Lewis Acid Catalyzed [4 + 2] Cycloaddition of N-Tosylhydrazones with ortho-Quinone Methides

Article abstract of DOI:10.1021/acs.joc.9b02040

A formal [4 + 2] cycloaddition of N-tosylhydrazones with ortho-quinone methides was developed, affording the facile synthesis of diverse 1,3-oxazine derivatives under mild conditions. In this transformation, N-tosylhydrazones are used as a 1,2-dipole synt

Full text of DOI:10.1021/acs.joc.9b02040

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Note
Lewis Acid Catalyzed [4 + 2]-Cycloaddition of N-
Tosylhydrazones with ortho-Quinone Methides
Chun-Ying Wang, Jia-Bin Han, Long Wang, and Xiang-Ying Tang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02040 • Publication Date (Web): 10 Oct 2019
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The Journal of Organic Chemistry
Lewis Acid Catalyzed [4 + 2]-Cycloaddition of N-Tosylhydrazones with ortho-Quinone Methides
1
2
Chun-Ying Wang, Jia-Bin Han, Long Wang and Xiang-Ying Tang*
3
4
5
6
School of Chemistry and Chemical Engineering, Hubei Key Laboratory of Bioinorganic Chemistry and
Materia Medica, Key Laboratory of Material Chemistry for Energy Conversion and Storage, Huazhong
University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, People’s Republic of China
7
8
9
ABSTRACT: A formal [4 + 2] cycloaddition of N-tosylhydrazones with ortho-quinone methides was
developed, affording facile synthesis of diverse 1,3-oxazine derivatives under mild conditions. In this
transformation, N-tosylhydrazones are used as a 1,2-dipole synthon under base free conditions.
Moreover, the substrate scope is broad and the products are formed with high diastereoselectivities in
most of the cases.
10
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60
Ar1
R1
R2
NHTs
N
Ar1
Ar1
Sc(OTf)3
NHTs
R1
N
Ar2
OH
Ar2
Ar2
O
OH
O
R2
39 examples
N-tosylhydrazones used as 1,2-dipole synthons
high diastereoselectivities
base free
N-tosylhydrazones are versatile and useful intermediates that have various applications in organic
synthesis.1-3 As versatile 1C synthons, they are usually used as carbene precursors in various
transformations, including carbene migratory insertions,4 [1 + n] cycloaddition reactions5 and carbene
induced C−H6 or X−H bond7 (X = heteroatoms) insertions and other useful reactions.8 For example, in
2015, Prof. Wang reported an interesting tandem carbene migratory insertion into Si-Si and Sn-Sn bonds
for the facile access of germinal bis(silane) and germinal bis(stannane) derivatives (Scheme 1a).4e Prof.
Aggarwal used N-tosylhydrazones to in situ generate diazo compounds and the subsequent asymmetric
cycloaddition of carbonyl compounds would deliver epoxides with excellent enantioselectivities (Scheme
1b).5h Prof. Zhang also reported a highly enantioselective Co-catalyzed radical cyclopropanation of
alkenes with N-tosylhydrazones to give di- or tri-substituted cyclopropanes (Scheme 1b).5c Recently, Prof.
Che and Xu reported a novel Iron porphyrin catalyzed X−H (X = Si, Sn, Ge) bond insertions with wide
substrate scope and excellent yields (Scheme 1c).7a On the other hand, as 1,3-dipole synthons, N-
tosylhydrazones readily underwent a wide range of formal [3 + n] cycloadditions.9 In 2015, Prof. Valdés
discovered a 1,3-dipolar cycloaddition/[1,5] sigmatropic rearrangement of N-tosylhydrazones with
terminal alkynes, affording synthetically valuable 3-substituted or 3,4-disubstituted pyrazoles (Scheme
1d).9f After that, Prof. Jiang and Wu also reported that N-tosylhydrazones could went through [3 + 2]
cycloaddition with in situ formed acetylene (Scheme 1d).9e Despite all these exciting achievements
described above, the applications of N-tosylhydrazones as 1,2-dipole synthons are extremely
unexplored.10 The reason may due to that most of the transformations of N-tosylhydrazones are performed
under basic conditions. Therefore, it is really worthy to try the reactions of N-tosylhydrazones under acidic
conditions,9b which may lead to new reactivities of N-tosylhydrazones.
Scheme 1. Reaction patterns of N-tosylhydrazones as 1C synthons and 1,3-dipole synthons
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As 1C synthons
FMe2Si
R1
SiMe2F
R2
(SiMe2F)2
Z
(a)
(b)
(c)
1
2
3
4
5
6
7
8
N2
NNHTs
base
Z
R3 R4
Z = O or CH2
R1 R2
R2
R1
R4
R3
R1 R2
XR5R6R7
R1 R2
R5R6R7XH
As 1,3-dipole synthons
R2
N
H
R1
R2
R1
N
NNHTs
base
(d)
N
+
N
R1 R2
9
R
H
10
11
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R
R
Ortho-quinone methides (o-QMs) are highly active intermediates that used frequently as Michael
acceptors and 1,4-dipoles.11-13 Recently, Prof. Schneider reported an interesting phosphoric acid catalyzed
[4 + 1] cycloannulation of o-QMs with diazo compounds, affording highly enantiomerically enriched cis-
2,3-dihydrobenzofurans (Scheme 2a).12d In addition, Prof. Guo also reported an elegant [4 + 3]
cycloaddition of aza-o-QMs with arylcarbohydrazonoyl chlorides to afford 2,3-dihydro ‑ 1H ‑
benzo[e][1,2,4]triazepines (Scheme 2b).13b Due to the amphiphilic property of N-tosylhydrazones, we
envisioned that a [4 + 1] or [4 + 3] cycloaddition of o-QMs with N-tosylhydrazones would take place to
furnish a five- or seven-membered ring system. Surprisingly, catalyzed by a Lewis acid, the [4 + 2]
cycloaddition product was obtained. To the best of our knowledge, N-tosylhydrazones have never been
involved in [4 + 2] cycloaddition reactions as 1,2-dipoles (Scheme 2c). Moreover, the 3,4-dihydro-2H-
benzo[e][1,3]oxazine skeleton exists in many natural products and synthetic pharmaceutical
compounds.14
Scheme 2. Previous reported [4 + 1] and [4 + 3] cycloadditions of o-QMs and our unprecedented [4
+ 2] cycloaddition using N-tosylhydrazones as 1,2-dipoles
Previous work:
(a) [4 + 1] cycloannulation of o-QMs with diazo compounds
O
R
O
R
Ar
N2
phosphoric acid
Ar
OH
R
OH
O
O
(b) [4 + 3] cycloaddition of aza-o-QMs with arylcarbohydrazonoyl chlorides
Ts
Cl
H
N
N
NTs
NHTs
Cl
R1
N
R2
Na2CO3
N
R2
N
R1
This work:
(c) [4 + 2] cycloaddition of o-QMs with N-tosylhydrazones
Ar1
O
Ar1
inital
design
Ar2
NTs
N
R1
R2
Ar2
or
R2
O
Ar1
OH
OH
NNHTs
R1 R2
Ar1
O
R1
[4 + 1]
[4 + 3]
Ar2
Ar1
Ar2
NHTs
N
Ar2
[4 + 2]
O
R1
R2
Our initial study commenced with the reaction between 2-(hydroxy(phenyl)methyl)phenol (1a) and
tosylhydrazone (2a). At the outset, in the presence of different bases, such as K2CO3, t-BuOK, DBU, and
Et3N, the reactions were found to be complex. Surprisingly, when the reaction was conducted under the
catalysis of a strong Lewis acid B(C6F5)3, unusual [4+2] cycloaddition product 3aa was obtained, albeit
in only 13% yield (Table 1, entry 1). The trans-configuration of 3aa was unambiguously confirmed by
X-Ray diffraction analysis (S1, see SI). Other boron catalysts , like BF3·Et2O and Ph2BOH, provided
similar yields (Table 1, entry 2−3). Among a set of metal Lewis acids that were screened, Cu(OTf)2 and
Sc(OTf)3 gave the highest yield, while Co(acac)3, Pd(OAc)2, Zn(OTf)2, Yb(OTf)2, and Fe(OTf)3 provided
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lower yields (Table 1, entries 4−10). Next, a variety of solvents were investigated. It was found that the
yield was improved to 50% using DCM as solvent, whereas PhCl and PhMe gave slightly diminished
yields (Table 1, entries 11−13). However, the reactions were very sluggish when conducted in MeCN,
THF and MeOH, probably due to the coordination of the solvents with the Lewis acid catalyst (Table 1,
entries 14−16). To our delight, the addition of 4 Å MS drastically improved the yield, furnishing 3aa in
80% yield (Table 1, entries 17−19). In addition, increasing the reaction temperature to 40 ℃ did not
improve the yield (Table 1, entry 20).
1
2
3
4
5
6
7
8
9
10
11
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59
60
Table 1. Optimization of the reaction conditionsa
Ph
Ph
OH
OH
NHTs
cat. (5 mol %)
NHTs
N
+
Ph
N
solvent, T, t, N2
O
Ph
1a
2a
3aa
entry
1
2
3
4
5
6
7
8
cat.
solvent
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
t (h)
1
yieldb (%)
13
T (℃)
25
25
25
70
70
25
25
25
25
25
25
25
25
25
25
25
25
25
25
40
B(C6F5)3
BF3·Et2O
Ph2BOH
Co(acac)2
Pd(OAc)2
Zn(OTf)2
Cu(OTf)2
Yb(OTf)3
Fe(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
1
1
12
12
1
1
1
1
1
11
14
20
trace
21
33
8
15
40
50
46
38
8
N.D.
N.D.
80
76
70
9
DCE
DCE
10
11
12
13
14
15
16
17c
18d
19e
20c
DCM
PhCl
PhMe
MeCN
THF
MeOH
DCM
DCM
DCM
DCM
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
68
aUnless otherwise stated, the reaction was performed with 1a (0.20 mmol), 2a (0.26 mmol) and cat. (5
mol %) in freshly distilled solvent (2 mL) under N2 atmosphere. DCE: 1,2-Dichloroethane. DCM:
Dichloromethane. bIsolated yields. c4 Å MS (100 mg). d4 Å MS (50 mg). e4 Å MS (200 mg).
With the optimized reaction conditions in hand, the generality of this special [4+2] cycloaddition with
respect to various diols 1 was firstly investigated. As shown in Table 2, better yields were notably obtained
when aromatic ring Ar1 was attached to an electron-withdrawing group (Table 2, 3ba and 3ca vs 3da).
The comparison of 3ea, 3fa with 3ga also showed that the yield was improved when aromatic ring Ar1
possessed an electron-withdrawing group. As for diols with electron-donating group or electron-
withdrawing groups on the Ar2 ring successfully anticipated in the reaction, affording the corresponding
products in moderate yields (Table 2, 3ga−3ja). The reaction could also tolerate biphenylyl and naphthyl
groups, delivering 3ka and 3la in moderate yields. Finally, as for thienyl substituted substrate, the reaction
could still afford the desired product 3ma in 36% yield with a d.r. value of 4:1.
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1
2
Table 2. Substrate Scope of 2−Hydroxybenzyl Alcoholsa
3
4
5
6
7
8
Ar1
Ar1
Sc(OTf)3 (5 mol %)
4 Å MS (100 mg)
NHTs
Ph
NHTs
+
OH
OH
N
Ph
N
DCM (2 mL), N2,
25 °C, 0.5 h
Ar2
Ar2
O
1b-1m
2a
Cl
3ba-3ma
F
F
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NHTs
NHTs
NHTs
Ph
Cl
NHTs
Ph
N
N
N
N
O
Ph
O
Ph
O
O
3ba
3ca
3da
3ea
, 66%
, 79%
Cl
, 71%
, 42%
Ph
Ph
Ph
Cl
NHTs
F
NHTs H3CO
Ph
NHTs
N
N
N
Cl
NHTs
N
O
Ph
O
O
Ph
O
Ph
3fa
3ga
3ha
3ia
, 56%
, 51%
, 38%
Ph
, 65%
S
Ph
N
NHTs
Ph
NHTs
Ph
N
O
NHTs
Ph
NHTs
N
N
F
O
O
O
Ph
3ja
3ka
3la
3ma
, 36%, dr 4:1
, 31%
, 61%
, 59%
aReactions were performed with 1b-1m (0.20 mmol), 2a (0.26 mmol) and Sc(OTf)3 (5 mol %) in freshly
distilled DCM (2 mL) under N2 atmosphere.
Table 3. Substrate Scope of Tosylhydrazones stemmed from various substituted aldehydesa
Ph
Ph
OH
OH
1a
Sc(OTf)3 (5 mol %)
4 Å MS (100 mg)
NHTs
NHTs
N
N
R1
+
DCM (2 mL), N2,
25 °C, 0.5 h
O
R1
2b-2m
3ab-3am
Ph
Ph
O
Ph
O
Ph
NHTs
NHTs
NHTs
N
NHTs
N
N
N
O
O
C2H5
OCH3
CH2Cl
CF3
3ab
3ac
3ad
3ae
, 60%
, 75%
, 73%
, 68%
Ph
Ph
Ph
Ph
NHTs
NHTs
NHTs
NHTs
N
N
N
N
O
O
O
O
F
Cl
3af
3ag
3ah
3ai
, 65%
, 73%
, 65%
, 66%
Ph
Ph
Ph
Ph
NHTs
NHTs
NHTs
N
N
NHTs
N
N
O
O
O
O
Ph
S
Br
I
3aj
3ak
3al
3am
, 62%
, 35%
, 43%
, 76%, dr 1:0.7
aReactions were performed with 1a (0.20 mmol), 2b-2m (0.26 mmol) and Sc(OTf)3 (5 mol %) in freshly
distilled DCM (2 mL) under N2 atmosphere.
After demonstrating the generality of this intriguing [4+2] cycloaddition with respect to diols, we then
switched our attention to the scope of tosylhydrazones which were simply prepared from various
substituted aldehydes (Table 3). As expected, tosylhydrazones with various electron-donating groups,
such as methyl, ethyl, and methoxy groups, served well in this reaction, providing the corresponding
products in 65%-75% yields (Table 3, 3ab, 3ac, 3ag and 3af). Moveover, tosylhydrazones with
chloromethyl, trifluoromethyl and halogen groups were well tolerated (3ad, 3ae, and 3ah−3ak). In
addition, cinnamyl tosylhydrazone could also take part in the reaction, affording the olefin containing 3,4-
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dihydro-2H-benzo[e][1,3]oxazine 3al in 76% yield with d.r. value of 1:0.7. This system was also
applicable for tosylhydrazone derived from 2-thenaldehyde, affording the thienyl-containing product 3am
in 62% yield.
1
2
3
4
5
6
7
8
Table 4. Substrate Scope of Tosylhydrazones Derived Ketonesa
Ph
Ph
OH
OH
1a
R1
Sc(OTf)3 (5 mol %)
4 Å MS (100 mg)
NHTs
R1
+
N
NHTs
9
R2
N
DCM (2 mL), N2,
25 °C, 0.5 h
O
R2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4a-4n
Ph
5aa-5an
Ph
Ph
Ph
O
NHTs
NHTs
NHTs
NHTs
NHTs
N
O
N
N
N
O
O
F
Cl
5aa
5ab
5ac
5ad
, 61%
, 56%
Ph
, 74%
, 38%
Ph
Ph
Ph
N
O
NHTs
NHTs
NHTs
N
N
N
O
O
Ph
O
Br
Cl
5ae
5af
5ag
5ah
, 41%
Ph
, 35%
, 42%
, 60%
Ph
Ph
Ph
NHTs
NHTs
NHTs
NHTs
O
N
O
N
N
N
O
O
O
H
5ai
5aj
5ak
5al
, 79%, dr = 1:0.7
, 36%
, 42%
, 34%
Ph
O
Ph
O
NHTs
OH
Ph
N
N
5am
5an
, 38%
, 76%, dr = 1:1
aReactions were performed with 1a (0.20 mmol), 4a-4n (0.26 mmol) and Sc(OTf)3 (5 mol %) in freshly
distilled DCM (2 mL) under N2 atmosphere.
To further broaden the reaction scope, tosylhydrazones prepared from ketones were examined. First of
all, tosylhydrazones stemed from acetophenones with various substituents such as methyl, fluoro, chloro
and bromo groups, were explored, and the reactions afforded the corresponding products in 35−74%
yields (Table 4, 5aa−5af). In addition, reaction conditions were also compatible for tosylhydrazones
prepared from cyclopropyl phenyl ketone, giving the corresponding product 5ag in 42% yield.
Furthermore, we tested tosylhydrazones prepared from cyclohexanone, offering the desired spiral
products 5ah in 60% yield. 1,2,3,4-Tetrahydronaphthalene, 3,4-dihydro-(1H)-benzopyrane and 9-
fluorenone derived tosylhydrazones were also suitable for this reaction, delivering the desired spiral
products in relatively lower yields, probably due to the sterical hindrance (Table 4, 5ai−5ak). To our
delight, natural products, such as camphor and (+)-dihydrocarvone derived tosylhydrazones were good
partners for this cycloaddition, providing the corresponding spiral products in 79% and 76% yield,
respectively (Table 4, 5al−5am). It is worth noting that this system was also compatible for benzaldoxime
and the desired product 5an was obtained in 38% yield.
To gain more mechanistic insight into this reaction, several control experiments were carried out
(Scheme 3). First, the reactivity of imine with o-QMs was tested, and only product 7 from nucleophilic
substitution by aniline was detected in 34% yield (Scheme 3a). Under the typical reaction conditions, the
reactions of 8 and 10 with hydrazone 2a gave quite different results. It was found that 8 could react with
hydrazone smoothly and provided the desired product 9 in 90% yield (Scheme 3b), while the reaction of
10 with 2a could not take place (Scheme 3c), indicating that the putative cation intermediate was not
stable enough in case of compound 10 used as starting material.
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Scheme 3. Control experiments.
1
2
3
4
5
6
7
8
9
Ph
Ph
Sc(OTf)3 (5 mol%)
4 Å MS (100 mg)
Ph
Ph
+
+
OH
N
Ph
N
N
(a)
DCM (2 mL), N2,
25 °C, 0.5 h
H
OH
1a
OH
7
, 34%
6
Sc(OTf)3 (5 mol%)
4 Å MS (100 mg)
NHTs
OH
OH
N
NHTs
NHTs
Ph
Ph
(b)
(c)
DCM (2 mL), N2,
25 °C, 0.5 h
O
9
, 90%
Ph
8
2a
Sc(OTf)3 (5 mol%)
4 Å MS (100 mg)
NHTs
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
OH
N
N
DCM (2 mL), N2,
25 °C, 0.5 h
OH
10
O
2a
N.D.
On the basis of the experimental results and previous studies in o-QMs chemistry,11-13 a plausible
mechanism is proposed and illustrated in Scheme 4. Firstly, in the presence of Lewis acid Sc(OTf)3, diols
are converted into o-QMs by dehydration. Then, o-QMs are activated by Sc(OTf)3 to form highly active
intermediates which consist of resonance structures A and A’. The following nucleophilic attack by imine
moiety of N-tosylhydrazone gives intermediates B, subsequent cyclization furnishes the final products 3
or 5 togother with the regeneration of catalyst.
Scheme 4. Plausible Mechanism
Ar2
Ar2
Ar2
NHTs
R1
Ar2
N
Sc(OTf)3
- H2O
NHTs
R1
R2
N
Ar1
Ar1
Ar1
OH
OH
Ar1
O
Sc(OTf)3
O
Sc(OTf)3
O
R2
B
Sc(OTf)3
1
A
A'
Ar2
NHTs
R1
-Sc(OTf)3
N
Ar1
O
R2
3
5
or
In summary, we have developed a highly diastereoselective [4 + 2] cycloaddition of o-QMs with N-
tosylhydrazones, which provided 3,4-dihydro-2H-benzo[e][1,3]oxazines in an easy and practical way
from readily accessible starting materials in considerable yields. Different from the basic reaction
conditions of N-tosylhydrazone transformations reported previously, this reaction mode develops new
reactivity of N-tosylhydrazones catalyzed by a Lewis acid. Further related studies of extended
transformations and applications are currently underway in our laboratory.
EXPERIMENTAL SECTION
General Remarks: H NMR and 13C{1H} NMR spectra were recorded on a 400 and 600 MHz
1
spectroscopy in CDCl3, acetone-d6 or DMSO-d6; Chemical shifts (δ) are expressed in ppm and J-values
are in Hz. Mass spectra were recorded with a HP-5989 instrument. Infrared spectra were recorded on a
Perkin-Elmer PE-983 spectrometer with absorption in cm-1. The solvents and chemicals were purchased
and used as reveived. All reactions were monitored by TLC with Huanghai GF254 silica gel coated plates.
Flash column chromatography was carried out using 300-400 mesh silica gel at increased pressure.
General Procedure for the Synthesis of 1. Method A15c: Under argon atmosphere, a solution of
substituted salicylaldehyde (5.0 mmol) in tetrahydrofuran (10 mL) was added dropwise to a solution of
the corresponding Grignard reagent (10.0 mmol, 1.0 M in THF, 10 mL), the mixture was stirred at room
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temperature. After complete conversion (monitored by TLC), the reaction mixture was quenched by
saturated ammonium chloride (10 mL) and extracted with EtOAc (30 mL × 3). The combined organic
layer was dried by anhydrous Na2SO4, and concentrated. The residue was chromatographed on silica gel
eluting with petroleum ether/EtOAc (5:1) to give the product as a white solid (1a, 1g-1j). Method B15a:
Under argon atmosphere, to a solution of magnesium (30.0 mmol) and a granule of I2 in anhydrous THF
(15 mL) was added dropwise a solution of Ar1X (X=Br, Cl) (30.0 mmol) in anhydrous THF (10 mL),
controlling the speed to maintain THF boiling. After adding, the system was refluxed for 1 h in oil bath.
Then cooled to 0 °C, a solution of substituted salicylaldehyde (10.0 mmol) in THF (5 mL) was added
dropwise to the mixture, and the mixture was stirred at room temperature. After complete conversion
(monitored by TLC), saturated NH4Cl was added dropwise to the system at 0 °C, then the resulting
solution was extracted with EtOAc (50 mL × 3). The combined organic extracts were dried with
anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed on silica gel eluting
with petroleum ether/EtOAc (5:1) to give the product as a white solid (1b-1f). Method C15d: Under the
nitrogen atmosphere, to an oven dried flask charged with a solution of the Ar1Br (12.5 mmol) in dry THF
(12.5 mL) was added n-BuLi (12.5 mmol, 1.6 M in hexane, 7.8 mL) dropwise at −78 °C. The resulted
mixture was stirred at the same temperature for 1 h and then a solution of substituted salicylaldehyde (5
mmol) in dry THF (2.5 mL) was added dropwise. The reaction mixture was allowed to be warmed to
room temperature and stirred overnight. Upon completion (monitored by TLC), the reaction mixture was
cooled to 0 °C and treated with saturated aqueous NH4Cl solution (20 mL). The mixture was extracted
with EtOAc (3 × 30 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated.
The residue was purified by silica gel chromatography to afford the pure products (1k-1m). 1a;15a 1b;15b
1c, 1g, 1i, 1k-1m;15e 1d, 8;15g 1f;15f were reported in previous literature; and 1e, 1h, 1j are reported for the
first time, and physical datas and spectroscopics are presented as follows.
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General Procedure for the Synthesis of 2 and 418. The aldehyde or ketone (5 mmol) was added dropwise
to a round-bottom flask charged with hydrazide or hydroxylamine (5 mmol) in methanol (5 mL) at 60 °C
in oil bath. After completion of the reaction (monitored by TLC), the resulted mixture was concentrated
in vacuo. Then the crude product was filtered, washed with petroleum ether/ethyl acetate (10:1) and dried
in vacuo to afford the corresponding pure hydrazones or oximes (2a-2m, 4a-4n). 2a, 2c;16a 2e, 2h, 2j,
4k;16b 2f, 4a-4f, 4h-4j;16c 4g;16d 2m, 2l;16e 4m;16f 4n;16g 2i;16h 4l;16i were reported in previous literature;
and 2b, 2d, 2g, 2k are reported for the first time, and physical datas and spectroscopics are presented as
follows.
General Procedure for the Synthesis of product 3, 5. A 10 mL reaction tube equipped with a magnetic
stir bar was charged with dried 4Å molecular sieve (100 mg), diols (0.2 mmol), tosylhydrazones (0.26
mmol), Sc(OTf)3 (5 mmol %) and DCM (2 mL) under N2. The reaction mixture was stirred at 25 °C for
0.5 h. After completion (checked by TLC), the solution was concentrated under reduced pressure and the
crude product was purified by silica gel column chromatography (PE:EA = 10:1 or 5:1) to afford 3, 5.
General Procedure of 1.0 mmol scale for the Synthesis of product 3aa: A 25 mL reaction tube
equipped with a magnetic stir bar was charged with dried 4Å molecular sieve (500 mg), diols (1 mmol),
tosylhydrazones (1.3 mmol), Sc(OTf)3 (5 mmol %) and DCM (10 mL) under N2. The reaction mixture
was stirred at 25 °C for 0.5 h. After completion (checked by TLC), the solution was concentrated under
reduced pressure and the crude product was purified by silica gel column chromatography (PE:EA = 10:1
or 5:1) to afford 3aa (338 mg, 74%).
1
4-Chloro-2-((4-fluorophenyl)(hydroxy)methyl)phenol (1e), faint yellow solid, mp: 87−88 °C; H NMR
(400 MHz, CDCl3) δ 7.83 (s, 1H), 7.36–7.31 (m, 2H), 7.13 (dd, J = 8.8, 2.8 Hz, 1H), 7.08–7.03 (m, 2H),
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6.82–6.79 (m, 2H), 5.92 (s, 1H), 3.10 (s, 1H); F NMR (376 MHz, CDCl3) δ -113.13 –-113.21 (m);
13C{1H} NMR (101 MHz, CDCl3) δ 162.6 (d, J = 248.5 Hz), 153.8, 136.9 (d, J = 3.2 Hz), 129.2, 128.6
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(d, J = 8.3 Hz), 128.0, 127.7, 124.8, 118.6, 115.8 (d, J = 21.6 Hz), 75.7; IR(KBr): ν 3292, 1602, 1507,
1485, 1222, 904, 728 cm-1; HRMS (ESI-TOF) m/z: [M-] Calcd for C13H9ClFO2 251.0280; Found
251.0275.
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4-Fluoro-2-(hydroxy(phenyl)methyl)phenol (1h), white solid, mp: 66−69 °C; 1H NMR (400 MHz, CDCl3)
δ 7.79 (s, 1H), 7.37–7.30 (m, 5H), 6.84 (td, J = 8.8, 2.8 Hz, 1H), 6.78–6.75 (m, 1H), 6.54 (dd, J = 8.8, 2.8
Hz, 1H), 5.89 (d, J = 3.2 Hz, 1H), 3.27 (d, J = 3.2 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ -124.07 – -
124.13 (m); 13C{1H} NMR (101 MHz, CDCl3) δ 157.4 (d, J = 238.8 Hz), 151.1 (d, J = 2.1 Hz), 141.2,
128.8, 128.5, 127.8 (d, J = 6.6 Hz), 126.8, 117.9 (d, J = 7.9 Hz), 115.5 (d, J = 23.0 Hz), 114.5 (d, J = 24.2
Hz), 76.2; IR(KBr): ν 3299, 1491, 1438, 1263, 1179, 942, 732 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C13H11FO2Na 241.0637; Found 241.0635.
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2-Fluoro-6-(hydroxy(phenyl)methyl)phenol (1j), colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H),
7.38–7.29 (m, 5H), 7.02–6.96 (m, 1H), 6.78–6.72 (m, 2H), 5.99 (s, 1H), 3.60 (s, 1H); 19F NMR (376 MHz,
CDCl3) δ -138.89 – -138.93 (m); 13C{1H} NMR (101 MHz, CDCl3) δ 151.5 (d, J = 241.6 Hz), 142.6 (d,
J = 13.9 Hz), 141.8, 130.1 (d, J = 2.1 Hz), 128.5, 128.0, 126.6, 122.9 (d, J = 3.4 Hz), 119.7 (d, J = 7.4
Hz), 115.0 (d, J = 18.4 Hz), 74.8 (d, J = 3.0 Hz); IR(KBr): ν 3279, 1619, 1475, 1259, 1020, 908, 728 cm-1;
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C13H11FO2Na 241.0637; Found 241.0637.
1
(E)-N'-(4-ethylbenzylidene)-4-methylbenzenesulfonohydrazide (2b), white solid, mp: 135−137 °C; H
NMR (400 MHz, Acetone-d6) δ 10.05 (s, 1H), 7.96 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz,
2H), 7.38 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 2.63 (q, J = 7.6 Hz, 2H), 2.37 (s, 3H), 1.18 (t, J =
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7.6 Hz, 3H); C{1H} NMR (101 MHz, Acetone-d6) δ 148.1, 147.4, 144.5, 137.5, 132.6, 130.3, 129.0,
128.6, 127.9, 29.3, 21.4, 15.8; IR (KBr): ν 3192, 2965, 1324, 1163, 1042, 942, 704 cm-1; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C16H18N2O2SH 303.1162; Found 303.1164.
(E)-N'-(4-(chloromethyl)benzylidene)-4-methylbenzenesulfonohydrazide (2d), white solid, mp: 131−132
°C; 1H NMR (400 MHz, Acetone-d6) δ 10.20 (s, 1H), 7.99 (s, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.63 (d, J =
8.4 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 4.71 (s, 2H), 2.37 (s, 3H); 13C{1H} NMR
(101 MHz, Acetone-d6) δ 147.2, 144.7, 140.6, 137.4, 135.0, 130.4, 129.9, 128.5, 128.0, 46.3, 21.4;
IR(KBr): ν 3193, 2959, 1362, 1164, 1053, 943, 704 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C15H15ClN2O2SH 323.0616; Found 323.0618.
(E)-N'-(2,6-dimethylbenzylidene)-4-methylbenzenesulfonohydrazide (2g), white solid, mp: 143–144 °C;
1H NMR (400 MHz, Acetone-d6) δ 10.11 (s, 1H), 8.33 (s, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0
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Hz, 2H), 7.12–7.09 (m, 1H), 7.00 (d, J = 7.6 Hz, 2H), 2.39 (s, 3H), 2.26 (s, 6H); C{1H} NMR (101
MHz, Acetone-d6) δ 148.1,144.6, 138.3, 137.5, 131.6, 130.3, 129.7, 129.5, 128.7, 21.4, 21.3; IR(KBr): ν
3192, 2967, 1324, 1162, 1057, 951, 706 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H18N2O2SH
303.1162; Found 303.1163.
1
(E)-N'-(4-iodobenzylidene)-4-methylbenzenesulfonohydrazide (2k), white solid, mp: 194–195 °C; H
NMR (600 MHz, DMSO-d6) δ 11.54 (s, 1H), 7.87 (s, 1H), 7.77–7.75 (m, 4H), 7.41 (d, J = 8.4 Hz, 2H),
7.35 (d, J = 7.8 Hz, 2H), 2.36 (s, 3H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 146.0, 143.5, 137.6, 136.1,
133.2, 129.7, 128.5, 127.2, 96.8, 21.0; IR(KBr): ν 3193, 2972, 1394, 1167, 1051, 879, 704 cm-1; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C14H13IN2O2SH 400.9815; Found 400.9818.
N-(2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3aa), white solid, mp:
129–130 °C, yield 81% (74.0 mg); 1H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 8.80 (s, 1H), 7.57–7.55
(m, 2H), 7.50–7.46 (m, 1H), 7.41–7.38 (m, 2H), 7.22–7.21 (m, 4H), 7.19–7.17 (m, 1H), 7.15–7.13 (m,
4H), 6.90 (d, J = 8.0 Hz, 2H), 6.85 (ddd, J1,2 = 7.4 Hz, J3 = 1.2 Hz, 1H), 6.59–6.58 (m, 2H), 2.27 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 166.0, 155.6, 143.8, 136.7, 133.5, 132.7, 131.6, 130.1, 129.2, 128.9,
128.8, 128.5, 128.3, 128.1, 127.4, 121.3, 119.5, 118.1, 69.0, 21.5; IR(KBr): ν 3062, 1598, 1487, 1185,
1159, 1086, 872, 754 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H24N2O3SNa 479.1400;
Found 479.1410.
N-(4-(4-fluorophenyl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ba),
white solid, mp: 127–128 °C, yield 79% (75.0 mg); 1H NMR (400 MHz, CDCl3) δ 10.01 (s, 1H), 8.80 (s,
1H), 7.57 (d, J = 7.3 Hz, 2H), 7.50 (dd, J1,2 = 7.2 Hz, 1H), 7.42 (dd, J1,2 = 7.4 Hz, 2H), 7.25–7.16 (m, 4H),
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7.13 (d, J = 8.2 Hz, 2H), 6.92–6.83 (m, 5H), 6.58 (d, J = 8.0 Hz, 1H), 6.53 (s, 1H), 2.28 (s, 3H); 19F NMR
(376 MHz, CDCl3) δ -114.86 – -114.93 (m); C{1H} NMR (101 MHz, CDCl3) δ 166.2, 162.0 (d, J =
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247.5 Hz), 155.5, 143.9, 133.4, 132.9, 132.5 (d, J = 3.0 Hz), 131.5, 130.3, 130.1 (d, J = 7.1 Hz), 129.3,
128.9, 128.8, 128.1, 121.2, 119.7, 118.2, 115.4 (d, J = 21.2 Hz), 68.5, 21.5; IR(KBr): ν 3074, 1601, 1505,
1487, 1185, 1160, 905, 724 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H23FN2O3SNa
497.1306; Found 497.1320.
N-(4-(4-chlorophenyl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ca),
white solid, mp: 77–81 °C, yield 71% (69.7 mg); 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 8.81 (s, 1H),
7.58 (d, J = 7.2 Hz, 2H), 7.50 (dd, J1,2 = 7.2 Hz, 1H), 7.42 (dd, J1,2 = 7.4 Hz, 2H), 7.17–7.12 (m, 8H), 6.90
(d, J = 8.0 Hz, 2H), 6.85 (dd, J1,2 = 7.0 Hz, 1H), 6.59 (d, J = 7.2 Hz, 1H), 6.52 (s, 1H), 2.27 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 166.1, 155.5, 144.0, 135.4, 133.4, 133.3, 132.9, 131.5, 130.3, 129.8,
129.3, 128.9, 128.8, 128.7, 128.1, 121.0, 119.7, 118.2, 68.4, 21.4; IR(KBr): ν 3292, 1600, 1185, 1161,
1085, 905, 726 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H23ClN2O3SNa 513.1010; Found
513.1020.
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4-Methyl-N-(2-phenyl-4-(p-tolyl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3da),
white
solid, mp: 109–111 °C, yield 42% (39.5 mg); 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.78 (s, 1H),
7.58 (d, J = 7.2 Hz, 2H), 7.50 (dd, J1,2 = 7.2 Hz, 2H), 7.42 (dd, J1,2 = 7.4 Hz, 2H), 7.19–7.11 (m, 6H), 6.89
(d, J = 8.0 Hz, 2H), 6.84 (dd, J1,2 = 7.4 Hz, 1H), 6.74 (d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.0 Hz, 1H), 6.51
(s, 1H), 3.69 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 166.3, 158.7, 155.6, 143.8, 133.5,
133.4, 132.8, 131.7, 130.0, 129.6, 129.2, 129.0, 128.8, 128.6, 128.1, 121.6, 119.5, 118.1, 113.8, 68.8,
55.1, 21.5; IR(KBr): ν 3067, 1608, 1510, 1161, 1087, 910, 729 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C28H26N2O3SH 471.1737; Found 471.1731.
N-(6-chloro-4-(4-fluorophenyl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3ea), white solid, mp: 157–158 °C, yield 66% (67.2 mg); 1H NMR (400 MHz,
CDCl3) δ 10.25 (s, 1H), 8.81 (s, 1H), 7.60 (d, J = 7.2 Hz, 2H), 7.53 (dd, J1,2 = 7.0 Hz, 1H), 7.45 (dd, J1,2
= 7.4 Hz, 2H), 7.21–7.15 (m, 4H), 7.11 (s, 1H), 7.08 (d, J = 8.8 Hz, 1H), 6.98 (d, J = 8.0 Hz, 2H), 6.92
(dd, J1,2 = 8.4 Hz, 2H), 6.50 (d, J = 8.4 Hz, 1H), 6.40 (s, 1H), 2.30 (s, 3H); 19F NMR (376 MHz, CDCl3)
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δ -114.38 – -114.40 (m); C{1H} NMR (101 MHz, CDCl3) δ 167.3, 162.1 (d, J = 248.5 Hz), 154.2,
144.3, 133.4, 133.2, 132.6, 131.7 (d, J = 3.0 Hz), 131.3, 130.0 (d, J = 8.1 Hz), 129.9, 129.4, 129.1, 129.0,
128.1, 124.1, 122.8, 119.7, 115.6 (d, J = 22.2 Hz), 67.8, 21.5; IR(KBr): ν 3734, 1600, 1508, 1344, 1183,
1157, 1059, 718 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H22ClFN2O3SH 509.1096; Found
509.1099.
N-(6-chloro-4-(4-chlorophenyl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3fa), white solid, mp: 152–154 °C, yield 51% (53.6 mg); 1H NMR (400 MHz,
CDCl3) δ 10.20 (s, 1H), 8.82 (s, 1H), 7.60 (d, J = 7.6 Hz, 2H), 7.53 (dd, J1,2 = 7.2 Hz, 1H), 7.44 (dd, J1,2
= 7.4 Hz, 2H), 7.21–7.19 (m, 4H), 7.14–7.07 (m, 4H), 6.97 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.4 Hz, 1H),
6.39 (s, 1H), 2.30 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.2, 154.2, 144.3, 134.6, 133.6, 133.4, 133.2,
132.6, 131.3, 129.9, 129.6, 129.4, 129.1, 129.0, 128.8, 128.1, 124.1, 122.5, 119.7, 67.7, 21.5; IR(KBr): ν
3733, 1599, 1486, 1385, 1183, 1158, 1086, 710 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C27H22Cl2N2O3SH 525.0801; Found 525.0804.
N-(6-chloro-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide (3ga), white
solid, mp: 158−159 °C, yield 38% (37.3 mg); 1H NMR (400 MHz, CDCl3) δ 10.25 (s, 1H), 8.81 (s, 1H),
7.58 (d, J = 7.4 Hz, 2H), 7.51 (dd, J1,2 = 7.2 Hz, 1H), 7.42 (dd, J1,2 = 7.4 Hz, 2H), 7.25–7.16 (m, 7H), 7.13
(d, J = 1.6 Hz, 1H),7.07 (dd, J = 8.4, 2.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.6 Hz, 1H), 6.44
(s, 1H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 167.0, 154.4, 144.1, 136.0, 133.6, 133.0, 132.7,
131.5, 129.7, 129.3, 129.1, 128.9, 128.6, 128.2, 128.1, 127.7, 124.0, 123.0, 119.5, 68.4, 21.5; IR(KBr): ν
3357, 1748, 1480, 1185, 1160, 1086, 906, 728 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C27H23ClN2O3SNa 513.1010; Found 513.1023.
N-(6-fluoro-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide (3ha), white
solid, mp: 148–149 °C, yield 65% (61.7 mg); 1H NMR (400 MHz, CDCl3) δ 9.92 (s, 1H), 8.79 (s, 1H),
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7.57 (d, J = 7.6 Hz, 2H), 7.49 (dd, J1,2 = 7.0 Hz, 1H), 7.41 (dd, J1,2 = 7.2 Hz, 2H), 7.23–7.21 (m, 6H),
7.17–7.15 (m, 1H), 6.97 (d, J = 7.9 Hz, 2H), 6.90 (dd, J = 9.2, 2.4 Hz 1H), 6.85 (td, J = 8.4, 2.4 Hz, 1H),
6.52 (dd, J = 8.4, 3.6 Hz, 1H), 6.47 (s, 1H), 2.29 (s, 3H); 19F NMR (376 MHz, CDCl3) δ -126.17 – -126.23
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(m); C{1H} NMR (101 MHz, CDCl3) δ 166.6, 156.1 (d, J = 238.4 Hz), 151.7, 144.1, 136.1, 133.6,
132.9, 131.5, 129.2, 128.9 (d, J = 3.0 Hz), 128.6, 128.2, 128.1, 127.7, 122.4 (d, J = 7.1 Hz), 119.1 (d, J =
23.2 Hz), 118.9 (d, J = 7.8 Hz), 116.4 (d, J = 22.2 Hz), 68.3, 21.5; IR(KBr): ν 3340, 1599, 1493, 1163,
1140, 1060, 905, 724 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H23FN2O3SNa 497.1306;
Found 497.1310.
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N-(6-methoxy-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ia), pale
yellow solid, mp: 136–137 °C, yield 56% (54.5 mg); 1H NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 8.78 (s,
1H), 7.56 (d, J = 7.6 Hz, 2H), 7.48 (dd, J1,2 = 7.2 Hz, 1H), 7.40, (dd, J1,2 = 7.4 Hz, 2H), 7.24–7.15 (m,
7H), 6.94 (d, J = 8.0 Hz, 2H), 6.74–6.73 (m, 2H), 6.53–6.50 (m, 2H), 3.78 (s, 3H), 2.29 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 165.9, 152.8, 149.5, 143.9, 136.6, 133.6, 132.7, 131.7, 129.2, 128.9, 128.8,
128.5, 128.3, 128.1, 127.5, 121.8, 118.8, 117.9, 116.0, 68.8, 55.9, 21.5; IR(KBr): ν 3029, 1598, 1495,
1162, 1085, 1040, 906, 724 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C28H26N2O4SNa 509.1505;
Found 509.1511.
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N-(8-fluoro-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ja), white
solid, mp: 156–157 °C, yield 31% (29.4 mg); 1H NMR (400 MHz, CDCl3) δ 10.47 (s, 1H), 8.77 (s, 1H),
7.60 (d, J = 7.6 Hz, 2H), 7.50 (dd, J1,2 = 7.2 Hz, 1H), 7.41 (dd, J1,2 = 7.4 Hz, 2H), 7.24–7.21 (m, 4H), 7.15
19
(d, J = 7.9 Hz, 3H), 6.98–6.93 (m, 4H), 6.78–6.73 (m, 1H), 6.57 (s, 1H), 2.30 (s, 3H); F NMR (376
MHz, CDCl3) δ -136.23 – -136.27 (m); 13C{1H} NMR (101 MHz, CDCl3) δ 167.7, 153.1 (d, J = 244.0
Hz), 144.3 (d, J = 7.8 Hz), 144.2 (d, J = 12.4 Hz), 136.2, 133.3, 133.1, 131.2, 129.3, 129.1, 128.7, 128.6,
128.3, 128.1 (d, J = 3.1 Hz), 128.0, 127.7, 123.8, 119.0 (d, J = 7.5 Hz), 116.3 (d, J = 19.2 Hz), 68.4, 21.4;
IR(KBr): ν 3029, 1598, 1493, 1185, 1161, 1086, 908, 727 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C27H23FN2O3SNa 497.1306; Found 497.1314.
N-(4-([1,1'-biphenyl]-4-yl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3ka), white solid, mp: 147–148 °C, yield 61% (65.0 mg); 1H NMR (400 MHz,
CDCl3) δ 10.04 (s, 1H), 8.84 (s, 1H), 7.58 (d, J = 7.6 Hz, 2H), 7.49–7.44 (m, 5H), 7.41–7.33 (m, 4H),
7.28 (d, J = 8.0 Hz, 3H), 7.22 (d, J = 7.2 Hz, 1H), 7.19–7.15 (m, 3H), 6.91–6.84 (m, 3H), 6.62–6.60 (m,
2H), 2.27 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 166.0, 155.6, 143.8, 140.4, 140.2, 135.8, 133.5,
133.4, 132.8, 131.6, 130.2, 129.2, 128.9, 128.8, 128.7, 128.6, 128.1, 127.3, 127.2, 126.9, 121.4, 119.6,
118.1, 68.8, 21.5; IR(KBr): ν 3029, 1598, 1486, 1185, 1159, 1086, 906, 728 cm-1; HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C33H28N2O3SNa 555.1713; Found 555.1714.
4-Methyl-N-(4-(naphthalen-2-yl)-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3la),
white solid, mp: 135–137 °C, yield 59% (59.8 mg); 1H NMR (400 MHz, CDCl3) δ 10.05 (s, 1H), 8.83 (s,
1H), 7.73 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 7.5 Hz, 1H), 7.55–7.51 (m, 3H), 7.47
(s, 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.37–7.31 (m, 4H), 7.25–7.19 (m, 2H), 7.16 (d, J = 8.3 Hz, 2H), 6.91–
6.85 (m, 3H), 6.72 (s, 1H), 6.64 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
166.1, 155.8, 143.8, 134.1, 133.5, 133.1, 132.7, 132.5, 131.5, 130.2, 129.1, 128.9, 128.8, 128.3, 128.2,
128.1, 127.6, 127.3, 126.1, 125.9, 121.2, 119.6, 118.2, 69.2, 21.4; IR(KBr): ν 3346, 1600, 1487, 1161,
1060, 904, 727 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C31H26N2O3SNa 529.1556; Found
529.1563.
4-Methyl-N-(2-phenyl-4-(thiophen-3-yl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3ma),
1
white solid, mp: 114–116 °C, yield 36% (33.3 mg), dr = 4:1; H NMR (400 MHz, CDCl3) δ 9.99 (s,
0.25H), 9.93 (s, 1H), 8.87 (s, 0.25H), 8.81 (s, 1H), 7.66–7.64 (m, 0.5H), 7.60–7.58 (m, 2H), 7.52–7.47
(m, 1.25H), 7.45–7.40 (m, 2.5H), 7.21–7.19 (m, 1.25H), 7.18–7.16 (m, 1.25H), 7.15–7.11 (m, 3.75H),
7.02 (dd, J = 5.2, 1.2 Hz, 1H), 6.89 (d, J = 8.0 Hz, 2.5H), 6.86–6.85 (m, 1.25H), 6.82 (ddd, J1,2 = 7.4 Hz,
J3 = 1.2 Hz, 1.25H), 6.75–6.73 (m, 0.25H), 6.65 (s, 0.25H), 6.62–6.60 (m, 0.25H), 6.57 (dd, J = 8.4, 1.2
Hz, 1H), 6.49 (s, 1H), 2.26 (s, 3.75H); 13C{1H} NMR (101 MHz, CDCl3) δ 168.0, 166.2, 155.3, 155.2,
143.9, 143.8, 140.7, 137.9, 133.3, 133.1, 133.0, 132.9, 132.8, 131.6, 131.5, 130.3, 130.1, 129.2, 129.1,
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128.9, 128.8, 128.7, 128.2, 128.1, 127.4, 126.7, 126.4, 126.1, 124.4, 122.2, 121.8, 119.4, 119.3, 118.2,
118.1, 66.0, 65.9, 21.4; IR(KBr): ν 2952, 1597, 1486, 1348, 1158, 1085, 734 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C25H22N2O3S2H 463.1145; Found 463.1149.
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N-(2-(4-ethylphenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ab),
white solid, mp: 73–75 °C, yield 75% (72.7 mg); 1H NMR (400 MHz, CDCl3) δ 10.22 (s, 1H), 8.77 (s,
1H), 7.50 (d, J = 8.0 Hz, 2H), 7.24–7.18 (m, 7H), 7.16–7.11 (m, 4H), 6.88 (d, J = 8.0 Hz, 2H), 6.83 (dd,
J1,2 = 7.2 Hz, 1H), 6.57–6.64 (m, 2H), 2.65 (q, J = 7.6 Hz, 2H), 2.27 (s, 3H), 1.21 (t, J = 7.6 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 166.9, 155.7, 150.0, 143.7, 136.8, 133.5, 133.4, 130.1, 129.2, 129.1,
128.8, 128.7, 128.4, 128.3, 128.1, 127.4, 121.2, 119.4, 118.1, 69.1, 29.0, 21.4, 15.1; IR(KBr): ν 2965,
1600, 1486, 1181, 1162, 1086, 908, 726 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C29H28N2O3SNa 507.1713; Found 507.1721.
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N-(2-(4-methoxyphenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3ac), white solid, mp: 122–125 °C, yield 73% (71.0 mg); 1H NMR (400 MHz,
CDCl3) δ 10.42 (s, 1H), 8.70 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.21–7.16 (m, 5H), 7.15–7.10 (m, 4H),
6.92–6.87 (m, 4H), 6.83 (dd, J1,2 = 7.4 Hz, 1H), 6.54–6.51 (m, 2H), 3.83 (s, 3H), 2.28 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 167.3, 163.5, 155.8, 143.6, 136.8, 133.6, 133.4, 131.1, 130.0, 128.7, 128.5,
128.4, 128.2, 127.4, 124.1, 121.2, 119.4, 118.1, 114.7, 69.2, 55.5, 21.5; IR(KBr): ν 2926, 1595, 1485,
1161, 1086, 1063, 833, 729 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H26N2O4SH 487.1686;
Found 487.1694.
N-(2-(4-(chloromethyl)phenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3ad), white solid, mp: 126–128 °C, yield 68% (68.7 mg); 1H NMR (400 MHz,
CDCl3) δ 9.80 (s, 1H), 8.78 (s, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.21, (m, 5H),
7.15–7.13 (m, 4H), 6.91 (d, J = 8.0 Hz, 2H), 6.85 (dd, J1,2 = 7.4 Hz, 1H), 6.60 (m, 2H), 4.54 (s, 2H), 2.28
(s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 164.1, 155.6, 143.9, 142.0, 136.7, 133.5, 133.4, 131.7, 130.2,
129.3, 129.1, 128.9, 128.5, 128.3, 128.1, 127.5, 121.4, 119.6, 118.0, 68.9, 45.2, 21.5; IR(KBr): ν 3064,
1602, 1487, 1184, 1162, 1086, 908, 727 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C28H25ClN2O3SH 505.1347; Found 505.1350.
4-Methyl-N-(4-phenyl-2-(4-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazin-3(4H)-
1
yl)benzenesulfonamide(3ae), white solid, mp: 69–71 °C, yield 60% (62.9 mg); H NMR (400 MHz,
CDCl3) δ 9.16 (s, 1H), 8.77 (s, 1H), 7.62 (m, 4H), 7.23–7.19 (m, 9H), 6.96, (d, J = 7.6 Hz, 2H), 6.88 (dd,
J1,2 = 7.2 Hz, 1H), 6.70 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H), 2.29 (s, 3H); 19F NMR (376 MHz, CDCl3) δ -
13
63.14 (brs); C{1H} NMR (101 MHz, CDCl3) δ 159.5, 155.4, 144.3, 136.6, 135.3, 133.4 (d, J = 31.3
Hz), 133.2, 130.3, 129.1, 128.6 (d, J = 3.2 Hz), 128.2, 128.1, 127.6, 126.2, 126.1 (d, J = 3.7 Hz), 126.0,
123.5 (d, J = 273.4 Hz), 121.8, 119.9, 118.0, 68.5, 21.5; IR (KBr): ν 3065, 1597, 1487, 1322, 1161, 1086,
907, 757, 727 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C28H23F3N2O3SNa 547.1274; Found
547.1284.
4-Methyl-N-(4-phenyl-2-(m-tolyl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3af),
white
solid, mp: 126–127 °C, yield 65% (61.2 mg); 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.76 (s, 1H),
7.38–7.37 (m, 1H), 7.35 (s, 1H), 7.29–7.28 (m, 2H), 7.22–7.18 (m, 5H), 7.16–7.13 (m, 4H), 6.89 (d, J =
8.0 Hz, 2H), 6.84 (dd, J1,2 = 7.4 Hz, 1H), 6.59–6.56 (m, 2H), 2.35 (s, 3H), 2.27 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 166.6, 155.7, 143.7, 139.0, 136.8, 133.6, 133.5, 133.4, 131.6, 130.1, 129.9, 129.1,
128.8, 128.5, 128.3, 128.1, 127.4, 125.7, 121.4, 119.5, 118.1, 69.0, 21.5, 21.2; IR(KBr): ν 3063, 1597,
1486, 1185, 1160, 1096, 908, 727 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C28H26N2O3SNa
493.1556; Found 493.1558.
N-(2-(2,6-dimethylphenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(3ag), white solid, mp: 119–120 °C, yield 73% (70.8 mg); 1H NMR (400 MHz,
CDCl3) δ 9.55 (s, 1H), 9.12 (s, 1H), 7.24 (m, 4H), 7.17–7.09 (m, 6H), 6.98 (d, J = 7.6 Hz, 2H), 6.88 (d, J
= 8.0 Hz, 2H), 6.82 (dd, J1,2 = 7.2 Hz, 1H), 6.62 (s, 1H), 6.47 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H), 2.03 (s,
6H); 13C{1H} NMR (101 MHz, CDCl3) δ 168.6, 155.6, 143.6, 138.3, 136.7, 133.8, 133.1, 130.6, 130.0,
129.7, 128.9, 128.8, 128.7, 128.6, 128.0, 127.5, 120.9, 119.5, 118.0, 68.6, 21.4, 20.1; IR(KBr): ν 3068,
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1596, 1487, 1185, 1160, 1059, 908, 726 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C29H28N2O3SNa 507.1713; Found 507.1715.
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N-(2-(4-fluorophenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ah),
white solid, mp: 95–98 °C, yield 65% (61.7 mg); 1H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 8.76 (s, 1H),
7.57 (dd, J = 7.8, 2.4 Hz, 2H), 7.21–7.18 (m, 5H), 7.16–7.06 (m, 6H), 6.90 (d, J = 8.0 Hz, 2H), 6.85 (dd,
13
J1,2 = 7.2 Hz, 1H), 6.58–6.57 (m, 2H), 2.28 (s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 165.4 (d, J =
256.4 Hz), 164.6, 155.6, 143.9, 136.7, 133.4, 133.1 (d, J = 9.2 Hz), 130.2, 128.8, 128.5, 128.3, 128.1,
128.0 (d, J = 3.1 Hz), 127.5, 121.3, 119.6, 118.0, 116.6 (d, J = 22.2 Hz), 69.0, 21.5; 19F NMR (376 MHz,
CDCl3) δ -104.68 – -104.69 (m); IR(KBr): ν 3066, 1600, 1510, 1185, 1156, 1086, 907, 727 cm-1; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C27H23FN2O3SH 475.1486; Found 475.1488.
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N-(2-(4-chlorophenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ai),
white solid, mp: 78–79 °C, yield 66% (64.8 mg); 1H NMR (400 MHz, CDCl3) δ 9.71 (s, 1H), 8.74 (s, 1H),
7.47 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.23–7.20 (m, 5H), 7.17–7.12 (m, 4H), 6.91 (d, J = 8.0
Hz, 2H), 6.86 (dd, J1,2 = 7.4 Hz, 1H), 6.60–6.58 (m, 2H), 2.28 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ 163.5, 155.5, 144.0, 138.9, 136.6, 133.5, 133.4, 130.2, 129.9, 129.6, 128.9, 128.5, 128.3, 128.1, 127.5,
121.4, 119.7, 118.0, 68.9, 21.5; IR(KBr): ν 3065, 1595, 1487, 1185, 1086, 907, 729 cm-1; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C27H23ClN2O3SH 491.1191; Found 491.1194.
N-(2-(4-bromophenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3aj),
white solid, mp: 71–76 °C, yield 35% (37.5 mg); 1H NMR (400 MHz, CDCl3) δ 9.66 (s, 1H), 8.73 (s, 1H),
7.53 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.23–7.19 (m, 5H), 7.17–7.12 (m, 4H), 6.92 (d, J = 8.0
Hz, 2H), 6.86 (dd, J1,2 = 7.2 Hz, 1H), 6.60–6.58 (m, 2H), 2.29 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ 163.4, 155.5, 144.0, 136.6, 133.5, 133.4, 132.6, 130.6, 130.2, 130.0, 128.9, 128.5, 128.3, 128.1, 127.5,
121.4, 119.7, 118.0, 68.9, 21.5; IR(KBr): ν 3065, 1589, 1486, 1163, 1087, 1022, 909, 732 cm-1; HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C27H23BrN2O3SNa 557.0505; Found 557.0515.
N-(2-(4-iodophenyl)-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(3ak),
white solid, mp: 59–60 °C, yield 43% (50.1 mg); 1H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 8.70 (s, 1H),
7.74 (d, J = 8.4 Hz, 2H), 7.23–7.19, (m, 7H), 7.17–7.12 (m, 4H), 6.91 (d, J = 8.0 Hz, 2H), 6.86 (dd, J1,2
=
7.2 Hz, 1H), 6.60–6.58 (m, 2H), 2.28 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 163.4, 155.5, 144.0,
138.5, 136.6, 133.5, 133.4, 131.2, 130.2, 129.9, 128.9, 128.5, 128.3, 128.1, 127.5, 121.4, 119.7, 118.0,
99.9, 68.9, 21.5; IR(KBr): ν 3063, 1602, 1484, 1184, 1039, 908, 730, 637, 587 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C27H23IN2O3SH 583.0547; Found 583.0552.
(E)-4-methyl-N-(4-phenyl-2-styryl-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3al),
white
solid, mp: 81–82 °C, yield 76% (73.4 mg), dr = 1:0.7; 1H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 8.58
(d, J = 10.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1.4H), 7.45–7.37 (m, 4.4H), 7.36–7.33 (m, 3.4H), 7.33–7.27 (m,
1.7H), 7.24–7.21 (m, 3.4H), 7.20–7.16 (m, 6.8H), 7.15–7.13 (m, 1.7H), 7.07–7.00 (m, 3.4H), 6.95–6.90
(m, 3.4H), 6.83 (ddd, J1,2 = 7.4 Hz, J3 = 1.2 Hz, 1H), 6.72 (dd, J = 16.0, 9.8 Hz, 1H), 6.57 (dd, J = 8.0,
0.8 Hz, 1H), 6.53–6.47 (m, 1.7H), 6.17 (s, 0.7H), 5.60 (s, 0.7H), 5.20 (dd, J = 16, 4.6 Hz, 0.7H), 5.06 (d,
J = 4.4 Hz, 0.7H), 2.26 (s, 3H), 2.18 (s, 2.1H); 13C{1H} NMR (101 MHz, CDCl3) δ 166.0, 155.8, 153.3,
146.8, 143.9, 143.8, 141.3, 136.9, 135.7, 134.7, 134.5, 133.8, 133.5, 130.4, 130.1, 129.5, 129.3, 129.1,
128.9, 128.8, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.4, 126.7, 123.0, 122.5, 121.7, 121.3,
119.4, 118.3, 117.7, 117.0, 83.6, 69.1, 67.9, 21.4; IR(KBr): ν 2988, 1597, 1485, 1348, 1159, 1087, 730
cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H26N2O3SH 483.1737; Found 483.1739.
4-Methyl-N-(4-phenyl-2-(thiophen-2-yl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(3am),
white solid, mp: 134–135 °C, yield 62% (57.5 mg); 1H NMR (400 MHz, CDCl3) δ 10.01 (s, 1H), 8.80 (s,
1H), 7.57–7.55 (m, 2H), 7.50–7.46 (m, 1H), 7.42–7.38 (m, 2H), 7.22–7.21 (m, 3H), 7.19–7.17 (m, 1H),
7.15–7.13 (m, 3H), 6.90 (d, J = 8.0 Hz, 2H), 6.85 (ddd, J1,2 = 7.4 Hz, J3 = 1.2 Hz, 1H), 6.59–6.57 (m, 2H),
2.27 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 166.0, 155.6, 143.8, 136.7, 133.5, 132.7, 131.6, 130.1,
129.2, 128.9, 128.8, 128.5, 128.3, 128.1, 127.4, 121.3, 119.5, 118.1, 69.0, 21.5; IR(KBr): ν 2923, 1589,
1487, 1349, 1160, 1086, 731 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22N2O3S2H 463.1145;
Found 463.1148.
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4-Methyl-N-(2-methyl-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(5aa), white
solid, mp: 135–136 °C, yield 56% (52.7 mg); 1H NMR (400 MHz, CDCl3) δ 10.92 (s, 1H), 7.53 (d, J =
7.2 Hz, 2H), 7.48 (dd, J1,2 = 7.2 Hz, 1H), 7.40 (dd, J1,2 = 7.2 Hz, 2H), 7.30 (d, J = 7.2 Hz, 2H), 7.21–7.11
(m, 6H), 7.06 (dd, J1,2 = 7.4 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.77 (dd, J1,2 = 7.0 Hz, 1H), 6.45–6.42 (m,
2H), 2.54 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 182.2, 155.5, 143.5, 137.0, 135.9,
133.0, 132.8, 131.9, 129.7, 129.0, 128.9, 128.5, 128.4, 128.3, 127.7, 127.2, 121.4, 119.3, 118.2, 70.5,
21.5, 19.5; IR(KBr): ν 3064, 1597, 1486, 1185, 1160, 1087, 907, 726 cm-1; HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C28H26N2O3SNa 493.1556; Found 493.1558.
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4-Methyl-N-(2-methyl-4-phenyl-2-(p-tolyl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(5ab),
white solid, mp: 79–82 °C, yield 74% (71.7 mg); 1H NMR (400 MHz, CDCl3) δ 11.03 (s, 1H), 7.45 (d, J
= 7.6 Hz, 2H), 7.29 (d, J = 7.2 Hz, 2H), 7.21–7.16 (m, 6H), 7.12 (d, J = 7.2 Hz, 2H), 7.05 (dd, J1,2 = 7.2
Hz, 1H), 6.89 (d, J = 7.6 Hz, 2H), 6.76 (dd, J1,2 = 7.0 Hz, 1H), 6.44–6.42 (m, 2H), 2.51 (s, 3H), 2.36 (s,
3H), 2.29 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 181.8, 155.5, 143.4, 142.6, 137.0, 133.1, 133.0,
132.8, 129.7, 129.6, 129.0, 128.4, 128.3, 127.7, 127.2, 121.4, 119.2, 118.2, 70.5, 21.5, 21.4, 19.2;
IR(KBr): ν 2923, 1597, 1485, 1350, 1162, 1087, 735 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C29H28N2O3SH 485.1893; Found 485.1895.
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N-(2-(4-fluorophenyl)-2-methyl-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(5ac), white solid, mp: 117–118 °C, yield 38% (37.1 mg); 1H NMR (400 MHz,
CDCl3) δ 10.81 (s, 1H), 7.61–7.53 (m, 2H), 7.28 (dd, J1,2 = 7.8 Hz, 2H), 7.20–7.15 (m, 4H), 7.13–7.04
(m, 5H), 6.90 (d, J = 8.0 Hz, 2H), 6.77 (dd, J1,2 = 7.0 Hz, 1H), 6.45–6.42 (m, 2H), 2.52 (s, 3H), 2.30 (s,
3H); 19F NMR (376 MHz, CDCl3) δ -106.92 (brs); 13C{1H} NMR (101 MHz, CDCl3) δ 180.9, 165.0 (d,
J = 254.7 Hz), 155.4, 143.6, 136.9, 133.0, 132.7, 132.0 (d, J = 3.2 Hz), 129.8, 129.5 (d, J = 9.0 Hz), 129.0,
128.5, 128.4, 128.3, 127.8, 121.3, 119.4, 118.1, 116.1 (d, J = 22.0 Hz), 70.5, 21.5, 19.4; IR(KBr): ν 2988,
1599, 1486, 1351, 1161, 1087, 735 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H25FN2O3SH
489.1643; Found 489.1644.
N-(2-(4-chlorophenyl)-2-methyl-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(5ad), white solid, mp: 72–76 °C, yield 61% (61.6 mg); 1H NMR (400 MHz,
CDCl3) δ 10.71 (s, 1H), 7.48–7.45 (m, 2H), 7.39–7.35 (m, 2H), 7.28 (d, J = 7.2 Hz, 2H), 7.20–7.16 (m,
3H), 7.14–7.11 (m, 3H), 7.08–7.04 (m, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.77 (ddd, J1,2 = 7.2 Hz, J3 = 1.2
Hz, 1H), 6.45 (s, 1H), 6.43 (dd, J = 8.2, 1.2 Hz, 1H), 2.52 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 181.0, 155.3, 143.6, 138.3, 136.8, 134.2, 132.9, 132.6, 129.8, 129.2, 128.9, 128.5, 128.4, 128.3,
128.2, 127.8, 121.2, 119.3, 118.1, 70.4, 21.5, 19.3; IR(KBr): ν 2988, 1594, 1487, 1352, 1163, 1088, 736
cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H25ClN2O3SH 505.1347; Found 505.1353.
N-(2-(3-chlorophenyl)-2-methyl-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(5ae), white solid, mp: 132–134 °C, yield 41% (41.4 mg); 1H NMR (400 MHz,
CDCl3) δ 10.53 (s, 1H), 7.45–7.28 (m, 6H), 7.20 – 7.11 (m, 6H), 7.06 (dd, J1,2 = 7.0 Hz, 1H), 6.90 (d, J =
7.2 Hz, 2H), 6.77 (dd, J1,2 = 6.8 Hz, 1H), 6.45–6.43 (m, 2H), 2.52 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 181.1, 155.4, 143.7, 137.7, 136.8, 134.9, 133.0, 132.7, 131.8, 130.3, 129.8, 128.9,
128.6, 128.4, 127.9, 127.6, 125.0, 121.2, 119.4, 118.2, 70.5, 21.5, 19.7; IR(KBr): ν 2988, 1598, 1486,
1352, 1161, 1087, 735 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H25ClN2O3SH 505.1347;
Found 505.1351.
N-(2-(4-bromophenyl)-2-methyl-4-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-
methylbenzenesulfonamide(5af), white solid, mp: 143–144 °C, yield 35% (38.5 mg); 1H NMR (400 MHz,
CDCl3) δ 10.68 (s, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.38, (d, J = 8.0 Hz, 2H), 7.29–7.27 (m, 2H), 7.21–7.11
(m, 6H), 7.06 (dd, J1,2 = 7.4 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 7.2 Hz, 1H), 6.44–6.41 (m,
2H), 2.52 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 181.2, 155.4, 143.7, 136.9, 134.8,
133.0, 132.7, 132.3, 129.8, 129.0, 128.6, 128.5, 128.4, 128.3, 127.8, 126.9, 121.3, 119.4, 118.2, 70.5,
21.5, 19.4; IR(KBr): ν 2925, 1598, 1486, 1350, 1162, 1086, 735 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C28H25BrN2O3SH 549.0842; Found 549.0843.
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N-(2-cyclopropyl-2,4-diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)-4-methylbenzenesulfonamide(5ag),
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white solid, mp: 150–152 °C, yield 42% (41.7 mg); 1H NMR (400 MHz, CDCl3) δ 10.69 (s, 1H), 7.40 (d,
J = 7.2 Hz, 2H), 7.33–7.25 (m, 6H), 7.19 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 7.6, 1.6 Hz, 1H), 7.02–6.98 (m,
1H), 6.84 (d, J = 8.0 Hz, 2H), 6.78–6.76 (m, 2H), 6.73 (ddd, J1,2 = 7.4 Hz, J3 = 1.2 Hz, 1H), 6.43 (s, 1H),
6.30 (dd, J = 8.0, 0.8 Hz, 1H), 3.12–3.06 (m, 1H), 2.23 (s, 3H) 1.23–1.16 (m, 1H), 0.90–0.80 (m, 2H),
0.20–0.14 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 189.3, 155.6, 143.3, 137.0, 133.0, 132.9, 132.7,
129.6, 129.4, 129.3, 128.4, 128.3, 128.2, 128.1, 127.7, 127.1, 121.1, 119.0, 118.3, 70.5, 21.4, 15.7, 9.3,
8.7; IR(KBr): ν 2709, 1588, 1485, 1349, 1162, 1087, 731 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C30H28N2O3SH 497.1893; Found 497.1893.
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4-Methyl-N-(4-phenylspiro[benzo[e][1,3]oxazine-2,1'-cyclohexan]-3(4H)-yl)benzenesulfonamide(5ah),
white solid, mp: 128–130 °C, yield 60% (53.8 mg); 1H NMR (400 MHz, CDCl3) δ 11.21 (s, 1H), 7.26–
7.21 (m, 4H), 7.17 (d, J = 7.6 Hz, 3H), 7.40 (q, J = 8.0 Hz, 2H), 6.89 (d, J = 7.6 Hz, 2H), 6.72 (dd, J1,2
=
7.4 Hz, 1H), 6.40 (d, J = 8.0 Hz, 1H), 6.30 (s, 1H), 2.84–2.81 (m, 1H), 2.52–2.42 (m, 1H), 2.28 (brs, 5H),
1.76–1.73 (m, 2H), 1.48 (m, 2H), 0.88 (m, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 189.8, 155.4, 143.3,
137.4, 133.0, 132.8, 129.6, 129.1, 128.4, 127.6, 121.3, 119.0, 118.3, 70.0, 35.7, 31.5, 27.1, 26.4, 25.1,
21.4; IR(KBr): ν 2937, 1632, 1483, 1185, 1162, 1087, 907, 728 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C26H28N2O3SH 449.1893; Found 449.1895.
4-Methyl-N-(4-phenyl-3',4'-dihydro-2'H-spiro[benzo[e][1,3]oxazine-2,1'-naphthalen]-3(4H)-
1
yl)benzenesulfonamide(5ai), white solid, mp: 149–150 °C, yield 36% (35.8 mg); H NMR (400 MHz,
CDCl3) δ 11.16 (s, 1H), 7.83 (d, J = 7.6 Hz, 1H), 7.39 (dd, J1,2 = 7.2 Hz, 1H), 7.31–7.29 (m, 3H), 7.20–
7.11 (m, 7H), 7.06 (dd, J1,2 = 7.8 Hz, 1H), 6.93 (d, J = 7.6 Hz, 2H), 6.76 (dd, J1,2 = 6.8 Hz, 1H), 6.48–
6.45 (m, 2H), 3.27–3.23 (m, 1H), 2.92–2.85 (m, 2H), 2.68–2.64 (m, 1H), 2.33 (s, 3H), 1.93–1.90 (m, 1H),
1.26–1.22 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 181.6, 155.5, 143.5, 142.5, 137.2, 133.0, 132.8,
132.5, 130.2, 129.7, 129.3, 129.0, 128.5, 128.4, 128.3, 127.6, 127.0, 126.0, 121.6, 119.2, 118.1, 70.3,
30.2, 29.5, 22.5, 21.5; IR(KBr): ν 2935, 1583, 1485, 1349, 1161, 1087, 735 cm-1; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C30H28N2O3SH 497.1893; Found 497.1897.
4-Methyl-N-(4-phenylspiro[benzo[e][1,3]oxazine-2,4'-chroman]-3(4H)-yl)benzenesulfonamide(5aj),
white solid, mp: 151–152 °C, yield 42% (41.9 mg); 1H NMR (400 MHz, CDCl3) δ 10.99 (s, 1H), 7.72 (d,
J = 7.6 Hz, 1H), 7.40 (dd, J1,2 = 7.2 Hz, 1H), 7.29 (d, J = 7.2 Hz, 2H), 7.18–7.06 (m, 7H), 6.99 (dd, J1,2
=
7.4 Hz, 1H), 6.93 (d, J = 7.6 Hz, 2H), 6.87 (d, J = 8.4 Hz, 1H), 6.77 (dd, J1,2 = 6.8 Hz, 1H), 6.48 (d, J =
8.0 Hz, 1H), 6.43 (s, 1H), 4.35–4.32 (m, 1H), 3.55–3.49 (m, 1H), 3.20–3.18 (m, 2H), 2.32 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 175.0, 158.8, 155.3, 143.7, 137.1, 135.0, 133.0, 132.5, 129.8, 128.9,
128.6, 128.5, 128.4, 127.8, 125.7, 121.6, 121.3, 119.3, 118.2, 118.1, 117.3, 70.4, 65.4, 28.4, 21.5;
IR(KBr): ν 2854, 1595, 1481, 1351, 1161, 1087, 733 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C29H26N2O4SH 499.1686; Found 499.1689.
4-Methyl-N-(4-phenylspiro[benzo[e][1,3]oxazine-2,9'-fluoren]-3(4H)-yl)benzenesulfonamide(5ak),
yellow solid, mp: 122–124 °C, yield 34% (36.1 mg); 1H NMR (400 MHz, CDCl3) δ 11.00 (s, 1H), 8.83
(d, J = 6.8 Hz, 1H), 7.62, (d, J = 6.8 Hz, 1H), 7.44–7.38 (m, 5H), 7.28–7.22 (m, 5H), 7.15 (d, J = 6.8 Hz,
1H), 7.09–7.06 (m, 1H), 6.99 (m, 3H), 6.91 (d, J = 7.2 Hz, 2H), 6.80–6.78 (m, 1H), 6.54 (s, 1H), 6.48 (d,
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J = 7.6 Hz, 1H), 2.31 (s, 3H); C{1H} NMR (101 MHz, CDCl3) δ 173.0, 155.3, 144.0, 143.7, 142.3,
136.8, 134.9, 133.9, 133.5, 133.4, 132.6, 131.7, 131.5, 129.8, 128.7, 128.6, 128.5, 128.2, 127.7, 123.7,
121.5, 120.1, 120.0, 119.3, 118.2, 71.3, 21.5; IR(KBr): ν 2788, 1593, 1484, 1353, 1162, 1085, 731 cm-1;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C33H26N2O3SH 531.1737; Found 531.1738.
4-Methyl-N-((1'R,2R,4'R)-1',7',7'-trimethyl-4-phenylspiro[benzo[e][1,3]oxazine-2,2'-
bicyclo[2.2.1]heptan]-3(4H)-yl)benzenesulfonamide(5al), white solid, mp: 163–164 °C, yield 79% (79.4
mg), dr = 1:0.7; 1H NMR (400 MHz, CDCl3) δ 11.15 (s, 1H), 11.11 (s, 0.7H), 7.35–7.33 (m, 3.4H), 7.23–
7.20 (m, 1.7H), 7.18–7.11 (m, 6.8H), 7.07–7.02 (m, 1.7H), 7.00–6.98 (m, 1.7H), 6.89 (d, J = 8.0 Hz,
3.4H), 6.74–6.71 (m, 0.7H), 6.71–6.67 (m, 1H), 6.40 (d, J = 8.0 Hz, 1.7H), 6.27–6.25 (m, 1.7H), 3.28–
3.22 (m, 0.7H), 2.88 (d, J = 19.2 Hz, 1H), 2.29–2.28 (m, 5.1H), 2.24–2.18 (m, 1H), 1.93 (d, J = 19.2 Hz,
0.7H), 1.83–1.76 (m, 3.4H), 1.59–1.54 (m, 1.7H), 1.43–1.34 (m, 1.7H), 1.00 (s, 2.1H), 0.97 (s, 2.1H),
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0.94 (s, 3H), 0.84 (s, 2.1H), 0.79 (s, 3H), 0.63–0.51 (m, 1H), 0.30–0.24 (m, 0.7H), – 0.21 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 200.7, 199.5, 155.6, 155.5, 143.3, 143.2, 137.6, 137.3, 132.9, 132.8, 132.5,
132.3, 129.6, 129.5, 129.4, 128.5, 128.4, 128.3, 128.2, 128.1, 127.7, 127.6, 121.4, 121.3, 119.1, 119.0,
118.3, 70.4, 70.0, 55.6, 55.2, 48.9, 47.3, 43.6, 43,4, 39.1, 37.8, 31.8, 31.5, 26.6, 26.4, 21.5, 21.4, 19.6,
18.4, 18.3, 18.2, 11.1, 10.9; IR(KBr): ν 2958, 1598, 1483, 1350, 1160, 1087, 733 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C30H34N2O3SH 503.2363; Found 503.2363.
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4-Methyl-N-(2'-methyl-4-phenyl-5'-(prop-1-en-2-yl)spiro[benzo[e][1,3]oxazine-2,1'-cyclohexan]-
3(4H)-yl)benzenesulfonamide(5am), white solid, mp: 120–122 °C, yield 76% (76.3 mg), dr = 1:1; H
1
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NMR (400 MHz, CDCl3) δ 11.00 (s, 1H), 10.73 (s, 1H), 7.32 (d, J = 7.2 Hz, 2H), 7.25–7.19 (m, 6H),
7.17–7.12 (m, 6H), 7.07–6.99 (m, 4H), 6.91 (d, J = 3.2 Hz, 2H), 6.89 (d, J = 2.8 Hz, 2H), 6.77–6.70 (m,
2H), 6.41–6.39 (m, 2H), 6.34 (s, 1H), 6.30 (s, 1H), 4.79–4.70 (m, 4H), 3.69–3.66 (m, 1H), 3.55–3.50 (m,
1H), 2.55–2.42 (m, 2H), 2.30 (s, 3H), 2.29 (s, 3H), 2.03–1.99 (m, 2H), 1.88–1.84 (m, 2H), 1.78 (s, 3H),
1.72–1.70 (m, 4H), 1.56–1.53 (m, 1H), 1.44–1.34 (m, 3H), 1.24–1.17 (m, 1H), 1.11 (d, J = 6.8 Hz, 3H),
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1.05 (d, J = 6.0 Hz, 3H), 1.01–0.95 (m, 1H), 0.77–0.67 (m, 1H); C{1H} NMR (101 MHz, CDCl3) δ
191.8, 191.5, 155.5, 155.3, 148.0, 147.5, 143.3, 143.2, 137.6, 136.9, 132.8, 132.7, 132.6, 129.6, 129.5,
129.4, 129.0, 128.5, 128.4, 128.3, 128.2, 128.1, 127.6, 127.5, 121.6, 119.1, 119.0, 118.1, 118.0, 109.9,
109.4, 69.9, 45.9, 45.1, 40.8, 40.7, 36.4, 36.3, 35.7, 35.1, 30.5, 30.3, 21.5, 21.4, 20.8, 20.2, 16.4, 16.2;
IR(KBr): ν 2932, 1581, 1485, 1350, 1162, 1087, 732 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C30H34N2O3SH 503.2363; Found 503.2367.
2,4-Diphenyl-2H-benzo[e][1,3]oxazin-3(4H)-ol(5an), white solid, mp: 61–62 °C, yield 38% (20.6 mg);
1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.68 (s, 1H), 7.56–7.54 (m, 2H), 7.40–7.33 (m, 8H), 7.25–
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7.22 (m, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.86 (dd, J1,2 = 7.4 Hz, 1H), 6.54 (s, 1H); C{1H} NMR (101
MHz, CDCl3) δ 155.4, 150.4, 138.6, 131.1, 130.5, 129.9, 129.8, 128.8, 128.4, 128.0, 127.5, 127.4, 126.3,
120.3, 117.6, 84.6; IR(KBr): ν 3435, 1585, 1455, 1264, 1096, 945, 733 cm-1; HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C20H17NO2H 304.1332; Found 304.1333.
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2-(Phenyl(phenylamino)methyl)phenol(7), a known compound17, yield 34% (18.7 mg); H NMR (400
MHz, CDCl3) δ 9.37 (s, 1H), 7.36–7.22 (m, 5H), 7.18–7.15 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 6.89–6.76
(m, 5H), 5.56 (s, 1H), 4.21 (s, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 156.4, 146.4, 141.2, 129.3, 129.1,
129.0, 128.6, 128.1, 127.6, 125.7, 120.9, 120.2, 117.2, 116.2, 64.1.
4-Methyl-N-((2R,4S)-4-methyl-2-phenyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)benzenesulfonamide(9), faint
yellow oil, yield 90% (71.0 mg); 1H NMR (400 MHz, CDCl3) δ 9.79 (s, 1H), 8.87 (s, 1H), 7.77 (d, J =
7.2 Hz, 2H), 7.59–7.49 (m, 3H), 7.15–7.10 (m, 3H), 7.05 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 8.0 Hz, 2H),
6.78 (t, J = 7.2 Hz, 1H), 6.51 (d, J = 8.0 Hz, 1H), 5.33 (q, J = 7.2 Hz, 1H), 2.26 (s, 3H), 1.50 (d, J = 7.2
13
Hz, 3H); C{1H} NMR (101 MHz, CDCl3) δ 166.4, 154.8, 143.6, 133.4, 132.9, 131.8, 131.2, 129.4,
129.3, 129.0, 128.7, 128.0, 124.7, 119.3, 117.8, 61.2, 21.4, 18.9; IR(KBr): ν 2930, 1580, 1487, 1348,
1160, 1085, 728 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22N2O3SH 395.1424; Found
395.1428.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.xxxxxx.
1H, 19F and 13NMR spectra of products, X-ray crystallography data and CIF file of product 3aa (PDF)
AUTHOR INFORMATION
Corresponding Author
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*E-mail: xytang@hust.edu.cn
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ORCID
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Xiang-Ying Tang: 0000-0003-3959-3715
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
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We are grateful for the financial support provided by the National Natural Science Foundation
of China (21871100), the Fundamental Research Funds for the Central Universities
(2017KFYXJJ166, 2019kfyRCPY096), Huazhong University of Science and Technology
(HUST), and the Opening Fund of Hubei Key Laboratory of Bioinorganic Chemistry and Materia
Medica (No. BCMM201805). We also thank the Analytical and Testing Center of HUST,
Analytical and Testing Center of the School of Chemistry and Chemical Engineering (HUST) for
access to their facilities.
REFERENCES
(1) Barluenga, J.; Valdés, C. Tosylhydrazones: New Uses for Classic Reagents in Palladium ‐
Catalyzed Cross‐Coupling and Metal‐Free Reactions. Angew. Chem., Int. Ed. 2011, 50, 7486–7500.
(2) Panda, S.; Maity, P.; Manna, D. Transition Metal, Azide, and Oxidant-Free Homo- and
Heterocoupling of Ambiphilic Tosylhydrazones to the Regioselective Triazoles and Pyrazoles. Org. Lett.
2017, 19, 1534–1537.
(3) Kong, Y.; Zhang, W.; Tang, M.; Wang, H. N-Alkylation of tosylhydrazones in the presence of
triphenylphosphine. Tetrahedron 2013, 69, 7487–7491.
(4) (a) Plaza, M.; Paraja, M.; Florentino, L.; Valdés, C. Domino Synthesis of Benzo-Fused β,γ-
Unsaturated Ketones from Alkenylboronic Acids and N-Tosylhydrazone-Tethered Benzonitriles. Org.
Lett.
2019,
21,
632–635.
(b)
Shrestha,
R.;
Lee,
Y.
R.
Base-Promoted
Denitrogenative/Deoxygenative/Deformylative Benzannulation of N-Tosylhydrazones with 3-
Formylchromones for Diverse and Polyfunctionalized Xanthones. Org. Lett. 2018, 20, 7167–7171. (c)
Sun, Q.; Li, L.; Liu, L.; Guan, Q.; Yang, Y.; Zha, Z.; Wang, Z. Copper-Catalyzed Geminal
Difunctionalization of Terminal Alkynes by Splitting Sulfonyl Hydrazones into Two Parts. Org. Lett.
2018, 20, 5592–5596. (d) Liu, Z.; Tan, H.; Fu, T.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. Pd(0)-Catalyzed
Carbene Insertion into Si–Si and Sn–Sn Bonds. J. Am. Chem. Soc. 2015, 137, 12800–12803. (e) Xiong,
W.; Qi, C.; He, H.; Ouyang, L.; Zhang, M.; Jiang, H. Base‐Promoted Coupling of Carbon Dioxide,
Amines, and N‐Tosylhydrazones: A Novel and Versatile Approach to Carbamates. Angew. Chem., Int.
Ed. 2015, 54, 3084–3087. (f) Allwood, D. M.; Blakemore, D. C.; Ley, S. V. Preparation of Unsymmetrical
Ketones from Tosylhydrazones and Aromatic Aldehydes via Formyl C–H Bond Insertion. Org. Lett.
2014, 16, 3064–3067. (g) Chen, Z.-S.; Duan, X.-H.; Wu, L.-Y.; Ali, S.; Ji, K.-G.; Zhou, P.-X.; Liu, X.-
Y.; Liang, Y.-M. Palladium‐Catalyzed Coupling of Propargylic Carbonates with N‐Tosylhydrazones:
Highly Selective Synthesis of Substituted Propargylic N‐Sulfonylhydrazones and Vinylallenes. Chem.
Eur. J. 2011, 17, 6918–6921. (h) Zhou, L.; Ye, F.; Zhang, Y.; Wang, J. Pd-Catalyzed Three-Component
Coupling of N-Tosylhydrazone, Terminal Alkyne, and Aryl Halide. J. Am. Chem. Soc. 2010, 132, 13590–
13591.
ACS Paragon Plus Environment

Page 17 of 20
1
The Journal of Organic Chemistry
(5) (a) Allouche, E. M. D.; Al-Saleh, A.; Charette, A. B. Iron-catalyzed synthesis of cyclopropanes by
in situ generation and decomposition of electronically diversified diazo compounds. Chem. Commun.
2018, 54, 13256–13259. (b) Jiang, H.; Chen, F.; Zhu, C.; Zhu, R.; Zeng, H.; Liu, C.; Wu, W. Two C–O
Bond Formations on a Carbenic Carbon: Palladium-Catalyzed Coupling of N-Tosylhydrazones and
Benzo-1,2-quinones To Construct Benzodioxoles. Org. Lett. 2018, 20, 3166–3169. (c) Wang, Y.; Wen,
X.; Cui, X.; Wojtas, L.; Zhang, X. P. Asymmetric Radical Cyclopropanation of Alkenes with In Situ-
Generated Donor-Substituted Diazo Reagents via Co(II)-Based Metalloradical Catalysis. J. Am. Chem.
Soc. 2017, 139, 1049–1052. (d) Cyr, P.; Côté-Raiche, A.; Bronner, S. M. Transition-Metal-Free Synthesis
of Tertiary Aminocyclopropanes. Org. Lett. 2016, 18, 6448–6451. (e) Otte, M.; Kuijpers, P. F.;
Troeppner, O.; Ivanović-Burmazović, I.; Reek, J. N. H.; de Bruin, B. Encapsulated Cobalt–Porphyrin as
a Catalyst for Size‐Selective Radical‐type Cyclopropanation Reactions. Chem. Eur. J. 2014, 20, 4880–
4884. (f) Jiang, H.; Fu, W.; Chen, H. Palladium‐Catalyzed Cross‐Coupling Reactions of Electron‐
Deficient Alkenes with N‐Tosylhydrazones: Functional‐Group‐Controlled C–CꢀBond Construction.
Chem. Eur. J., 2012, 18, 11884–11888. (g) Barluenga, J.; Quiñones, N.; Tomás-Gamasa, M.; Cabal, M.-
P. Intermolecular Metal‐Free Cyclopropanation of Alkenes Using Tosylhydrazones. Eur. J. Org. Chem.
2012, 2012, 2312–2317. (h) Aggarwal, V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon, K. M.; Palmer, M.
J.; Patel, M.; Porcelloni, M.; Richardson, J.; Stenson, R. A.; Studley, J. R.; Vasse, J.-L.; Winn, C. L. A
New Protocol for the In Situ Generation of Aromatic, Heteroaromatic, and Unsaturated Diazo Compounds
and Its Application in Catalytic and Asymmetric Epoxidation of Carbonyl Compounds. Extensive Studies
To Map Out Scope and Limitations, and Rationalization of Diastereo- and Enantioselectivities. J. Am.
Chem. Soc. 2003, 125, 10926–10940.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) For selected recent examples, see: (a) Wang, Y.; Wen, X.; Cui, X.; Zhang, X. P. Enantioselective
Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C–H Alkylation.
J. Am. Chem. Soc. 2018, 140, 4792–4796. (b) Das, B. G.; Chirila, A.; Tromp, M.; Reek, J. N. H.; de Bruin,
B. CoIII–Carbene Radical Approach to Substituted 1H-Indenes. J. Am. Chem. Soc. 2016, 138, 8968–8975.
(c) Reddy, A. R.; Zhou, C.-Y.; Guo, Z.; Wei, J.; Che, C.-M. Ruthenium–Porphyrin ‐ Catalyzed
Diastereoselective Intramolecular Alkyl Carbene Insertion into C–H Bonds of Alkyl Diazomethanes
Generated In Situ from N‐Tosylhydrazones. Angew. Chem., Int. Ed. 2014, 53, 14175–14180.
(7) For selected examples, see: (a) Wang, E.-H.; Ping, Y.-J.; Li, Z.-R.; Qin, H.; Xu, Z.-J.; Che, C.-M.
Iron Porphyrin Catalyzed Insertion Reaction of N-Tosylhydrazone-Derived Carbenes into X–H (X = Si,
Sn, Ge) Bonds. Org. Lett. 2018, 20, 4641–4644. (b) Liu, Z.; Li, Q.; Yang, Y.; Bi, X. Silver(I)-promoted
insertion into X–H (X = Si, Sn, and Ge) bonds with N-nosylhydrazones. Chem. Commun. 2017, 53, 2503–
2506. (c) Yadav, A. K.; Srivastava, V. P.; Yadav, L. D. S. An easy access to fluoroalkanes by
deoxygenative hydrofluorination of carbonyl compounds via their tosylhydrazones. Chem. Commun.
2013, 49, 2154–2156. (d) Barluenga, J.; Tomás-Gamasa, M.; Aznar, F.; Valdés, C. Metal-free carbon–
carbon bond-forming reductive coupling between boronic acids and tosylhydrazones. Nat. Chem. 2009,
1, 494–499.
(8) For selected examples, see: (a) Ragupathi, A.; Sagadevan, A.; Charpe, V. P.; Lin, C.-C.; Hwu, J.-
R.; Hwang, K. C. Visible-light-driven copper-catalyzed aerobic oxidative cascade cyclization of N-
tosylhydrazones and terminal alkynes: regioselective synthesis of 3-arylcoumarins. Chem. Commun.
2019, 55, 5151–5154. (b) Zhang, X.; Liu, Z.; Yang, X.; Dong, Y.; Virelli, M.; Zanoni, G.; Anderson, E.
A.; Bi, X. Use of trifluoroacetaldehyde N-tfsylhydrazone as a trifluorodiazoethane surrogate and its
synthetic applications. Nat. Commun. 2019, 10, 284–292. (c) Ishikawa, T.; Kimura, M.; Kumoi, T.; Iida,
H. Coupled Flavin-Iodine Redox Organocatalysts: Aerobic Oxidative Transformation from N-
Tosylhydrazones to 1,2,3-Thiadiazoles. ACS Catal. 2017, 7, 4986–4989. (d) Zhang, Y.; Zhang, X.; Yao,
R.; Wen, Y.; Huang, J.; Xu, X. 1,3-Dipolar Cycloaddition of Alkyne-Tethered N-Tosylhydrazones:
Synthesis of Fused Polycyclic Pyrazoles. J. Org. Chem. 2016, 81, 11072–11080. (e) Tan, H.; Houpis, I.;
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Page 18 of 20
Liu, R.; Wang, Y.; Chen, Z. Olefin Preparation via Palladium-Catalyzed Oxidative De-Azotative and De-
Sulfitative Internal Cross-Coupling of Sulfonylhydrazones. Org. Lett. 2015, 17, 3548–3551.(f) Li, X.;
Liu, X.; Chen, H.; Wu, W.; Qi, C.; Jiang, H. Copper‐Catalyzed Aerobic Oxidative Transformation of
Ketone‐Derived N‐Tosyl Hydrazones: An Entry to Alkynes. Angew. Chem., Int. Ed. 2014, 53, 14485–
14489. (g) Cai, Z.-J.; Lu, X.-M.; Zi, Y.; Yang, C.; Shen, L.-J.; Li, J.; Wang, S.-Y.; Ji, S.-J. I2/TBPB
Mediated Oxidative Reaction of N-Tosylhydrazones with Anilines: Practical Construction of 1,4-
Disubstituted 1,2,3-Triazoles under Metal-Free and Azide-Free Conditions. Org. Lett. 2014, 16, 5108–
5111.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(9) (a) Zhang, Q.; Tang, M. Regioselective Synthesis of Highly Functionalized Pyrazoles from N-
Tosylhydrazones. Org. Lett. 2019, 21, 1917–1920. (b) Panda, S.; Pradhhan, N.; Manna, D. Ring-Opening
of Indoles: An Unconventional Route for the Transformation of Indoles to 1H-Pyrazoles Using Lewis
Acid. ACS Comb. Sci. 2018, 20, 573–578. (c) Panda, S.; Maity, P.; Manna, D. Transition Metal, Azide,
and Oxidant-Free Homo- and Heterocoupling of Ambiphilic Tosylhydrazones to the Regioselective
Triazoles and Pyrazoles. Org. Lett. 2017, 19, 1534–1537. (d) Crespin, L.; Biancalana, L.; Morack, T.;
Blakemore, D. C.; Ley, S. V. One-Pot Acid-Catalyzed Ring-Opening/Cyclization/Oxidation of Aziridines
with N-Tosylhydrazones: Access to 1,2,4-Triazines. Org. Lett. 2017, 19, 1084–1087. (e) Yu, Y.; Huang,
W.; Chen, Y.; Gao, B.; Wu, W.; Jiang, H. Calcium carbide as the acetylide source: transition-metal-free
synthesis of substituted pyrazoles via [1,5]-sigmatropic rearrangements. Green Chem. 2016, 18, 6445–
6449. (f) Pérez-Aguilar, M. C.; Valdés, C. Synthesis of Chiral Pyrazoles: A 1,3 ‐ Dipolar
Cycloaddition/[1,5] Sigmatropic Rearrangement with Stereoretentive Migration of a Stereogenic Group.
Angew. Chem., Int. Ed. 2015, 54, 13729–13733. (g) Kong, Y.; Tang, M.; Wang, Y. Regioselective
Synthesis of 1,3,5-Trisubstituted Pyrazoles from N-Alkylated Tosylhydrazones and Terminal Alkynes.
Org. Lett. 2014, 16, 576–579.
(10) The cycloaddition of 3-diazooxindoles serving as dipolarophiles was reported, see: Mei, L.-Y.;
Tang, X.-Y.; Shi, M. One ‐ Pot Tandem Diastereoselective and Enantioselective Synthesis of
Functionalized Oxindole‐Fused Spiropyrazolidine Frameworks. Chem. Eur. J. 2014, 20, 13136–13142.
(11) For selected reviews, see: (a) Yang, B.; Gao, S. Recent advances in the application of Diels–Alder
reactions involving o-quinodimethanes, aza-o-quinone methides and o-quinone methides in natural
product total synthesis. Chem. Soc. Rev. 2018, 47, 7926–7953. (b) Bruins, J. J.; Bauke, A.; van Delft, F.
ortho ‐ Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and Selective
Biofunctionalization. Chem. Eur. J. 2018, 24, 4749–4756. (c) Jaworski, A. A.; Scheidt, K. A. Emerging
Roles of in Situ Generated Quinone Methides in Metal-Free Catalysis. J. Org. Chem. 2016, 81, 10145–
10153. (d) Wang, Z.; Sun, J. Recent Advances in Catalytic Asymmetric Reactions of o-Quinone Methides.
Synthesis 2015, 47, 3629–3644. (e) Bai, W.-J.; David, J. G.; Feng, Z.-G.; Weaver, M. G.; Wu, K.-L.;
Pettus, T. R. R. The Domestication of ortho-Quinone Methides. Acc. Chem. Res. 2014, 47, 3655–3664.
(f) Willis, N. J.; Bray, C. D. ortho‐Quinone Methides in Natural Product Synthesis. Chem. Eur. J. 2012,
18, 9160–9173. (g) Ferreira, S. B.; da Silva, F. d. C.; Pinto, A. C.; Gonzaga, D. T. G.; Ferreira, V. F.
Syntheses of chromenes and chromanes via o‐quinone methide intermediates. J. Heterocycl. Chem.
2009, 46, 1080–1097.
(12) For selected examples, see: (a) Du, J.-Y.; Ma, Y.-H.; Meng, F.-X.; Zhang, R.-R.; Wang, R.-N.;
Shi, H.-L.; Wang, Q.; Fan, Y.-X.; Huang, H.-L.; Cui, J.-C.; Ma, C.-L. Lewis Base-Catalyzed [4 + 3]
Annulation of ortho-Quinone Methides and MBH Carbonates: Synthesis of Functionalized
Benzo[b]oxepines Bearing Oxindole Scaffolds. Org. Lett. 2019, 21, 465–468. (b) Wong, C. R.; Hummel,
G.; Cai, Y.; Schaus, S. E.; Panek, J. S. [4 + 2]-Cycloaddition and 1,4-Addition of ortho-Quinone Methides
by a Chiral Crotyl Silane. Org. Lett., 2019, 21, 32–35. (c) Zhang, J.; Liu, X.; Guo, S.; He, C.; Xiao, W.;
Lin, L.; Feng, X. Enantioselective Formal [4 + 2] Annulation of ortho-Quinone Methides with ortho-
ACS Paragon Plus Environment

Page 19 of 20
The Journal of Organic Chemistry
Hydroxyphenyl α,β-Unsaturated Compounds. J. Org. Chem. 2018, 83, 10175–10185. (d) Suneja, A.;
Schneider, C. Phosphoric Acid Catalyzed [4 + 1]-Cycloannulation Reaction of ortho-Quinone Methides
and Diazoketones: Catalytic, Enantioselective Access toward cis-2,3-Dihydrobenzofurans. Org. Lett.
2018, 20, 7576–7580. (e) Spanka, M.; Schneider, C. Phosphoric Acid Catalyzed Aldehyde Addition to in
Situ Generated o-Quinone Methides: An Enantio- and Diastereoselective Entry toward cis-3,4-Diaryl
Dihydrocoumarins. Org. Lett. 2018, 20, 4769–4772. (f) Jeong, H. J.; Kim, D. Y. Enantioselective
Decarboxylative Alkylation of β-Keto Acids to ortho-Quinone Methides as Reactive Intermediates:
Asymmetric Synthesis of 2,4-Diaryl-1-benzopyrans. Org. Lett. 2018, 20, 2944–2947. (g) Wang, Z.;
Wang, T.; Yao, W.; Lu, Y. Phosphine-Catalyzed Enantioselective [4 + 2] Annulation of o-Quinone
Methides with Allene Ketones. Org. Lett. 2017, 19, 4126–4129. (h) Liang, M.; Zhang, S.; Jia, J.; Tung,
C.-H.; Wang, J.; Xu, Z. Synthesis of Spiroketals by Synergistic Gold and Scandium Catalysis. Org. Lett.
2017, 19, 2526–2529. (i) Lee, A.; Scheidt, K. A. N-Heterocyclic carbene-catalyzed enantioselective
annulations: a dual activation strategy for a formal [4+2] addition for dihydrocoumarins. Chem. Commun.
2015, 51, 3407–3410. (j) El-Sepelgy, O.; Haseloff, S.; Alamsetti, S. K.; Schneider, C. Brønsted Acid
Catalyzed, Conjugate Addition of β‐Dicarbonyls to In Situ Generated ortho‐Quinone Methides–
Enantioselective Synthesis of 4‐Aryl‐4H‐Chromenes. Angew. Chem., Int. Ed. 2014, 53, 7923–7927.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) (a) Liao, H.-H.; Hsiao, C.-C.; Atodiresei, I.; Rueping, M. Multiple Hydrogen‐Bond Activation
in Asymmetric Brønsted Acid Catalysis. Chem. Eur. J. 2018, 24, 7718–7723. (b) Guo, Z.; Jia, H.; Liu,
H.; Wang, Q.; Huang, J.; Guo, H. A [4 + 3] Annulation Reaction of aza-o-Quinone Methides with
Arylcarbohydrazonoyl Chlorides for Synthesis of 2,3-Dihydro-1H-benzo[e][1,2,4]triazepines. Org. Lett.
2018, 20, 2939–2943. (c) Walden, D. M.; Jaworski, A. A.; Johnston, R. C.; Todd Hovey, M.; Baker, H.
V.; Meyer, M. P.; Scheidt, K. A.; Cheong, P. H.-Y. Formation of Aza-ortho-quinone Methides Under
Room Temperature Conditions: Cs2CO3 Effect. J. Org. Chem. 2017, 82, 7183–7189. (d) Chatupheeraphat,
A.; Liao, H.-H.; Mader, S.; Sako, M.; Sasai, H.; Atodiresei, I.; Rueping, M. Asymmetric Brønsted Acid
Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral
Thioethers and Ethers. Angew. Chem., Int. Ed. 2016, 55, 4803–4807. (e) Liao, H.-H.; Chatupheeraphat,
A.; Hsiao, C.-C.; Atodiresei, I.; Rueping, M. Asymmetric Brønsted Acid Catalyzed Synthesis of
Triarylmethanes–Construction of Communesin and Spiroindoline Scaffolds. Angew. Chem., Int. Ed.
2015, 54, 15540–15544. (f) Lee, A.; Younai, A.; Price, C. K.; Izquierdo, J.; Mishra, R. K.; Scheidt, K. A.
Enantioselective Annulations for Dihydroquinolones by in Situ Generation of Azolium Enolates. J. Am.
Chem. Soc. 2014, 136, 10589–10592.
(14) (a) Cheng, X.; Cao, X.; Xuan, J.; Xiao, W.-J. Silver(I)- and Base-Mediated [3 + 3]-Cycloaddition
of C,N-Cyclic Azomethine Imines with Aza-oxyallyl Cations. Org. Lett. 2018, 20, 52–55. (b) Jin, Q.;
Gao, M.; Zhang, D.; Jiang, C.; Yao, N.; Zhang, J. Base-mediated [2 + 4] cycloadditions of in situ formed
azaoxyallyl cations with N-(2-chloromethyl)aryl amides. Org. Biomol. Chem. 2018, 16, 7336–7339.
(15) (a) Lanzi, M.; Merad, J.; Boyarskaya, D. V.; Maestri, G.; Allain, C.; Masson, G. Visible-Light-
Triggered C–C and C–N Bond Formation by C–S Bond Cleavage of Benzylic Thioethers. Org. Lett. 2018,
20, 5247–5250. (b) Yadagiri, D.; Chaitanya, M.; Reddy, A. C. S.; Anbarasan, P. Rhodium Catalyzed
Synthesis of Benzopyrans via Transannulation of N-Sulfonyl-1,2,3-triazoles with 2-Hydroxybenzyl
Alcohols. Org. Lett. 2018, 20, 3762−3765. (c) Zhou, J.; Huang, W.-J.; Jiang, G.-F. Synthesis of Chiral
Pyrazolone and Spiropyrazolone Derivatives through Squaramide-Catalyzed Reaction of Pyrazolin-5-
ones with o-Quinone Methides. Org. Lett. 2018, 20, 1158–1161. (d) Zhao, W.; Wang, Z.; Chu, B.; Sun,
J. Enantioselective Formation of All ‐ Carbon Quaternary Stereocenters from Indoles and Tertiary
Alcohols Bearing A Directing Group. Angew. Chem., Int. Ed. 2015, 54, 1910–1913. (e) Lai, Z.; Wang,
Z.; Sun, J. Organocatalytic Asymmetric Nucleophilic Addition to o-Quinone Methides by Alcohols. Org.
Lett. 2015, 17, 6058−6061. (f) Liang, D.; Wang, M.; Bekturhun, B.; Xiong, B.; Liu, Q. One-Pot Synthesis
of Polyfunctionalized 4H-Chromenes and Dihydrocoumarins Based on Copper(II) Bromide-Catalyzed
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Page 20 of 20
C−C Coupling of Benzylic Alcohols with Ketene Dithioacetals. Adv. Synth. Catal. 2010, 352, 1593 –
1599. (g) Fan, J.; Wang, Z. Facile construction of functionalized 4H-chromene via tandem benzylation
and cyclization. Chem. Commun. 2008, 5381–5383.
1
2
3
4
5
6
7
8
9
(16) (a) Wang, Y.; Wen, X.; Cui, X.; Wojtas, L.; Zhang, X. P. Asymmetric Radical Cyclopropanation
of Alkenes with In Situ-Generated Donor-Substituted Diazo Reagents via Co(II)-Based Metalloradical
Catalysis. J. Am. Chem. Soc. 2017, 139, 1049−1052. (b) Ni, M.; Zhang, J.; Liang, X.; Jiang, Y.; Loh, T.-
P. Directed C–C bond cleavage of a cyclopropane intermediate generated from N-tosylhydrazones and
stable enaminones: expedient synthesis of functionalized 1,4-ketoaldehydes. Chem. Commun., 2017, 53,
12286–12289. (c) Zhang, B.-H.; Lei, L.-S.; Liu, S.-Z.; Mou, X.-Q.; Liu, W.-T.; Wang, S.-H.; Wang, J.;
Bao, W.; Zhang, K. Zinc-promoted cyclization of tosylhydrazones and 2-(dimethylamino)malononitrile:
an efficient strategy for the synthesis of substituted 1-tosyl-1H-pyrazoles. Chem. Commun. 2017, 53,
8545–8548. (d) Ye, F.; Ma, X.; Xiao, Q.; Li, H.; Zhang, Y.; Wang, J. C(sp)–C(sp3) Bond Formation
through Cu-Catalyzed Cross-Coupling of N-Tosylhydrazones and Trialkylsilylethynes. J. Am. Chem. Soc.
2012, 134, 5742−5745. (e)Li, P.; Zhao, J.; Wu, C.; Larock, R. C.; Shi, F. Synthesis of 3-Substituted
Indazoles from Arynes and N-Tosylhydrazones. Org. Lett. 2011, 13, 3340–3343. (f) Johansson, S. G. H.;
Emilsson, K.; Grøtli, M.; Börje, A. Structural Influence on Radical Formation and Sensitizing Capacity
of Alkylic Limonene Hydroperoxide Analogues in Allergic Contact Dermatitis. Chem. Res. Toxicol. 2010,
23, 677–688. (g) Celik, H.; Ekmekci, G.; Ludvik, J.; Picha, J.; Zuman, P. Electroreduction of Aromatic
Oximes:ꢀ Diprotonation, Adsorption, Imine Formation, and Substituent Effects. J. Phys. Chem. B. 2006,
110, 6785−6796. (h) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; de Vicente, J. Generation of
Phosphoranes Derived from Phosphites. A New Class of Phosphorus Ylides Leading to High E Selectivity
with Semi-stabilizing Groups in Wittig Olefinations. J. Am. Chem. Soc. 2003, 125, 6034-6035. (i)
Bamford, W. R.; Stevens, T. S. The decomposition of toluene-p-sulphonylhydrazones by alkali. J. Chem.
Soc. 1952, 4735-4740.
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11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) Hosseinzadeh, R.; Lasemi, Z.; Oloub, M.; Pooryousef, M. A green protocol for the one-pot
multicomponent Petasis boronic Mannich reaction using ball milling. J. Iran. Chem. Soc. 2017, 14, 347–
355.
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