Boron-masking strategy for the selective synthesis of oligoarenes via iterative Suzuki-Miyaura coupling

Article abstract of DOI:10.1021/ja067975p

The iterative synthesis of oligoarenes via an organoborane-based cross-coupling reaction (i.e., the Suzuki-Miyaura coupling) has been achieved by using a series of "masked" haloarylboronic acids as building blocks whose ordinarily reactive boronyl groups are temporarily protected by a new masking group derived from 1,8-diaminonaphthalene. Copyright

Full text of DOI:10.1021/ja067975p

Published on Web 01/04/2007
Boron-Masking Strategy for the Selective Synthesis of Oligoarenes via
Iterative Suzuki-Miyaura Coupling
Hiroyoshi Noguchi, Kosho Hojo, and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity
Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Received November 8, 2006; E-mail: suginome@sbchem.kyoto-u.ac.jp
Scheme 1. Boron-Masking Strategy in the Synthesis of
Biarylboronic Acid via Suzuki-Miyaura Coupling
The palladium-mediated coupling of organoboronic acid deriva-
tives with organic halides, i.e., the Suzuki-Miyaura coupling
(SMC), is one of the most reliable and convenient reactions for
C-C bond formation.1 The high efficiency of the reaction, high
stability of the organoboron compounds toward air and moisture,
and high functional group compatibility make SMC one of the most
widely used of all the available cross-coupling systems. Recent
advances have provided new catalyst systems which permit the
highly efficient synthesis of a variety of organic compounds,2
including oligo- and polyarene derivatives, which are of significant
importance in materials science and technology.3
In this report, we describe a novel strategy for an iterative SMC,4
which leads to the synthesis of a wide range of functionalized
oligoarenes. The critical design element is the use of an efficient
masking group for the boronyl group, which temporarily renders it
inactive, allowing the use of bifunctional (nucleophile/electrophile)
arenes in the coupling reaction. As far as we are aware, a masking/
unmasking strategy has never been used to control reactivity of
organoboronic acids in the coupling reaction.5
Scheme 2. Iterative Suzuki-Miyaura Coupling Using Masked
Haloarylboronic Acids for Selective Synthesis of Oligoarenes
To illustrate the approach, the synthesis of biarylboronic acids
A-B via SMC is shown in Scheme 1. The coupling of arylboronic
acid A with haloboronic acid B would not provide the desired
compound, leading instead to the formation of a mixture of
oligoarenes A-Bn and Bn via oligomerization of B.6 This difficulty
would be overcome if the oligomerization of B could be suppressed
through masking of the boronyl group of B. Coupling of the
“masked” haloarylboronic acid B′ with A would then provide the
masked biarylboronic acid derivative A-B′ selectively. After
unmasking, the desired A-B is obtained. It is important to note
that these steps (i.e., coupling and subsequent unmasking) can be
applied a second time, leading to the formation of terarylboronic
acid derivatives A-B-C by coupling with reagent C′ (Scheme
2). This iterative SMC offers a new efficient route to oligoarene
derivatives (e.g., A-B-C-D). Despite the potential merit of this
strategy, no effective masking group for the boronyl group in SMC
has been described thus far. However, the usefulness of iterative
synthesis has been well documented,7 and efficient iterative SMC
using a different approach involving a “hydroxy-activating strategy”
appeared recently.4e
1a-e bearing this masked boronyl group, which were isolated either
by recrystallization or even by column chromatography on silica
gel in high yields. Although other diamines and amine derivatives
such as 4,5-dimethyl-o-phenylenediamine, N,N′-dimethylethylene-
diamine, 1,2-diaminocyclohexane, o-aminobenzyl alcohol, and
anthranilic acid were examined for the masking group, they were
all unstable toward aqueous workup or silica gel column chroma-
tography.
For the masking group to be truly practical, there are some
requirements including (1) easy installation, (2) high stability during
coupling and isolation processes, and (3) easy unmasking. Since it
is commonly accepted that the Lewis acidity of the boron atom is
the key factor governing the reactivity of the organoboronic acid
in SMC,1a we decided to introduce a masking group that lowers
the Lewis acidity of the boron atom. Amino groups seemed to be
good candidates for the masking group since the nitrogen atoms
donate their lone pair electrons to the vacant p-orbital of the boron
atom, thus lowering the acidity significantly in comparison with
that of the corresponding boronic acids and their esters.8 To increase
overall stability, diamines, which form cyclic diaminoboranes, were
examined.
The masked haloarylboronamides 1a-e, having a 1,8-diami-
nonaphthalene group, were subjected to SMC with arylboronic acids
in the presence of a Pd[P(tBu)3]2 catalyst with 2 equiv of CsF (Table
1).2a Reactions of p-tolylboronic acid (2a) with o-, m-, and
p-bromophenylboronamide 1a-c afforded the corresponding biaryls
3a-c in high yields, in which the masked boronyl groups were
left intact (entries 1-3). It is noteworthy that the coupling took
place so selectively that no oligomers were formed as byproducts.
In addition, methoxy-substituted 1d afforded the corresponding
coupling product selectively in high yield (entry 4). With 1d,
arylboronic acids 2b-d also afforded the corresponding coupling
products 3e-g in high yields (entries 5-7). Thiophene derivative
Commercially available haloarylboronic acids were treated with
1,8-diaminonaphthalene in refluxing toluene with azeotropic re-
moval of water, affording the corresponding naphthalene-1,8-
diamido derivatives 1 in high yields (eq 1).9 We prepared haloarenes
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C O M M U N I C A T I O N S
Table 1. Pd-Catalyzed Coupling of Arylboronic Acids with
Scheme 3. Synthesis of Teraryl, Quarteraryls, and Quinquearyls
Bromoarylboronic Acid 1,8-Diaminonaphthalene Amidesa
via Iterative Cross-Couplinga
a Reaction conditions: (a) H2SO4 aq. or HCl aq., THF, rt;
(b) Pd[P(tBu3)]2 (2 mol %), CsF (2 equiv), THF, 60 °C.
a 2 (0.43 mmol), 1 (0.43 mmol), Pd[P(tBu3)]2 (8.5 µmol), and CsF (0.85
mmol). b Isolated yield.
Scheme 4. Functionalization of the Terminus of Quinquearyl
Derivative 8
1e also afforded the corresponding 2-tolylthiophene derivative 3h
in the coupling with 2a (entry 8).
The protocol was extended to the selective synthesis of higher
oligoarenes. To unmask the 1,8-diaminonaphthalene group, the
biarylboronamide 3 was treated with diluted sulfuric acid or
hydrochloric acid at room temperature. We observed clean depro-
tection of the 1,8-diaminonaphthalene group, which could be
removed from the reaction mixture just by washing with acid. The
unmasked boronic acids were then subjected to the cross-coupling
with 1. The second coupling also proceeded efficiently, giving
terarylboronamide 4 in high yield (Scheme 3). Repetition of the
unmasking-coupling sequence using 4 provided quateraryl and
quinquearyl derivatives 5 and 6 selectively. Furthermore, starting
with the same terarylboronamide 4, quateraryl- and quinquearyl-
boronic acid derivatives 7 and 8 were isolated in high yields via
iterative cross-coupling using 1c.
Finally, functionalization of the oligomer was facilitated by virtue
of the reactivity of the boryl group at the terminus of the quinquearyl
8. After the unmasking step, hydrogen peroxide oxidation,10 cross-
coupling with alkenyl halide,1,2 and Rh-catalyzed conjugate addition
to methyl vinyl ketone11 were applied to the quinquearylboronic
acid 8, affording the corresponding products 9-11 (Scheme 4).
In summary, we have established new strategy for the iterative
SMC by using 1,8-diaminonaphthalene as an efficient masking
group for the boronyl group. The masking group is robust enough
to avoid undesirable coupling and is easily unmasked by simple
treatment with aqueous acid. The applicability of this strategy to
the automated synthesis of oligoarene derivatives is of great
interest.7 Furthermore, the concept of boron masking or protection
may be extended to a variety of reactions, where the native boronyl
group is not tolerated.
Reaction conditions: (a) H2O2, NaOH aq.; (b) (E)-BrCHdCHPh,
Pd[P(tBu)3]2, NaOH aq.; (c) CH2dCHCOCH3, Rh(acac)(C2H4), BINAP.
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