Phenanthrene synthesis by iron-catalyzed [4 + 2] benzannulation between alkyne and biaryl or 2-alkenylphenyl Grignard reagent

Article abstract of DOI:10.1021/ja201931e

The [4 + 2] benzannulation reaction of internal or terminal alkynes with 2-biaryl, 2-heteroarylphenyl, or 2-alkenylphenyl Grignard reagents in the presence of Fe(acac)₃, 4,4′-di-tert-butyl-2,2′-bipyridyl, and 1,2-dichloro-2-methylpropane takes place at room temperature in 1 h to give 9-substituted or 9,10-disubstituted phenanthrenes and congeners in moderate to excellent yields. The reaction tolerates sensitive functional groups such as bromide and olefin. When applied to a 1,3-diyne, the annulation reaction takes place on both acetylenic moieties to give a bisphenanthrene derivative.

Full text of DOI:10.1021/ja201931e

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Phenanthrene Synthesis by Iron-Catalyzed [4 þ 2] Benzannulation
between Alkyne and Biaryl or 2-Alkenylphenyl Grignard Reagent
Arimasa Matsumoto, Laurean Ilies, and Eiichi Nakamura*
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S Supporting Information
b
Scheme 1. Iron-Catalyzed [4 þ 2] Benzannulation
ABSTRACT: The [4 þ 2] benzannulation reaction of
internal or terminal alkynes with 2-biaryl, 2-heteroarylphe-
nyl, or 2-alkenylphenyl Grignard reagents in the presence of
Fe(acac)3, 4,40-di-tert-butyl-2,20-bipyridyl, and 1,2-dichloro-
2-methylpropane takes place at room temperature in 1 h to
give 9-substituted or 9,10-disubstituted phenanthrenes and
congeners in moderate to excellent yields. The reaction
tolerates sensitive functional groups such as bromide and
olefin. When applied to a 1,3-diyne, the annulation reaction
takes place on both acetylenic moieties to give a bisphenan-
threne derivative.
side product suggests the feasibility of the carbometalation
pathway but does not exclude the ferracycle pathway.
The reaction was smoothly catalyzed by a variety of iron salts,
such as FeCl3, Fe(acac)2, FeCl2, and Fe(OAc)2 having purities
henanthrene is an important organic structure in materials
science,1 and it is also a partial structure of superconducting
P
picene2 and carbon nanotubes.3 Among the numerous synthetic
routes to the phenanthrene class of aromatics,4ꢀ6 the [4 þ 2]
benzannulation reaction between an alkyne and a biaryl com-
pound has not attracted much attention,7,8 despite its ability to
create quickly a large variety of phenanthrene compounds. We
report herein an iron-catalyzed coupling between an internal or
terminal alkyne and a biaryl or alkenylaryl Grignard reagent that
forms 9-substituted and 9,10-disubstituted phenanthrenes and
congeners in moderate to excellent yields (Scheme 1). The
reaction features attractive synthetic attributes such as the use of
an inexpensive and environmentally benign iron catalyst,9,10 mild
reaction conditions, and tolerance of a wide variety of functional
groups, including aryl bromide, which are unavailable for similar
reactions known in the literature.7,8 The method permits the use
of 2-furyl- and 2-thienylphenyl Grignard reagents, thereby pro-
viding a new synthetic route to naphtho[1,2-b]furan and
naphtho[1,2-b]thiophene. Among various mechanistic possibi-
lities, such as carbometalation11 followed by CꢀH bond acti-
vation12 or the intermediacy of a biphenyl ferracycle (Scheme 1),
evidence favors the latter.
ranging from 98 up to 99.995%. When FeF3 H2O was used as
3
the catalyst, a higher temperature (60 °C) and longer reaction
time (12 h) were needed to afford the product in 69% yield. Salts
of other metals, such as Pd(OAc)2 and CuI, did not catalyze this
reaction at all or were much less effective [Co(acac)2 and Ni-
(acac)2; see the Supporting Information for details]. The reac-
tion required dtbpy (10 mol %) as a ligand and 1,2-dichloroiso-
butane (2 equiv) as an oxidant,12a,b the absence of which
completely shut down the desired reaction and led to partial
polymerization of the alkyne.
The reaction stopped at 47% conversion of diphenylacetylene
when only 1 equiv of the 2-biphenyl Grignard reagent was used,
hence indicating the necessary use of 2 equiv, one for the CꢀC
bond formation and another to accept a hydrogen atom in the CꢀH
bond activation step. The corresponding diarylzinc reagent could
also be utilized at the expense of decreased yield (51%).
The scope of the reaction is summarized in Table 1. A variety
of alkynes possessing aromatic, alkenyl, alkyl, or trimethylsilyl
substituents took part in the annulation reaction in moderate to
excellent yield. Diarylacetylenes possessing an electron-with-
drawing group (entries 2 and 3) or an electron-donating group
(entries 4 and 5) reacted in good to excellent yield. It is notable
that chloro and bromo substituents survived the present reaction
conditions (entries 2 and 3). We did not find any dehalogenated
product or any product arising from a cross-coupling reaction
involving the halide group. The reaction therefore shares the
same selectivity profile that we found previously.12b
The 1 g scale synthesis of 9,10-diphenylphenanthrene is
illustrative (Scheme 1): a mixure of diphenylacetylene (0.98 g,
5.5 mmol) and 2-biphenylmagnesium bromide in Et2O (20 mL,
0.6 M, 12 mmol) was added dropwise to a solution of Fe(acac)3
(0.19 g, 0.55 mmol), 4,40-di-tert-butyl-2,20-bipyridine (dtbpy,
0.15 g, 0.55 mmol), and 1,2-dichloro-2-methylpropane (1.3 mL,
11 mmol) in tetrahydrofuran (THF) (25 mL) at ambient
temperature. The reaction mixture was stirred for 1 h to afford
9,10-diphenylphenanthrene in 96% isolated yield, together with a
trace amount (<2%) of the 2-vinyl-1,10-biphenyl derivative. This
Received: March 3, 2011
Published: April 07, 2011
r
2011 American Chemical Society
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Table 1. Iron-Catalyzed Annulation of Aryl Grignard Re-
agents with Alkynesa
reaction of 1-phenylpropyne with a methyl-substituted biaryl
Grignard reagent (entry 13) gave the two expected regiomers
without selectivity (55:45). This lack of regioselectivity contra-
dicts what we would expect from the carbometalation path-
way11,7d (Scheme 1, bottom left) but is consistent with the
ferracycle path (bottom right). As described in the Supporting
Information, D2O quenching of a reaction between a biaryl
Grignard reagent and a stoichiometric amount of Fe(acac)3 and
dtbpy gave back a biaryl showing partial ortho deuteration on
both benzene rings, which also provides support for a ferracycle
or related intermediate.
2-(2-Thienyl)- and 2-(2-furyl)phenyl Grignard reagents
(entries 14 and 15) also took part in the reaction to produce a
relatively unexplored type of heteroaromatic system. The reac-
tion using a 2-(cyclohexen-1-yl)phenyl Grignard reagent (entry
16) also proceeded smoothly to give a naphthalene derivative in
high yield.
The reaction between 1,4-diphenylbutadiyne and 2-biphenyl-
magnesium bromide resulted in twofold annulation to give a
bisphenanthrene compound (eq 1), further demonstrating the
power of this [4 þ 2] annulation reaction. This class of
congested, twisted aromatic compounds is of considerable
interest in the design of organoelectronic devices.13 We note in
passing that 9,10-diarylphenanthrenes are known14 to give
dibenzo[g,p]chrysene derivatives under oxidative thermal con-
ditions, which adds to the utility of the present annulation
reaction for the synthesis of functional materials.
In summary, we have developed a new [4 þ 2] benzannulation
method that allows the coupling of a variety of alkynes with diaryl
and related Grignard reagents. Because of the high activity of the
iron-based catalytic system, this reaction takes place under mild
conditions and enables the construction of sterically congested
systems. The oxidative coupling conditions allow the reaction to
take place with remarkable chemoselectivity, such as the toler-
ance of bromide, chloride, trimethylsilyl, trifluoromethyl, and
olefinic groups. Some evidence suggests the involvement of a
ferracycle intermediate, an intriguing mechanistic possibility
under investigation in our laboratory.
a Reaction conditions: a solution of Fe(acac)3 (10 mol %) and di-tert-
butyl-2,20-bipyridyl (10 mol %) in THF (1.0 mL) was added to a
solution of alkyne (0.5 mmol) and 1,2-dichloroisobutane (2.0 equiv) in
THF (1.0 mL), after which the Grignard reagent (2.2 equiv) was added
dropwise. The reaction mixture was stirred at rt for 1 h. See the
c
Supporting Information for details. b Isolated yield. The reaction was
run on a 1 g scale. d A mixture of alkyne and Grignard reagent in ether
was added slowly over 10 min. e A solution of the alkyne and a solution of
the Grignard reagent in diethyl ether were added separately over 10 min.
f The reaction was performed at 60 °C.
’ ASSOCIATED CONTENT
The observed sensitivity of an enyne toward polymerization
(data not shown) was attenuated by slow addition of the enyne,
and we thus obtained (E)-9-phenyl-10-styrylphenanthrene in
good yield with retention of the olefin geometry (entry 6).
Similarly, trifluoromethylphenylacetylene (entry 7) gave the
desired product in good yield when the alkyne was added slowly.
1-Phenylpropyne (entry 8), 4-octyne (entry 9), and bis-
(trimethylsilyl)acetylene (entry 10) also reacted in good yield.
The silyl groups in the product in entry 10 could serve as a
platform for further functionalization. Phenylacetylene could
also be utilized under slow-addition conditions (entry 11) to
obtain a 9-monosubstituted phenanthrene.
S
Supporting Information. Experimental procedures and
b
physical properties of the compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
nakamura@chem.s.u-tokyo.ac.jp
’ ACKNOWLEDGMENT
When two nonequivalent ortho hydrogen atoms were avail-
able on the aryl Grignard reagent (entries 12 and 13), the
reaction took place at the less hindered position.12aꢀc The
We thank MEXT (KAKENHI Specially Promoted Research
to E.N., no. 22000008; Strategic Promotion of Innovative Re-
search and Development from the Japan Science and Technology
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Agency, JST) and the Global COE Program for Chemistry Innova-
tion. A.M. thanks the Japan Society for the Promotion of Science for
the Research Fellowship for Young Scientists (21 8684).
3
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