Synthesis of phenanthridin-6-yldiphenylphosphine oxides by oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides

Article abstract of DOI:10.1016/j.tet.2014.05.039

A Mn(III)-promoted oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides is reported, providing phenanthridin-6- yldiphenylphosphine oxides in good yields. Radical phosphonation and isocyanide insertion are believed to be involved in the reaction process.

Full text of DOI:10.1016/j.tet.2014.05.039

Tetrahedron 70 (2014) 4652e4656
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of phenanthridin-6-yldiphenylphosphine oxides by
oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine
oxides
,
b,c,
Yuewen Li a, Guanyinsheng Qiu b, Qiuping Ding a , Jie Wu
*
*
a Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical Engineering,
Jiangxi Normal University, Nanchang, Jiangxi 330022, China
b Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A Mn(III)-promoted oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides is re-
ported, providing phenanthridin-6-yldiphenylphosphine oxides in good yields. Radical phosphonation
and isocyanide insertion are believed to be involved in the reaction process.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 22 February 2014
Received in revised form 1 May 2014
Accepted 8 May 2014
Available online 20 May 2014
Keywords:
Diarylphosphine oxide
2-Isocyanobiphenyl
Manganous(III) acetate
Phenanthridin-6-yldiphenylphosphine
oxide
Oxidative cyclization
1. Introduction
be employed in our program for the synthesis of natural products-
like compounds.
Phosphine-containing compounds are widely found in medi-
cines1 and organo-ligands.2 Consequently, tremendous effort has
been focused on the incorporation of phosphorus atom into tar-
geted molecules with the aim of improving their properties. To
date, it is generally accepted that cross-couplings of electrophiles3,4
with H-phosphonates in the presence of transition metals (such as
palladium, copper, and nickel salts)4d,5,6 have become practical and
powerful methods to construct C(sp2)eP bonds, as represented by
Hirao reactions. Recently, the alternatives for the formation of
C(sp2)eP bonds through CeH activation have been developed,
where substrates with a directing group were crucial for the final
outcome.7 In particular, radical phosphonation triggered by Mn(III)
or silver salt was demonstrated to be a facile route for the prepa-
ration of the phosphine-containing products with high effi-
ciency.7e,8,9 Considering the remarkable significance of
phosphonations, we anticipated that radical phosphonation would
So far, isocyanide insertion has been attracted growing em-
phasis in the community of chemistry due to its contributions into
palladium-catalyzed imidoylative and cyanative reactions.10 Our
continuous interest in isocyanide insertion prompted us to focus on
the radical process of isocyanide insertion. Recently, 2-
isocyanobiphenyl 1 was identified as a versatile building block for
the construction of nitrogen-containing heterocycles.11 As a privi-
leged structure, the phenanthridine core is one of common struc-
tural units existed widely in many natural alkaloids, which show
antibacterial, antitumor, and antileukemic activities.12 For example,
Trisphaeridine12b is used as DNA intercalator and Fagaronine was
reported as protein kinase C and DNA topoisomerase 1 inhibitor.12c
Inspired by the radical phosphonation and the advances of iso-
cyanide insertion, we envisioned that phosphated phenanthridines
3 could be generated through a reaction of 2-isocyanobiphenyls 1
with diarylphosphine oxides 2, which would combine radical
phosphonation and isocyanide insertion in a one-pot procedure
(Scheme 1).13
As mentioned above, we reasoned that a phosphonate radical A
would be afforded under proper conditions by the treatment of
* Corresponding authors. Tel.: þ86 21 6510 2412; fax: þ86 21 6564 1740; e-mail
addresses: dqpjxnu@gmail.com (Q. Ding), jie_wu@fudan.edu.cn (J. Wu).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.05.039

Y. Li et al. / Tetrahedron 70 (2014) 4652e4656
4653
improved by switching the additive to Ag2CO3, or PhI(OAc)2 (Table
1, entries 2 and 4). To our delight, the expected phosphonated
phenanthridine 3a was obtained when anhydrous Cu(OAc)2 or
silver(I) acetate was used as an additive (Table 1, entries 3 and 5).
Further evaluation found that Mn(OAc)3 was the best choice,
leading to the desired product 3a in 63% yield (Table 1, entry 7).
Other solvents were examined subsequently (Table 1, entries
8e13). However, no better yields were afforded, and toluene was
still the most efficient one. The loading of additive made great
impact on the outcome, and the desire product 3a was isolated in
73% yield when the amount of Mn(OAc)3 was increased to 3.0 equiv
(Table 1, entry 14). The reaction temperature was evaluated as well.
Gratifyingly, a satisfied yield (80%) was obtained when the reaction
was conducted at 40 ꢀC (Table 1, entry 17).
After obtaining the optimized reaction conditions, we started to
explore the substrate scope of this transformation. The results are
shown in Table 2. The 2-isocyanobiphenyls 1 bearing either
electron-rich or electron-deficient substituents on the aromatic
ring were all compatible under the standard conditions, and the
expected phenanthridin-6-yldiphenylphosphine oxides 3 were
afforded in good yields. The reaction proceeded with excellent
regioselectivity. For example, compound 3c was generated exclu-
sively when the 2-isocyanobiphenyl 1c with two non-equivalent
ortho hydrogen atoms was employed. Additionally, 4-(2-
isocyanophenyl)pyridine 1i and 1-(2-isocyanophenyl)naphthalene
1l were suitable substrates as well in this annulation reaction.
Moreover, other diarylphosphites were used in the reaction, and
the corresponding products (3m and 3n) were furnished in good
yields.
Scheme 1. A proposed route to phenanthridin-6-yldiphenylphosphine oxides by oxi-
dative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides.
Mn(III) or silver salt with diarylphosphine oxide 2. Since the aryl
phosphonate radical would be easily trapped by 2-
isocyanobiphenyl, this species would undergo a radical addition
into 2-isocyanobiphenyl leading to imdoyl radical B. Subsequently,
an oxidative cyclization would be happened to generate in-
termediate C. The following transformation would furnish cyclo-
hexadienyl cation D, which would be ultimately aromatized to
produce the targeted product 3 (Scheme 1).
2. Results/discussion
Table 2
Therefore, to verify the feasibility of the projected route as il-
lustrated in Scheme 1, we started to explore the practicability of
this transformation. Initially, the reaction of 2-isocyanobiphenyl 1a
with diphenylphosphine oxide 2a was selected as the model. The
preliminary screening results were summarized in Table 1. At the
outset, the reaction was performed in the presence of silver oxide in
toluene at 70 ꢀC (Table 1, entry 1). However, only a trace amount of
the desired product 3a was detected. The result could not be
Synthesis of phenanthridin-6-yldiphenylphosphine oxides 3 by oxidative cyclization
of 2-isocyanobiphenyls 1 with diphenylphosphine oxides 2a
Table 1
Initial studies for the oxidative cyclization of 2-isocyanobiphenyl 1a with diphe-
nylphosphine oxide 2a
Entry
Additive (equiv)
Solvent
T (ꢀC)
Yield (%)a
1
2
3
4
5
6
7
8
Ag2O/2.0
Ag2CO3/2.0
AgOAc/2.0
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
CH3CN
THF
DMF
1,4-Dioxane
CH3OH
Toluene
Toluene
Toluene
Toluene
Toluene
70
70
70
70
70
70
70
70
70
70
70
70
70
70
90
50
40
25
trace
Trace
24
nd
19
38
63
62
47
46
Trace
53
Trace
73
70
73
80
67
PhI(OAc)2/2.0
Cu(OAc)2/2.0
Mn(acac)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/2.0
Mn(OAc)3/3.0
Mn(OAc)3/3.0
Mn(OAc)3/3.0
Mn(OAc)3/3.0
Mn(OAc)3/3.0
9
10
11
12
13
14
15
16
17
18
a
Isolated yield based on 2-isocyanobiphenyl 1a.

4654
Y. Li et al. / Tetrahedron 70 (2014) 4652e4656
To probe into the reaction mechanism, we investigated the
J¼12.1 Hz), 127.90, 127.80, 127.67, 124.25, 122.03; Exact mass calcd
for C25H19NOP [MþH]þ 380.1204, found 380.1197.
reaction in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO), which is known as an effective radical scavenger. As
expected, no desired product (3a) was detected when 2.5 equiv of
TEMPO was added in the reaction under the standard conditions
shown in Table 2 (Scheme 2, Eq. a). Instead, a distinctive com-
4.1.2. (10-Methylphenanthridin-6-yl)diphenylphosphine oxide (3b).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.46 (d, J¼8.1 Hz, 1H),
8.84e8.81 (m, 1H), 8.07e8.04 (m, 1H), 7.94e7.88 (m, 4H), 7.70e7.66
(m, 3H), 7.58 (t, J¼8.1 Hz, 1H), 7.52e7.48 (m, 2H), 7.46e7.41 (m, 4H),
pound 4 (31P NMR
d 34.5, exact mass calcd for C21H29NO2P
[MþH]þ 358.1758; found 358.1723) was observed. Therefore,
a control experiment without the addition of 2-isocyanobiphenyl
1a was performed (Scheme 2, Eq. b), which demonstrated the
proposed radical process initiated by the formation of phospho-
nate radical A.
3.10 (s, 3H); 31P NMR (162 MHz, CDCl3) 29.36 (s); 13C NMR
d
(100 MHz, CDCl3)
d
157.24 (d, J¼128.4 Hz), 143.82 (d, J¼23.9 Hz),
135.18, 133.05 (d, J¼105.2 Hz), 132.26 (d, J¼9.1 Hz), 132.00 (d,
J¼6.5 Hz), 131.55, 131.41, 131.03 (d, J¼10.5 Hz), 129.17 (d, J¼23.4 Hz),
128.59 (d, J¼11.7 Hz), 128.07 (d, J¼12.1 Hz), 127.87 (d, J¼7.1 Hz),
127.14 (d, J¼23.0 Hz),126.54,125.67,122.05, 26.95; Exact mass calcd
for C26H21NOP [MþH]þ 394.1361, found 394.1326.
4.1.3. (9-Methylphenanthridin-6-yl)diphenylphosphine
oxide
9.39 (d, J¼8.5 Hz,
(3c). Yellow solid; 1H NMR (400 MHz, CDCl3)
d
1H), 8.57e8.56 (m, 1H), 8.41 (s, 1H), 8.04e8.01 (m, 1H), 7.95 (d,
J¼7.7 Hz, 2H), 7.92 (d, J¼7.7 Hz, 2H), 7.68e7.66 (m, 2H), 7.51e7.48
(m, 3H), 7.46e7.39 (m, 4H), 2.60 (s, 3H); 31P NMR (162 MHz, CDCl3)
d
28.19 (s); 13C NMR (100 MHz, CDCl3)
d
156.52 (d, J¼128.7 Hz),
143.82 (d, J¼23.4 Hz), 141.56, 134.03 (d, J¼104.0 Hz), 132.81 (d,
J¼6.5 Hz), 132.44 (d, J¼9.1 Hz), 132.02 (d, J¼8.9 Hz), 131.63, 131.07,
129.62, 128.52, 128.35, 128.14 (d, J¼12.0 Hz), 126.09 (d, J¼23.6 Hz),
124.20, 122.08, 121.71, 22.40; Exact mass calcd for C26H21NOP
[MþH]þ 394.1361, found 394.1358.
Scheme 2. Oxidative cyclization of 2-isocyanobiphenyl with diphenylphosphine oxide
in the presence of TEMPO.
4.1.4. (8-Methylphenanthridin-6-yl)diphenylphosphine oxide (3d).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d 9.33 (s, 1H), 8.53e8.51 (m,
2H), 8.04e8.01 (m, 1H), 7.97e7.92 (m, 4H), 7.70e7.64 (m, 3H),
7.52e7.48 (m, 2H), 7.46e7.41 (m, 4H), 2.55 (s, 3H); 31P NMR
3. Conclusions
(162 MHz, CDCl3) d d 156.28 (d,
29.42 (s); 13C NMR (100 MHz, CDCl3)
In conclusion, we have reported a facile route for the synthesis
of diverse phenanthridin-6-yldiphenylphosphine oxides through
a Mn(III)-promoted oxidative cyclization of 2-isocyanobiphenyls
with diarylphosphine oxides. The reaction proceeds efficiently
with excellent regioselectivity. Broad reaction scope is demon-
strated and different functional groups are compatible under the
conditions. This transformation allows the direct formation of CeP
bond and provides a rapid access to phenanthridine ring systems.
J¼128.5 Hz), 142.42 (d, J¼23.3 Hz), 138.06, 133.19 (d, J¼104.0 Hz),
132.90, 132.35 (d, J¼9.1 Hz), 131.61, 131.01, 130.48 (d, J¼6.8 Hz),
128.69, 128.19, 128.07, 127.73, 124.43, 121.95 (d, J¼6.0 Hz), 21.94;
Exact mass calcd for C26H21NOP [MþH]þ 394.1361, found 394.1327.
4.1.5. (8-Fluorophenanthridin-6-yl)diphenylphosphine oxide (3e).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.32 (dd, J¼10.2, 2.6 Hz,
1H), 8.63e8.60 (m, 1H), 8.51e8.50 (m, 1H), 8.07e8.05 (m, 1H),
8.00e7.93 (m, 4H), 7.73e7.67 (m, 2H), 7.60e7.43 (m, 7H); 31P NMR
4. Experimental section
4.1. General
(162 MHz, CDCl3) d d 161.25 (d,
27.53 (s); 13C NMR (100 MHz, CDCl3)
J¼249.3 Hz),156.94 (d, J¼125.4 Hz),142.42 (d, J¼22.6 Hz),132.64 (d,
J¼105.0 Hz), 132.32 (d, J¼9.1 Hz), 131.83, 131.18, 129.23, 128.93 (d,
J¼9.4 Hz), 128.60, 128.24 (d, J¼12.1 Hz), 124.60 (d, J¼8.3 Hz), 123.94,
121.88,120.50 (d, J¼24.4 Hz),113.19 (d, J¼23.3 Hz); Exact mass calcd
for C25H18FNOP [MþH]þ 398.1110, found 398.1099.
General procedure for the synthesis of phenanthridin-6-
yldiphenylphosphine oxides by oxidative cyclization of 2-
isocyanobiphenyls with diarylphosphine oxides in the presence of
manganous(III) acetate: Manganous(III) acetate (145.0 mg,
0.6 mmol) was added to a solution of 2-isocyanobiphenyl 1
(0.2 mmol) and diarylphosphine oxide 2 (0.3 mmol) in toluene
(2.0 mL) under N2 atmosphere. The mixture was stirred at 40 ꢀC for
8e10 h. After completion of the reaction as indicated by TLC, the
reaction mixture was filtered through a thin layer of silica gel and
washed by CH2Cl2 (3ꢁ5.0 mL). The residue was concentrated in
vacuo and purified by column chromatography on silica gel (eluted
with PE/EA¼4:1) to provide the product 3.
4.1.6. (8-Chlorophenanthridin-6-yl)diphenylphosphine oxide (3f).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.66 (d, J¼2.1 Hz, 1H),
8.54e8.48 (m, 2H), 8.07e8.04 (m,1H), 8.00e7.94 (m, 4H), 7.77e7.70
(m, 3H), 7.54e7.50 (m, 2H), 7.47e7.43 (m, 4H); 31P NMR (162 MHz,
CDCl3)
d d 155.81 (d,
27.28 (s); 13C NMR (100 MHz, CDCl3)
J¼128.1 Hz), 142.61 (d, J¼22.8 Hz), 133.95, 132.74 (d, J¼104.0 Hz),
132.33 (d, J¼9.1 Hz), 131.81, 131.14, 130.95 (d, J¼6.7 Hz), 129.21 (d,
J¼21.7 Hz), 128.74 (d, J¼22.6 Hz), 128.24 (d, J¼12.2 Hz), 123.66,
123.75, 121.99; Exact mass calcd for
414.0815, found 414.0807.
C
25H18ClNOP [MþH]þ
4.1.1. Phenanthridin-6-yldiphenylphosphine oxide (3a).6d Yellow
solid; 1H NMR (400 MHz, CDCl3)
d
9.51 (d, J¼8.3 Hz, 1H), 8.63 (d,
4.1.7. Diphenyl(8-(trifluoromethyl)phenanthridin-6-yl)phosphine
oxide (3g). Yellow solid; 1H NMR (400 MHz, CDCl3)
10.04 (s, 1H),
J¼8.3 Hz, 1H), 8.57e8.58 (m, 1H), 8.06e8.03 (m, 1H), 8.00e7.92 (m,
4H), 7.83 (t, J¼7.7 Hz, 1H), 7.71e7.66 (m, 3H), 7.52e7.48 (m, 2H),
d
8.71 (d, J¼8.7 Hz, 1H), 8.58e8.55 (m, 1H), 8.13e8.10 (m, 1H),
7.47e7.42 (m, 4H); 31P NMR (162 MHz, CDCl3) 28.25 (s); 13C NMR
d
8.02e7.97 (m, 5H), 7.80e7.75 (m, 5H), 7.55e7.50 (m, 2H), 7.48e7.44
(100 MHz, CDCl3)
132.94 (d, J¼94.0 Hz), 132.54, 132.47, 132.25 (d, J¼9.1 Hz), 131.61,
131.00 (d, J¼9.9 Hz), 128.72, 128.56 (d, J¼10.0 Hz), 128.10 (d,
d
156.79 (d, J¼128.4 Hz), 142.67 (d, J¼23.3 Hz),
(m, 4H); 31P NMR (162 MHz, CDCl3) 26.80 (s); 13C NMR (100 MHz,
d
CDCl3)
d
157.07 (d, J¼127.1 Hz), 143.28 (d, J¼22.5 Hz), 134.68 (d,
J¼6.2 Hz),132.32 (d, J¼9.1 Hz),132.61 (d, J¼105.0 Hz),131.90,131.21,

Y. Li et al. / Tetrahedron 70 (2014) 4652e4656
4655
129.91, 129.67, 129.39, 128.28 (d, J¼12.2 Hz), 127.23 (d, J¼23.0 Hz),
5H), 7.70e7.65 (m, 3H), 7.24 (dd, J¼7.9, 2.6 Hz, 4H), 2.36 (s, 6H); 31
P
126.91,126.26 (d, J¼3.6 Hz),123.32,123.19,122.45; Exact mass calcd
NMR (162 MHz, CDCl3)
d
29.35 (s); 13C NMR (100 MHz, CDCl3)
for C26H18F3NOP [MþH]þ 448.1078, found 448.1034.
d
157.12 (d, J¼128.6 Hz),142.76 (d, J¼23.2 Hz), 142.12, 132.53, 132.32
(d, J¼9.6 Hz), 132.02 (d, J¼104 Hz), 131.06 (d, J¼20.4 Hz), 130.11,
128.96 (d, J¼12.6 Hz), 128.67 (d, J¼9.1 Hz), 127.83, 127.65, 124.34,
122.07, 21.60; Exact mass calcd for C27H23NOP [MþH]þ 408.1517,
found 408.1481.
4.1.8. (8-Methoxyphenanthridin-6-yl)diphenylphosphine oxide (3h).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.02 (d, J¼2.6 Hz, 1H),
8.52 (d, J¼8.7 Hz, 1H), 8.48 (d, J¼8.0 Hz, 1H), 8.04 (dd, J¼8.0, 1.3 Hz,
1H), 8.00e7.94 (m, 4H), 7.67e7.63 (m, 2H), 7.53e7.49 (m, 2H),
7.47e7.42 (m, 5H), 3.93 (s, 3H); 31P NMR (162 MHz, CDCl3)
d
27.59
4.1.14. Bis(3,5-dimethylphenyl)(phenanthridin-6-yl)phosphine oxide
(s); 13C NMR (100 MHz, CDCl3)
d
158.81, 155.45 (d, J¼129.4 Hz),
(3n). Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.47 (d, J¼8.2 Hz,
142.07 (d, J¼23.2 Hz), 133.06 (d, J¼104.6 Hz), 132.31 (d, J¼9.1 Hz),
131.66, 131.06, 129.45 (d, J¼22.9 Hz), 128.82, 128.17 (d, J¼12.1 Hz),
127.64, 127.05 (d, J¼6.6 Hz), 124.54, 123.62, 122.62, 121.63, 107.53,
55.64 (s); Exact mass calcd for C26H21NO2P [MþH]þ 410.1310, found
410.1303.
1H), 8.61 (d, J¼8.4 Hz, 1H), 8.57e8.54 (m, 1H), 8.08e8.06 (m, 1H),
7.8e7.78 (m, 1H), 7.71e7.65 (m, 3H), 7.56 (s, 2H), 7.53 (s, 2H), 7.12 (s,
2H), 2.30 (s, 12H); 31P NMR (162 MHz, CDCl3)
d
28.45 (s); 13C NMR
(100 MHz, CDCl3)
d
157.02 (d, J¼127.6 Hz), 142.68 (d, J¼23.2 Hz),
137.68 (d, J¼12.8 Hz), 133.45, 132.47 (d, J¼6.5 Hz), 132.45 (d,
J¼103.0 Hz), 130.97 (d, J¼27.0 Hz), 129.78 (d, J¼9.2 Hz), 128.55 (d,
J¼9.7 Hz), 127.87, 127.72, 124.28, 121.98, 21.28; Exact mass calcd for
4.1.9. Benzo[c][2,7]naphthyridin-5-yldiphenylphosphine oxide (3i).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
10.79 (s, 1H), 8.93 (s, 1H),
C
29H27NOP [MþH]þ 436.1830, found 436.1802.
8.55 (d, J¼7.8 Hz, 1H), 8.38 (d, J¼4.3 Hz, 1H), 8.11 (d, J¼7.9 Hz, 1H),
7.98 (d, J¼7.7 Hz, 2H), 7.95 (d, J¼7.7 Hz, 2H), 7.85e7.76 (m, 2H),
7.55e7.52 (m, 2H), 7.49e7.45 (m, 5H); 31P NMR (162 MHz, CDCl3)
Acknowledgements
d
27.32 (s); 13C NMR (100 MHz, CDCl3)
d
157.49 (d, J¼126.8 Hz),
Financial support from the National Natural Science Foundation
of China (Nos. 21032007, 21172038) is gratefully acknowledged.
152.43, 148.71, 143.84 (d, J¼22.3 Hz), 137.32 (d, J¼5.9 Hz), 134.70 (d,
J¼105.0 Hz), 132.28 (d, J¼9.1 Hz), 132.02, 131.14 (d, J¼29.5 Hz),
129.45, 128.83, 128.35 (d, J¼12.1 Hz), 122.99 (d, J¼21.3 Hz), 122.62,
122.17, 115.40; Exact mass calcd for C24H18N2OP [MþH]þ 381.1157,
found 381.1128.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.05.039.
These data include MOL file and InChiKey of the most important
compounds described in this article.
4.1.10. (2-Methylphenanthridin-6-yl)diphenylphosphine oxide (3j).13
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.47 (d, J¼8.3 Hz, 1H), 8.61
(d, J¼8.3 Hz, 1H), 8.35 (s, 1H), 7.95e7.90 (m, 5H), 7.80 (t, J¼7.7 Hz, 1H),
7.65 (t, J¼7.7 Hz, 1H), 7.52e7.48 (m, 3H), 7.45e7.40 (m, 4H), 2.61 (s,
3H); 31P NMR (162 MHz, CDCl3)
d
28.36 (s); 13C NMR (100 MHz,
References and notes
CDCl3)
d
155.53 (d, J¼129.7 Hz), 141.18 (d, J¼23.4 Hz), 139.09, 133.04
1. For example see: Sawa, M.; Kiyoi, T.; Kurokawa, K.; Kumihara, H.; Yamamoto,
M.; Miyasaka, H.; Ito, Y.; Hirayama, R.; Inoue, T.; Kirii, T.; Nishiwaki, E.; Ohmoto,
H.; Maeda, Y.; Ishibushi, E.; Inoue, Y.; Yoshino, K.; Kondo, H. J. Med. Chem. 2002,
45, 919.
2. (a) Ackermann, L.; Althammer, A. Org. Lett. 2006, 8, 3457; (b) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457.
(d, J¼104.7 Hz), 132.32 (d, J¼9.1 Hz), 131.63, 130.83 (d, J¼11.7 Hz),
130.45, 128.46, 128.15 (d, J¼12.1 Hz), 127.78 (d, J¼10.1 Hz), 124.21,
122.08, 121.65, 22.17; Exact mass calcd for C26H21NOP [MþH]þ
394.1361, found 394.1370.
3. (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Synthesis 1981, 56; (b) Schwan,
A. Chem. Soc. Rev. 2004, 33, 218; (c) Jeught, S.; Stevens, C. Chem. Rev. 2009, 109,
2672; (d) Montchamp, J.-K. Acc. Chem. Rev. 2014, 47, 77.
4.1.11. (2-Fluorophenanthridin-6-yl)diphenylphosphine
oxide
9.50 (d, J¼8.2 Hz,
(3k).13 Yellow solid; 1H NMR (400 MHz, CDCl3)
d
4. (a) Deal, E.; Petit, C.; Montchamp, J.-L. Org. Lett. 2011, 13, 3270; (b) Tran, G.;
Pardo, D.; Tsuchiya, T.; Hillebrand, S.; Vors, J.-P.; Cossy, J. Org. Lett. 2013, 15,
5550; (c) Kalek, M.; Jezowska, M.; Stawinski, J. Adv. Synth. Catal. 2009, 351,
3207; (d) Xu, J.; Zhang, P.; Gao, Y.; Chen, Y.; Tang, G.; Zhao, Y. J. Org. Chem. 2013,
78, 8176; (e) Jouvin, K.; Veillard, R.; Theunissen, C.; Alayrac, C.; Gaumont, A.-C.;
Evano, G. Org. Lett. 2013, 13, 4592; (f) Luo, Y.; Wu, J. Organometallics 2009, 28,
6823; (g) Rmmelt, S. M.; Ranochiari, M.; Bokhoven, J. Org. Lett. 2012, 14, 2188;
(h) Kalek, M.; Johansson, T.; Jezowska, M.; Stawinski, J. Org. Lett. 2012, 12, 4752;
(i) Kalek, M.; Johansson, T.; Jezowska, M.; Stawinski, J. Org. Lett. 2010, 12, 4702;
(j) Kalek, M.; Ziadi, A.; Stawinski, J. Org. Lett. 2008, 10, 4637.
5. (a) Gao, Y.; Wang, G.; Chen, L.; Xu, P.; Zhao, Y.; Zhou, Y.; Han, L.-B. J. Am. Chem.
Soc. 2009, 131, 7956; (b) Huang, C.; Tang, X.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org.
Chem. 2006, 71, 5020; (c) Zhuang, R.; Xu, J.; Cai, Z.; Tang, G.; Fang, M.; Zhao, Y.
Org. Lett. 2011, 13, 2110; (d) Gelman, D.; Jiang, L.; Buchwald, S. Org. Lett. 2003, 5,
2315; (e) Jouvin, K.; Veillard, R.; Theunissen, C.; Alayrac, C.; Gaumont, A.-C.;
Evano, G. Org. Lett. 2013, 15, 4592.
6. (a) Liu, L.; Wang, Y.; Zeng, Z.; Xu, P.; Gao, Y.; Yin, Y.; Zhao, Y. Adv. Synth. Catal.
2013, 355, 659; (b) Hu, G.; Chen, W.; Fu, T.; Peng, Z.; Qiao, H.; Gao, Y.; Zhao, Y.
Org. Lett. 2013, 15, 5362; (c) Zhang, X.; Liu, H.; Hu, X.; Tang, G.; Zhu, J.; Zhao, Y.
Org. Lett. 2011, 13, 3478; (d) Zhao, Y.-L.; Wu, G.-J.; Han, F.-S. Chem. Commun.
2012, 5868.
7. For selected examples see: (a) Hou, C.; Ren, Y.; Lang, R.; Hu, X.; Xia, C.; Li, F.
Chem. Commun. 2012, 5181; (b) Mi, X.; Huang, M.; Zhang, J.; Wang, C.; Wu, Y.
Org. Lett. 2013, 15, 6266; (c) Feng, C.; Ye, M.; Xiao, K.; Li, S.; Yu, J.-Q. J. Am. Chem.
Soc. 2013, 135, 9322; (d) Li, C.; Yano, T.; Ishida, N.; Murakami, M. Angew. Chem.,
Int. Ed. 2013, 52, 9801; (e) Mao, X.; Ma, X.; Zhang, S.; Hu, H.; Zhu, C.; Cheng, Y.
Eur. J. Org. Chem. 2013, 4245; (f) Kuninobu, Y.; Yoshida, T.; Takai, K. J. Org. Chem.
2011, 76, 7370; (g) Yang, B.; Yang, T.-T.; Li, X.-A.; Wang, J.-J.; Yang, S.-D. Org. Lett.
2013, 15, 5024.
1H), 8.49 (d, J¼8.4 Hz, 1H), 8.16 (dd, J¼10.0, 2.7 Hz, 1H), 8.03 (dd,
J¼9.0, 5.7 Hz, 1H), 7.94e7.89 (m, 4H), 7.85e7.80 (m, 1H), 7.70 (td,
J¼8.4, 1.2 Hz, 1H), 7.53e7.49 (m, 2H), 7.46e7.40 (m, 5H); 31P NMR
(162 MHz, CDCl3) d d 162.43 (d,
28.45 (s); 13C NMR (100 MHz, CDCl3)
J¼250.1 Hz), 156.11 (d, J¼128.1 Hz), 139.64 (d, J¼23.4 Hz), 133.54 (d,
J¼9.3 Hz), 132.78 (d, J¼104.0 Hz), 132.27 (d, J¼9.1 Hz), 131.76,
131.09, 128.61 (d, J¼13.7 Hz), 128.21 (d, J¼12.2 Hz), 127.75 (d,
J¼23.1 Hz),125.98 (d, J¼8.2 Hz), 122.30, 117.82 (d, J¼24.5 Hz), 107.08
(d, J¼23.4 Hz); Exact mass calcd for C25H18FNOP [MþH]þ 398.1110,
found 398.1078.
4.1.12. Benzo[k]phenanthridin-6-yldiphenylphosphine oxide (3l).
Yellow solid; 1H NMR (400 MHz, CDCl3)
d
9.38 (d, J¼8.9 Hz, 1H),
9.10e9.08 (m, 1H), 9.05e9.02 (m, 1H), 8.16e8.14 (m, 1H), 8.04e8.01
(m, 1H), 7.97e7.91 (m, 5H), 7.78e7.70 (m, 4H), 7.54e7.49 (m, 2H),
7.47e7.42 (m, 4H); 31P NMR (162 MHz, CDCl3) 29.49 (s); 13C NMR
d
(100 MHz, CDCl3)
d
155.18 (d, J¼129.3 Hz), 144.75 (d, J¼23.4 Hz),
134.78, 133.02 (d, J¼104.5 Hz), 132.37 (d, J¼9.2 Hz), 131.70, 130.94,
128.75 (d, J¼7.1 Hz), 128.46, 128.37 (d, J¼3.6 Hz), 128.18, 128.18 (d,
J¼12.0 Hz), 127.42, 127.16, 126.74, 124.54, 123.90; Exact mass calcd
for C29H21NOP [MþH]þ 430.1361, found 430.1354.
8. For selected examples see: (a) Kagayama, T.; Nakano, A.; Sakaguchi, S.; Ishii, Y.
Org. Lett. 2006, 8, 407; (b) Mu, X.-J.; Zou, J.-P.; Qian, Q.-F.; Zhang, W. Org. Lett.
2006, 8, 5291; (c) Pan, X.-Q.; Zou, J.-P.; Zhang, G.-L.; Zhang, W. Chem. Commun.
2010, 1721; (d) Zhou, J.; Zhang, G.-L.; Zou, J.-P.; Zhang, W. Eur. J. Org. Chem. 2011,
4.1.13. Phenanthridin-6-yldi-p-tolylphosphine oxide (3m). Yellow
solid; 1H NMR (400 MHz, CDCl3)
d
9.47 (d, J¼8.2 Hz, 1H), 8.62 (d,
J¼8.3 Hz, 1H), 8.58e8.55 (m, 1H), 8.06e8.04 (m, 1H), 7.83e7.78 (m,

4656
Y. Li et al. / Tetrahedron 70 (2014) 4652e4656
3412; (e) Li, D.-P.; Pan, X.-Q.; An, L.-T.; Zou, Z.-P.; Zhang, W. J. Org. Chem. 2014,
79, 1850.
Daniliuc, C.; Studer, A. Angew. Chem., Int. Ed. 2013, 52, 10792; (c) Wang, Q.;
Dong, X.; Xiao, T.; Zhou, L. Org. Lett. 2013, 15, 4846; (d) Leifert, D.; Daniliuc, C.;
Studer, A. Org. Lett. 2013, 15, 6286; (e) Cheng, Y.; Jiang, H.; Zhang, Y.; Yu, S. Org.
Lett. 2013, 15, 5520.
9. For selected examples see: (a) Zhang, C.; Li, Z.; Zhu, L.; Yu, L.; Wang, Z.; Li, C. J.
Am. Chem. Soc. 2013, 135, 14082; (b) Chen, Y.-R.; Duan, W.-L. J. Am. Chem. Soc.
2013, 135, 16754; (c) Li, Y.-M.; Sun, M.; Wang, H.-L.; Tian, Q.-P.; Yang, S.-D.
Angew. Chem., Int. Ed. 2013, 52, 3972; (d) Jin, X.; Yamaguchi, K.; Mizuno, N. Org.
Lett. 2013, 15, 418.
12. (a) Denny, W. A. Curr. Med. Chem. 2002, 9, 1655; (b) Abdel-Halim, O. B.; Mor-
ikawa, T.; Ando, S.; Matsuda, H.; Yoshikawa, M. J. Nat. Prod. 2004, 67, 1119; (c)
Phillips, S. D.; Castle, R. N. J. Heterocycl. Chem. 1981, 18, 223.
10. For reviews, see: (a) Qiu, G.; Ding, Q.; Wu, J. Chem. Soc. Rev. 2013, 42, 5257; (b)
Lang, S. Chem. Soc. Rev. 2013, 42, 4867; (c) Vlaar, T.; Maes, B. U. W.; Ruijter, E.;
Orru, R. V. A. Angew. Chem., Int. Ed. 2013, 52, 7084.
13. Very recently, Studer and co-workers reported the synthesis of 6-
phosphorylated phenanthridines via
a silver-promoted reaction of 2-iso-
cyanobiphenyls. The reaction proceeded in the presence of 3.0 equiv of silver
acetate at 100 ꢀC in DMF. Zhang, B.; Daniliuc, C. G.; Studer, A. Org. Lett. 2014,
16, 250.
11. For recently examples see: (a) Tobisu, M.; Koh, K.; Furukawa, T.; Chatani, N.
}
Angew. Chem., Int. Ed. 2012, 51, 11363; (b) Zhang, B.; Muck-Lichtenfeld, C.;