Rapid synthesis of crowded aromatic architectures from silyl acetylenes

Article abstract of DOI:10.1021/ol501874s

Congested aromatic systems were prepared by benzannulating silyl-protected arylacetylenes. The silyl groups may be retained in the naphthalene products and transformed into iodides in high yield. The desirable attributes of this strategy, particularly its remarkable tolerance of sterically hindered alkynes, are showcased in the efficient synthesis of a congested, branched oligo(naphthalene). As such, benzannulations of diaryl and silyl-protected acetylenes show outstanding promise for accessing new aromatic architectures.

Full text of DOI:10.1021/ol501874s

Letter
pubs.acs.org/OrgLett
Rapid Synthesis of Crowded Aromatic Architectures from Silyl
Acetylenes
Samuel J. Hein, Hasan Arslan, Ivan Keresztes, and William R. Dichtel*
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, United States
S
* Supporting Information
ABSTRACT: Congested aromatic systems were prepared by
benzannulating silyl-protected arylacetylenes. The silyl groups
may be retained in the naphthalene products and transformed
into iodides in high yield. The desirable attributes of this
strategy, particularly its remarkable tolerance of sterically
hindered alkynes, are showcased in the efficient synthesis of a
congested, branched oligo(naphthalene). As such, benzannu-
lations of diaryl and silyl-protected acetylenes show out-
standing promise for accessing new aromatic architectures.
xtended aromatic structures have attracted intense interest
for organic optoelectronic devices, including photovoltaics1
using cross-coupling reactions. We apply this method iteratively
E
to access a branched oligo(naphthalene) product so hindered
that it exhibits restricted bond rotations at 140 °C in
tetrachloroethane. This compound demonstrates both the utility
of silyl-substituted naphthalene synthons and the remarkable
ability of the benzannulation reaction to modify hindered
alkynes.
We first evaluated the benzannulation of phenylacetylenes
protected by silyl groups that differ in size and relative stability.
Typical reaction conditions include excess CF3CO2H (10 equiv
per alkyne) because its conjugate base is thought to promote the
and field effect transistors,2 as well as for accessing porous
polymers.3 Improved synthetic approaches have provided
increasingly elaborate systems, such as poly(o-arylenes),4
contorted hexabenzocorones (HBCs),5 and cyclo(p-phenyl-
enes).6 These architectures exemplify the diverse structural
landscape available for fundamental and applied studies. For
example, oligo(o-phenylenes) exhibit specific helical conforma-
tions7 and spectral properties that arise from either fully extended
or coiled conformations,8 but this structural motif was virtually
unexplored9 until cross-coupling conditions tolerant of their
steric hindrance were identified. We recently adapted a
benzannulation reaction first reported by Yamamoto10 to prepare
congested aromatic systems containing 2,3-diarylnaphthalene
functionalities. This reaction is the first cycloaddition capable of
modifying the relatively unreactive alkynes along the backbone of
a poly(phenylene ethynylene) (PPE).11 It also tolerates sterically
demanding aryl substituents on the alkynes, as demonstrated by
its use in recent syntheses of contorted HBCs12 and a (6,6)
carbon nanotube segment precursor.13 Furthermore, 13C-labeled
and fluorine-substituted cycloaddition partners proved that the
benzannulation reaction proceeds regioselectively for most
diarylacetylene substrates.11,14 This feature will facilitate the
synthesis of low-symmetry products as single regioisomers.
Here we integrate the benzannulation reaction into a general
strategy to produce larger aromatic systems by expanding its
utility to silyl-protected acetylenes. Only a limited number of
these substrates have been explored in benzannulation
reactions,15 and they are unreported as substrates for the
Cu(OTf)2 or ZnCl2-mediated reactions described below. A
broad range of silyl protecting groups is tolerated, including bulky
triisopropyl (TIPS) and tert-butyldimethyl silyl (TBS) acety-
lenes. Under typical benzannulation conditions, these groups are
protodesilylated to provide the corresponding 2-arylnaphthalene.
We modified the reaction conditions to retain the silyl group,
such that they may be transformed to iodides and derivatized
Table 1. Benzannulation of Silyl-Protected Phenylacetylenes
Using Reduced Equivalents of CF3CO2H Retains Silyl Groups
Larger than TMS in the Naphthalene Products 3b−e
isolated yield (%)
substrate
R
3
4
1a
1b
1c
1d
1e
Si(Me)3
none
67
40
Si(Et)3
none
none
none
none
Si-t-Bu(Me)2
Si(i-Pr)3
85
89
SiPh(Me)2
78
Received: June 27, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol501874s | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 2. Benzannulation of Various TIPS-Protected
a
Acetylenes
Figure 1. Partial GC/MS total ion count chromatograms of the crude
reaction mixtures for the benzannulation of 1d in the presence of varying
[CF3CO2H]. The TIPS group is retained in the presence of 1 equiv of
CF3CO2H. Partial protodesilylation occurs with 10 equiv of CF3CO2H
to provide 4, which is the dominant product when either 20 or 40 equiv
of the acid are employed.
a
Alkyne: (0.05 g) 2: (2 equiv), Cu(OTf)2: (0.05 equiv), CF3CO2H: (1
equiv), 30 min, 100 °C.
formation of naphthalenes over naphthyl ketone side products.10
These conditions provide desilylated 2-phenylnaphthalene 4 as
the major or only benzannulation product for various silyl-
protected phenylacetylenes, even for relatively robust TIPS, TBS,
and dimethylphenylsilyl (DMPS) groups. In contrast, reducing
the initial concentration of CF3CO2H (1 equiv per alkyne),
provides nearly complete retention of the silyl eithers in
naphthalene products 3b−e (Table 1). After an aqueous workup
and purification by flash chromatography, 3b−e were isolated in
good to excellent yields.
Substrates 1b and 1c provided only small amounts of
protodesilylated product 4, as observed by GC/MS, whose
identity was confirmed by comparison to an independently
prepared sample. No evidence for the formation of 4 was
observed for larger substrates 1d and 1e. In contrast, the TMS
group was unstable to even 1 equiv of CF3CO2H, and 4 was the
only observed benzannulation product. Alternative benzannula-
tion conditions16 employ ZnCl2 without added Brønsted acids
but are less active than the Cu(OTf)2/CF3CO2H conditions.
Compound 1a was smoothly benzannulated in the presence of
ZnCl2 to provide 3a in good isolated yield (75%), alongside trace
amounts of 4. Collectively, these experiments indicate that the
Cu-catalyzed benzannulation reaction proceeds efficiently for
silyl-protected alkynes and that silyl groups larger than TMS are
stable to the modified reaction conditions. TMS groups are
tolerated under alternative ZnCl2-catalyzed conditions that do
not employ stoichiometric CF3CO2H.
during the benzannulation reaction by using increased
[CF3CO2H]. GC/MS analysis of crude reaction mixtures of
the benzannulation of 1d that employed up to 20 equiv of
CF3CO2H provided mixtures of 3d and 4 (Figure 1), whereas 4
was formed exclusively at higher [CF3CO2H] (40 equiv) without
introducing additional side products. These experiments indicate
that robust silyl protecting groups may be retained or removed in
situ by adjusting the initial quantities of acid.
The substrate scope of the benzannulation reaction was
expanded beyond phenylacetylene by evaluating a series of
aromatic systems containing TIPS-protected acetylenes (Table
2). An alkyne with an electron-rich aromatic system, such as the
methoxy substituted derivative 5, is well tolerated. Electron-
withdrawing aromatic systems, such as pyridine derivate 7, which
is likely to be protonated under the reaction conditions, are poor
substrates. Common electron-rich heterocycles, such as thio-
phenes and furans, are tolerated, as demonstrated by the
acceptable isolated yields for the double benzannulations of 9
and 11, respectively. Naphthalene-substituted derivatives of
thiophenes and furans are relatively unexplored, and naphtha-
lene-substituted oligothiophenes were recently shown to form
nanofibers on mica.17 Finally, substrate 13, which features an
alkyne flanked by bulky 2,6-dimethylphenyl and TIPS sub-
stituents, is benzannulated in good yield, further highlighting the
remarkable tolerance of this reaction to sterically crowded
substrates.
The benzannulation of these model silyl-protected phenyl-
acetylene substrates provides naphthalene building blocks with
variable silyl and aryl groups at the 2- and 3-positions,
respectively. Although new C−C bonds may be formed at silyl
sites directly under Hiyama cross-coupling conditions,18 we
explored converting the silyl group to a halide to take advantage
It will often be desirable to retain the silyl group to direct
further functionalization at the 2-position of the naphthalene
product (see below). However, some synthetic routes will
employ a silyl protecting group that should not be retained after
benzannulation. Even the large TIPS group may be removed
B
dx.doi.org/10.1021/ol501874s | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 3. Iodization/Protodesilylation of Each Silyl
Naphthalane
Scheme 1
entry
3
R
isolated yields (%)
1
2
3
4
3b
3c
3d
3e
Si(Et)3
90
Si-t-Bu(Me)2
Si(i-Pr)3
93
92
SiPh(Me)2
none
of a full range of available transition metal-catalyzed C−C, C−N,
C−O, and C−F bond-forming reactions. Silyl groups of each of
the isolated naphthalenes 3b−d underwent rapid and quantita-
tive conversion to 2-iodo-3-phenylnaphthalene 15 upon treat-
ment with ICl in CH2Cl2 (Table 3). The reaction proceeded to
completion after only 5 min at rt, in contrast to previous reports
thatemployed longer reaction timesand elevated temperatures.19
The DMPS naphthalene 3e is incompatible with this procedure,
as desilylated product 4, iodobenzene, and unidentified
chlorinated products were observed by GC/MS instead of 15
(see Figure S43, Supporting Information). These observations
indicate that triethylsilyl (TES), TBS, and TIPS groups are
readily converted to aryl iodide substrates, which readily undergo
many C−C bond-forming reactions.
1,2-Diaryl linkages are quite sterically hindered, which made
oligo- and poly(o-phenylenes) essentially unstudied prior to
recent pioneering reports by Hartley20 and Aida.21 This
substitution pattern also figures prominently in the bottom-up
synthesis of graphene nanoribbons (GNRs) and other carbon
nanostructures.22 The outstanding efficiency and steric tolerance
of the benzannulation reaction, combined with the synthetic
versatility of halogenated naphthalenes derived from silyl
acetylenes, suggests a new strategy to access highly crowded
aromatic architectures. To explore this possibility, 15 was joined
to 1,3,5-triethynyl benzene under Sonogashira cross-coupling
conditions to provide the trialkyne 16. Its internal alkynes remain
accessible for another benzannulation reaction, providing
oligo(arylene) 17, in which each aromatic subunit is a part of at
least one o-aryl linkage (Scheme 1). Compound 17 was
characterized using high-resolution mass spectrometry, varia-
ble-temperature 1D and 2D NMR spectroscopy, and UV/vis and
photoemission spectroscopies.
Figure 2. Schematic depiction of the major Cs symmetric conformer and
minor C3v conformer of compound 17. A more complete description of
its conformational behavior is provided in the Supporting Information.
ability of the benzannulation reaction to modify congested
aromatic systems.
1
The H and 13C NMR spectra of 17 indicate that the o-aryl
linkages of 17 restrict the C−C bond rotation around the central
In conclusion, we have broadened the scope of the
benzannulation reaction to silyl-protected phenylacetylenes. By
varying the acid concentration, the silyl groups may either be
removed or retained in the resulting phenylnaphthalene
products. The reaction tolerates electron-donating substitutents
and electron-rich heterocycles. When the silyl group is retained, it
may be transformed to an iodide under mild conditions to enable
further elaboration using various transition-metal-catalyzed
cross-coupling reactions. We demonstrate the utility of these
transformations in the iterative synthesis of a highly congested
aromatic system that exhibits restricted C−C bond rotations,
even at elevated temperatures. These results, combined with the
excellent regioselectivity of the benzannulation reaction, provide
a powerful means to access sterically hindered aromatic
architectures.
trisubstituted benzene ring, even at elevated temperature. At rt,
1
its H and 13C NMR spectra exhibit 48 and 46 resonances,
respectively, corresponding to a mixture of conformers under-
going slow exchange with respect to each measurement (see
Figures S34−35, Supporting Information). The major con-
formation exhibits Cs symmetry, in which one of the oligo(aryl)
substituents on the central benzene ring is anti with respect to the
other two (Figure 2). When rotation about the inner C−C bonds
is slow on the NMR time scale, the hydrogens of the central
benzene ring appear as two distinct singlets that integrate in a 2:1
ratio. A minor conformation with C3v symmetry, in which the
three oligo(aryl) substituents are syn, is also observed. These
hindered bond rotations that persist at elevated temperature
demonstrate the extreme steric hindrance of 17 and highlight the
C
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Letter
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and characterization data for all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
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(12) Arslan, H.; Uribe-Romo, F. J.; Smith, B. J.; Dichtel, W. R. Chem.
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AUTHOR INFORMATION
Corresponding Author
■
*E-mail: wdichtel@cornell.edu.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
Rubahna, H.-C; Lutzenb, A. Phys. Chem. Chem. Phys. 2014, 16, 5747−
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This work was supported by the Beckman Young Investigator
Program of the Arnold and Mabel Beckman Foundation, the NSF
(CHE-1124754), the Doctoral New Investigator Program of the
ACS Petroleum Research Fund (52019-DNI7), a Sloan Research
Fellowship from the Alfred P. Sloan Foundation, and a Camille
Dreyfus Teacher-Scholar Award from the Camille and Henry
Dreyfus Foundation.
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