Direct assembly of polyarenes via C-C coupling using PIFA/BF 3?Et2O

Article abstract of DOI:10.1021/ja107467c

Direct oxidative Kita-type coupling between naphthalene and substituted benzenes was found to proceed via four-component coupling, leading to a linear tetraarene with a binaphthalene core. The methodology was extendable to the coupling of unfunctionalized

Full text of DOI:10.1021/ja107467c

Published on Web 12/03/2010
Direct Assembly of Polyarenes via C-C Coupling Using PIFA/BF3 · Et2O
Enrico Faggi,† Rosa M. Sebastia´n,† Roser Pleixats,† Adelina Vallribera,† Alexandr Shafir,*,†
Alejandra Rodr´ıguez-Gimeno,‡ and Carmen Ram´ırez de Arellano‡
Department of Chemistry, UniVersitat Auto`noma de Barcelona, 08193-Cerdanyola del Valle`s, Barcelona, Spain, and
Departamento de Qu´ımica Orga´nica, UniVersidad de Valencia, 46100-Burjassot, Spain
Received August 18, 2010; E-mail: alexandr.shafir@uab.cat
naphthalene and mesitylene in the presence of PIFA/BF3 ·Et2O led
Abstract: Direct oxidative Kita-type coupling between naphthalene
to a 63% yield of 1a after 3 h at -78 °C.
and substituted benzenes was found to proceed via four-component
coupling, leading to a linear tetraarene with a binaphthalene core.
The methodology was extendable to the coupling of unfunctionalized
1,1′-binaphthalene with mesitylene to give a linear hexaarene
product in a remarkably chemoselective manner in 87% yield. The
method represents an attractive alternative to the traditional syn-
theses of related oligonaphthalene products via a sequence of metal-
catalyzed cross-coupling steps.
Surprisingly, the thin-layer chromatography analysis of the
mixture revealed not only 1a but also a ladder of spots that were
fluorescent under 365 nm light, suggesting the presence of more
extended aromatic systems. Mass spectrometric analysis of the
principal component A (m/z 490, largest Rf) suggested a formal
dehydrodimerization of 1a. Further assignment was guided by the
observation by 1H NMR spectroscopy of three Me resonances in a
6:6:6 integral ratio, indicating the inequivalence of the two o-Me
groups within each mesityl moiety.6 On the basis of these data, A
was identified as 4,4′-dimesityl-1,1′-binaphthyl (2a), and this
Direct oxidative coupling of arenes dates back to 1912, when
Scholl and Seer reported the formation of biaryls from arenes in
the presence of stoichiometric FeCl3.1 Although several promising
metal-catalyzed direct arene-arene (Ar-Ar) coupling reactions
have been reported in recent years,2 variants of the classical Scholl
coupling continue enjoying widespread use, especially in intramo-
lecular processes.3 Despite the prevalent use of metal halides in
such processes, Kita and co-workers have developed a combination
of BF3 ·Et2O with phenyliodine bis(trifluoroacetate) (PIFA) that is
highly effective in promoting direct C-C coupling.4,5 The method
was initially used in intramolecular coupling reactions4a and later
applied to direct intermolecular cross-coupling.4b Thus, Ar-Ar
coupling between naphthalenes and polyalkylbenzenes was found
to take place at the 1 position of the naphthalene.4c The process
was later used by the Kita group for the arylation of thiophenes
and pyrroles4d and by others in the construction of C-C5a,b and
C-N bonds.5d The presence of BF3 ·Et2O was found to be crucial
in the activation of the hypervalent iodine reagent, although more
recently Tse and co-workers5b showed that a catalytic amount of
HAuCl4 could be used in combination with PhI(OAc)2 in a related
arene-arene coupling.
assignment was confirmed by X-ray diffraction analysis (Figure
1).7,8 Similarly, the minor components B and C were identified as
the tri- and tetranaphthalenes 3a and 4a, respectively (Scheme 1).
Figure 1. (left) Connectivity of 2a. (right) Molecular structure of 2a,
showing one of the two independent molecules. Dihedral angle ranges (deg):
Mes-Naph, 81.6-86.9; Naph-Naph, 70.4-73.8.
Since in principle the formation of 2a, 3a, and 4a corresponds
to an overoxidation process, the 1a/oligomer ratio should depend
on the amount of the PIFA oxidant employed. Indeed, as shown in
Figure 2, the process proved to be highly sensitive to the amount
of the hypervalent iodine reagent, reaching optimal yields of 1a at
1.0 equiv of PIFA and predominantly giving 2a (45%) when this
amount was raised to 1.8 equiv.
Scheme 1. Kita Coupling between Naphthalene and Mesitylene
Figure 2. Yields of 1a and 2a as a function of the amount of PIFA used.
Reaction conditions: 0.5 mmol of C10H8, 1.5 mmol of mesitylene (3 equiv),
1.0 mmol of BF3 ·Et2O, and PIFA (as indicated) in CH2Cl2 at -78 °C.
n-C11H24 was used as an internal standard.
As part of our group’s work on new hypervalent iodine reagents,
we applied the Kita conditions to the synthesis of 1-mesitylnaph-
thalene (1a).4c As reported in Scheme 1, the reaction between
The rest of the products were identified as a mixture of higher
oligomers and bismesitylnaphthalene, the latter resulting from a
second arylation of 1a. We thought that the product ratios should
be sensitive to the amount of mesitylene used and wondered whether
† Universitat Auto`noma de Barcelona.
‡ Universidad de Valencia.
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C O M M U N I C A T I O N S
using less mesitylene would inhibit the formation of bismesityl-
naphthalene in favor of an increased yield of 2a. Unfortunately,
while lowering the amount of mesitylene did suppress the second
arylation of 1a, no improvement in the yield of 2a occurred; instead,
a higher percentage of oligomeric products was obtained (see the
Supporting Information).
Thus, with the use of an excess of PIFA, the protocol was
extended to a series of electron-rich arenes and afforded the
corresponding tetraaryl products 2a-d in yields of 45-23%
(Scheme 2), with the remaining products consisting of higher
oligomers.9 In these examples, 3 equiv of BF3 ·Et2O was used to
ensure complete activation of PIFA.
2f. The trend is in line with the increased reactivity of tetra- and
pentamethylbenzenes, which makes the capping reaction faster than
the homocoupling of 1,1′-binaphthalene. High yields were also
obtained in the case of 4b and 4c derived from 1,3,5-triethyl- and
1-tert-butyl-3,5-dimethylbenzene, respectively. Additionally, 2,4,6-
trimethyl-1,1′-biphenyl and 1,3,5-triisopropylbenzene gave products
4d and 4g in 42 and 40% yield.
Table 1. Oxidative Four-Component Kita Coupling Involving
Binaphthalene and Electron-Rich Benzenesa
Scheme 2. Direct Four-Component Coupling between Naphthalene
and Substituted Arenes
In order to extend the method to larger polyaromatic compounds,
we considered two possible mechanistic sequences: (a) formation
of 1a followed by its dehydrodimerization and (b) initial oligo-
merization of naphthalene followed by C-C coupling at the 4 and
4′ positions. The viability of manifold a was confirmed by the
efficient dehydrodimerization of 1a (eq 1; see the Supporting
Information).
a Isolated products.
1a. Kita conditions8 2a Yield: 45%
(1)
To further rationalize the ratios observed, we note that the
formation of 4 from binaphthalene must follow either a dimeriza-
tion/arylation sequence11 (Scheme 4, path A) or a arylation/
dimerization sequence (path B). Furthermore, the monarylation
product 6, an intermediate in path B, may undergo a second
arylation to give 2 (path C).
Next, route b was tested. Since this sequence might start with
the formation of a bisnaphthalene through a known oxidative
coupling reaction,10 we submitted 1,1′-binaphthalene to the reaction
conditions. To our surprise, this coupling only produced 5% 2a,
affording instead an 87% yield of hexaarene 4a (Scheme 3 top).
The connectivity of this product was confirmed by its independent
synthesis via a bromination/Suzuki coupling sequence to give
tetranaphthalene 5 (Scheme 3 bottom), which then underwent Kita
coupling with mesitylene.
Scheme 4. Plausible Reaction Paths from Binaphthalene to 2 and
4
Scheme 3. Coupling between 1,1′-Binaphthalene and Mesitylene
Preliminary results indicated that all three paths may be
operational under the reaction conditions and may compete to give
different products. We found particularly interesting the possible
competition between paths B and C, as these would lead to two
different products. Our initial hypothesis was that mesitylene would
favor path B to give 4 while the more reactive pentamethylbenzene
would favor path C via a rapid second arylation. To probe this
hypothesis, monomesitylated 6a was prepared and was tested in
two reactions, one with mesitylene and the other with pentameth-
ylbenzene (Scheme 5). As expected, mesitylene gave 4a as the main
product (path B favored) while pentamethylbenzene produced
almost exclusively the mixed diarylated product 2af (72% yield,
Intrigued by such a convergent transformation, we proceeded to
test other polyalkylbenzenes. The effect of the substitution pattern
of the Ar-H component was assessed by comparing tris-, tetra-,
and pentamethylbenzenes (Table 1, entries a, e, and f). The 4/2
selectivity ratio was found to be 17.2 for mesitylene (entry a),
decreased to 4.2 for the tetramethylbenzene (entry e), and was
inverted for the pentamethylbenzene (0.03), which gave instead 95%
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C O M M U N I C A T I O N S
selectivity >10:1; path C favored) (see the Supporting Information).
The somewhat reduced selectivity in the case of mesitylene to give
4a may be explained by the exclusion of path A in this case.
Acknowledgment. This work is dedicated to Professor Carmen
Na´jera on the occasion of her 60th birthday. Financial support from
the Ministerio de Ciencia e Innovacio´n (MICINN) of Spain [Projects
CTQ2008-05409-C02-01, CTQ2009-07881, and Consolider Ingenio
2010 (CSD2007-00006)] and DURSI-Generalitat de Catalunya
(SGR 2009-1441) is gratefully acknowledged. We thank Dr. J.
Orduna for the MALDI-TOF spectra and B. Noverges and Dr. G.
Guirado for CV measurements; we also thank Prof. J. Marquet for
insightful discussions.
Scheme 5. Competition between Paths B and C Using
Monomesitylbinaphthalene 6a and Two Different Arenes
Supporting Information Available: Experimental procedures,
spectral and analytical data for all products, and crystallographic data
for 2a (CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
Following a suggestion by a referee, we also determined that,
as Scheme 4 indicates, the rates associated with paths B and C
(and therefore the 4/2 ratio) are sensitive to the amount of ArH
employed. Thus, while the use of 4 equiv of mesitylene in the
arylation of binaphthalene led to selective formation of 4a (Table
1), the use of 12 equiv of mesitylene led to an erosion in the
selectivity down to a 2a/4a ratio of ∼1:1. It is interesting to note,
however, that even under such biased conditions, the reaction still
affords significant amounts of the tetranaphthalene product 4a.
There remains a question as to what governs the different
reactivity of naphthalene, binaphthalene, and higher oligonaphtha-
lenes under the Kita conditions. Thus, while monoarylated 1a or
dimeric 2a was the principal product with naphthalene and selective
dimerization was observed for binaphthalene, we found that both
ternaphthyl and tetranaphthyl (5) underwent selective diarylation
to give 3 and 4, respectively. Although we were able to observe
the presence of the formal dimerization product Ar-(Nap)6-Ar
from ternaphthyl by MALDI-TOF mass spectrometry, the yield
of this oligomer did not exceed 3-4%. The difficulty in explaining
this trend is due to the relatively scarce mechanistic studies of the
Kita coupling. If the proposal of a radical-based mechanism is
accepted,4c the differential reactivity must be governed by the
relative redox potentials of the species involved. Our measurements
in both CH2Cl2 and N,N-dimethylformamide confirmed that bi-
naphthalene (Eox ) 1.69 V) and monarylated 6a (Eox ) 1.72 V)
are more easily oxidized than naphthalene (Eox ) 1.80 V), consistent
with a greater tendency of the binaphthyl derivatives to undergo
dimerization. However, further mechanistic studies are required to
explain the reactivities of ter- and tetranaphthyl and to rule out a
potential Scholl-type acid-base mechanism.
It is expected that the three stereogenic Ar-Ar junctions (aR or
aS) present in 4a would lead to the existence of atropisomeric forms.
With a 23.5 kcal/mol interconversion barrier, these forms should
be observable by NMR spectroscopy.12,13 Indeed, the 13C NMR
spectrum of 4a contains a complex set of signals suggestive of the
presence of several diastereomers (see the Supporting Informa-
tion).14
Traditionally, oligonaphthalenes have been the subject of con-
siderable interest in the field of dyes and organic optical devices,
where they serve either as precursors to the long aromatic systems15
or in their own right.16 Since their synthesis has typically involved
a sequence of metal-catalyzed cross-coupling reactions, the protocol
reported herein represents a remarkably direct one-step access to
4a by a regioselective intermolecular four-component assembly via
the functionalization of six C-H bonds to give three new C-C
bonds. Current work is focused on further establishing the scope
and limitations of this approach.
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Å, b ) 9.6651(8) Å, c ) 24.423(2) Å, ꢀ ) 106.87(2)°; V ) 5603.5(10)
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PhI(OAc)2, PhI(OH)(OTs), and MoCl5; and only traces of 2a were obtained
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