Rhodium-Catalyzed Oxidative Annulation of (2-Arylphenyl)boronic Acids with Alkynes: Selective Synthesis of Phenanthrene Derivatives

Article abstract of DOI:10.1055/s-0035-1561940

A rhodium-catalyzed annulative coupling of (2-arylphenyl)boronic acids with alkynes has been developed for the facile construction of phenanthrene frameworks. The reaction proceeded without external bases, and dioxygen worked as a terminal oxidant. Deuter

Full text of DOI:10.1055/s-0035-1561940

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–D
letter
A
T. Nagata et al.
Letter
Synlett
Rhodium-Catalyzed Oxidative Annulation of (2-Arylphenyl)boron-
ic Acids with Alkynes: Selective Synthesis of Phenanthrene Deriva-
tives
Tomoya Nagataa
Tetsuya Satoh*b
Yuji Nishiic
R2
R3
cat. [Cp*RhCl2]2
cat. Cu(OAc)2•H2O
B(OH)2
+
R2
R3
DMF, 100 °C, 2 h
under air
Masahiro Miura*a
R1
R2, R3 = alkyl, aryl, CO2Et
R1
16 examples
up to 98% yield
a Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
miura@chem.eng.osaka-u.ac.jp
b Department of Chemistry, Graduate School of Science, Osaka City
University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan
satoh@sci.osaka-cu.ac.jp
c Frontier Research Base for Global Young Researchers, Graduate
School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Received: 29.01.2016
Accepted after revision: 28.02.2016
Published online: 24.03.2016
volve a mechanism involving C2 metalation, which occurs
by substituting C2-functional group (X in Scheme 1), and
subsequent C2′–H bond cleavage prior to or posterior to
alkyne insertion.
DOI: 10.1055/s-0035-1561940; Art ID: st-2016-u0061-l
Abstract A rhodium-catalyzed annulative coupling of (2-arylphe-
nyl)boronic acids with alkynes has been developed for the facile con-
struction of phenanthrene frameworks. The reaction proceeded with-
X
M
H
3
2
2'
metallation
out external bases, and dioxygen worked as
a terminal oxidant.
Deuterium-labeling experiments indicated the involvement of five-
membered rhodacycle intermediates.
R
R
Pd catalyst: X = I (refs. 8a,b), CO2H (ref. 8c)
Fe catalyst: X = MgBr (ref. 9)
Key words alkynes, arylboronic acids, phenanthrenes, rhodium, oxi-
dative coupling, C–H functionalization
R
R
Ir catalyst: X = COCl (ref. 10)
Rh catalyst: X = B(OH)2 (this work)
The chemistry of polycyclic aromatic hydrocarbons
(PAHs) has attracted much interest because of their increas-
ing importance in organic materials chemistry.1 Despite
their plain chemical compositions, PAHs exhibit diverse
chemical and physical properties based on the molecular
architectures, ranging from simple acene and phenacene
derivatives to elaborate three-dimensional compounds
such as fullerenes2 and carbon nanotubes.3
Phenanthrenes are one of the most simple and stable
compound classes among PAHs,4 so that it would be rather
easy to modify their properties by the installation of func-
tional groups. In fact, various phenanthrene derivatives
have been synthesized focusing on their excellent optical
and electric properties5 as well as interesting biological ac-
tivities.6 It is a growing tendency to apply transition-metal-
catalyzed C–H bond transformations to the synthesis of ar-
omatic functional molecules from the viewpoint of step-
and atom-efficiency.7 For the construction of phenanthrene
frameworks, the annulative coupling reactions of appropri-
ate C2-functionalized 1,1′-biphenyls with alkynes have
emerged as promising methods under palladium,8 iron,9
and iridium10 catalysis (Scheme 1). All these reactions in-
Scheme 1 Phenanthrene synthesis via annulative coupling with
alkynes
We previously reported the rhodium-catalyzed oxida-
tive 1:2 coupling reaction of arylboronic acids with alkynes
to produce linearly fused aromatic molecules such as naph-
thalene and anthracene derivatives.11 On the basis of these
findings, it may be conceived that (2-arylphenyl)boronic
acids can be converted into the corresponding phenan-
threnes under a similar catalytic system. Indeed, we
demonstrated a single example to construct 9,10-diphenyl-
phenanthrene by the method.11b Subsequently, we report
herein that the rhodium-catalyzed strategy allows to pre-
pare variously substituted phenanthrene derivatives via the
oxidative 1:1 coupling of the boronic acids and alkynes us-
ing dioxygen as a terminal oxidant. This catalytic system
triggers a selective C2′–H scission over the formation of 1:2
coupling product via C3–H cleavage, and, additionally, 9,9′-
biphenanthrenes are formed upon applying diynes into the
present protocol. Preliminary mechanistic insights ob-
tained from deuterium-labeling experiments are also de-
scribed.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

B
T. Nagata et al.
Letter
Synlett
At the outset in the present work, we examined the test
reaction of [1,1′-biphenyl]-2-ylboronic acid (1a) with 4-oc-
tyne (2a) as a typical aliphatic alkyne in the presence of
R2
R2
B(OH)2
[Cp*RhCl2]2 (2.0 mol%)
Cu(OAc)2•H2O (10 mol%)
R2
R2
+
DMF, 100 °C, air, 2 h
[Cp*RhCl2]2
(Cp* = pentamethylcyclopentadienyl)
and
R1
Cu(OAc)2·H2O under air. Expectedly, the corresponding
phenanthrene 3aa was obtained selectively in 83% isolated
yield under the optimal reaction conditions (Equation 1).12
It was confirmed that the reaction did not proceed without
adding either the rhodium catalyst or the copper co-cata-
lyst.
1
2
3
MeO
OMe
F3C
CF3
nPr
nPr
B(OH)2
[Cp*RhCl2]2 (2.0 mol%)
Cu(OAc)2•H2O (10 mol%)
81% yield (3ab)
65% yield (3ac)
59% yield (3ad)
nPr
nPr
+
EtO2C
CO2Et
DMF, 100 °C, air, 2 h
1a
2a
3aa: 83% yield
MeO
OMe
Equation 1 Rhodium-catalyzed oxidative annulation of [1,11′-biphe-
nyl]-2-yl-boronic acid (1a) with 4-octyne (2a)
We thus investigated the substrate scope for alkynes
and boronic acids under the conditions employed in Equa-
tion 1 (Scheme 2). The reaction of 1a with diphenylacety-
lene (2b) successfully afforded the corresponding phenan-
threne compound 3ab in 81% yield. 4,4′-Dimethoxy- and
4,4′-bis(trifluoromethyl)-substituted diphenylacetylenes 2c
and 2d also reacted to give 3ac and 3ad in good yields,
whereas a stoichiometric amount of the copper salt was re-
quired to achieve a high yield for the production of ethoxy-
carbonyl-substituted 3ae. Use of phenylacetylene as a ter-
minal alkyne gave a poor result, giving only a ca. 5% yield of
the product (not shown). 1,4-Dimethoxy-substituted 2-bu-
tyne 2f was converted into 3af in 57% yield. Diethyl acety-
lenedicarboxylate (2g) gave a mixture of annulation prod-
uct 3ag and hydroarylation product 3ag′. On the other
hand, acetylene-monoester 2h gave phenanthrene 3ah as a
sole product, albeit with a low yield. Various 2-arylphenyl
boronic acids 1b–f smoothly underwent cyclization upon
treatment with alkyne 2a and the desired phenanthrenes
3ba–fa were obtained in high to excellent yields. It is noted
that the yields of compounds 3ba and 3da were significant-
ly improved compared with the previous method using the
corresponding acid chlorides under iridium catalysis.10
This annulation protocol was successfully expanded to
the synthesis of 9,9′-biphenanthrenes using diynes as cou-
pling partners (Equation 2).9,13 Thus, 1,4-dialkylbuta-1,3-
diynes 4a and 4b underwent twofold cyclization to give 5aa
and 5ab upon treatment of boronic acid 1a using a stoichio-
metric amount of the copper salt. This class of twisted aro-
matic molecules has recently attracted considerable inter-
est for their unique redox and electric properties.14
57% yield (3af)
72% yield (3ae)a
EtO2C CO2Et
EtO2C
Ph
EtO2C
CO2Et
+
19% yield (3ag) + 17% yield (3ag')
26% yield (3ah)
nPr
nPr
nPr
nPr
Me
68% yield (3ba)
nPr
nPr
81% yield (3ca)
nPr
nPr
nPr
nPr
OMe
CF3
Ph
98% yield (3da)
87% yield (3ea)
84% yield (3fa)
Scheme 2 Substrate scope for alkynes and boronic acids. a 2.0 equiv of
Cu(OAc)2·H2O was used under N2.
B(OH)2
R
[Cp*RhCl2]2 (2.0 mol%)
Cu(OAc)2•H2O (4.0 equiv)
1a
R
+
DMF, 100 °C, N2, 2 h
R
R
rac
4
To gain some mechanistic insights into the present cata-
lytic system, a number of deuterium-labeling experiments
were conducted using 1a-d5 (Scheme 3). When 1a-d5 was
treated with alkyne 2a for three minutes under the catalytic
R = Me (5aa) 58% yield
R = Et (5ab) 57% yield
Equation 2 Twofold annulation with diynes
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

C
T. Nagata et al.
Letter
Synlett
conditions, 3aa-d4 was obtained in 25% yield along with re-
covered 1a-d5 without any loss of its deuterium content
(Scheme 3, A). This result clearly indicated that the C2′–H
cleavage should be irreversible. Additionally, KIE values for
1a against 1a-d5 which were calculated from a set of paral-
lel reactions and an intermolecular competition, 1.11 and
0.96, respectively, suggested that the C2′–H cleavage event
is not involved in the rate-determining step (for details, see
Supporting Information). The reaction of an asymmetric
alkyne 2x afforded a 1:1 mixture of isomers 3ax-d4 and
3ax′-d4 in 89% yield (Scheme 3, B). Because we previously
observed that such an insertion of alkyl(aryl)alkynes into a
Rh–C bond proceeded regioselectively,11 this result strongly
suggested the involvement of five-membered rhodacycle
intermediates in the catalytic cycle (vide infra).
[O]
2CuX2
2CuX
R
R
B(OH)2
Cp*Rh
Cp*RhX2
1
3
XB(OH)2
R
Cp*
Rh
Cp*
R
Rh
X
C
A
Cp*
Rh
– HX
A)
B(OH)2
R
R
2
B
nPr
nPr
B(OH)2
d5
Scheme 4 A plausible catalytic cycle for the rhodium-catalyzed annu-
lative coupling
[Cp*RhCl2]2 (2.0 mol%)
Cu(OAc)2•H2O (10 mol%)
1a–d5
+
+
DMF, 100 °C, air, 3 min
nPr
nPr
d4
3aa–d4: 25% yield
d5
2a
75% yield
nBu
tionalized phenanthrene derivatives from readily available
boronic acids. This catalytic system called for no external
bases, and atmospheric dioxygen in air basically worked as
terminal oxidant. Some twisted 9,9′-biphenanthrenes were
also accessible upon applying diynes, so that the present
protocol would be a practical synthetic tool for such a series
of π-conjugated compounds.
nBu
Ph
Ph
B)
[Cp*RhCl2]2 (2.0 mol%)
Cu(OAc)2•H2O (10 mol%)
1a–d5
+
+
DMF, 100 °C, air, 2 h
nBu
Ph
d4
89% yield (3ax–d4:3ax'–d4 = 1:1)
d4
2x
Scheme 3 Deuterium-labeling experiments
Acknowledgment
Based on these observations, a plausible mechanism for
the annulative coupling is illustrated in Scheme 4. A rhodi-
um(III) complex undergoes transmetalation with boronic
acid 1 to afford intermediate A. Consequently, C2′–H cleav-
age takes place to generate the five-membered rhodacycle
complex B, which is followed by insertion of alkyne 2 into
one of two Rh–C bonds. Since this insertion proceeds with
almost the same frequency in the Rh–C bonds of the com-
plex B, use of the asymmetric alkyne 2x resulted in the for-
mation of 1:1 mixture of the regioisomers (Scheme 3, B).
Thus, complex C produces the corresponding phenanthrene
3 by reductive elimination, and the catalytically active rho-
dium(III) species are regenerated by copper(II)-mediated
oxidation to close the catalytic cycle.
This work was supported by Grants-in-Aid for Scientific Research
from the MEXT, JSPS, and JST (ACT-C) of Japan.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561940.
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References and Notes
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In conclusion, we have described a rhodium-catalyzed
oxidative annulation of (2-arylphenyl)boronic acids with
alkynes that ensured the rapid access to a range of func-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

D
T. Nagata et al.
Letter
Synlett
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vents, product 3 was isolated by column chromatography on
silica gel.
9,10-Dipropylphenanthrene (3aa) [CAS Reg. No. 19793-67-0]10
Purified by column chromatography with hexane as eluent
(54.2 mg, 83%); white solid. 1H NMR (400 MHz, CDCl3): δ = 1.19
(t, J = 7.3 Hz, 6 H), 1.71–1.84 (m, 4 H), 3.11–3.22 (m, 4 H), 7.57–
7.68 (m, 4 H), 8.08–8.17 (m, 2 H), 8.74 (dd, J = 7.2, 2.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 15.0, 24.2, 31.7, 123.1, 124.9,
125.5, 126.7, 130.0, 131.5, 134.0. HRMS: m/z calcd for C20H23
[M + H+]: 263.1794; found: 263.1771.
For other compounds, see the Supporting Information.
(13) Procedure for Equation 2
To a 20 mL two-necked flask were added arylboronic acid 1a
(1.0 mmol, 198 mg), alkyne 4 (0.25 mmol), [(Cp*RhCl2)2] (0.01
mmol, 6 mg), Cu(OAc)2·H2O (1.0 mmol, 200 mg), 1-methylnaph-
thalene (ca. 50 mg) as internal standard, and DMF (3 mL). The
resulting mixture was stirred under N2 at 100 °C for 2 h. Then,
the reaction mixture was cooled to room temperature and fil-
tered through a Celite pad with CH2Cl2. After evaporating the
solvents, product 5 was isolated by column chromatography on
silica gel.
10,10′-Dimethyl-9,9′-biphenanthrene (5aa)
Purified by column chromatography with hexane–toluene
(95:5, v/v) as eluent and then preparative GPC (55.6 mg, 58%);
white solid; mp 268–269 °C. 1H NMR (400 MHz, CDCl3): δ = 2.37
(s, 6 H), 7.22 (dd, J = 8.2, 1.1 Hz, 2 H), 7.29 (ddd, J = 8.2, 6.8, 1.1
Hz, 2 H), 7.58 (ddd, J = 8.3, 6.8, 1.4 Hz, 2 H), 7.70–7.80 (m, 4 H),
8.19–8.26 (m, 2 H), 8.81 (d, J = 8.3 Hz, 2 H), 8.85–8.92 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 16.8, 122.7, 123.2, 125.2, 126.0,
126.5, 127.0, 127.0, 127.2, 129.8, 130.4, 131.5, 132.0, 132.1,
134.8. HRMS: m/z calcd for C30H23 [M + H+]: 383.1794; found:
383.1796.
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F. J. Am. Chem. Soc. 2010, 132, 14006.
10,10′-Diethyl-9,9′-biphenanthrene (5ab)
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(12) General Procedure for Equation 1 and Scheme 2
To a 20 mL two-necked flask were added arylboronic acid 1
(0.25 mmol), alkyne 2 (0.25 mmol), [(Cp*RhCl2)2] (0.005 mmol,
3 mg), Cu(OAc)2·H2O (0.025 mmol, 5 mg), 1-methylnaphthalene
(ca. 50 mg) as internal standard, and DMF (3 mL). The resulting
mixture was stirred under air at 100 °C for 2 h. Then, the reac-
tion mixture was cooled to room temperature and filtered
through an alumina pad with CH2Cl2. After evaporating the sol-
Purified by preparative GPC (58.1 mg, 57%); white solid; mp
260–261 °C. 1H NMR (400 MHz, CDCl3): δ = 1.03 (t, J = 7.5 Hz, 6
H), 2.75–2.93 (m, 4 H), 7.21–7.30 (m, 4 H), 7.58 (ddd, J = 8.3, 6.3,
1.9 Hz, 2 H), 7.70–7.79 (m, 4 H), 8.20–8.27 (m, 2 H), 8.80 (d,
J = 8.3 Hz, 2 H), 8.87–8.93 (m, 2 H). 13C NMR (100 MHz, CDCl3):
δ = 14.3, 24.4, 122.6, 123.4, 125.5, 126.1, 126.4, 126.7, 126.9,
127.9, 129.9, 130.9, 131.1, 132.2, 134.3, 136.7. HRMS: m/z calcd
for C32H27 [M + H+]: 411.2107; found: 411.2086.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D