Radical arylalkoxycarbonylation of 2-isocyanobiphenyl with carbazates: Dual C-C bond formation toward phenanthridine-6-carboxylates

Article abstract of DOI:10.1021/jo500842e

A sequential oxidative radical alkoxycarbonylation and aromatization of 2-isocyanobiphenyl with carbazates was developed to furnish phenanthridine-6- carboxylates. Various functional groups such as methoxy, chloro, fluoro, trifluoromethoxy, and trifluoromethyl groups were tolerated well under the reaction conditions. The sequential radical addition-cyclization strategy represents a practical route to access phenanthridine-6-carboxylates.

Full text of DOI:10.1021/jo500842e

Note
pubs.acs.org/joc
Radical Arylalkoxycarbonylation of 2‑Isocyanobiphenyl with
Carbazates: Dual C−C Bond Formation toward Phenanthridine-6-
carboxylates
Changduo Pan,† Jie Han,† Honglin Zhang,† and Chengjian Zhu*,†,‡
†State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing
210093, P. R. China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Road, Shanghai 200032, P. R. China
S
* Supporting Information
ABSTRACT: A sequential oxidative radical alkoxycarbonyla-
tion and aromatization of 2-isocyanobiphenyl with carbazates
was developed to furnish phenanthridine-6-carboxylates.
Various functional groups such as methoxy, chloro, fluoro,
trifluoromethoxy, and trifluoromethyl groups were tolerated
well under the reaction conditions. The sequential radical addition−cyclization strategy represents a practical route to access
phenanthridine-6-carboxylates.
arbonylation reactions are powerful tools for the
by carbamoyl chlorides,6 oxaziridine,7 and diethyl azodicarbox-
ylate are well-documented.8
C
construction of C−C bonds in synthetic chemistry.1
Among these reactions, alkoxycarbonylation is highly valuable
since it enables the direct introduction of an ester moiety into
organic compounds.2 Generally, CO and alcohols are applied as
the source of the ester group in alkoxycarbonylation of ArX
(Scheme 1, eq 1). Recently, great efforts have been dedicated to
Radical chemistry has attracted much attention in organic
synthesis in the past decades.9 However, the radical process for
the preparation of esters is less developed.10 Yu reported the
Pd-catalyzed oxidative ethoxycarbonylation of the aromatic C−
H bond with diethyl azodicarboxylate by ethoxyacyl radicals.8
Carbazate was also applied to the construction of esters by
alkoxycarbonyl radicals.11 A sequential radical pathway is
synthetically very promising since it could furnish short
synthetic steps to access heterocycles.12 Recently, isocyanides
were developed to form 6-substituted phenanthridines that are
abundant in natural products and pharmaceuticals,13 proceed-
ing through the addition of a radical to the isonitrile to form an
imidolyl radical, followed by intramolecular cyclization. For
example, 6-arylation,14 6-trifluoromethylation,15 6-phosphory-
lation,16 6-acylation,17 and 6-alkylation18 of 2-isocyanobiphenyl
with different radical precursors were developed. Herein we
report an oxidative alkoxycarbonylation of 2-isocyanobiphenyl
with carbazates to provide phenanthridine-6-carboxylates by
sequential radical addition−cyclization reactions (Scheme 1, eq
3).
Scheme 1. Alkoxycarbonylation of ArX or ArH
Initially, the reaction of 2-isocyanobiphenyl (1a) with methyl
carbazate (2a) in the presence of the radical initiator tert-butyl
hydroperoxide (TBHP) with FeCl2 as the catalyst was
examined. To our delight, the desired methyl phenanthridine-
6-carboxylate (3aa) was obtained in 51% yield (Table 1, entry
1). After screening of a series of catalysts, such as FeCl2,
Fe(acac)2, FeCl3, and CuI, Fe(acac)2 was found to be the most
efficient (Table 1, entry 2). Subsequently, we attempted to
developing the efficient alkoxycarbonylation of C−H bonds
(Scheme 1, eq 2).3 For example, Zhang developed a rhodium-
catalyzed alkoxycarbonylation of sp2 C−H bonds with CO
toward esters.4 In 2012, Huang described a Pd-catalyzed
alkoxycarbonylation of sp3 C−H bonds with CO.5 Other
significant achievements in alkoxycarbonylation of C−H bonds
Received: April 15, 2014
Published: May 7, 2014
© 2014 American Chemical Society
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Note
a
a
Table 1. Optimization of the Reaction Conditions
Table 2. Substrate Scope
entry
[M]
FeCl2
radical initiator
solvent
yield (%)
1
2
TBHP
TBHP
TBHP
TBHP
DTBP
BPO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
51
76
37
32
26
33
8
Fe(acac)2
FeCl3
3
4
CuI
5
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
none
6
7
DCP
8
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
83
93
77
70
75
33
9
PhF
10
11
12
13
PhCF3
benzene
PhCl
PhF
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [M] (5 mol %),
radical initiator (0.6 mmol), and solvent (1.5 mL) under a N2
atmosphere for 12 h at 80 °C. TBHP was used as a 70% solution in
water. DTBP = di-tert-butyl peroxide. BPO = benzoyl peroxide. DCP =
dicumyl peroxide.
promote the yield by surveying solvents such as DCE, PhF,
PhCF3, PhCl, and benzene. Among the solvents screened, PhF
was the best, providing 3aa in 93% yield (Table 1, entry 9).
Using DTBP, BPO, or DCP instead of TBHP resulted in low
yields (Table 1, entries 5−7). The control experiment
demonstrated that the radical reaction could also occur without
catalyst but gave an unsatisfying result (Table 1, entry 13).
Consequently, the optimum reaction conditions were deter-
mined to be Fe(acac)2 (5 mol %) and TBHP (3 equiv) in PhF
at 80 °C under N2 (Table 1, entry 9).
To explore the substrate scope of this protocol, the
optimized reaction conditions were applied to a series of 2-
isocyanobiaryl compounds. As shown in Table 2, various
functional groups such as methoxy, chloro, fluoro, trifluor-
omethoxy, and trifluoromethyl groups were tolerated well
under the present oxidative conditions, affording the products
in good yields. We studied the effect of the substituents on the
aromatic ring with the isocyanide group. As expected, the
corresponding phenanthridine-6-carboxylates were obtained in
good yields. Aromatic rings possessing electron-donating
groups (1b−d; Table 2) gave higher yields than those with
electron-withdrawing groups (1f−j; Table 2). Subsequently, the
effects of substituents at the 4-position of the aromatic ring
without the isocyanide group were investigated. The iso-
cyanides 1k−m bearing electron-donating groups provided the
corresponding products in higher yields than did the electron-
withdrawing analogues 1o and 1p. Notably, halogen groups
were tolerable, which was suitable for potential further
functionalization. 2-Isocyanobiphenyl bearing an ortho sub-
stituent revealed a lower reactivity due to the steric effect
(Table 2, 3ra). To investigate the regioselectivity of the
cyclization, 2-isocyanobiphenyl 1s bearing a m-methyl group
was investigated, and it afforded a mixture of two regioisomers
in a 2:1 ratio (Table 2, 3sa + 3sa′). As expected, when ethyl
carbazate 2b as an ethoxycarbonyl surrogate was employed, the
arylethoxycarbonylation also ran well to afford ethyl phenan-
thridine-6-carboxylate (3ab) in good yield.
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), Fe(acac)2 (5 mol
%), TBHP (0.6 mmol, 70% solution in water), and PhF (1.5 mL)
under a N2 atmosphere for 12 h at 80 °C. The ratio of isomers was
determined by H NMR analysis of the isolated products.
b
1
To have a better understanding of the difunctionalization of
2-isocyanobiphenyl, some mechanistic experiments were
carried out. A 1:1 mixture of substrates 1a and 1a′ was used
to determine the intermolecular kinetic isotope effect, and no
kinetic isotope effect (kH/kD = 1) was observed (Scheme 2, eq
1). This result revealed that the arylation step may be
compatible with either the SEAr mechanism or the free radical
mechanism.19 When 2.0 equiv of 2,2,6,6-tetramethylpiperidine
oxide (TEMPO) was added as a radical inhibitor, the desired
product was not observed and the TEMPO−COOMe adduct
was detected by ESI (Scheme 2, eq 2), providing evidence
favoring the free radical mechanism.
On the basis of the above experimental results, a possible
mechanism is proposed in Scheme 3. Initially, Fe(II)-assisted
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Note
H2O), and PhF (1.5 mL) was added to a sealed tube. The sealed tube
was evacuated and back-filled with N2. The reaction mixture was
vigorously stirred at 80 °C for 12 h. After the completion of the
reaction, the solvent was evaporated under reduced pressure, and the
residue was purified by flash column chromatography or preparative
TLC on GF254 (petroleum/ethyl acetate) to afford the desired
product 3.
Scheme 2. Preliminary Mechanistic Study
Methyl Phenanthridine-6-carboxylate (3aa).21 White solid (44
1
mg, 93%). H NMR (CDCl3, 400 MHz): δ 8.64−8.61 (m, 2H), 8.56
(d, J = 8.3 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H),
7.79−7.69 (m, 3H), 4.12 (s, 3H). 13C NMR {1H} (CDCl3, 100
MHz): δ 166.5, 150.3, 142.6, 133.4, 131.1, 130.9, 129.0, 128.7, 127.9,
127.3, 124.9, 123.5, 122.1, 122.0, 53.2.
Methyl 2-Methylphenanthridine-6-carboxylate (3ba). Green solid
1
(40.6 mg, 81%), mp 162−164 °C. H NMR (CDCl3, 400 MHz): δ
Scheme 3. Proposed Mechanism
8.64 (d, J = 8.4 Hz, 2H), 8.61 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 8.18
(d, J = 8.4 Hz, 1H), 7.84 (t, J = 8.2 Hz, 1H), 7.70 (t, J = 8.1 Hz, 1H),
7.60−7.57 (m, 1H), 4.14 (s, 3H), 2.62 (s, 3H). 13C NMR {1H}
(CDCl3, 100 MHz): δ 166.5, 149.1, 140.7, 139.1, 133.1, 131.1, 130.9,
130.5, 127.8, 127.4, 124.9, 123.6, 122.1, 121.6, 53.2, 22.2. HRMS (ESI)
m/z: calcd for C16H13NNaO2 [M + Na]+ 274.0838, found 274.0840.
Methyl 3-Methylphenanthridine-6-carboxylate (3ca). White solid
1
(41.6 mg, 83%), mp 81−83 °C. H NMR (CDCl3, 400 MHz): δ
8.61−8.56 (m, 2H), 8.42 (d, J = 8.4 Hz, 1H), 8.06 (s, 1H), 7.83 (t, J =
8.3 Hz, 1H), 7.67 (t, J = 8.3 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 4.14 (s,
3H), 2.57 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ 166.6,
150.2, 142.7, 139.3, 133.5, 131.1, 130.5, 130.4, 127.5, 127.3, 123.2,
122.6, 121.9, 121.8, 53.2, 21.5. HRMS (ESI) m/z: calcd for
C16H13NNaO2 [M + Na]+ 274.0838, found 274.0839.
Methyl 3-Methoxyphenanthridine-6-carboxylate (3da). Yellowish
solid (45.9 mg, 86%), mp 110−112 °C. 1H NMR (CDCl3, 400 MHz):
δ 8.60 (d, J = 8.3 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 8.45−8.42 (m,
1H), 7.81 (t, J = 8.1 Hz, 1H), 7.67−7.62 (m, 2H), 7.37−7.34 (m, 1H),
4.15 (s, 3H), 3.97 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ
166.5, 160.3, 150.5, 144.2, 133.7, 131.2, 127.4, 126.9, 123.2, 122.7,
121.6, 120.3, 119.1, 110.2, 55.7, 53.3. HRMS (ESI) m/z: calcd for
C16H13NNaO3 [M + Na]+ 290.0788, found 290.0787.
Methyl 2-(Trifluoromethoxy)phenanthridine-6-carboxylate (3ea).
Brown liquid (43 mg, 67%). 1H NMR (CDCl3, 400 MHz): δ 8.65 (d, J
= 8.0 Hz, 1H), 8.57 (d, J = 8.3 Hz, 1H), 8.37 (s, 1H), 8.32 (d, J = 9.0
Hz, 1H), 7.92 (t, J = 8.3 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.63 (d, J =
8.2 Hz, 1H), 4.15 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ
166.2, 150.8, 148.96, 148.94, 140.8, 133.0, 132.8, 131.6, 128.8, 127.6,
126.0, 123.6, 122.4, 122.2, 113.5, 53.3. 19F NMR (376 MHz, CDCl3):
δ −57.5. HRMS (ESI) m/z: calcd for C16H10F3NNaO3 [M + Na]+
344.0505, found 344.0503.
homolysis of TBHP into tert-butoxy radical and tert-
butylperoxy radical occurs. With the aid of Fe(II), the
homolysis of TBHP into tert-butoxy radical may be accelerated
by single-electron transfer along with the formation of an
Fe(III) species.20 Then, C−N bond cleavage of the carbazate
forms alkoxycarbonyl radical A with the release of N2 through
stepwise hydrogen abstraction.11 Then radical A attacks the
NC bond of 2-isocyanobiaryl 1a to form imidoyl radical B,
which upon intramolecular cyclization with an aryl ring gives
radical intermediate C. Finally, hydrogen abstraction of radical
intermediate C takes place, providing the desired product 3aa.
In summary, we have developed a novel sequential radical
bimolecular C−C coupling of 2-isocyanobiaryls with carbazates
to provide phenanthridine-6-carboxylates. As the oxidant for
this procedure, cheap and commercially available TBHP is
used. The procedure involves dual C−C bond formation by
sequential radical addition and cyclization reactions.
Methyl 3-Fluorophenanthridine-6-carboxylate (3fa). Yellowish
solid (36.2 mg, 71%), mp 128−130 °C. 1H NMR (CDCl3, 400 MHz):
δ 8.57−8.50 (m, 3H), 7.93−7.90 (m, 1H), 7.86 (t, J = 8.2 Hz, 1H),
7.70 (t, J = 8.1 Hz, 1H), 7.50−7.45 (m, 1H), 4.15 (s, 3H). 13C NMR
{1H} (CDCl3, 100 MHz): δ 166.3, 162.7 (d, JC−F = 247.8 Hz), 151.7,
143.8 (d, JC−F = 11.9 Hz), 133.2, 131.6, 127.8, 127.5, 124.1 (d, JC−F
=
9.4 Hz), 123.0, 121.9, 121.6, 117.9 (d, JC−F = 23.8 Hz), 115.2 (d, JC−F
= 20.6 Hz), 53.3. 19F NMR (376 MHz, CDCl3): δ −110.9. HRMS
(ESI) m/z: calcd for C15H10FNNaO2 [M + Na]+ 278.0588, found
278.0586.
EXPERIMENTAL SECTION
■
Methyl 2-Fluorophenanthridine-6-carboxylate (3ga). Yellowish
solid (35.2 mg, 69%), mp 144−146 °C. 1H NMR (CDCl3, 400 MHz):
δ 8.66 (d, J = 8.2 Hz, 1H), 8.50 (d, J = 8.3 Hz, 1H), 8.29−8.25 (m,
1H), 8.17−8.14 (m, 1H), 7.87 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 8.3 Hz,
1H), 7.53−7.48 (m, 1H), 4.15 (s, 3H). 13C NMR {1H} (CDCl3, 100
MHz): δ 166.3, 162.8 (d, JC−F = 248.6 Hz), 149.4 (d, JC−F = 2.9 Hz),
139.4 (d, JC−F = 1.3 Hz), 133.3 (d, JC−F = 9.4 Hz), 132.8 (d, JC−F = 4.3
Hz), 131.2, 128.6, 127.5, 126.6 (d, JC−F = 9.4 Hz), 123.5, 122.3, 118.2
(d, JC−F = 24.4 Hz), 107.1 (d, JC−F = 23.4 Hz), 53.3. 19F NMR (376
MHz, CDCl3): δ −109.4. HRMS (ESI) m/z: calcd for C15H10FNNaO2
[M + Na]+ 278.0588, found 278.0589.
General Information. NMR spectra were measured on 400 MHz
1
NMR spectrometers (400 MHz for H, 100 MHz for 13C, 376 MHz
for 19F) using CDCl3 as the solvent with tetramethylsilane (TMS) as
the internal standard. Chemical shifts (δ) are given in parts per million
relative to TMS, and coupling constants (J) are given in hertz. 13C
NMR spectra were recorded at 100 MHz with complete proton
decoupling. HRMS was performed on a TOF LC/MS equipped with
an ESI probe operating in positive or negative ion mode. 2-
Isocyanobiaryl compounds were prepared according to the reported
procedure.14a
General Procedure for the Sequential Radical Coupling of 2-
Isocyanobiaryls with NH2NHCOOMe. A mixture of 2-isocyano-
biaryl 1 (0.2 mmol), NH2NHCOOMe (2a) (0.4 mmol, 36 mg),
Fe(acac)2 (5 mol %, 2.5 mg), TBHP (0.6 mmol, 70% solution in
Methyl 2-Chlorophenanthridine-6-carboxylate (3ha). White solid
1
(35.2 mg, 65%), mp 132−133 °C. H NMR (CDCl3, 400 MHz): δ
8.62 (d, J = 8.3 Hz, 1H), 8.52 (d, J = 8.3 Hz, 1H), 8.50 (s, 1H), 8.19
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Note
(d, J = 8.8 Hz, 1H), 7.87 (t, J = 8.3 Hz, 1H), 7.74 (t, J = 8.2 Hz, 1H),
7.71−7.68 (m, 1H), 4.15 (s, 3H). 13C NMR {1H} (CDCl3, 100
MHz): δ 166.2, 150.4, 140.9, 134.9, 132.4, 132.3, 131.5, 129.7, 128.6,
127.5, 125.9, 123.7, 122.2, 121.8, 53.3. HRMS (ESI) m/z: calcd for
C15H10ClNNaO2 [M + Na]+ 294.0292, found 294.0289.
(ESI) m/z: calcd for C16H10F3NNaO2 [M + Na]+ 328.0556, found
328.0556.
Methyl Benzo[i]phenanthridine-5-carboxylate (3qa). Colorless
liquid (48.2 mg, 84%). 1H NMR (CDCl3, 400 MHz): δ 8.51 (d, J = 8.3
Hz, 1H), 8.46 (d, J = 9.0 Hz, 1H), 8.31 (d, J = 8.3 Hz, 1H), 8.26 (d, J
= 8.3 Hz, 1H), 8.05 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.75
(t, J = 8.2 Hz, 1H), 7.69−7.58 (m, 3H), 4.14 (s, 3H). 13C NMR {1H}
(CDCl3, 100 MHz): δ 169.9, 150.4, 143.3, 133.9, 132.8, 132.6, 130.1,
129.4, 129.1, 128.5, 128.1, 127.6, 127.1, 124.7, 124.4, 122.6, 119.7,
119.0, 53.4. HRMS (ESI) m/z: calcd for C19H13NNaO2 [M + Na]+
310.0838, found 310.0837.
Methyl 3-(Trifluoromethyl)phenanthridine-6-carboxylate (3ia).
1
Semisolid (40.9 mg, 67%). H NMR (CDCl3, 400 MHz): δ 8.64−
8.61 (m, 3H), 8.57 (s, 1H), 7.94−7.89 (m, 2H), 7.81−7.77 (m, 1H),
4.16 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ 166.0, 151.7,
141.8, 132.6, 131.8, 130.9 (q, JC−F = 32.9 Hz), 129.1, 128.4 (q, JC−F
=
4.1 Hz), 127.6, 127.1, 124.4 (q, JC−F = 3.1 Hz), 124.0, 123.2, 122.5,
53.4. 19F NMR (376 MHz, CDCl3): δ −62.4. HRMS (ESI) m/z: calcd
for C16H10F3NNaO2 [M + Na]+ 328.0556, found 328.0558.
Methyl 10-Chlorophenanthridine-6-carboxylate (3ra). White
solid (28.1 mg, 52%), mp 109−111 °C. 1H NMR (CDCl3, 400
MHz): δ 9.83 (d, J = 8.6 Hz, 1H), 8.47 (d, J = 8.2 Hz, 1H), 8.31 (d, J =
8.0 Hz, 1H), 7.96 (d, J = 7.7 Hz, 1H), 7.87−7.82 (m, 1H), 7.79−7.75
(m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 4.16 (s, 3H). 13C NMR {1H}
(CDCl3, 100 MHz): δ 166.6, 151.1, 143.7, 135.0, 131.5, 131.0, 130.3,
129.5, 128.2, 127.7, 126.7, 126.4, 125.7, 123.9, 53.4. HRMS (ESI) m/z:
calcd for C15H10ClNNaO2 [M + Na]+ 294.0292, found 294.0294.
Methyl 7-Methylphenanthridine-6-carboxylate (3sa) and Methyl
9-Methylphenanthridine-6-carboxylate (3sa′). Brown liquid (33 mg,
Methyl 2-(Trifluoromethyl)phenanthridine-6-carboxylate (3ja).
1
White solid (42 mg, 69%), mp 112−114 °C. H NMR (CDCl3, 400
MHz): δ 8.73 (s, 1H), 8.54 (d, J = 8.3 Hz, 1H), 8.49 (d, J = 8.3 Hz,
1H), 8.27 (d, J = 8.5 Hz, 1H), 7.88−7.81 (m, 2H), 7.70−7.66 (m,
1H), 4.07 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ 166.1,
152.5, 143.9, 133.1, 131.9, 131.8, 130.2 (q, JC−F = 32.7 Hz), 128.8,
127.6, 125.4, 125.0 (q, JC−F = 3.1 Hz), 124.5, 123.6, 122.7, 122.1, 119.9
(q, JC−F = 4.2 Hz), 53.4. 19F NMR (376 MHz, CDCl3): δ −62.0.
HRMS (ESI) m/z: calcd for C16H10F3NNaO2 [M + Na]+ 328.0556,
found 328.0555.
1
66%). H NMR (CDCl3, 400 MHz): δ 8.55−8.51 (m, 3H), 8.41 (s,
0.51H), 8.26 (d, J = 8.3 Hz, 0.5H), 8.19 (d, J = 8.3 Hz, 1H), 7.77−7.66
(m, 4H), 7.53 (d, J = 8.5 Hz, 0.59H), 7.49 (d, J = 7.2 Hz, 1.12H), 4.24
(s, 1.45H), 4.11 (s, 2.9H), 2.72 (s, 3H), 2.63 (s, 1.5H). HRMS (ESI)
m/z: calcd for C16H13NNaO2 [M + Na]+ 274.0838, found 274.0837.
Ethyl Phenanthridine-6-carboxylate (3ab).21 Compound 3ab
was obtained using 1a and NH2NHCOOEt (2b). White solid (39.1
Methyl 8-Methylphenanthridine-6-carboxylate (3ka). White solid
1
(40.2 mg, 80%), mp 80−81 °C. H NMR (CDCl3, 400 MHz): δ
8.53−8.50 (m, 2H), 8.36 (s, 1H), 8.27−8.25 (m, 1H), 7.75−7.66 (m,
3H), 4.15 (s, 3H), 2.58 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz):
δ 166.6, 150.1, 142.2, 138.1, 133.0, 131.4, 130.8, 128.6, 126.6, 125.0,
123.6, 122.2, 121.9, 53.2, 21.9. HRMS (ESI) m/z: calcd for
C16H13NNaO2 [M + Na]+ 274.0838, found 274.0840.
1
mg, 78%). H NMR (CDCl3, 400 MHz): δ 8.63 (d, J = 8.3 Hz, 1H),
8.57−8.52 (m, 2H), 8.29 (d, J = 7.8 Hz, 1H), 7.86 (t, J = 8.2 Hz, 1H),
7.78−7.69 (m, 3H), 4.64 (q, J = 7.2 Hz, 2H), 1.53 (t, J = 7.2 Hz, 3H).
13C NMR {1H} (CDCl3, 100 MHz): δ 166.2, 151.0, 142.4, 133.4,
131.3, 130.7, 129.1, 128.6, 127.9, 127.3, 124.8, 123.3, 122.2, 122.0,
62.5, 14.4.
Intermolecular Competition Experiment with Isotopically
Labeled 1a′. A mixture of 2-isocyanobiaryl 1a (0.1 mmol) and the
labeled analogue 1a′ (0.1 mmol), NH2NHCOOMe 2a (0.4 mmol),
Fe(acac)2 (5 mol %, 2.5 mg), TBHP (0.6 mmol, 70% in H2O), and
PhF (1.5 mL) was added to a sealed tube, which was evacuated and
back-filled with N2. The reaction mixture was vigorously stirred at 80
°C for 12 h. After the completion of the reaction, the solvent was
evaporated under reduced pressure, and the residue was purified by
flash column chromatography on silica gel or preparative TLC on
GF254 to afford the desired products 3aa and 3aa′. 1H NMR (CDCl3,
400 MHz): δ 8.67−8.62 (m, 1H), 8.59 (d, J = 7.7 Hz, 1H), 7.88 (d, J =
8.2 Hz, 0.51H), 7.80−7.71 (m, 2.52H), 4.15 (s, 3H).
Methyl 8-Methoxyphenanthridine-6-carboxylate (3la). Yellow
solid (43.6 mg, 82%), mp 203−205 °C. 1H NMR (CDCl3, 400
MHz): δ 8.56−8.54 (m, 1H), 8.50−8.48 (m, 1H), 8.28−8.25 (m, 1H),
8.15 (s, 1H), 7.72−7.70 (m, 2H), 7.51−7.48 (m, 1H), 4.15 (s, 3H),
3.99 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ 166.6, 159.1,
148.5, 141.8, 131.0, 128.9, 128.1, 125.3, 125.2, 123.7, 122.5, 121.6,
106.7, 55.6, 53.2. HRMS (ESI) m/z: calcd for C16H13NNaO3 [M +
Na]+ 290.0788, found 290.0786.
Methyl 8-(tert-Butyl)phenanthridine-6-carboxylate (3ma). Brown
liquid (48.6 mg, 83%). 1H NMR (CDCl3, 400 MHz): δ 8.65−8.64 (m,
1H), 8.59−8.53 (m, 2H), 8.29−8.26 (m, 1H), 7.97−7.95 (m, 1H),
7.76−7.69 (m, 2H), 4.16 (s, 3H), 1.46 (s, 9H). 13C NMR {1H}
(CDCl3, 100 MHz): δ 166.7, 151.1, 150.2, 142.4, 131.4, 130.9, 129.7,
128.7, 125.0, 123.6, 122.8, 122.0, 121.9, 53.2, 35.2, 31.2. HRMS (ESI)
m/z: calcd for C19H19NNaO2 [M + Na]+ 316.1308, found 316.1305.
Methyl 8-Phenylphenanthridine-6-carboxylate (3na). Yellowish
solid (53.8 mg, 86%), mp 136−138 °C. 1H NMR (CDCl3, 400 MHz):
δ 8.86 (s, 1H), 8.67 (d, J = 8.6 Hz, 1H), 8.56 (d, J = 8.4 Hz, 1H), 8.29
(d, J = 7.4 Hz, 1H), 8.10 (d, J = 8.6 Hz, 1H), 7.77−7.73 (m, 4H), 7.51
(t, J = 7.4 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 4.16 (s, 3H). 13C NMR
{1H} (CDCl3, 100 MHz): δ 166.5, 150.2, 142.5, 140.7, 140.0, 132.4,
131.0, 130.5, 129.0, 128.9, 128.0, 127.5, 125.3, 124.8, 124.0, 122.8,
122.1, 53.3. HRMS (ESI) m/z: calcd for C21H15NNaO2 [M + Na]+
336.0995, found 336.0994.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of compounds 3aa−sa and 3ab and
19F NMR spectra of compounds 3ea, 3fa, 3ga, 3ia, 3ja, and
3pa. This material is available free of charge via the Internet at
http://pubs.acs.org.
Methyl 8-Chlorophenanthridine-6-carboxylate (3oa). White solid
1
(36.8 mg, 68%), mp 126−128 °C. H NMR (CDCl3, 400 MHz): δ
AUTHOR INFORMATION
■
8.81 (d, J = 8.3 Hz, 1H), 8.51 (d, J = 8.3 Hz, 1H), 8.49 (s, 1H), 8.20
(d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 8.3 Hz, 1H),
7.41−7.68 (m, 1H), 4.15 (s, 3H). 13C NMR {1H} (CDCl3, 100
MHz): δ 166.5, 150.3, 140.7, 134.9, 132.4, 132.2, 131.6, 129.8, 128.6,
127.5, 125.9, 123.6, 122.1, 121.7, 53.3. HRMS (ESI) m/z: calcd for
C15H10ClNNaO2 [M + Na]+ 294.0292, found 294.0290.
Corresponding Author
*E-mail: cjzhu@nju.edu.cn.
Notes
The authors declare no competing financial interest.
Methyl 8-(Trifluoromethyl)phenanthridine-6-carboxylate (3pa).
1
Yellowish solid (45 mg, 74%), mp 90−92 °C. H NMR (CDCl3, 400
ACKNOWLEDGMENTS
■
MHz): δ 9.04 (s, 1H), 8.69 (d, J = 8.7 Hz, 1H), 8.54 (d, J = 8.0 Hz,
1H), 8.30 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.86−7.76 (m,
2H), 4.17 (s, 3H). 13C NMR {1H} (CDCl3, 100 MHz): δ 165.9,
149.4, 143.1, 135.4, 131.2, 130.2, 129.7 (q, JC−F = 32.7 Hz), 129.4,
126.9 (q, JC−F = 3.1 Hz), 125.2 (q, JC−F = 4.5 Hz), 124.0, 123.2, 122.9,
122.5, 122.4, 53.4. 19F NMR (376 MHz, CDCl3): δ −62.3. HRMS
We gratefully acknowledge the National Natural Science
Foundation of China (21172106 and 21372114), the National
Basic Research Program of China (2010CB923303), and the
Research Fund for the Doctoral Program of Higher Education
of China (20120091110010) for their financial support. C.P.
5377
dx.doi.org/10.1021/jo500842e | J. Org. Chem. 2014, 79, 5374−5378

The Journal of Organic Chemistry
Note
DOI: 10.1039/C4CC00743C. (c) Wang, L.; Sha, W.; Dai, Q.; Feng,
X.; Wu, W.; Peng, H.; Chen, B.; Cheng, J. Org. Lett. 2014, 16, 2088.
(19) Jones, W. D. Acc. Chem. Res. 2003, 36, 140.
thanks the National Natural Science Foundation of China for
support (21272178).
(20) Liu, W.; Li, Y.; Liu, K.; Li, Z. J. Am. Chem. Soc. 2011, 133,
10756.
(21) Chiba, S.; Zhang, L.; Ang, G.; Hui, B. Org. Lett. 2010, 12, 2052.
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