Palladium-Catalyzed Dimerization of Bis(2-biphenylyl)acetylene toward Sterically Hindered Acephenanthrylene

Article abstract of DOI:10.1021/acs.orglett.8b01334

The reaction of 2,2′′-(1,2-ethynediyl)bis-1,1′-biphenyl under homogeneous (heterogeneous) catalysis with Pd/C/TMS-Cl results in a dimerization and the additional formation of five- and six-membered rings. The steric demand of the acetylene prevents a [2 + 2 + 2] cycloaddition, but paves the way toward an alternative reaction. By the formation of an unexpected planar acephenanthrylene, the system avoids steric stain. The synthetic scope and requirements are explored, and a reaction mechanism is proposed.

Full text of DOI:10.1021/acs.orglett.8b01334

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium-Catalyzed Dimerization of Bis(2-biphenylyl)acetylene
toward Sterically Hindered Acephenanthrylene
Maximilian Ackermann,†,‡ Jan Freudenberg,†,‡ Daniel Jansch,†,‡ Frank Rominger,† Uwe H. F. Bunz,†,§
̈
,∥
̈
and Klaus Mullen*
†
̈
Organisch-Chemisches Institut, Ruprecht-Karls-Universitat Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
‡InnovationLab, Speyerer Straße 4, 69115 Heidelberg, Germany
§
̈
Centre for Advanced Materials, Ruprecht-Karls-Universitat Heidelberg, Im Neuenheimer Feld 225, 69120 Heidelberg, Germany
∥Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
S
* Supporting Information
ABSTRACT: The reaction of 2,2′′-(1,2-ethynediyl)bis-1,1′-
biphenyl under homogeneous (heterogeneous) catalysis with
Pd/C/TMS-Cl results in a dimerization and the additional
formation of five- and six-membered rings. The steric demand
of the acetylene prevents a [2 + 2 + 2] cycloaddition, but
paves the way toward an alternative reaction. By the formation
of an unexpected planar acephenanthrylene, the system avoids
steric stain. The synthetic scope and requirements are
explored, and a reaction mechanism is proposed.
Scheme 1. Two Mechanistic Pathways to Form an Aromatic
System from a Metallacyclopentadiene
ver since Reppe’s pioneering report on cyclotrimerization
a
,
6
1
Eof acetylene by nickel complexes in the 1940s, transition-
metal-catalyzed cyclotrimerization reactions of alkynes have
attracted tremendous interest. The ease of obtaining
substituted or annulated benzene cores from an acetylene
precursor puts this reaction in a series with the versatile Diels−
Alder reaction, Bergman cyclization, and condensation with
pyrylium salts.2 Although cobalt complexes such as CpCoL2 (L
= CO, PR3, alkenes) and Co2(CO)8 tolerate a variety of
functional groups and are highly active catalytic systems,
elemental palladium or its complexes,3 molybdenum carbonyls,
as well as mononuclear and binuclear halide complexes of
(early) transition metals have also been explored for
cyclotrimerizations.4
a
M denotes the catalytically active metal center with ligands and
charge.
For late transition metals, mechanistic studies suggest
coordination of two alkynes at the low-valent metal center
and subsequent concerted oxidative cyclization to give a
metalla-cyclopentadiene. This intermediate reacts either in a [4
+ 2] cycloaddition to a metallanorbornadiene, liberating the
arene, or via alkyne insertion to a metallacycloheptatriene,
followed by reductive elimination (Scheme 1).5,6 While
alkylated terminal and internal alkynes react rather smoothly,7
harsher conditions and prolonged reactions times are necessary
for bis(aryl)acetylenes due to higher steric demand, mostly
resulting in poor yields.8 Even fewer reports exist for successful
cyclization of ortho-substituted diphenylacetylenes, albeit with
low conversions.9
unprecedented alkyne dimerization with subsequent annula-
tion reactions was observed and elucidated.
Bis(2-biphenylyl)acetylene 2 was synthesized in one step by
Sonogashira coupling of 2-iodobiphenyl 1 and acetylene in
97% yield (Scheme 2).
Alkyne 2 was subjected to various cyclization conditions that
were successfully applied for trimerization of diphenylacetylene
to hexaphenylbenzene (Table 1).3,11
The use of cobalt, rhodium, or nickel catalysts did not result
in cyclotrimerization (entries 2−5); instead, the starting
material was (completely) recovered. However, with palladium
on carbon in the presence of trimethylsilyl chloride in THF
(entry 1), product 4 was isolated in 21% yield. Notably, the
To overcome these limitations, we initially focused on
conditions for the trimerization of the sterically demanding
bis(2-biphenylyl)acetylene 2. While employing a metal catalyst
capable of both oxidative cyclization and CH-insertions,10 an
Received: April 27, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Two new carbon−carbon bonds are formed at the ortho-
positions of the same former biphenyl moiety (see Figure 1).
In order to elucidate the steric demand necessary to
promote dimerization, instead of cyclotrimerization, three
1,2-disubstituted alkynes 5−7 (Figure 2) were subjected to our
Scheme 2. Synthesis of Bis(2-biphenylyl)acetylene 2 and
Subsequent Cyclization
a
a
See Table 1 for conditions and yields of step 2.
Figure 2. 1,2-Disubstituted alkynes 5−7 subjected to standard
coupling conditions.
Table 1. Cyclodimerization Reactions of Compound 2
3
(%)
4
entry
conditions
(%) 2 (%)
standard reaction conditions (see Table 1). However, neither
of the alkynes reacted in significant amounts, and >95% of
starting materials was reisolated. Therefore, both o-phenyl
substituents are deemed necessary for dimerization.
a
a
c
c
c
c
c
b
c
c
c
c
c
1
2
3
4
5
6
Pd/C, TMS-Cl, THF, reflux, 7 d
Co2(CO)8, THF, reflux, 7 d
ClCo(PPh3)3, THF, reflux, 7 d
CpCo(CO)2
ClRh(PPh3)3, THF, reflux, 7 d
Ni(acac)2, IMes*HCl, nBuMgCl, THF,
reflux, 7 d
0
0
0
21
0
0
0
0
79
100
100
100
100
100
c
c
c
0
Acephenanthrylenes are only sparsely investigated in the
literature due to their poor synthetic availability. They are
either prepared via low-yielding flash vacuum pyrolysis12 or
solution-phase Friedel−Crafts cyclizations involving many
synthetic steps.13 Our group’s early attempts to obtain 9a by
palladium-catalyzed pentannulation of 9-bromophenanthrene
8 with diphenylacetylene led to 10a instead.14 Recently, 9a was
accessed utilizing a different catalytic system.15 However, when
we used bis(2-biphenylyl)acetylene 2 under the reported
conditions for π-extension, the formation of biphenylylated
methylenefluorene 11 was observed. Whereas acephenanthry-
lene 9b or triphenylene 10b did not form, 11 was isolated in
48% yield, as well as 46% of starting material 8 (Scheme 3).
Thus, sterically crowded biphenylated acephenanthrylenes are
not accessible via this approach, while our reaction requires the
ortho-phenylated tolane (vide infra).
c
0
c
0
0
a
a
a
a
b
7
8
Pd/C, TMS-Cl, dioxane, reflux, 7 d
Pd/C, TMS-Cl, THF, reflux, 30 d
0
1
22
99
78
a
0
a
b
c
Isolated yield. Reisolated. Determined via GCMS.
reaction was less successful in dioxane (entry 7), and an
increase of the reaction time to 30 days in THF (entry 8) did
not improve the yields. Although the reaction proceeded rather
slowly, it was highly selective, as unreacted bis(2-biphenylyl)-
acetylene 2 was quantitatively reisolated. Instead of the desired
cyclotrimerization product 3, the product’s identity was
unambiguously determined by single-crystal X-ray diffraction
using a single crystal grown from a concentrated solution in
petroleum ether/ethyl acetate to be tris(biphenylated)
acephenanthrylene 4 (Figure 1). Due to the nonplanar
Scheme 3. Attempted Pd-Catalyzed Annulation of 9-
Bromophenanthrene 8 toward 9 and Observed Formation
of Methylenefluorene 11
Figure 1. Structural formula (both former biphenyl moieties are
highlighted), newly formed C−C bonds in black and ORTEP
representation of 4.
To gain insight into the reaction mechanism of the
dimerization/annulation, a series of control experiments was
carried out (Table 2). Entry 1 lists the initial reaction
conditions. The yield did not increase when an excess (4
equiv) of TMS-Cl was employed (entry 2). Subjecting the
reaction to microwave irradiation for 24 h (entry 3) resulted in
traces of an undeterminable set of byproducts without the
formation of the desired product. By treating Pd/C with TMS-
Cl in THF under reflux, filtration of the remaining Pd/C and
utilization of the filtrate (entry 4) as the reaction medium
corroborated the homogeneous nature of the dimerization, as
minor amounts of 4 were formed. This is in agreement with
the report by Maier et al. for such a catalytic system.3 By
replacing palladium on carbon with palladium dichloride
(entry 5), the reaction yield was reproduced, confirming
homogeneous catalysis. No conversion was observed via thin-
layer chromatography or GCMS when using only palladium on
geometry of 4, π−π-stacking of the acephenanthrylene core
is inhibited, resulting in good solubility in common organic
solvents, i.e., chloroform or ethyl acetate. Nevertheless,
structure elucidation of the polycyclic hydrocarbon (PAH)
by a combination of NMR/IR spectroscopy and elemental
analysis as well as mass spectrometry alone was virtually
impossible, especially due to the proton NMR spectrum
exhibiting only aromatic signals from several rotamers.
To the best of our knowledge, 4 is the first example of a
sterically congested 4,5,6-arylated acephenanthrylene. The
generation of 4 is a consequence of dimerization of bis(2-
biphenylyl)acetylene 2 with the subsequent formation of
additional 5- and 6-membered rings after C−H-activation.
B
DOI: 10.1021/acs.orglett.8b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
benzylidenefluorenes19 from 1,2-disubstituted alkynes. How-
ever, in contrast to these literature-known transformations, the
present reaction proceeds first via subsequent alkyne insertion,
similar to Miura’s synthesis of hexaarylbutadienes,20 and only
then undergoes 5-exo-dig-cyclizations. Notably, reduced steric
demand in 5 does not sufficiently induce C−H-activation.
Final C−H-activation releases the steric strain of the
overcrowded intermediates. Subsequent elimination of palla-
dium(0) planarizes the system and furnishes acephenanthry-
lene 4.
Our considerations are further supported by the observed
formation of 11 from 8; intermediately generated palladated
phenanthrene derivative S1 is supposedly not involved in the
mechanism, as we did not observe the analogous formation of
fluorenylidene S3 starting from 2 (see Figure S18). In contrast
to our findings, Pd-catalyzed alkyne annulation via dual C−H-
activation of bis(2-biphenylyl)acetylene 2 in the presence of
cesium pivalate and MnO2 as an oxidant favored intra-
molecular reaction and led to 9,9′-bifluorenylidene.16 Thus,
the outcome of the Pd-catalyzed reaction of 2 can be
controlled by variation the catalytic system.
In summary, the reaction of sterically demanding bipheny-
lated acetylene 2 with Pd/C/TMS-Cl under heterogeneous
catalysis results in selective dimerization and two subsequent
C−H-activations, yielding the 3-fold arylated acephenanthry-
lene 4 in a single step. The steric demand of the starting
material prevents a [2 + 2 + 2] cycloaddition. Instead,
planarization is favored, and two additional 5- and 6-
membered rings are formed. Control experiments exclude a
free-radical mechanism and reveal its homogeneous nature. In
the future, we will extend this method toward the facile
preparation of arylated acephenanthrylene derivatives.
Table 2. Control Reactions (Isolated Yields) for the
Dimerization of 1 in Refluxing THF
a
b
3
4
2
no.
conditions
(%) (%)
(%)
1
2
Pd/C (6 mol %), TMS-Cl (1 equiv)
Pd/C (6 mol %), TMS-Cl (4 equiv)
Pd/C (6 mol %), TMS-Cl (1 equiv)
Pd/C (6 mol %), TMS-Cl (1 equiv)
PdCl2 (6 mol %), TMS-Cl (1 equiv)
Pd/C (6 mol %)
PdCl2 (6 mol %)
TMS-Cl (1 equiv)
Pd/C (6 mol %), TMS-Cl (1 equiv), TEMPO
(6 equiv)
0
0
0
0
0
0
0
0
0
21
20
0
1
18
0
0
0
15
79
80
100
99
c
3
4
d
5
6
7
8
9
82
100
100
100
85
10 Pd/C (6 mol %), TMS-Cl (1 equiv), NEt3
(5 equiv)
0
0
100
a
b
c
d
Reaction time 7 d. Reisolated. Microwave: 80 °C, 24 h. Catalyst
refluxed for 2 h in THF, filtrate used as solvent/catalyst.
carbon or palladium dichloride without the addition of TMS-
Cl (entries 6 and 7). As silyl radicals are capable of inducing
cyclotrimerization of tolanes,17 TMS-Cl was employed as the
sole reactant. However, this did not lead to product formation
(entry 8). Hence, both TMS-Cl and palladium, although not
necessarily in its heterogeneous form, are essential for the
generation of 4. To rule out a (partial) radical reaction
mechanism often involved during the generation of multiple
arylated, sterically congested products,17 (2,2,6,6-tetramethyl-
piperidin-1-yl)oxyl (TEMPO, 4 equiv) was added as radical
scavenger, giving only negligible differences in the isolated
yields (entry 9). The addition of 5 equiv of triethylamine
inhibited conversion of bis(2-biphenylyl)acetylene 2, probably
due to coordination at the metal center (entry 10).
A proposed reaction mechanism is depicted in Scheme 4. As
a 4-fold biphenylated palladol possesses significant strain
ASSOCIATED CONTENT
■
S
* Supporting Information
Scheme 4. Proposed Mechanism for the Dimerization/
Cyclization of Bis(2-biphenylyl)acetylene 2 to
Acephenanthrylene 4
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b01334.
a
Experimental procedures, spectroscopic/spectrometric
data and crystal structures of the products (PDF)
Accession Codes
CCDC 1563153, 1818918, and 1837725−1837726 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
AUTHOR INFORMATION
■
a
Ar = 2-biphenylyl.
Corresponding Author
*E-mail: muellen@mpip-mainz.mpg.de.
ORCID
energy, as evidenced by simple molecular mechanics
calculations (see Supporting Information), it is thus unlikely
to be formed after a concerted oxidative cyclization. Therefore,
we suggest an alternative pathway involving ortho-CH-
activation after oxidative addition of TMS-Cl to palladium(0)
and the formation of a palladium(II) intermediate, similar to
the palladium-catalyzed synthesis of bifluorenylidenes18 or
Uwe H. F. Bunz: 0000-0002-9369-5387
̈
Klaus Mullen: 0000-0001-6630-8786
Notes
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.8b01334
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ACKNOWLEDGMENTS
■
We acknowledge the support of the German Federal Ministry
of Education and Research through Grant Nos. FKZ
13N13695 and FKZ 13N13659, as well as the fruitful
discussions with Dr. Matthias Rudolph at the Ruprecht-
̈
Karls-Universitat Heidelberg.
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DOI: 10.1021/acs.orglett.8b01334
Org. Lett. XXXX, XXX, XXX−XXX