Preparation of 6-substituted phenanthridines from o-biaryl ketoximes via the Beckmann rearrangement

Article abstract of DOI:10.1016/j.tet.2021.132244

Treatment of anti alkyl o-biaryl ketoximes and anti aryl o-biaryl ketoximes with Tf₂O at 120 °C, followed by quenching with Et₃N gave 6-alkylphenanthridines and 6-arylphenanthridines in good yields, respectively. These reactions proceeded through the O-triflation of the ketoximes, the Beckmann rearrangement, and the electrophilic cyclization of the formed nitrilium group onto the aromatic ring.

Full text of DOI:10.1016/j.tet.2021.132244

Tetrahedron 91 (2021) 132244
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Preparation of 6-substituted phenanthridines from o-biaryl ketoximes
via the Beckmann rearrangement
,
, *
Kohei Nakamura a, Eiji Kobayashi a, Katsuhiko Moriyama a b, Hideo Togo a
a Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba, 263-8522, Japan
b Molecular Chirality Research Center, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba, 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Treatment of anti alkyl o-biaryl ketoximes and anti aryl o-biaryl ketoximes with Tf2O at 120 ꢀC, followed
by quenching with Et3N gave 6-alkylphenanthridines and 6-arylphenanthridines in good yields,
respectively. These reactions proceeded through the O-triflation of the ketoximes, the Beckmann rear-
rangement, and the electrophilic cyclization of the formed nitrilium group onto the aromatic ring. © 2021
Elsevier Science. All rights reserved.
Article history:
Received 7 March 2021
Received in revised form
26 April 2021
Accepted 17 May 2021
Available online 28 May 2021
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
Phenanthridine
Ketoxime
Beckmann rearrangement
Cyclization
1. Introduction
presence of Pd(OTf)2, Xphos, and Cs2CO3 [3e]; the preparation of 6-
unsubstituted phenanthridines through a successive treatment of
The phenanthridine core is one of the major nitrogen-
containing tricyclic heteroaromatics because it is an essential unit
of a variety of natural alkaloids and biologically active compounds
[1]. Examples of biologically active phenanthridines include Tri-
spheridine (an anticancer property) and Ethidium (a trypanocidal
drug), as shown in Fig. 1.
Synthetic studies of phenanthridine core have been carried out
extensively [2]. In particular, the Pd-catalyzed preparation of 6-
substituted phenanthridines is widely known [3], and typical ex-
amples of reactions that employ Pd catalysts and proceed via the
intermolecular pathway and the intramolecular pathway are
shown in eqs. 1 and 2, respectively, in Scheme 1 [3a,3b]. Recent
synthetic studies of the preparation of phenanthridines with Pd
catalysts are as follows: the preparation of 6-alkylphenanthridines
with aromatic ketoximes and aryl iodides in the presence of
Pd(OAc)2 and Ag2O [3c]; the preparation of 6-(trifluoromethyl)
phenanthridines with 2-bromophenylboronic acid and fluorinated
imidoyl chlorides in the presence of PdCl2(PPh3)2 and Cs2CO3 [3d];
the preparation of 6-unsubstituted phenanthridines with N-(o-
halophenyl)methanesulfonamides and benzyl bromides in the
arylboronic acids and N-(2-bromophenyl)acetamides in the pres-
ence of Pd(OAc)2, followed by K2S2O8 and Cu(OTf)2 [3f]; and others
[3ge3j].
The construction of 6-substituted phenanthridines by the re-
actions of o-isocyanobiaryls and radical precursors through the
formation of imino-carbon-centered radical (imidoyl radical) has
also become very popular, as shown in eq. 3 [4ae4c]. Recent syn-
thetic studies of the preparation of 6-substituted phenanthridines
from o-isocyanobiaryls are as follows: the preparation of 6-(a-hy-
droxy)alkylphenanthridines with polyfluorinated alcohols and
dicumyl peroxide (DCP) [4d]; the preparation of 6-(tri-
chloromethyl)phenanthridines with benzoyl peroxide (BPO) in CCl4
[4e]; the preparation of 6-phosphorylphenanthridines with
diphenyl phosphine oxide and diphenyliodonium triflate [4f]; the
preparation of phenanthridines bearing ether groups at 6-position
with ethers and tert-butyl hydrogen peroxide (TBHP) in the pres-
ence of Fe(acac)2 [4g]; the preparation of 6-(2-cyanopropan-2-yl)
phenanthridines with azobis(isobutyronitrile) (AIBN) [4h]; the
preparation of 6-alkylphenanthridines with alkanoic acids and
K2S2O8 in the presence of Ag2CO3 [4i]; the preparation of 6-(tri-
fluoromethyl)phenanthridines with CF3SO2Na under fluorescent
lighting
conditions
[4j];
the
preparation
of
6-
benzylphenanthridines with di-tert-butyl peroxide (DTBP) in the
presence of Fe(acac)3 in toluene [4k]; the preparation of 6-
* Corresponding author.
E-mail address: togo@faculty.chiba-u.jp (H. Togo).
https://doi.org/10.1016/j.tet.2021.132244
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
under photolytic conditions was also reported, as shown in eq. 4
[5]. Recent synthetic studies for the preparation of 6-substituted
phenanthridines are as follows: the preparation of 6-alkyl and 6-
arylphenanthridines with Grignard reagents and o-cyanobiaryls,
and then Cu(OAc)2 [5b]; the preparation of 6-substituted and 6-
unsubstituted phenanthridines with O-aroyl o-biaryloximes in
the presence of fac-Ir(ppy)3 under visible light irradiation [5c]; the
preparation of 6-unsubstituted phenanthridines with o-phenyl-
benzaldehydes and ArCO2NH2 in the presence of fac-Ir(ppy)3 under
visible light irradiation [5d]; the preparation of 6-unsubstituted
phenanthridines with 2-cyano-20-bromobiphenyls and LiBHEt3
[5e]; the preparation of 6-unsubstituted phenanthridines with o-
arylbenzaldehydes and O-acyl hydroxylamine in the presence of
fac-Ir(ppy)3 under visible light irradiation [5f]; the preparation of 6-
unsubstituted phenanthridines with o-arylbenzaldehydes and NH3
in methanol under electrochemical conditions [5g]; and the prep-
aration of 6-methylphenanthridines with o-arylbenzaldoximes and
2,2,6,6-tetramethylpiperidine 1-oxyl under electrochemical con-
ditions [5h].
Fig. 1. Biologically active phenanthridines.
Recently, we have also reported the preparation of 6-aryl- and 6-
alkylphenanthridines from o-cyanobiaryl and o-biaryl ketones
through the formation of ketimines and iminyl radicals with iodine
(eq. 4, X ¼ H) [6a,6b], and the preparation of 6-arylphenanthridines
and 6-unsubstituted phenanthridines from N-(o-arylbenzyl) tri-
t
fluoromethanesulfonamides with DIH, and then BuOK [6c]. Other
related reactions for the preparation of 6-unsubstituted phenan-
thridines with N-(o-arylbenzyl) p-toluenesulfonamides and DIB in
the presence of iodine under blue LED irradiation conditions [7a]
and for the preparation of 6-alkyl- and 6-arylphenanthridines with
2-amino-2’-(arylmethyl)biaryls, iodine, and Cs2CO3 [7b] were also
reported.
On the other hand, the Beckmann rearrangement of oximes
derived from ketones is a very attractive reaction to obtain sec-
ondary amides [8]. However, to the best of our knowledge, syn-
thetic studies for the preparation of 6-substituted phenanthridines
with o-biaryl ketoximes and trifluoromethanesulfonic anhydride
(Tf2O) through the Beckmann rearrangement have been never re-
ported. We would like to report herein a simple method for the
preparation of 6-alkyl- and 6-arylphenanthridines with anti o-
biaryl ketoximes and Tf2O.
2. Results and discussion
First, Tf2O (2.0 equiv.) was added to a mixture of anti methyl o-
(p-methylphenyl)phenyl ketoxime 1Ba (0.5 mmol) in 1,2-
dichloroethane (DCE, 2.0 mL) at 0 ꢀC in a 30 mL sealed tube.
Then, treatment of the mixture at 80 ꢀC for 17 h, followed by
quenching with Et3N (0.5 mL) at room temperature gave 6,8-
dimethylphenanthridine 2Ba in 72% yield, as shown in Table 1
(entry 1). The structure of 6,8-dimethylphenanthridine 2Ba was
supported by X-ray crystallographic analysis (see Supporting In-
formation). When ketoxime 1Ba in DCE was treated with Tf2O at
100 ꢀC for 17 h, phenanthridine 2Ba was obtained in 79% yield
(entry 2). However, when ketoxime 1Ba in DCE was treated with
Tf2O at 100 ꢀC for 64 h and 8 h, the yield of phenanthridine 2Ba was
slightly decreased, respectively (entries 3, 4). When the amount of
DCE was changed to 1.0 mL and 4.0 mL and the reaction was per-
formed under the same conditions as those of entry 2, phenan-
thridine 2Ba was obtained in 80% and 69% yields, respectively
(entries 5, 6). Moreover, treatment of ketoxime 1Ba with Tf2O (2.0
equiv.) in chlorobenzene (1.0 mL) at 120 ꢀC for 17 h gave phenan-
thridine 2Ba in 87% yield (entry 7). The yield of phenanthridine 2Ba
was slightly decreased when the reaction was carried out at 140 ꢀC
for 17 h (entry 8). When TfCl (CF3SO2Cl, 2.0 equiv.), AlCl3 (2.0
equiv.), and Al(OTf)3 (2.0 equiv.) instead of Tf2O were used under
Scheme 1. Typical Construction Methods of Phenanthridine Core.
methylphenanthridines with (diacetoxyiodo)benzene (DIB), 2-
nitropropane, and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) [4l];
the preparation of 6-(cyanomethyl)phenanthridines with S-cya-
nomethyl dithiocarbonate in the presence of fac-Ir(ppy)3 under LED
irradiation [4m]; and others [4ne4t].
Moreover, the construction of 6-substituted phenanthridines by
the reaction of imino-nitrogen-centered radical (iminyl radical)
2

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
Table 1
Anti o-(p-methoxyphenyl)phenyl ketoxime 1C and anti o-(p-chlor-
ophenyl)phenyl ketoxime 1D bearing methyl (a), ethyl (b), n-butyl
(d), and p-methylphenyl (g) groups also reacted with Tf2O to give 6-
substituted 8-methoxyphenanthridines 2Ca, 2Cb, 2Cd, and 2Cg,
and 6-substituted 8-chlorophenanthridines 2Da (X-ray crystallo-
graphic analysis, see Supporting Information), 2Db, 2Dd, and 2Dg
in good to moderate yields, respectively. The same treatment of anti
o-(p-fluorophenyl)phenyl methyl ketoxime 1Ea, methyl o-(p-
nitrophenyl)phenyl ketoxime 1Fa, methyl o-(o-methylphenyl)
phenyl ketoxime 1Ga, and methyl o-(m-nitrophenyl)phenyl
ketoxime 1Ha with Tf2O also generated 8-fluoro-6-
methylphenanthridine 2Ea, 6-methyl-8-nitrophenanthridine 2Fa,
Optimization of reaction Conditions.
Entry
Solvent (mL)
Conditions
Yield (%)
1
2
3
4
5
6
7
8
DCE (2.0)
DCE (2.0)
DCE (2.0)
DCE (2.0)
DCE (1.0)
DCE (4.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
Chlorobenzene (1.0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
ꢀC, then 80 ꢀC, 17 h
ꢀC, then 100 ꢀC, 17 h
ꢀC, then 100 ꢀC, 64 h
ꢀC, then 100 ꢀC, 8 h
ꢀC, then 100 ꢀC, 17 h
ꢀC, then 100 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 140 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
ꢀC, then 120 ꢀC, 17 h
72
79
72
70
80
69
87
77
6,10-dimethylphenanthridines
2Ga,
and
6-methyl-9-
nitrophenanthridine 2Ha in good to excellent yields, respectively.
On the other hand, when syn p-chlorophenyl o-(p-methyl-
phenyl)phenyl ketoxime 1Bj’ (0.5 mmol) was treated with Tf2O
under the same conditions, 2-methyl-9-fluorenone 3B was gener-
ated through the Beckmann rearrangement of the p-chlorophenyl
group in 99% yield after hydrolysis with aq. HCl, as shown in
Scheme 3. Thus, the present method for the preparation of 6-
substituted phenanthridines 2 from o-biaryl ketoximes is limited
to the use of anti alkyl and aryl o-biaryl ketoximes 1.
a
9
0 (53)b
81 (17)b
17 (79)b
0
85
61
87
10c
11d
12e
13f
Once 6-substituted phenanthridines were obtained, they could
be smoothly transformed into 6-substituted phenanthridine de-
14g
15h
rivatives.
Treatment
of
6-(40-bromophenyl)-8-
a
TfCl (2.0 equiv.) was used instead of Tf2O (2.0 equiv.).
Yield of N-[o-(p-methylphenyl)phenyl]acetamide.
AlCl3 (2.0 equiv.) was used instead of Tf2O (2.0 equiv.).
Al(OTf)3 (2.0 equiv.) was used instead of Tf2O (2.0 equiv.).
TsCl (1.2 equiv.) and Et3N (2.0 equiv.) were used instead of Tf2O (2.0 equiv.).
Ts2O (2.0 equiv.) was used instead of Tf2O (2.0 equiv.).
methylphenanthridine 2Bk with NBS in CCl4 gave 8-
bromomethyl-6-(40-bromophenyl)phenanthridine 4Bk in 81%
yield, as shown in Scheme 4. The Pd-catalyzed coupling reactions of
6-(40-bromophenyl)-8-methylphenanthridine 2Bk with phenyl-
boronic acid and K2CO3 in DMF and with phenylacetylene and CuI
b
c
d
e
f
g
h
Tf2O (2.0 equiv.) and Et3N (3.0 equiv.) were used instead of Tf2O (2.0 equiv.).
Sat. aq. NaHCO3 (20.0 mL) was used instead of Et3N (0.5 mL).
in
a
mixture of DMF and Et3N gave 6-(p-biphenyl)-8-
methylphenanthridine 5Bk and 8-methyl-6-[4’-(phenylethynyl)
phenyl]phenanthridine 6Bk in 78% and 67% yields, respectively.
Treatment of 6-(40-bromophenyl)-8-methylphenanthridine 2Bk
with methyl triflate in DCE at 50 ꢀC generated 6-(40-bromophenyl)-
5,8-dimethylphenanthridinium triflate 7Bk in 85% yield.
A possible reaction pathway for the formation of 6-alkyl- and 6-
arylphenanthridines 2 from the reaction of anti o-biaryl ketoximes
1 and Tf2O is shown in Scheme 5. Anti alkyl or aryl o-biaryl
ketoxime 1 reacts with Tf2O to form O-triflate intermediate I. A 1,2-
rearrangement of the biaryl group smoothly occurs to form nitri-
lium salt intermediate II together with the generation of triflate
anion. Nitrilium salt intermediate II smoothly generates tri-
fluoromethanesulfonic imidic anhydride III. Once tri-
fluoromethanesulfonic imidic anhydride III is formed, it rapidly
generates phenanthridinium salt IV through electrophilic cycliza-
tion onto the aromatic ring. Quench with Et3N or aq. NaHCO3
provides 6-alkyl- or 6-arylphenanthridine 2.
the same conditions, phenanthridine 2Ba was obtained in 0%, 81%,
and 17% yields, together with N-[o-(p-methylphenyl)phenyl]acet-
amide in 53%, 17%, and 79% yields, respectively (entries 9e11). Thus,
Tf2O showed the best reactivity among Tf2O, TfCl, AlCl3, and
Al(OTf)3.
When ketoxime 1Ba was treated with TsCl (1.2 equiv.)/Et3N (2.0
equiv.), Ts2O (2.0 equiv.), and Tf2O (2.0 equiv.)/Et3N (3.0 equiv.)
instead of Tf2O (2.0 equiv.) at 120 ꢀC for 17 h, phenanthridine 2Ba
was obtained in 0%, 85%, and 61% yields, respectively (entries
12e14). Thus, Ts2O showed the same reactivity as Tf2O (entry 13).
When the reaction mixture was quenched with sat. aq. NaHCO3
(20.0 mL) instead of Et3N (0.5 mL), the yield of phenanthridine 2Ba
was the same as that in entry 7 (entry 15).
Based on those results, treatment of anti alkyl o-biphenyl
ketoxime 1A and anti alkyl o-(p-methylphenyl)phenyl ketoxime 1B
(0.5 mmol) bearing methyl (a), ethyl (b), isopropyl (c), n-butyl (d),
tert-butyl (e), and cyclohexyl (f) groups with Tf2O (2.0 equiv.) in
chlorobenzene (1.0 mL) at 120 ꢀC for 17 h gave the corresponding 6-
3. Conclusion
Anti alkyl o-biaryl ketoximes and anti aryl o-biaryl ketoximes
react with Tf2O under warming conditions to give 6-
alkylphenanthridines and 6-arylphenanthridines, respectively, in
good yields through the Beckmann rearrangement. We believe that
the present simple reaction would be another useful method for the
preparation of 6-alkylphenanthridines and 6-arylphenanthridines.
alkylphenanthridines
2Aa~2Af
and
6-alkyl-8-
methylphenanthridines 2Ba, 2Bb, and 2Bd in good to excellent
yields, as shown in Scheme 2. As a gram-scale experiment, treat-
ment of anti methyl o-(p-methylphenyl)phenyl ketoxime 1Ba
(5.0 mmol) with Tf2O under the same conditions gave 6,8-
dimethylphenanthridine 2Ba in 83% yield. The same treatment of
anti aryl o-(p-methylphenyl)phenyl ketoxime 1B bearing p-meth-
ylphenyl (g), p-methoxyphenyl (h), p-fluorophenyl (i), p-chlor-
ophenyl (j), p-bromophenyl (k), naphthalen-2-yl (l), benzofuran-2-
yl (m), and benzothiophen-2-yl (n) groups with Tf2O under the
same conditions except the amount of chlorobenzene (2.0 mL) in
1Bl and 1Bm provided the corresponding 6-aryl-8-
methylphenanthridines 2Bg ~ 2Bn in good to excellent yields.
4. Experimental section
4.1. General
1H NMR spectra were measured on 400 MHz spectrometers.
Chemical shifts were recorded as follows: chemical shift in ppm
from internal tetramethylsilane on the
d scale, multiplicity
3

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
Scheme 2. Transformation of Oximes 1 into Phenanthridine 2.
(s ¼ singlet; d ¼ doublet; t ¼ triplet; q ¼ quartet; sext ¼ sextet;
m ¼ multiplet; br ¼ broad), coupling constant (Hz), integration, and
assignment. 13C NMR spectra were measured on 100 MHz spec-
trometers. Chemical shifts were recorded in ppm from the solvent
resonance employed as the internal standard (CDCl3 at 77.0 ppm, or
DMSO‑d6 at 39.5 ppm). Characteristic peaks in the infrared (IR)
spectra were recorded in wave number, cmꢁ1 on a JASCO FT/IR-
4100 spectrometer. Melting points were determined using a
Yamato Melting Point Apparatus Model MP-21. High-resolution
mass spectra (HRMS) were recorded by Thermo Fisher Scientific
Exactive Orbitrap mass spectrometers. Melting points were un-
corrected. Thin-layer chromatography (TLC) was performed using
4

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
Scheme 3. Reaction of syn p-Chlorophenyl o-(p-Methylphenyl)phenyl Ketoxime 1Bj’.
Scheme 5. Possible Reaction Pathway for 6-Alkyl- and 6-Arylphenanthridines 2 from
o-Biaryl Ketoxime.
Water (50.0 mL) was added to the reaction mixture, and the
product was extracted with a mixture of hexane and AcOEt (4 : 1,
50.0 mL ꢂ 3). The organic layer was washed with brine and dried
over Na2SO4. After filtration and removal of the solvent under
reduced pressure, the residue was purified by column chromatog-
raphy (hexane: EtOAc ¼ 8:1) on silica gel to give o-biphenyl methyl
ketone A (922.2 mg, 94%). B ~ G were obtained in 98%~99% yields by
the same method.
4.2.2. Typical procedure for preparation of anti ketoximes 1Aa~1Ha
A solution of o-biphenyl methyl ketone A (981.2 mg, 5.0 mmol),
NH2OH･HCl (694.9 mg, 10.0 mmol), and K2CO3 (1382.0 mg,
5.0 mmol) in EtOH (10.0 mL) in a screw-capped tube (50.0 mL) was
heated at 80 ꢀC for 18 h. Then, the reaction mixture was quenched
with water (50.0 mL), and the product was extracted with CHCl3
(50.0 mL ꢂ 3). The organic layer was dried over Na2SO4. After
filtration and removal of the solvent under reduced pressure, the
residue was purified by short column chromatography on silica gel
(hexane/AcOEt ¼ 4:1). The 1st recrystallization of the oxime iso-
mers (from hexane/AcOEt ¼ 10:1) gave (E) o-biphenyl methyl
ketoxime 1Aa (491.2 mg, 47%) as a pure state. 1Ba~1Ga were ob-
tained in 39%~48% yields by the same method. The yield of the
oximes could be a little improved by the 2nd recrystalization of the
filtrates.
4.2.3. Typical procedure for preparation of anti ketoximes 1Ab~1Db
EtMgBr (0.97 mol/L solution in THF, 9.27 mL, 9.0 mmol) was
added dropwise to a solution of 2-cyanobiphenyl (537.7 mg,
3.0 mmol) in THF (6.0 mL) at room temperature under argon at-
mosphere. The mixture was warmed at 70 ꢀC for 6 h. Then, the
reaction mixture was quenched with aq. HCl (4.0 M, 30.0 mL) and
was extracted with CHCl3 (30.0 mL ꢂ 3). The organic layer was
dried over Na2SO4. After filtration and removal of the solvent under
reduced pressure, a solution of the residue, NH2OH･HCl (416.9 mg,
6.0 mmol), and K2CO3 (414.6 mg, 3.0 mmol) in EtOH (6.0 mL) in a
screw-capped tube (50.0 mL) was heated at 80 ꢀC for 18 h. Then, the
reaction mixture was quenched with water (30.0 mL) and extracted
with CHCl3 (30.0 mL ꢂ 3). The organic layer was dried over Na2SO4.
After filtration and removal of the solvent under reduced pressure,
the residue was purified by short column chromatography on silica
gel (hexane/AcOEt ¼ 4:1). The 1st recrystallization of the oxime
isomers (from hexane/AcOEt ¼ 10:1) gave (E) o-biphenyl ethyl
ketoxime 1Ab (0.1824 g, 27%) as a pure state. 1Bb~1Db were ob-
tained in 32%~35% yields by the same method. The yield of the
oximes could be a little improved by the 2nd recrystalization of the
filtrates.
Scheme 4. Derivatization of 2Bk.
0.25 mm silica gel plates (60F254). The products were purified by
column chromatography on neutral silica gel 60 N (63e200 mesh).
4.2. Preparation of starting materials 1
4.2.1. Typical procedure for preparation of ketones A, B, C, D, E, F, G,
and H
To a solution of o-bromoacetophenone (995.3 mg, 5.0 mmol)
and phenylboronic acid (731.6 mg, 6.0 mmol) in DMF (50.0 mL) was
added PdCl2(PPh3)2 (175.5 mg, 0.25 mmol) under argon atmo-
sphere. The mixture was stirred for 0.5 h at room temperature.
Then, K2CO3 (1382.0 mg, 10.0 mmol) in H2O (10.0 mL) was added to
the mixture, and the obtained mixture was stirred at 70 ꢀC for 18 h.
5

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
4.2.4. Typical procedure for preparation of anti ketoximes 1Ac, 1Ae,
1Af, 1Bg~1Bn, 1Cg, and 1Dg
3.05 (sept, 1H, J ¼ 7.0 Hz), 7.24e7.26 (m, 1H), 7.30e7.46 (m, 8H); 13
C
NMR (100 MHz, CDCl3):
d
¼ 18.7 (2C), 29.8, 126.9, 127.2, 128.1 (2C),
n-BuLi (1.55 M solution in hexane, 3.45 mL, 5.5 mmol) was
added dropwise to a solution of p-bromotoluene (855.2 mg,
5.0 mmol) in THF (10.0 mL) at ꢁ50 ꢀC under argon atmosphere.
After 0.5 h, 2-cyano-40-methylbiphenyl (1160.0 mg, 6.0 mmol) was
added to the mixture. The obtained mixture was gradually warmed
to room temperature and stirred for 0.5 h. Then, MeOH (1.0 mL) was
added to the mixture and the obtained mixture was stirred for
0.5 h. After filtration and removal of the solvent under reduced
pressure, K2CO3 (691.1 mg, 5.0 mmol) was added to a solution of the
residue and NH2OH･HCl (694.9 mg, 10.0 mmol) in EtOH (10.0 mL)
under argon atmosphere. The mixture was heated at 80 ꢀC for 18 h.
Then, the reaction mixture was quenched with water (50.0 mL) and
extracted with CHCl3 (50.0 mL ꢂ 3). The organic layer was dried
over Na2SO4. After filtration and removal of the solvent under
reduced pressure, the residue was purified by short column chro-
matography on silica gel (hexane/AcOEt ¼ 8:1) to give (E) p-
methylphenyl o-(p-methylphenyl)phenyl ketoxime 1Bg (300.3 mg,
20% over 3 steps). 1Ac, 1Ae, 1Af, 1Bh~1Bn, 1Cg, and 1Dg were ob-
tained in 20e25% yields by the same method with both iso-
butyronitrile, pivalonitrile, or cyclohexanecarbonitrile and aryl
bromides, benzofuran, or benzothiophene.
128.5, 129.9 (2C), 130.0, 130.1, 135.0, 141.1, 141.4, 165.9; HRMS (ESI):
Calcd for C16H18ON [MþH]þ ¼ 240.1383, Found ¼ 240.1382.
4.2.9. (E) o-biphenyl n-butyl ketoxime (1Ad)
White solid; mp: 96e99 ꢀC; IR (neat): 3212, 1451, 1330, 916, 739,
697 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.71 (t, 3H, J ¼ 7.2 Hz),
1.04e1.21 (m, 4H), 2.09 (t, 2H, J ¼ 7.7 Hz), 7.32e7.48 (m, 9H), 8.01 (s,
1H); 13C NMR (100 MHz, CDCl3):
d
¼ 13.6, 22.6, 27.7, 28.4,127.3 (2C),
128.4 (2C), 128.9 (3C), 129.8, 130.1, 135.8, 140.4, 140.9, 163.2; HRMS
(ESI): Calcd for C17H20ON [MþH]þ ¼ 254.1539, Found ¼ 254.1539.
4.2.10. (E) o-biphenyl tert-butyl ketoxime (1Ae)
White solid; mp: 109e116 ꢀC; IR (neat): 3217, 1479, 1007, 912,
740 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 0.88 (s, 9H), 7.17e7.19 (m,
1H), 7.31e7.35 (m, 3H), 7.37e7.42 (m, 3H), 7.47e7.49 (m,2H), 7.59 (s,
1H); 13C NMR (100 MHz, CDCl3):
¼ 27.5 (3C), 37.3, 126.9, 127.1,
d
128.0 (2C), 128.2, 129.2, 129.8, 130.4 (2C), 137.0, 140.6, 141.5, 166.5;
HRMS (ESI): Calcd for
Found ¼ 254.1539.
C
17H20ON [MþH]þ
¼
254.1539,
4.2.11. (E) o-biphenyl cyclohexyl ketoxime (1Af)
White solid; mp: 140e145 ꢀC; IR (neat): 3280, 1479, 1448, 1047,
4.2.5. Typical Procedure for preparation of anti ketoximes 1Ad, 1Bd,
1Cd, and 1Dd
743 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.84e1.60 (m, 10H),
2.79e2.85 (m, 1H), 7.24 (d, 1H, J ¼ 6.5 Hz), 7.32e7.45 (m, 8H); 13C
n-BuLi (1.55 mol/L solution in hexane, 2.13 mL, 3.3 mmol) was
added dropwise to a solution of 2-cyanobiphenyl (537.7 mg,
3.0 mmol) in THF (6.0 mL) at 0 ꢀC under argon atmosphere. After
1 h, the mixture was stirred for 1 h at room temperature. MeOH
(1.0 mL) was added to the mixture and the obtained mixture was
stirred for 0.5 h at room temperature. After filtration and removal of
the solvent under reduced pressure, K2CO3 (414.6 mg, 3.0 mmol)
was added to a mixture of the residue and NH2OH･HCl (416.9 mg,
6.0 mmol) in EtOH (6.0 mL) under argon atmosphere. The mixture
was heated at 80 ꢀC for 18 h. The reaction mixture was quenched
with water (30.0 mL) and extracted with CHCl3 (30.0 mL ꢂ 3). The
organic layer was dried over Na2SO4. After filtration and removal of
the solvent under reduced pressure, the residue was purified by
short column chromatography on silica gel (hexane/AcOEt ¼ 4:1).
The 1st recrystallization of the ketoxime isomers (from hexane/
AcOEt ¼ 10:1) gave (E) o-biphenyl n-butyl ketoxime 1Ad (266.4 mg,
35%) as a pure state. 1Bd, 1Cd, and 1Dd were obtained in 30%~38%
yields by the same method. The yield of the oximes could be a little
improved by the 2nd recrystalization of the filtrates.
NMR (100 MHz, CDCl3):
127.1, 128.1 (2C), 128.4, 130.0 (3C), 130.1, 135.0, 141.0, 141.4, 165.3;
HRMS (ESI): Calcd for
Found ¼ 280.1692.
d
¼ 25.8, 26.2 (2C), 28.5 (2C), 39.8, 126.8,
C
19H22ON [MþH]þ
¼
280.1696,
4.2.12. (E) methyl o-(p-methylphenyl)phenyl ketoxime (1Ba)
White solid; mp: 125e128 ꢀC; IR (neat): 3237, 1445, 1017, 927,
760 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.69 (s, 3H), 2.39 (s, 3H),
7.21 (d, 2H, J ¼ 7.9 Hz), 7.28e7.30 (m, 2H), 7.33e7.45 (m, 4H), 7.61 (s,
1H); 13C NMR (100 MHz, CDCl3):
d
¼ 15.9, 21.2, 127.1, 128.8 (2C),
129.0, 129.1, 129.2 (2C), 130.3, 136.7, 137.1, 138.0, 140.5, 159.5; HRMS
(ESI): Calcd for C15H16ON [MþH]þ ¼ 226.1226, Found ¼ 226.1224.
4.2.13. (E) ethyl o-(p-methylphenyl)phenyl ketoxime (1Bb)
White solid; mp: 142e146 ꢀC; IR (neat): 3214, 1463, 1323, 911,
822, 748 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.77 (t, 3H,
J ¼ 7.6 Hz), 2.15 (q, 2H, J ¼ 7.6 Hz), 2.39 (s, 3H), 7.20 (d, 2H,
J ¼ 7.9 Hz), 7.31 (d, 2H, J ¼ 8.1 Hz), 7.34e7.35 (m, 2H), 7.36e7.38 (m,
1H), 7.40e7.46 (m, 1H),; 13C NMR (100 MHz, CDCl3):
d
¼ 10.0, 21.2,
22.1, 127.0, 128.8 (2C), 128.9, 129.1 (2C), 129.9, 130.1, 135.3, 137.0,
4.2.6. (E) o-biphenyl methyl ketoxime (1Aa)
138.0, 140.4, 164.5; HRMS (ESI): Calcd for
C16H18ON
White solid; mp: 98e105 ꢀC; IR (neat): 3202, 1478, 1433, 1363,
[MþH]þ ¼ 240.1383, Found ¼ 240.1383.
921, 742 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 1.68 (s, 3H),
7.33e7.47 (m, 9H), 8.72 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
¼ 16.0,
4.2.14. (E) n-butyl o-(p-methylphenyl)phenyl ketoxime (1Bd)
White solid; mp: 125e128 ꢀC; IR (neat): 3303, 1443, 1379, 1090,
127.3, 127.4, 128.4 (2C), 128.9 (2C), 129.0, 129.1, 130.3, 136.7, 140.5,
140.9, 159.1; HRMS (ESI): Calcd for C14H14ON [MþH]þ ¼ 212.1070,
Found ¼ 212.1074.
1047, 733 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.71 (t, 3H,
J ¼ 7.1 Hz), 1.05e1.21 (m, 4H), 2.11 (t, 2H, J ¼ 0.73 Hz), 2.39 (s, 3H),
7.20 (d, 2H, J ¼ 7.9 Hz), 7.29e7.31 (m, 2H), 7.33e7.37 (m, 3H),
4.2.7. (E) o-biphenyl ethyl ketoxime (1Ab)
7.41e7.45 (m, 1H), 7.87 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
¼ 13.7,
White solid; mp: 93e94 ꢀC; IR (neat): 3224, 1477, 1449, 1327,
21.2, 22.7, 27.7, 28.4, 127.0, 128.8 (3C), 129.1 (2C), 129.8, 130.1, 135.7,
911, 738 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.77 (t, 3H,
J ¼ 7.6 Hz), 2.14 (q, 2H, J ¼ 7.6 Hz), 7.32e7.47 (m, 9H), 8.02 (s, 1H);
13C NMR (100 MHz, CDCl3):
137.0, 138.0, 140.4, 163.4; HRMS (ESI): Calcd for C18H22ON
[MþH]þ ¼ 268.1696, Found ¼ 268.1695.
d
¼ 10.0, 22.2, 127.3 (2C), 128.4 (2C),
128.9, 129.0 (2C), 129.9, 130.1, 135.4, 140.5, 140.9, 164.0; HRMS (ESI):
4.2.15. (E) p-methylphenyl o-(p-methylphenyl)phenyl ketoxime
(1Bg)
Calcd for C15H16ON [MþH]þ ¼ 226.1226, Found ¼ 226.1228.
White solid; mp: 143e147 ꢀC; IR (neat): 3216, 1443, 1402, 916,
4.2.8. (E) o-biphenyl isopropyl ketoxime (1Ac)
764 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.25 (s, 3H), 2.29 (s, 3H),
White solid; mp: 104e108 ꢀC; IR (neat): 3245, 1467, 1002, 916,
6.94 (d, 2H, J ¼ 8.1 Hz), 7.00 (d, 2H, J ¼ 7.9 Hz), 7.08e7.11 (m, 4H),
742 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.72 (d, 6H, J ¼ 7.0 Hz),
7.33 (td, 1H, J ¼ 7.9, 1.6 Hz), 7.38 (dd, 1H, J ¼ 7.4, 1.6 Hz), 7.42e7.48
6

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
(m, 2H); 13C NMR (100 MHz, CDCl3):
128.5 (2C), 128.9 (3C), 129.6 (2C), 130.2, 130.3, 130.4, 136.2, 136.3,
d
¼ 21.1, 21.3, 126.9, 127.9 (2C),
4.2.21. (Z) benzofuran-
a
-yl o-(p-methylphenyl)phenyl ketoxime
(1Bm)
138.0, 138.7, 142.1, 158.0; HRMS (ESI): Calcd for
C21H20ON
Pale yellow solid; mp: 196e207 ꢀC; IR (neat): 3251, 1449, 1255,
[MþH]þ ¼ 302.1539, Found ¼ 302.1540.
1047, 739 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.17 (s, 3H), 6.94 (d,
2H, J ¼ 7.9 Hz), 7.16e7.20 (m, 3H), 7.27e7.31 (m, 2H), 7.43e7.47 (m,
2H), 7.53e7.58 (m, 4H), 8.73 (s, 1H); 13C NMR (100 MHz, CDCl3):
4.2.16. (E) p-methoxyphenyl o-(p-methylphenyl)phenyl ketoxime
(1Bh)
d
¼ 21.1, 110.1, 111.6, 121.4, 123.0, 125.8, 127.0, 127.8, 128.0 (2C), 129.0
(2C), 129.2, 129.7 (2C), 130.1, 137.1, 137.4, 141.5, 150.8, 151.5, 155.2;
White solid; mp: 140e145 ꢀC; IR (neat): 3052, 1509, 1256, 1159,
HRMS (ESI): Calcd for
Found ¼ 328.1332.
C
22H18O2N [MþH]þ
¼
328.1332,
828, 761 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.28 (s, 3H), 3.74 (s,
3H), 6.64e6.66 (m, 2H), 7.00 (d, 2H, J ¼ 7.9 Hz), 7.09 (d, 2H,
J ¼ 8.1 Hz), 7.19e7.21 (m, 2H), 7.33 (dd, 1H, J ¼ 7.4, 1.1 Hz), 7.38 (td,
1H, J ¼ 7.4, 1.6 Hz), 7.43e7.50 (m, 2H),; 13C NMR (100 MHz, CDCl3):
4.2.22. (Z) benzothiophen-a-yl o-(p-methylphenyl)phenyl ketoxime
(1Bn)
d
¼ 21.1, 55.2, 112.6 (2C), 125.6, 126.9, 128.5 (2C), 128.9 (2C), 129.0,
White solid; mp: 189e199 ꢀC; IR (neat): 3157, 2916, 1456, 1314,
130.3, 130.4, 131.5 (2C), 136.2, 136.3, 137.9, 142.1, 157.4, 159.5; HRMS
1132, 964, 743 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 2.24 (s, 3H),
(ESI): Calcd for C21H20O2N [MþH]þ ¼ 318.1489, Found ¼ 318.1486.
7.02 (d, 2H, J ¼ 7.9 Hz), 7.23 (d, 2H, J ¼ 8.1 Hz), 7.27 (s, 1H), 7.30e7.38
(m, 2H), 7.43e7.58 (m, 4H), 7.69 (d, 1H, J ¼ 7.2 Hz), 7.81 (d, 1H,
J ¼ 7.9 Hz); 13C NMR (100 MHz, CDCl3):
¼ 21.1, 122.0, 124.3, 124.5,
d
4.2.17. (E) p-fluorophenyl o-(p-methylphenyl)phenyl ketoxime
(1Bi)
125.7, 127.0, 128.6 (3C), 128.9 (2C), 129.5, 129.7, 130.5, 130.8, 133.2,
134.1, 136.6, 137.2, 137.5, 142.4, 152.0; HRMS (ESI): Calcd for
White solid; mp: 130e135 ꢀC; IR (neat): 3278, 1506, 1233, 919,
C
22H18ONS [MþH]þ ¼ 344.1104, Found ¼ 344.1103.
761 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 2.28 (s, 3H), 6.75e6.80
(m, 2H), 6.97e7.04 (m, 4H), 7.11e7.16 (m, 2H), 7.31 (dd, 1H, J ¼ 7.6,
4.2.23. (E) o-(p-methoxyphenyl)phenyl methyl ketoxime (1Ca)
White solid; mp: 132e135 ꢀC; IR (neat): 3220, 1608, 1439, 1243,
1.4 Hz), 7.40 (td, 1H, J ¼ 7.5, 1.6 Hz), 7.47 (td, 1H, J ¼ 7.5, 1.6 Hz), 7.54
(dd, 1H, J ¼ 7.2, 1.6 Hz),; 13C NMR (100 MHz, CDCl3):
d
¼ 21.0, 114.1
922, 761 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.70 (s, 3H), 3.85 (s,
3H), 6.93e6.96 (m, 2H), 7.31e7.38 (m, 4H), 7.40e7.45 (m, 2H), 7.76
(s, 1H); 13C NMR (100 MHz, CDCl3):
(d, 2C, JC-F ¼ 21.6 Hz), 127.1, 128.5 (2C), 128.9 (2C), 129.0 (d, JC-
¼ 3.8 Hz), 129.3, 130.3 (2C), 131.8 (d, 2C, JC-F ¼ 8.5 Hz), 136.0, 136.5,
F
d
¼ 15.9, 55.3, 113.9 (2C), 127.0,
137.7, 142.2, 157.1, 162.3 (d, JC-F ¼ 249.0 Hz); HRMS (ESI): Calcd for
20H17ONF [MþH]þ ¼ 306.1289, Found ¼ 306.1290.
129.0, 129.1, 130.0 (2C), 130.2, 133.3, 136.6, 140.1, 159.0, 159.5; HRMS
C
(ESI): Calcd for C15H16O2N [MþH]þ ¼ 242.1176, Found ¼ 242.1178.
4.2.18. (E) p-chlorophenyl o-(p-methylphenyl)phenyl ketoxime
(1Bj)
4.2.24. (E) ethyl o-(p-methoxyphenyl)phenyl ketoxime (1Cb)
White solid; mp: 109e113 ꢀC; IR (neat): 3241, 1605, 1515, 1441,
White solid; mp: 125e129 ꢀC; IR (neat): 3055, 1490, 1442, 1320,
1247, 749 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.78 (t, 3H,
995, 924 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 2.29 (s, 3H),
J ¼ 7.6 Hz), 2.16 (q, 2H, J ¼ 7.6 Hz), 3.84 (s, 3H), 6.92e6.96 (m, 2H),
7.33e7.37 (m, 5H), 7.41e7.45 (m, 1H), 8.25 (s, 1H); 13C NMR
6.98e7.03 (m, 4H), 7.07 (brs, 4H), 7.31 (d, 1H, J ¼ 7.0 Hz), 7.40 (t, 1H,
J ¼ 7.0 Hz), 7.47 (t,1H, J ¼ 7.0 Hz), 7.52 (d, 1H, J ¼ 7.4 Hz), 7.70 (s, 1H);
(100 MHz, CDCl3):
d
¼ 9.9, 22.1, 55.2, 113.8 (2C), 126.8, 128.9, 129.9,
13C NMR (100 MHz, CDCl3):
d
¼ 21.1, 127.1, 127.4 (2C), 128.6 (2C),
130.0 (3C), 133.2, 135.3, 140.0, 159.0, 164.3; HRMS (ESI): Calcd for
C
16 H18O2N [MþH]þ ¼ 256.1332, Found ¼ 256.1333.
128.9 (2C), 129.4, 130.3, 130.4, 130.9 (2C), 131.4, 134.4, 135.7, 136.6,
137.7, 142.2, 157.3; HRMS (ESI): Calcd for
C
20H17ON35Cl
[MþH]þ ¼ 322.0993, Found ¼ 322.0996.
4.2.25. (E) n-butyl o-(p-methoxyphenyl)phenyl ketoxime (1Cd)
White solid; mp: 99e107 ꢀC; IR (neat): 3254, 1608, 1516, 1245,
763 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.71 (t, 3H, J ¼ 7.1 Hz),
4.2.19. (E) p-bromophenyl o-(p-methylphenyl)phenyl ketoxime
(1Bk)
1.05e1.21 (m, 4H), 2.12 (t, 2H, J ¼ 7.5 Hz), 3.85 (s, 3H), 6.92e6.96 (m,
2H), 7.32e7.36 (m, 5H), 7.40e7.44 (m, 1H), 8.25 (s, 1H); 13C NMR
White solid; mp: 125e128 ꢀC; IR (neat): 3056, 2911, 1484, 984,
(100 MHz, CDCl3):
d
¼ 13.7, 22.7, 27.7, 28.3, 55.3, 113.8 (2C), 126.9,
914, 818, 762 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 2.30 (s, 3H),
128.8, 129.8 (2C), 130.0 (3C), 133.3, 135.7, 140.0, 159.0; HRMS (ESI):
6.98e7.03 (m, 6H), 7.21e7.24 (m, 2H), 7.31 (dd, 1H, J ¼ 7.5, 1.2 Hz),
Calcd for C18H22O2N [MþH]þ ¼ 284.1645, Found ¼ 284.1644.
7.40 (td, 1H, J ¼ 7.5, 1.6 Hz), 7.47 (td, 1H, J ¼ 7.5, 1.5 Hz), 7.52 (dd, 1H,
J ¼ 7.5, 1.2 Hz), 7.61 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
¼ 21.1,
4.2.26. (E) o-(p-methoxyphenyl)phenyl p-methylphenyl ketoxime
(1Cg)
122.9, 127.1, 128.6 (2C), 129.0 (2C), 129.4, 130.3, 130.4 (3C), 131.1
(2C), 131.8, 135.7, 136.6, 137.7, 142.2, 157.3; HRMS (ESI): Calcd for
White solid; mp: 114e124 ꢀC; IR (neat): 3290, 1517, 1440, 1242,
C
C
20H17ON79Br [MþH]þ
¼
366.0488, Found
¼
366.0492,
1048, 930 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.25 (s, 3H), 3.77 (s,
20H17ON81Br [MþH]þ ¼ 368.0468, Found ¼ 368.0471.
3H), 6.72e6.75 (m, 2H), 6.94 (d, 2H, J ¼ 7.9 Hz), 7.08e7.14 (m, 4H),
7.31 (dd, 1H, J ¼ 7.6, 1.1 Hz), 7.37 (td, 1H, J ¼ 7.5, 1.5 Hz), 7.44 (td, 1H,
J ¼ 7.5, 1.6 Hz), 7.50 (dd, 1H, J ¼ 7.4, 1.4 Hz), 7.84 (s, 1H); 13C NMR
4.2.20. (E) o-(p-methylphenyl)phenyl naphthalen-b-yl ketoxime
(1Bl)
(100 MHz, CDCl3):
129.5 (2C), 130.2 (4C), 130.4, 133.4, 136.2, 138.7, 141.7, 158.0, 158.5;
HRMS (ESI): Calcd for
Found ¼ 318.1483.
d
¼ 21.3, 55.2, 113.3 (2C), 126.8, 128.0 (2C), 129.0,
White solid; mp: 163e165 ꢀC; IR (neat): 3314, 1457, 1284, 1047,
747 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.21 (s, 3H), 6.90 (d, 2H,
C
21H20O2N [MþH]þ
¼
318.1489,
J ¼ 7.6 Hz), 7.03 (d, 2H, J ¼ 8.1 Hz), 7.29 (dd, 1H, J ¼ 8.6, 1.7 Hz), 7.33
(dd, 1H, J ¼ 7.5, 1.5 Hz), 7.37e7.50 (m, 4H), 7.55e7.60 (m, 3H), 7.64
(d,1H, J ¼ 8.1 Hz), 7.71 (d,1H, J ¼ 7.9 H),; 13C NMR (100 MHz, CDCl3):
4.2.27. (E) o-(p-chlorophenyl)phenyl methyl ketoxime (1Da)
White solid; mp: 137e139 ꢀC; IR (neat): 3255, 1477, 1090, 928,
d
¼ 21.0,125.8,126.5,126.6,126.7,127.0,127.4,128.4 (3C),128.9 (2C),
129.2, 129.4, 130.3, 130.4, 130.8, 132.3, 133.0, 136.3, 136.4, 137.9,
142.3, 158.2; HRMS (ESI): Calcd for C24H20ON [MþH]þ ¼ 338.1539,
Found ¼ 338.1537.
760 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.73 (s, 3H), 7.31e7.47 (m,
8H), 7.67 (s, 1H); 13C NMR (100 MHz, CDCl3):
¼ 16.0, 127.7, 128.7
(2C), 129.1, 129.2, 130.2 (3C), 133.5, 136.7, 139.2, 139.4, 158.8; HRMS
d
7

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
(ESI):
Found ¼ 246.0680.
Calcd for C14H13ON35Cl
[MþH]þ
¼
246.0680,
4.3. Typical procedure for preparation of phenanthridines 2
To a solution of (E)-biphenyl methyl ketoxime 1Aa (105.6 mg,
0.5 mmol) in chlorobenzene (1.0 mL) was added Tf2O (0.164 mL,
1.0 mmol) at 0 ꢀC under argon atmosphere. The obtained mixture
was gradually warmed to 120 ꢀC and stirred for 17 h. Then, the
reaction mixture was quenched with Et3N (0.5 mL) and stirred for
10 min. Water (10.0 mL) was added to the reaction mixture, and the
product was extracted with CHCl3 (10.0 mL ꢂ 3). The organic layer
was dried over Na2SO4. After filtration and removal of the solvent
under reduced pressure, the residue was purified by short column
chromatography on silica gel (hexane/AcOEt ¼ 4:1) to give 6-
methylphenanthridine 2Aa (93.3 mg, 97%).
4.2.28. (E) o-(p-chlorophenyl)phenyl ethyl ketoxime (1Db)
White solid; mp: 148e150 ꢀC; IR (neat): 3212, 2986, 1480, 1456,
1072, 915, 739 cmꢁ1 1H NMR (400 MHz, CDCl3):
¼ 0.80 (t, 3H,
;
d
J ¼ 7.6 Hz), 2.17 (q, 2H, J ¼ 7.6 Hz), 7.33e7.41 (m, 7H), 7.45 (td, 1H,
J ¼ 7.5, 2.0 Hz), 7.73 (s,1H); 13C NMR (100 MHz, CDCl3):
¼ 9.9, 22.3,
d
127.6, 128.6 (2C), 129.0, 129.9, 130.0, 130.3 (2C), 133.5, 135.3, 139.2,
139.3,
163.7;
HRMS
(ESI):
Calcd
for
C
15H15ON35Cl
[MþH]þ ¼ 260.0837, Found ¼ 260.0836.
4.2.29. (E) n-butyl o-(p-chlorophenyl)phenyl ketoxime (1Dd)
White solid; mp: 144e149 ꢀC; IR (neat): 3248, 1476, 1442, 1091,
829, 763 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 0.73 (t, 3H,
J ¼ 7.1 Hz), 1.09e1.22 (m, 4H), 2.13 (t, 2H, J ¼ 7.6 Hz), 7.33e7.40 (m,
7H), 7.42e7.46 (m, 1H); 13C NMR (100 MHz, CDCl3):
4.3.1. 6-Methylphenanthridine (2Aa)
Yield: 93.3 mg (97%); pale yellow solid; mp: 79e81 ꢀC; IR (neat):
d
¼ 13.7, 22.7,
1612, 1583, 1371, 749, 720 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
27.7, 28.6, 127.6, 128.6 (2C), 129.0, 129.8, 130.0, 130.2 (2C), 133.5,
135.7, 139.1, 139.4, 162.9; HRMS (ESI): Calcd for C17H19ON35Cl
[MþH]þ ¼ 288.1150, Found ¼ 288.1152.
d
¼ 3.06 (s, 3H), 7.61e7.65 (m, 1H), 7.69e7.74 (m, 2H), 7.85 (t, 1H,
J ¼ 7.78 Hz), 8.10 (dd, 1H, J ¼ 8.1, 0.9 Hz), 8.24 (d, 1H, J ¼ 8.1 Hz), 8.55
(d, 1H, J ¼ 8.3 Hz), 8.64 (d, 1H, J ¼ 8.3 Hz); 13C NMR (100 MHz,
CDCl3):
d
¼ 23.4, 121.9, 122.3, 123.7, 125.9, 126.3, 126.5, 127.3, 128.6,
4.2.30. (E) o-(p-chlorophenyl)phenyl p-methylphenyl ketoxime
(1Dg)
129.3, 130.4, 132.5, 143.7, 158.9; HRMS (ESI): Calcd for C14H12N
[MþH]þ ¼ 194.0964, Found ¼ 194.0961.
White solid; mp: 136e144 ꢀC; IR (neat): 3235, 1473, 1086, 990,
916, 746 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.27 (s, 3H), 6.96 (d,
4.3.2. 6-Ethylphenanthridine (2Ab)
2H, J ¼ 7.9 Hz), 7.07e7.12 (m, 4H), 7.14e7.18 (m, 2H), 7.29 (dd, 1H,
J ¼ 7.3,1.6 Hz), 7.41 (td,1H, J ¼ 7.4,1.6 Hz), 7.44e7.52 (m, 2H), 7.68 (s,
Yield: 100.4 mg (97%); pale yellow solid; mp: 54e57 ꢀC; IR
(neat): 1584, 1485, 1373, 745, 724 cmꢁ1; 1H NMR (400 MHz, CDCl3):
1H); 13C NMR (100 MHz, CDCl3):
d
¼ 21.3, 127.5, 127.9 (2C), 128.1
d
¼ 1.52 (t, 3H, J ¼ 7.6 Hz), 3.42 (q, 2H, J ¼ 7.6 Hz), 7.62 (td,1H, J ¼ 7.7,
(2C), 129.1, 129.6 (2C), 130.0, 130.1, 130.3 (2C), 130.5, 132.8, 136.2,
139.1, 139.3, 140.9, 157.5; HRMS (ESI): Calcd for C20H17ON35Cl
[MþH]þ ¼ 322.0993, Found ¼ 322.0988.
1.4 Hz), 7.68e7.74 (m, 2H), 7.84 (td, 1H, J ¼ 7.7, 1.4 Hz), 8.13 (d, 1H,
J ¼ 8.2 Hz), 8.27 (d, 1H, J ¼ 8.4 Hz), 8.55 (dd, 1H, J ¼ 8.2, 1.4 Hz), 8.65
(d, 1H, J ¼ 8.4 Hz); 13C NMR (100 MHz, CDCl3):
¼ 13.5, 29.4, 121.9,
d
122.4, 123.6, 125.0, 126.2 (2C), 127.2, 128.5, 129.5, 130.2, 132.9, 143.7,
4.2.31. (E) o-(p-fluorophenyl)phenyl methyl ketoxime (1Ea)
White solid; mp: 130e132 ꢀC; IR (neat): 3062, 2987, 1515, 1225,
163.2; HRMS (ESI): Calcd for
Found ¼ 208.1121.
C
15H14
N
[MþH]þ
¼
208.1121,
841, 758, 559 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 1.70 (s, 3H),
7.07e7.13 (m, 2H), 7.33e7.46 (m, 6H), 7.80 (s, 1H); 13C NMR
(100 MHz, CDCl3):
4.3.3. 6-Isopropylphenanthridine (2Ac)
Yield: 104.5 mg (94%); orange oil; IR (neat): 1582, 1486, 1382,
756, 724 cmꢁ1 1H NMR (400 MHz, CDCl3):
d
¼ 16.0, 115.4 (d, 2C, JC-F ¼ 21.6 Hz) 127.5, 129.1,
129.2, 130.2, 130.5 (d, 2C, JC-F ¼ 7.5 Hz), 136.7, 136.9 (d, JC-F ¼ 3.8 Hz),
139.5, 158.8, 162.3 (d, JC-F ¼ 247.1 Hz); HRMS (ESI): Calcd for
;
d
¼ 1.52 (d, 6H,
J ¼ 7.0 Hz), 4.01 (sept, 1H, J ¼ 7.0 H), 7.61 (td, 1H, J ¼ 7.6, 1.5 Hz),
7.67e7.73 (m, 2H), 7.82 (td, 1H, J ¼ 7.6, 1.4 Hz), 8.14 (dd, 1H, J ¼ 8.2,
1.0 Hz), 8.33 (d, 1H, J ¼ 8.3 Hz), 8.55 (dd, 1H, J ¼ 8.2, 1.5 Hz), 8.67 (d,
C
14H13ONF [MþH]þ ¼ 230.0976, Found ¼ 230.0979.
4.2.32. (E) methyl o-(p-nitrophenyl)phenyl ketoxime (1Fa)
1H, J ¼ 8.3 Hz); 13C NMR (100 MHz, CDCl3):
¼ 21.9 (2C), 31.4, 121.8,
d
White solid; mp: 198e203 ꢀC; IR (neat): 3200, 1516, 1347, 922,
122.5, 123.4, 124.7, 125.6, 126.1, 127.0, 128.3, 129.9 (2C), 132.9, 143.8,
858, 745 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 1.79 (s, 3H),
7.38e7.40 (m, 1H), 7.45e7.50 (m, 4H), 7.54e7.56 (m, 2H), 8.26e8.29
(m, 2H); 13C NMR (100 MHz, DMSO‑d6):
165.8; HRMS (ESI): Calcd for
Found ¼ 222.1276.
C
16H16
N
[MþH]þ
¼
222.1277,
d
¼ 16.0, 123.6 (2C), 128.6,
128.8,129.4,130.0 (2C),130.2,137.4,137.9,146.4,148.1,154.5,; HRMS
4.3.4. 6-n-Butylphenanthridine (2Ad)
Yield: 117.5 mg (>99%); pale yellow oil; IR (neat): 1584, 1486,
755, 723 cmꢁ1 1H NMR (400 MHz, CDCl3):
(ESI): Calcd for C14H13O3N2 [MþH]þ ¼ 257.0921, Found ¼ 257.0925.
;
d
¼ 1.01 (t, 3H,
4.2.33. (E) methyl o-(o-methylphenyl)phenyl ketoxime (1Ga)
White solid; mp: 99e102 ꢀC; IR (neat): 3058, 1577, 1457, 918,
J ¼ 7.5 Hz), 1.57 (six, 2H, J ¼ 7.5 Hz), 1.87e1.95 (m, 2H), 3.38 (t, 2H,
J ¼ 8.0 Hz), 7.60e7.64 (m, 1H), 7.68e7.73 (m, 2H), 7.81e7.85 (m, 1H),
8.12 (dd, 1H, J ¼ 8.2, 1.4 Hz), 8.26 (d, 1H, J ¼ 8.2 Hz), 8.55 (dd, 1H,
J ¼ 8.2, 1.1 Hz), 8.65 (d, 1H, J ¼ 8.2 Hz); 13C NMR (100 MHz, CDCl3):
758 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.61 (s, 3H), 2.13 (s, 3H),
7.14e7.28 (m, 5H), 7.34e7.46 (m, 3H), 8.37 (s, 1H); 13C NMR
(100 MHz, CDCl3):
¼ 15.1, 20.1, 125.6,127.3,127.6,128.5 (2C), 130.0,
d
d
¼ 14.0, 23.1, 31.7, 36.1, 121.8, 122.3, 123.5, 125.1, 126.1, 126.2, 127.1,
130.1, 130.5, 135.8, 137.3, 140.3, 140.5, 158.4; HRMS (ESI): Calcd for
128.4, 129.4, 130.1, 132.8, 143.6, 162.4; HRMS (ESI): Calcd for
C
15H16ON [MþH]þ ¼ 226.1226, Found ¼ 226.1225.
C
17H18N [MþH]þ ¼ 236.1434, Found ¼ 236.1429.
4.2.34. (E) methyl o-(m-nitrophenyl)phenyl ketoxime (1Ha)
Brown solid; mp: 124e128 ꢀC; IR (neat): 3237, 1524, 1347, 922,
4.3.5. 6-tert-Butylphenanthridine (2Ae)
Yield: 83.5 mg (75%); pale yellow oil; IR (neat): 1568, 1476, 1365,
734 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.79 (s, 3H), 7.40 (d, 1H,
985, 759 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
¼ 1.73 (s, 9H),
J ¼ 7.2 Hz), 7.45e7.52 (m, 3H), 7.58 (t, 1H, J ¼ 8.0 Hz), 7.62 (s, 1H),
7.59e7.67 (m, 2H), 7.69 (td, 1H, J ¼ 7.5, 1.6 Hz), 7.79 (td, 1H, J ¼ 7.6,
1.4 Hz), 8.11e8.13 (m, 1H), 8.53 (dd, 1H, J ¼ 8.1, 1.4 Hz), 8.63 (dd, 1H,
J ¼ 8.3, 0.5 Hz), 8.69 (dd, 1H, J ¼ 8.3, 0.7 Hz); 13C NMR (100 MHz,
7.71 (d, 1H, J ¼ 7.9 Hz), 8.21e8.23 (m, 1H), 8.28 (t, 1H, J ¼ 1.9 Hz); 13
C
NMR (100 MHz, CDCl3):
d
¼ 16.2, 122.2, 123.7, 128.6, 129.3 (3C),
130.2, 135.1, 136.7, 137.9, 142.7, 148.3, 157.6; HRMS (ESI): Calcd for
CDCl3):
d
¼ 31.2 (3C), 40.2, 121.6, 122.9, 123.4, 124.3, 125.9, 126.4,
C
14H13N2O3 [MþH]þ ¼ 257.0921, Found ¼ 257.0920.
128.2, 128.3, 129.2, 130.2, 134.0, 142.9, 166.6; HRMS (ESI): Calcd for
8

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
C17H18N [MþH]þ ¼ 236.1434, Found ¼ 236.1430.
4.3.12. 6-(40-Fluorophenyl)-8-methylphenanthridine (2Bi)
Yield: 130.9 mg (91%); pale yellow solid; mp: 119e123 ꢀC; IR
(neat): 1508, 1362, 1227, 735 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
4.3.6. 6-Cyclohexylphenanthridine (2Af)
d
¼ 2.53 (s, 3H), 7.24e7.29 (m, 2H), 7.66e7.76 (m, 5H), 7.82 (s, 1H),
Yield: 122.9 mg (94%); pale yellow oil; IR (neat): 1572, 1486,
8.21 (dd, 1H, J ¼ 8.0, 1.2 Hz), 8.58e8.62 (m, 2H); 13C NMR (100 MHz,
1446, 756, 721 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 1.38e1.63 (m,
CDCl3):
d
¼ 21.8, 115.4 (d, 2C, JC-F ¼ 21.6 Hz), 121.8, 122.2, 123.8,
3H), 1.83e2.09 (m, 7H), 3.58e3.65 (m, 1H), 7.60 (td, 1H, J ¼ 7.5,
1.4 Hz), 7.67e7.72 (m, 2H), 7.82 (td, 1H, J ¼ 7.7, 1.4 Hz), 8.13 (dd, 1H,
J ¼ 8.1,1.1 Hz), 8.32 (d,1H, J ¼ 8.3 Hz), 8.54 (d,1H, J ¼ 8.1 Hz), 8.66 (d,
125.3, 126.9, 127.9, 128.4, 130.2, 131.3, 131.5 (d, 2C, JC-F ¼ 8.5 Hz),
132.4, 136.0 (d, JC-F ¼ 2.8 Hz), 137.2, 143.4, 159.9, 163.1 (d, JC-
¼ 247.1 Hz); HRMS (ESI): Calcd for C20H15NF [MþH]þ ¼ 288.1183,
1H, J ¼ 8.3 Hz); 13C NMR (100 MHz, CDCl3):
¼ 26.3, 26.9 (2C), 32.3
d
F
Found ¼ 288.1178.
(2C), 42.0, 121.8, 122.5, 123.3, 124.7, 125.6, 126.1, 127.0, 128.3, 129.9
(2C), 133.0, 143.8, 165.2; HRMS (ESI): Calcd for
C19H20N
4.3.13. 6-(40-Chlorophenyl)-8-methylphenanthridine (2Bj)
[MþH]þ ¼ 262.1590, Found ¼ 262.1588.
Yield: 143.8 mg (95%); white solid; mp: 157e160 ꢀC; IR (neat):
1576, 1362, 1047, 752 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.53 (s,
4.3.7. 6,8-Dimethylphenanthridine (2Ba)
3H), 7.54e7.57 (m, 2H), 7.66e7.76 (m, 5H), 7.81 (s, 1H), 8.20 (dd, 1H,
Yield: 90.2 mg (87%); pale yellow solid; mp: 77e86 ꢀC; IR (neat):
J ¼ 7.9, 1.1 Hz), 8.59 (d, 1H, J ¼ 7.7 Hz), 8.61 (d, 1H, J ¼ 8.3 Hz); 13
C
1580, 1481, 1376, 1207, 765, 725 cmꢁ1
¼ 2.61 (s, 3H), 3.02 (s, 3H), 7.60 (td, 1H, J ¼ 7.6, 1.1 Hz), 7.65e7.70
(m, 2H), 7.98 (s, 1H), 8.08 (dd,1H, J ¼ 8.2,1.1 Hz), 8.49e8.52 (m, 2H);
13C NMR (100 MHz, CDCl3):
;
1H NMR (400 MHz, CDCl3):
NMR (100 MHz, CDCl3):
127.8, 128.5, 128.7 (2C), 130.2, 131.1 (2C), 131.3, 132.4, 134.7, 137.3,
d
¼ 21.8, 121.8, 122.2, 123.8, 125.1, 127.0,
d
138.4, 143.4, 159.7; HRMS (ESI): Calcd for
C
20H15N35Cl
d
¼ 21.7, 23.3, 121.7, 122.1, 123.8, 125.9
[MþH]þ ¼ 304.0888, Found ¼ 304.0886.
(2C), 126.1, 128.1, 129.2, 130.2, 132.0, 137.1, 143.3, 158.5,; HRMS (ESI):
Calcd for C15H14N [MþH]þ ¼ 208.1121, Found ¼ 208.1118.
4.3.14. 6-(40-Bromophenyl)-8-methylphenanthridine (2Bk)
Yield: 165.9 mg (95%); pale yellow solid; mp: 156e160 ꢀC; IR
4.3.8. 6-Ethyl-8-methylphenanthridine (2Bb)
(neat): 1528, 1477, 1362, 1045, 819 cmꢁ1 1H NMR (400 MHz,
;
Yield: 105.1 mg (95%); pale yellow solid; mp: 69e71 ꢀC; IR
CDCl3):
d
¼ 2.53 (s, 3H), 7.61e7.64 (m, 2H), 7.66e7.76 (m, 5H), 7.81
(neat): 1580, 1456, 1373, 1198, 824, 763 cmꢁ1 1H NMR (400 MHz,
;
(s, 1H), 8.20 (dd, 1H, J ¼ 8.2, 1.2 Hz), 8.59 (d, 1H, J ¼ 7.6 Hz), 8.61 (d,
CDCl3):
d
¼ 1.51 (t, 3H, J ¼ 7.5 Hz), 2.62 (s, 3H), 3.40 (q, 2H,
1H, J ¼ 8.5 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 21.8, 121.8, 122.2,
J ¼ 7.5 Hz), 7.58e7.62 (m, 1H), 7.66e7.70 (m, 2H), 8.04 (s, 1H), 8.10
(dd, 1H, J ¼ 8.1, 1.1 Hz), 8.51 (d, 1H, J ¼ 8.2 Hz), 8.54 (d, 1H,
123.0, 123.8, 125.1, 127.1, 127.8, 128.5, 130.2, 131.4 (3C), 131.6 (2C),
132.5, 137.3, 138.8, 143.4, 159.7; HRMS (ESI): Calcd for C20H15N79Br
J ¼ 8.5 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 13.5, 21.8, 29.3, 121.7,
[MþH]þ
¼
348.0382, Found
¼
348.0385, C20H15N81Br
122.3, 123.7, 125.1, 125.7, 126.1, 128.0, 129.4, 130.7, 131.9, 137.0, 143.4,
[MþH]þ ¼ 350.0362, Found ¼ 350.0361.
162.9; HRMS (ESI): Calcd for
Found ¼ 222.1279.
C
16H16N
[MþH]þ
¼
222.1277,
4.3.15. 8-Methyl-6-(naphthalen-20-yl)phenanthridine (2Bl)
Yield: 159.6 mg (>99%); pale yellow solid; mp: 112e116 ꢀC; IR
(neat): 1560, 1190, 1138, 819, 741 cmꢁ1; 1H NMR (400 MHz, CDCl3):
4.3.9. 6-n-Butyl-8-methylphenanthridine (2Bd)
Yield: 120.7 mg (97%); white solid; mp: 58e61 ꢀC; IR (neat):
1577, 1463, 1194, 758, 734 cmꢁ1 1H NMR (400 MHz, CDCl3):
d
¼ 2.49 (s, 3H), 7.55e7.60 (m, 2H), 7.67e7.77 (m, 3H), 7.85 (dd, 1H,
;
J ¼ 8.4, 1.7 Hz), 7.90 (s, 1H), 7.96e7.98 (m, 2H), 8.04, (d, 1H,
J ¼ 8.3 Hz), 8.22 (s, 1H), 8.25 (dd, 1H, J ¼ 8.2, 1.2 Hz), 8.61e8.64 (m,
d
¼ 1.02 (t, 3H, J ¼ 7.4 Hz),1.52e1.62 (m, 2H),1.87e1.95 (m, 2H), 2.62
2H); 13C NMR (100 MHz, CDCl3):
d
¼ 21.7, 121.8, 122.1, 123.8, 125.5,
(s, 3H), 3.35 (t, 2H, J ¼ 8.0 Hz), 7.57e7.62 (m, 1H), 7.65e7.70 (m, 2H),
8.02 (s, 1H), 8.10 (dd, 1H, J ¼ 8.2, 1.1 Hz), 8.51 (d, 1H, J ¼ 8.4 Hz), 8.54
126.3, 126.5, 126.9, 127.3, 127.7, 128.0, 128.2, 128.4, 128.5, 129.0,
130.2, 131.3, 132.3, 133.2, 133.3, 137.1, 137.4, 143.5, 160.9; HRMS
(ESI): Calcd for C24H18N [MþH]þ ¼ 320.1434, Found ¼ 320.1431.
(d, 1H, J ¼ 8.6 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 14.1, 21.9, 23.1,
31.7, 36.2, 121.7, 122.3, 123.7, 125.3, 125.8, 126.1, 128.1, 129.4, 130.7,
131.9, 137.0, 143.4, 162.2; HRMS (ESI): Calcd for
C18H20N
[MþH]þ ¼ 250.1590, Found ¼ 250.1585.
4.3.16. 6-(Benzofuran-20-yl)-8-methylphenanthridine (2Bm)
Yield: 136.2 mg (88%); orange solid; mp: 91e93 ꢀC; IR (neat):
4.3.10. 8-Methyl-6-(40-methylphenyl)phenanthridine (2Bg)
1548, 1360, 1315, 1173, 751, 731 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
Yield: 135.1 mg (95%); white solid; mp: 100e103 ꢀC; IR (neat):
d
¼ 2.63 (s, 3H), 7.34 (td, 1H, J ¼ 7.6. 0.9 Hz), 7.42 (td, 1H, J ¼ 7.7,
1560, 1458, 1363, 818, 754, 734 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
1.4 Hz), 7.54 (d, 1H, J ¼ 0.9 Hz), 7.67e7.77 (m, 5H), 7.27 (dd, 1H,
J ¼ 8.0, 1.0 Hz), 8.57e8.59 (m, 2H), 8.62 (d, 1H, J ¼ 8.5 Hz),; 13C NMR
d
¼ 2.49 (s, 3H), 2.51 (s, 3H), 7.38 (d, 2H, J ¼ 8.1 Hz), 7.62e7.74 (m,
5H), 7.90 (s, 1H), 8.21 (dd, 1H, J ¼ 8.1, 1.4 Hz), 8.57e8.61 (m, 2H); 13
C
(100 MHz, CDCl3):
d
¼ 21.9, 109.4, 111.9, 121.7, 121.8, 122.2, 123.3,
NMR (100 MHz, CDCl3):
126.7, 128.2 (2C), 129.0 (2C), 129.6 (2C), 130.2, 131.2, 132.2, 137.0,
d
¼ 21.4, 21.7, 121.7, 122.0, 123.7, 125.4,
124.0,124.7,125.3,127.1,127.4,128.3,128.5,130.4,131.4,132.5,137.6,
143.4, 149.6, 154.8, 155.4; HRMS (ESI): Calcd for
C22H16ON
[MþH]þ ¼ 310.1226, Found ¼ 310.1222.
137.1, 138.4, 143.5, 161.0; HRMS (ESI): Calcd for
C21H18N
[MþH]þ ¼ 284.1434, Found ¼ 284.1431.
4.3.17. 6-(Benzothiophen-20-yl)-8-methylphenanthridine (2Bn)
Yield: 143.7 mg (88%); brown solid; mp: 160e171 ꢀC; IR (neat):
4.3.11. 6-(40-Methoxyphenyl)-8-methylphenanthridine (2Bh)
Yield: 109.2 mg (73%); pale yellow solid; mp: 159e162 ꢀC; IR
1552, 1476, 1180, 813, 749, 725 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
(neat): 1609, 1513, 1253, 1178, 1025, 751 cmꢁ1; 1H NMR (400 MHz,
d
¼ 2.60 (s, 3H), 7.41e7.46 (m, 2H), 7.68 (td, 1H, J ¼ 7.3, 1.4 Hz),
CDCl3):
(m, 5H), 7.92 (s, 1H), 8.21 (dd, 1H, J ¼ 8.1, 1.1 Hz), 8.56e8.61 (m, 2H);
13C NMR (100 MHz, CDCl3):
¼ 21.7, 55.4, 113.8 (2C), 121.7, 122.1,
123.7, 125.4, 126.6, 128.2, 128.3, 130.1, 131.1 (2C), 131.3, 132.1, 132.4,
d
¼ 2.53 (s, 3H), 3.93 (s, 3H), 7.08e7.12 (m, 2H), 7.63e7.74
7.72e7.75 (m, 2H), 7.85 (s, 1H), 7.92e7.97 (m, 2H), 8.23 (dd, 1H,
J ¼ 8.1, 1.1 Hz), 8.41 (s, 1H), 8.58 (dd, 1H, J ¼ 8.1, 1.6 Hz), 8.62 (d, 1H,
d
J ¼ 8.6 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 21.9, 121.8, 122.3 (2C),
123.8, 124.3, 124.5, 125.0, 125.1, 125.8, 127.3, 127.4, 128.5, 130.3,
131.5, 132.5, 137.6, 140.0, 140.7, 142.7, 143.3, 153.8,; HRMS (ESI):
Calcd for C22H16NS [MþH]þ ¼ 326.0998, Found ¼ 326.0995.
137.0, 143.5, 160.0, 160.6; HRMS (ESI): Calcd for
C21H18ON
[MþH]þ ¼ 300.1383, Found ¼ 300.1378.
9

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
4.3.18. 8-Methoxy-6-methylphenanthridine (2Ca)
4.3.24. 6-n-Butyl-8-chlorophenanthridine (2Dd)
Yield: 86.3 mg (77%); brown solid; mp: 64e69 ꢀC; IR (neat):
Yield: 129.8 mg (96%); pale yellow solid; mp: 85e88 ꢀC; IR
1616, 1530, 1463, 1384, 1220, 755 cmꢁ1; 1H NMR (400 MHz, CDCl3):
(neat): 1577, 1464, 1099, 821, 757 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 3.02 (s, 3H), 4.01 (s, 3H), 7.48 (dd,1H, J ¼ 9.0, 2.7 Hz), 7.52 (d, 1H,
d
¼ 1.02 (t, 3H, J ¼ 7.4 Hz), 1.56 (sext, 2H, J ¼ 7.4 Hz), 1.86e1.94 (m,
J ¼ 2.7 Hz), 7.60 (td, 1H, J ¼ 7.5, 1.4 Hz), 7.66 (td, 1H, J ¼ 7.5, 1.6 Hz),
8.1 (dd, 1H, J ¼ 8.0, 1.4 Hz), 8.46 (dd, 1H, J ¼ 8.1, 1.6 Hz), 8.55 (d, 1H,
2H), 3.33 (t, 2H, J ¼ 8.1 Hz), 7.61e7.65 (m, 1H), 7.71e7.75 (m, 1H),
7.78 (dd, 1H, J ¼ 8.8, 2.2 Hz), 8.12 (dd, 1H, J ¼ 8.2, 1.0 Hz), 8.20 (d, 1H,
J ¼ 2.0 Hz), 8.49 (d, 1H, J ¼ 8.1 Hz), 8.57 (d, 1H, J ¼ 8.8 Hz); 13C NMR
J ¼ 9.0 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 23.5, 55.5, 106.8, 120.7,
121.4, 123.8, 124.0, 126.4, 126.8, 127.2, 127.6, 129.2, 142.8, 157.9,
158.6; HRMS (ESI): Calcd for C15H14ON [MþH]þ ¼ 224.1070,
Found ¼ 224.1066.
(100 MHz, CDCl3):
d
¼ 14.0, 23.0, 31.4, 35.9, 121.7, 122.8, 124.1, 125.5,
126.1, 126.6, 128.8, 129.6, 130.6, 131.1, 133.0, 143.6, 161.1; HRMS
(ESI): Calcd for C17H17N35Cl [MþH]þ ¼ 270.1044, Found ¼ 270.1044.
4.3.19. 6-Ethyl-8-methoxyphenanthridine (2Cb)
4.3.25. 8-Chloro-6-(40-methylphenyl)phenanthridine (2Dg)
Yield: 94.4 mg (80%); pale yellow solid; mp: 90e93 ꢀC; IR (neat):
Yield: 138.7 mg (91%); brown solid; mp: 140e142 ꢀC; IR (neat):
1530, 1479, 1462, 1373, 1217, 742 cmꢁ1; 1H NMR (400 MHz, CDCl3):
1560, 1470, 1359, 967, 751, 733 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼ 1.52 (t, 3H, J ¼ 7.6 Hz), 3.38 (q, 2H, J ¼ 7.6 Hz), 4.00 (s, 3H),
d
¼ 2.49 (s, 3H), 7.39 (d, 2H, J ¼ 7.9 Hz), 7.62 (d, 2H, J ¼ 8.1 Hz),
7.45e7.48 (m, 1H), 7.57e7.61 (m, 2H), 7.63e7.67 (m, 1H), 8.10 (dd,
1H, J ¼ 7.9, 1.4 Hz), 8.46 (d, 1H, J ¼ 8.2 Hz), 8.56 (d, 1H, J ¼ 9.3 Hz);
7.68e7.72 (m, 1H), 7.75e7.82 (m, 2H), 8.12 (d, 1H, J ¼ 2.0 Hz), 8.23
(d, 1H, J ¼ 6.7 Hz), 8.57 (d, 1H, J ¼ 8.1 Hz), 8.64 (d, 1H, J ¼ 8.8 Hz); 13
C
13C NMR (100 MHz, CDCl3):
d
¼ 13.1, 29.4, 55.4, 106.5, 120.3, 121.3,
NMR (100 MHz, CDCl3):
d
¼ 21.4, 121.8, 123.0, 124.0, 126.2, 127.2,
123.6, 124.0, 126.2 (2C), 127.1, 127.5, 129.4, 142.8, 158.5, 162.1; HRMS
127.9, 129.1, 129.3 (2C), 129.5 (2C), 130.4, 131.0, 131.8, 133.0, 136.2,
(ESI): Calcd for C16H16ON [MþH]þ ¼ 238.1226, Found ¼ 238.1225.
138.9, 143.7, 160.2; HRMS (ESI): Calcd for
C
20H15N35Cl
[MþH]þ ¼ 304.0888, Found ¼ 304.0883.
4.3.20. 6-n-Butyl-8-methoxyphenanthridine (2Cd)
Yield: 112.0 mg (84%); yellow solid; mp: 52e56 ꢀC; IR (neat):
1618, 1462, 1219, 1039, 759 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
4.3.26. 8-Fluoro-6-methylphenanthridine (2Ea)
Yield: 101.6 mg (96%); brown solid; mp: 88e90 ꢀC; IR (neat):
d
¼ 1.02 (t, 3H, J ¼ 7.4 Hz), 1.56 (sext, 2H, J ¼ 7.4 Hz), 1.88e1.96 (m,
1533, 1479, 1379, 1181, 857, 764 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
2H), 3.33 (t, 2H, J ¼ 8.1 Hz), 4.00 (s, 3H), 7.45e7.48 (m, 1H),
7.57e7.61 (m, 2H), 7.63e7.67 (m, 1H), 8.09 (dd, 1H, J ¼ 8.1, 1.1 Hz),
8.46 (d, 1H, J ¼ 8.1 Hz), 8.56 (d, 1H, J ¼ 9.0 Hz); 13C NMR (100 MHz,
d
¼ 3.02 (s, 3H), 7.58e7.74 (m, 2H), 7.72 (td, 1H, J ¼ 8.1, 1.4 H), 7.84
(dd, 1H, J ¼ 9.7, 2.5 Hz), 8.10 (d, 1H, J ¼ 8.1 Hz), 8.49 (d, 1H,
J ¼ 7.2 Hz), 8.64 (dd, 1H, J ¼ 9.1, 5.3 Hz); 13C NMR (100 MHz, CDCl3):
CDCl3):
d
¼ 14.0, 23.0, 31.2, 36.1, 55.4, 106.7, 120.2, 121.3, 123.6,
d
¼ 23.4,111.1 (d, JC-F ¼ 21.6 Hz),119.5 (d, JC-F ¼ 23.5 Hz),121.7,123.2,
124.0, 126.2, 126.3, 127.1, 127.4, 129.4, 142.8, 158.4, 161.4; HRMS
(ESI): Calcd for C18H20ON [MþH]þ ¼ 266.1539, Found ¼ 266.1536.
124.9 (d, JC-F ¼ 8.5 Hz), 126.7, 127.1 (d, JC-F ¼ 7.5 Hz), 128.5, 129.2,
129.5, 143.3, 157.9 (d, JC-F ¼ 3.8 Hz), 161.3 (d, JC-F ¼ 248.1 Hz); HRMS
(ESI): Calcd for C14H11NF [MþH]þ ¼ 212.0870, Found ¼ 212.0870.
4.3.21. 8-Methoxy-6-(40-methylphenyl)phenanthridine (2Cg)
Yield: 70.7 mg (47%); yellow solid; mp: 136e139 ꢀC; IR (neat):
1615, 1461, 1213, 820, 754, 737 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
4.3.27. 6-Methyl-8-nitrophenanthridine (2Fa)
Yield: 119.0 mg (>99%)pale yellow solid; mp: 227e234 ꢀC; IR
d
¼ 2.48 (s, 3H), 3.84 (s, 3H), 7.37 (d, 2H, J ¼ 7.9 Hz), 7.47e7.52 (m,
(neat): 1540, 1477, 1331, 766 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
2H), 7.63e7.71 (m, 4H), 8.21 (dd, 1H, J ¼ 8.0, 1.5 Hz), 8.53 (dd, 1H,
J ¼ 7.7, 1.6 Hz), 8.61 (d, 1H, J ¼ 9.1 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 3.14 (s, 3H), 7.72 (t, 1H, J ¼ 8.3 Hz), 7.85 (td, 1H, J ¼ 7.6, 1.4 Hz),
d
¼ 21.4, 55.4, 108.9, 120.9, 121.4, 123.7, 123.8, 126.6, 126.8, 127.7
8.16 (dd, 1H, J ¼ 8.2, 1.4 Hz), 7.58 (d, 1H, J ¼ 8.3 Hz), 8.64 (dd, 1H,
J ¼ 9.2, 2.2 Hz), 8.78 (d, 1H, J ¼ 9.2 Hz), 9.14 (d, 1H, J ¼ 2.2 Hz); 13
C
(2C), 129.1 (2C), 129.4 (2C), 130.2, 137.0, 138.5, 143.0, 158.3, 160.5;
HRMS (ESI): Calcd for
Found ¼ 300.1380.
C
21H18ON [MþH]þ
¼
300.1383,
NMR (100 MHz, CDCl3):
d
¼ 23.4, 122.4, 122.7, 122.8, 124.1 (2C),
125.3, 127.3, 129.8, 130.8, 136.7, 145.0, 146.1, 159.0,; HRMS (ESI):
Calcd for C14H11O2N2 [MþH]þ ¼ 239.0815, Found ¼ 239.0817.
4.3.22. 8-Chloro-6-methylphenanthridine (2Da)
Yield: 113.8 mg (>99%); pale yellow solid; mp: 110e115 ꢀC; IR
(neat): 1579, 1474, 1374, 1046, 755 cmꢁ1 1H NMR (400 MHz,
CDCl3):
4.3.28. 6,10-Dimethylphenanthridine (2Ga)
;
Yield: 86.6 mg (84%); brown solid; mp: 86e94 ꢀC; IR (neat):
d
¼ 3.03 (s, 3H), 7.64 (t,1H, J ¼ 8.3 Hz), 7.73 (t,1H, J ¼ 7.2 Hz),
1589, 1434, 1374, 758, 722 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
7.80 (dd, 1H, J ¼ 9.1, 2.2 Hz), 8.10 (d, 1H, J ¼ 8.3 Hz), 8.20 (d, 1H,
d
¼ 3.05 (s, 3H), 3.14 (s, 3H), 7.59e7.63 (m, 2H), 7.69e7.74 (m, 2H),
J ¼ 2.2 Hz), 8.50 (d, 1H, J ¼ 7.9 Hz), 8.58 (d, 1H, J ¼ 9.0 Hz); 13C NMR
8.13e8.18 (m, 2H), 8.79 (d, 1H, J ¼ 8.6 Hz); 13C NMR (100 MHz,
(100 MHz, CDCl3):
d
¼ 23.2, 121.7, 123.0, 123.9, 125.7, 126.6 (2C),
CDCl3):
d
¼ 24.2, 26.9, 125.0, 125.2, 125.5, 126.5, 126.7, 127.4, 127.8,
128.9, 129.4, 130.8 (2C), 133.0, 143.5, 157.6; HRMS (ESI): Calcd for
129.6, 132.0, 134.7, 135.5, 144.8, 159.2; HRMS (ESI): Calcd for
C
C
14H11N35Cl [MþH]þ ¼ 228.0575, Found ¼ 228.0574.
15H14N [MþH]þ ¼ 208.1121, Found ¼ 208.1116.
4.3.23. 8-Chloro-6-ethylphenanthridine (2Db)
Yield: 114.4 mg (95%); pale yellow solid; mp: 90e95 ꢀC; IR
4.3.29. 6-Methyl-9-nitrophenanthridine (2Ha)
(neat): 1573, 1462, 1046, 831, 753 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
Yield: 96.2 mg (81%); brown solid; mp: 191e195 ꢀC; IR (neat):
¼ 1.51 (t, 3H, J ¼ 7.6 Hz), 3.37 (q, 2H, J ¼ 7.6 Hz), 7.62e7.66 (m, 1H),
1536, 1505, 1343, 1047, 755 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
7.71e7.75 (m, 1H), 7.78 (dd, 1H, J ¼ 8.9, 2.1 Hz), 8.12 (d, 1H,
J ¼ 8.1 Hz), 8.23 (d, 1H, J ¼ 2.0 Hz), 8.49 (d, 1H, J ¼ 8.3 Hz), 8.58 (d,
d
¼ 3.11 (s, 3H), 7.75 (td, 1H, J ¼ 7.6, 1.4 Hz), 7.83 (td, 1H, J ¼ 7.6,
1.4 Hz), 8.17 (d, 1H, J ¼ 8.3 Hz), 8.39 (d, 1H, J ¼ 9.0 Hz), 8.48 (dd, 1H,
1H, J ¼ 9.0 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 13.2, 29.2, 121.7,
J ¼ 9.0, 2.2 Hz), 8.62 (d, 1H, J ¼ 7.0 Hz), 9.52 (d, 1H, J ¼ 2.2 Hz); 13
C
122.9, 124.2, 125.4, 125.9, 126.6, 128.8, 129.7, 130.7, 131.2, 133.1,
NMR (100 MHz, CDCl3):
d
¼ 23.5, 118.4, 120.9, 122.1, 123.1, 127.5,
143.6,
161.9;
HRMS
(ESI):
Calcd
for
C
15H13N35Cl
128.2, 128.3, 129.8, 130.1, 132.9, 144.2, 148.3, 157.9; HRMS (ESI):
[MþH]þ ¼ 242.0731, Found ¼ 242.0728.
Calcd for C14H11N2O2 [MþH]þ ¼ 239.0815, Found ¼ 239.0816.
10

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
4.4. Transformation of 2Bk into 8-(Bromomethyl)-6-(40-
bromophenyl)phenanthridine (4Bk)
washed with brine (30 mL ꢂ 2) and dried over Na2SO4. After
filtration and removal of the solvent under reduced pressure, the
residue was purified by column chromatography on silica gel
(hexane: EtOAc ¼ 10 : 1) to give 8-methyl-6-[4’-(phenylethynyl)
phenyl]phenanthridine 6Bk (123.3 mg, 67%).
A mixture of 2Bk (174.1 mg, 0.5 mmol), NBS (97.9 mg,
0.55 mmol) and BPO (32.3 mg, 0.1 mmol) in CCl4 (1.0 mL) was
stirred under irradiation with a tungsten lamp (300 W) for 3 h at
30 ꢀCe40 ꢀC. Then, water (10.0 mL) was added to the reaction
mixture, and the product was extracted with CHCl3 (20.0 mL ꢂ 3).
The organic layer was dried over Na2SO4. After filtration and
removal of the solvent under reduced pressure, the residue was
purified by short column chromatography on silica gel (hexane/
AcOEt ¼ 10:1) to give 8-(bromomethyl)-6-(40-bromophenyl)phe-
nanthridine 4Bk (172.0 mg, 81%).
4.6.1. 8-Methyl-6-[4’-(phenylethynyl)phenyl]phenanthridine (6Bk)
Yield: 123.3 mg (67%); white solid; mp: 165e168 ꢀC; IR (neat):
2324, 1566, 1363, 1327, 752, 741, 690 cmꢁ1 1H NMR (400 MHz,
;
CDCl3):
7.67e7.76 (m, 7H), 7.86 (s, 1H), 8.22 (d, 1H, J ¼ 8.2 Hz), 8.58e8.62
(m, 2H); 13C NMR (100 MHz, CDCl3):
d
¼ 2.53 (s, 3H), 7.37e7.41 (m, 3H), 7.59e7.61 (m, 2H),
d
¼ 21.8, 89.2, 90.4, 121.8,
122.2, 123.1, 123.6, 123.8, 125.2, 127.0, 127.9, 128.4 (4C), 129.8 (2C),
130.3, 131.3, 131.6 (2C), 131.7 (2C), 132.4, 137.2, 139.7, 143.4, 160.2;
4.4.1. 8-(Bromomethyl)-6-(40-bromophenyl)phenanthridine (4Bk)
Yield: 172.0 mg (81%); pale yellow solid; mp: 220e223 ꢀC; IR
HRMS (ESI): Calcd for
Found ¼ 370.1584.
C28H20
N
[MþH]þ
¼
370.1590,
(neat): 1557, 1369, 1210, 1011, 909, 755, 608 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
¼ 4.64 (s, 2H), 7.62e7.64 (m, 2H), 7.72e7.75 (m,
4.7. Transformation of 2Bk into 6-(40-Bromophenyl)-5,8-
dimethylphenanthridinium trifluoromethanesulfonate (7Bk)
3H), 7.77e7.81 (m, 1H), 7.93 (dd, 1H, J ¼ 8.5, 1.9 Hz), 8.03 (d, 1H,
J ¼ 1.6 Hz), 8.22 (d, 1H, J ¼ 8.2 Hz), 8.61 (d, 1H, J ¼ 8.2 Hz), 8.71 (d,
1H, J ¼ 8.6 Hz); 13C NMR (100 MHz, CDCl3):
d
¼ 33.0, 122.1, 123.3,
A mixture of 2Bk (174.1 mg, 0.5 mmol) and TfOMe (0.55 mL) in
DCM (2.0 mL) was heated at 50 ꢀC for 24 h under argon atmosphere.
The reaction mixture was cooled, and filtered and washed with
ether to give 6-(40-bromophenyl)-5,8-dimethylphenanthridinium
trifluoromethanesulfonate 7Bk (216.9 mg, 85%).
123.4 (2C), 124.9, 127.4, 128.3, 129.3, 130.4, 131.4 (2C), 131.6, 131.8
(2C), 133.4, 136.9, 138.3, 143.9, 159.6; HRMS (ESI): Calcd for
C
C
C
20H14N79Br2 [MþH]þ
¼
425.9488, Found
427.9468, Found
¼
425.9483,
427.9460,
20H14N79Br81Br [MþH]þ
¼
¼
20H14N81Br2 [MþH]þ ¼ 429.9447, Found ¼ 429.9439.
4.7.1. 6-(40-Bromophenyl)-5,8-dimethylphenanthridinium
trifluoromethanesulfonate (7Bk)
4.5. Transformation of 2Bk into 6-(p-Biphenyl)-8-
methylphenanthridine (5Bk)
Yield: 216.9 mg (85%); pale yellow solid; mp: 213e225 ꢀC; IR
(neat): 1592, 1260, 1222, 1152, 1025, 634 cmꢁ1; 1H NMR (400 MHz,
To a mixture of 2Bk (174.1 mg, 0.5 mmol) and phenylboronic
acid (73.2 mg, 0.6 mmol) in DMF (5.0 mL) was added PdCl2(PPh3)2
(14.0 mg, 0.02 mmol) under argon atmosphere. The obtained
mixture was stirred at room temperature for 0.5 h. Then, K2CO3
(69.1 mg, 0.5 mmol) in H2O (1.0 mL) was added to the mixture, and
the obtained mixture was stirred at 70 ꢀC for 5.5 h. Then, water
(10.0 mL) was added to the reaction mixture, and the product was
extracted with a mixture of hexane and AcOEt (4 : 1, 30.0 mL ꢂ 3).
The organic layer was washed with brine (30.0 mL ꢂ 2) and dried
over Na2SO4. After filtration and removal of the solvent under
reduced pressure, the residue was purified by column chromatog-
raphy (hexane/EtOAc ¼ 10:1) on silica gel to give 6-(p-biphenyl)-8-
methylphenanthridine 5Bk (135.4 mg, 78%).
CDCl3):
d
¼ 2.53 (s, 3H), 4.48 (s, 3H), 7.43 (s, 1H), 7.61e7.64 (m, 2H),
7.89e7.92 (m, 2H), 8.00e8.09 (m, 3H), 8.48 (d, 1H, J ¼ 8.4 Hz), 8.77
(d, 1H, J ¼ 8.6 Hz), 8.84 (dd, 1H, J ¼ 8.2, 1.6 Hz); 13C NMR (100 MHz,
CDCl3):
d
¼ 21.7, 43.7, 120.5, 122.9, 123.8, 125.1, 125.8, 126.6, 129.6,
130.6 (3C), 131.5, 132.2, 133.0 (2C), 133.3, 134.9, 139.4, 140.8, 162.2;
HRMS (ESI): Calcd for
Found 362.0533,
Found ¼ 364.0512, CF3SO3 [M]－ ¼ 148.9515, Found ¼ 148.9515.
C
21H17N79Br [M]þ
¼
362.0539,
364.0519,
¼
C
21H17N81Br [M]þ
¼
4.8. (Z) p-chlorophenyl o-(p-Methylphenyl)phenyl ketoxime (1Bj')
White solid; mp: 147e149 ꢀC; IR (neat): 3250, 1490, 1320, 998,
927, 765 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
¼ 2.29 (s, 3H), 7.04 (d,
2H, J ¼ 7.6 Hz), 7.14e7.18 (m, 4H), 7.23e7.26 (m, 2H), 7.27e7.31 (m,
4.5.1. 6-(p-Biphenyl)-8-methylphenanthridine (5Bk)
1H), 7.44e7.54 (m, 3H), 7.76 (s, 1H); 13C NMR (100 MHz, CDCl3):
Yield: 135.4 mg (78%); white solid; mp: 184e189 ꢀC; IR (neat):
1564, 1474, 1363, 1327, 750, 734 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼ 21.1, 127.0, 128.1 (2C), 128.2 (2C), 128.3 (2C), 128.8 (2C), 129.0,
129.3, 130.1, 131.4, 134.1, 135.1, 137.0, 137.4, 141.1, 158.0; HRMS (ESI):
d
¼ 2.55 (s, 3H), 7.41 (t, 1H, J ¼ 7.4 Hz), 7.49e7.53 (m, 2H), 7.67e7.76
(m, 5H), 7.79e7.84 (m, 4H), 7.97 (s, 1H), 8.24 (d, 1H, J ¼ 8.2 Hz),
8.60e8.64 (m, 2H); 13C NMR (100 MHz, CDCl3):
Calcd for C20H17ONCl [MþH]þ ¼ 322.0993, Found ¼ 322.0999.
d
¼ 21.8, 121.8,
4.9. 2-Methyl-9-fluorenone (3B)
122.2, 123.8, 125.3, 126.9, 127.2 (4C), 127.5, 128.1, 128.4, 128.9 (2C),
130.2 (2C), 130.3, 131.3, 132.3, 137.2, 138.9, 140.8, 141.5, 143.5, 160.6;
HRMS (ESI): Calcd for
Found ¼ 346.1585.
Yield: 54.5 mg (>99%); yellow solid; mp: 89e91 ꢀC; IR (neat):
C26H20N
[MþH]þ
¼
346.1590,
1709, 1602, 1457, 763, 735 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼ 2.38 (s, 3H), 7.24e7.30 (m, 2H), 7.40 (d, 1H, J ¼ 7.6 Hz), 7.46e7.49
(m, 3H), 7.63 (d, 1H, J ¼ 7.4 Hz); 13C NMR (100 MHz, CDCl3):
¼ 21.3,
d
4.6. Transformation of 2Bk into 8-methyl-6-[4’-(phenylethynyl)
phenyl]phenanthridine (6Bk)
120.0, 120.1, 124.2, 124.9, 128.5, 134.2, 134.3, 134.6, 135.1, 139.2,
141.8, 144.6, 194.2; HRMS (APCI): Calcd for
C14H11O
[MþH]þ ¼ 195.0804, Found ¼ 195.0805.
To a mixture of 2Bk (174.1 mg, 0.5 mmol), ethynylbenzene
(82.4 mL, 0.75 mmol), and CuI (3.8 mg, 0.02 mmol) in a mixture of
Et3N and DMF (5 : 4, 4.5 mL) was added PdCl2(PPh3)2 (14.0 mg,
0.02 mmol) under argon atmosphere. The obtained mixture was
stirred at 60 ꢀC for 24 h. Then, water (10.0 mL) was added to the
reaction mixture, and the product was extracted with a mixture of
hexane and AcOEt (4 : 1, 30.0 mL ꢂ 3). The organic layer was
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
11

K. Nakamura, E. Kobayashi, K. Moriyama et al.
Tetrahedron 91 (2021) 132244
(g) Y. Xu, Y. Chen, W. Li, Q. Xie, L. Shao, J. Org. Chem. 81 (2016) 8426e8435;
(h) W. Song, P. Yan, D. Shen, Z. Chen, X. Zeng, G. Zhong, J. Org. Chem. 82 (2017)
4444e4448;
(i) Q. Yao, X. Zhou, X. Zhang, C. Wang, P. Wang, M. Li, Org. Biomol. Chem. 15
(2017) 957e971;
(j) J. Li, C.A.D. Caiuby, M.W. Paixao, C. Li, Eur. J. Org Chem. (2018) 2498e2503;
(k) L. Wang, W. Xiong, Y. Peng, Q. Ding, Org. Biomol. Chem. 16 (2018)
8837e8844;
Acknowledgment
This work was supported by JSPS KAKENHI Grant Number
JP18K05118 in Japan.
Appendix A. Supplementary data
(l) S. Lu, H. Li, Y. Gong, S. Zhang, J. Zhang, S. Xu, J. Org. Chem. 83 (2018)
15415e15425;
(m) P. Lopez-Mendoza, L.D. Miranda, Org. Biomol. Chem. 18 (2020) 3487e3491;
(n) X. Li, D. Liang, W. Huang, H. Sun, L. Wang, M. Ren, B. Wang, Y. Ma, Tetra-
hedron 73 (2017) 7094e7099;
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2021.132244.
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(o) Y. Wang, J. Wang, G. Li, G. He, G. Chen, Org. Lett. 19 (2017) 1442e1445;
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