ = 254 nm):
1
t
R
(major) = 17.02 min, t
R
(minor) = 19.51 min, 94% ee; H
(
c) D. Pettersen, R. P. Herrera, L. Bernardi, F. Fini,
NMR (400 MHz, CDCl ): δ = 7.30–7.32 (m, 1H), 7.26–7.28 (m,
3
V. Sgarzani, R. Fernandez, J. M. Lassaletta and A. Ricci,
Synlett, 2006, 239; (d) R. P. Herrera, D. Monge, E. Martín-
Zamora, R. Fernández and J. M. Lassaletta, Org. Lett., 2007,
1
H), 7.04–7.08 (m, 1H), 6.78 (d, J = 8.0 Hz, 1H), 4.41 (d, J = 12.0
Hz, 1H), 4.11 (d, J = 12.0 Hz, 1H), 3.22 (s, 3H), 3.13 (s, 3H),
1
3
0
1
2
1
.90 (s, 9H) ppm; C NMR (100 MHz, CDCl ): δ = 174.0, 143.4,
3
9
, 3303; (e) D. Monge, S. Daza, P. Bernal, R. Fernández and
29.0, 124.5, 124.3, 121.8, 107.0, 80.5, 72.3, 66.6, 51.7, 25.4,
5.1 ppm; IR (neat): 2977, 2192, 1733, 1708, 1607, 1598, 1488,
403, 1341, 1106, 799 cm ; MS (ESI): m/z = 276.1 [M + H] .
J. M. Lassaletta, Org. Biomol. Chem., 2013, 11, 326. For the
imino aza-enamine reaction, see: (f) D. J. Dixon and
A. L. Tillman, Synlett, 2005, 2635; (g) M. Rueping,
E. Sugiono, T. Theissmann, A. Kuenkel, A. Kockritz,
A. Pews-Davtyan, N. Nemati and M. Beller, Org. Lett., 2007,
9, 1065; (h) T. Hashimoto, M. Hirose and K. Maruoka,
J. Am. Chem. Soc., 2008, 130, 7556.
−1
+
+
+
HRMS (ESI-TOF): m/z [M + H] , calcd for C H N O
22 3 2
1
5
2
76.1707, found 276.1705.
(S,E)-5-Bromo-3-[(tert-butyldiazenyl)methyl]-3-methoxy-1-
methylindolin-2-one (4h)
4
S. Breitler and E. M. Carreira, J. Am. Chem. Soc., 2015, 137,
The crude product was purified by preparative TLC (petroleum
ether/EtOAc = 5/1) to afford a colorless oil, 38.1 mg, 86% yield;
5296.
2
5
5 (a) S. Kobayashi, Y. Mori, J. S. Fossey and M. M. Salter,
Chem. Rev., 2011, 111, 2626; (b) J. M. Keith and
E. N. Jacobsen, Org. Lett., 2004, 6, 153; (c) G. T. Notte and
J. L. Leighton, J. Am. Chem. Soc., 2008, 130, 6676.
[
3
α] = −5 (c = 0.17, in CHCl ); HPLC (Chiralpak AD, hexane/
D
−
1
i-PrOH = 98/2, flow rate = 0.8 mL min , λ = 254 nm): t
R
1
(
(
(
minor) = 9.32 min, tR (major) = 10.88 min, 94% ee; H NMR
400 MHz, CDCl ): δ = 7.43 (d, J = 7.2 Hz, 1H), 7.39 (s, 1H), 6.68
d, J = 8.0 Hz, 1H), 4.33 (d, J = 12.4 Hz, 1H), 4.12 (d, J = 12.4
3
6
(a) A. Crespo-Peña, D. Monge, E. Martín-Zamora,
E. Alvarez, R. Fernandez and J. M. Lassaletta, J. Am. Chem.
Soc., 2012, 134, 12912; (b) D. Monge, A. M. Crespo-Peña,
E. Martín-Zamora, E. Álvarez, R. Fernández and
1
3
Hz, 1H), 3.21 (s, 3H), 3.14 (s, 3H), 0.95 (s, 9H) ppm; C NMR
100 MHz, CDCl ): δ = 174.4, 143.4, 132.8, 128.6, 127.8, 115.6,
09.6, 81.4, 73.0, 67.9, 53.0, 26.5, 26.3 ppm; IR (neat): 2969,
352, 1731, 1712, 1607, 1600, 1486, 1359, 1341, 1106,
(
3
1
2
8
J. M. Lassaletta, Chem.
– Eur. J., 2013, 19, 8421;
10 cm− ; MS (ESI): m/z = 354.1 [M + H] ; HRMS (ESI-TOF): m/z
1
+
(c) I. Serrano, D. Monge, E. Álvarez, R. Fernández and
J. M. Lassaletta, Chem. Commun., 2015, 51, 4077;
+
+
[
M + H] , calcd for C H BrN O 354.0812, found 354.0814.
15 21 3 2
(
d) J. A. Carmona, G. de Gonzalo, I. Serrano, A. M. Crespo-
Peña, M. Šimek, D. Monge, R. Fernández and
J. M. Lassaletta, Org. Biomol. Chem., 2017, 15, 2993;
Conflicts of interest
(
e) E. Matador, M. de Gracia Retamosa, D. Monge,
The authors declare no competing financial interest.
J. Iglesias-Sigüenza, R. Fernández and J. M. Lassaletta,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2055–2062 | 2061

View Article Online
Paper
Organic & Biomolecular Chemistry
Chem. – Eur. J., 2018, 24, 6854. For a review, see:
f) E. Matador, M. de Gracia Retamosa, D. Monge,
Chem., 2019, 17, 7172; (i) B.-K. Tao, H. Yang, Y.-Z. Hua and
M.-C. Wang, Org. Biomol. Chem., 2019, 17, 4301.
(
R. Fernández and J. M. Lassaletta, Chem. Commun., 2020, 12 1,6-Conjugation: (a) Y.-Y. Gao, Y.-Z. Hua and M.-C. Wang,
5
6, 9256.
Y. Wang, Q. Wang and J. Zhu, Angew. Chem., Int. Ed., 2017,
6, 5612.
Adv. Synth. Catal., 2018, 360, 80. Phospha-Michael
addition: (b) S. Liu, N. Shao, F.-Z. Li, X.-C. Yang and
M.-C. Wang, Org. Biomol. Chem., 2017, 15, 9465;
(c) N. Shao, Y.-Y. Luo, H.-J. Lu, Y.-Z. Hua and M.-C. Wang,
Tetrahedron, 2018, 74, 2130.
7
8
9
5
J. E. Baldwin, R. M. Adlington, J. C. Bottaro, J. N. Kolhe,
M. W. D. Perry and A. U. Jain, Tetrahedron, 1986, 42, 4223.
For a review of chiral dinuclear metal catalysts, see: 13 (a) Y.-Z. Hua, J.-W. Chen, H. Yang and M.-C. Wang, J. Org.
B. M. Trost, C.-I. Hung and G. Mata, Angew. Chem., 2020,
9, 4240. Asymmetric copolymerization: (a) Y.-Z. Hua,
L.-J. Lu, P.-J. Huang, D.-H. Wei, M.-S. Tang, M.-C. Wang
Chem., 2018, 83, 1160; (b) X.-W. Wang, Y.-Z. Hua and
M.-C. Wang, J. Org. Chem., 2016, 81, 9227; (c) Y.-Z. Hua,
X.-W. Han, X.-C. Yang, X. Song, M.-C. Wang and
J.-B. Chang, J. Org. Chem., 2014, 79, 11690; (d) Y.-Z. Hua,
X.-W. Han, L.-H. Huang and M.-C. Wang, Chin. J. Org.
Chem., 2018, 38, 237.
5
and J.-B. Chang, Chem. – Eur. J., 2014, 20, 12394;
(
b) Y.-Z. Hua, X.-C. Yang, M.-M. Liu, X. Song, M.-C. Wang
and J.-B. Chang, Macromolecules, 2015, 48, 1651.
1
0 Y. Yi, Y.-Z. Hua, H.-J. Lu, L.-T. Liu and M.-C. Wang, Org. 14 S. Liu, W.-C. Gao, Y.-H. Miao and M.-C. Wang, J. Org.
Lett., 2020, 22, 2527. Chem., 2019, 84, 2652.
1 (a) M.-M. Liu, X.-C. Yang, Y.-Z. Hua, J.-B. Chang and 15 S. Liu, G.-W. Li, X.-C. Yang, D.-Y. Zhang and M.-C. Wang,
M.-C. Wang, Org. Lett., 2019, 21, 2111; (b) M.-M. Liu, Org. Biomol. Chem., 2017, 15, 7147.
X.-C. Yang, Y.-Z. Hua, J.-B. Chang and M.-C. Wang, Org. 16 Y. Zhang, Y. He, Z. Zhou, W. Xia, C. Cheng, M. Wang,
1
Lett., 2019, 21, 7089; (c) Y.-Z. Hua, M.-M. Liu, P.-J. Huang,
X. Song, M.-C. Wang and J.-B. Chang, Chem. – Eur. J., 2015,
B. Chen, Z. Zhou, J. Pang and L. Qiu, J. Org. Chem., 2015,
80, 6968.
2
1, 11994; (d) Y.-J. Guo, X. Guo, D.-Z. Kong, H.-J. Lu, 17 (a) Y. Xiao, Z. Wang and K. Ding, Chem. – Eur. J., 2005, 11,
L.-T. Liu, Y.-Z. Hua and M.-C. Wang, J. Org. Chem., 2020,
3668; (b) Y. Xiao, Z. Wangang, K. Ding and C. K. Ding,
Macromolecules, 2006, 39, 128.
8
5, 4195; (e) X.-C. Yang, M.-M. Liu, F. Mathey, H. Yang,
Y.-Z. Hua and M.-C. Wang, J. Org. Chem., 2019, 84, 7762; 18 (a) B. M. Trostang, K. Ding and C. H. Ito, J. Am. Chem. Soc.,
(
f) S. Liu, Z.-H. Xu, X. Wang, H.-R. Zhu and M.-C. Wang,
2000, 122, 12003; (b) B. M. Trost, V. S. C. Yeh, H. Ito and
N. Bremeyer, Org. Lett., 2002, 4, 2621.
J. Org. Chem., 2019, 84, 13881; (g) X.-C. Yang, M. Xu,
J.-B. Wang, M.-M. Liu, F. Mathey, Y.-Z. Hua and 19 J. M. Lehn, J. Saba and D. M. Hoffman, Inorg. Chem., 2007,
M.-C. Wang, Org. Biomol. Chem., 2020, 18, 3917; 46, 993.
h) Y.-H. Miao, Y.-Z. Hua and M.-C. Wang, Org. Biomol. 20 S.-F. Wang and J. Warkentin, Can. J. Chem., 1988, 66, 2256.
(
2062 | Org. Biomol. Chem., 2021, 19, 2055–2062
This journal is © The Royal Society of Chemistry 2021