CH activation-based transformation of naphthalenes to 3-iodo-2-naphthylboronic acid derivatives for use in iterative coupling synthesis of helical oligo(naphthalene-2,3-diyl)s

Article abstract of DOI:10.1246/bcsj.20170026

Oligo(naphthalene-2,3-diyl)s were synthesized by iterative cross-coupling of 1,8-diaminonaphthalene-modified 3-iodo- 2-naphthylboronic acids prepared from naphthalenes via Ircatalyzed CH borylation, Ru-catalyzed ortho-CH silylation directed by an anthrani

Full text of DOI:10.1246/bcsj.20170026

Advance Publication Cover Page
C–H Activation-Based Transformation of Naphthalenes to
3-Iodo-2-naphthylboronic Acid Derivatives for Use in Iterative
Coupling Synthesis of Helical Oligo(naphthalene-2,3-diyl)s
Takeshi Yamamoto, Aoi Ishibashi, Masashi Koyanagi, Hideki Ihara,
Nils Eichenauer, and Michinori Suginome*
Advance Publication on the web February 6, 2017
doi:10.1246/bcsj.20170026
© 2017 The Chemical Society of Japan

chirality-related molecular functions including their use as
highly enantioselective and chirality-switchable catalysts.
Structurally well-related poly/oligo(naphthalene-2,3-diyl)s are
also highly attractive structural motifs, while their synthesis
remains under development.7 Given that the SMC has been
the most reliable protocol in the synthesis of oligoarene
derivatives, the development of a new efficient synthesis of
C–H Activation-Based Transformation
of Naphthalenes to
3-Iodo-2-naphthylboronic Acid
Derivatives for Use in Iterative
Coupling Synthesis of Helical
Oligo(naphthalene-2,3-diyl)s
monomers
for
the
synthesis
of
poly/oligo-
(naphthalene-2,3-diyl)s is eagerly desired. We recently
reported the facile synthesis of o-iodobenzeneboronic acids
through C–H silylation directed by the boronyl group onto
which a removable directing group is introduced.8 Herein, we
report on the application of directed C–H silylation, in
combination with nondirected C–H borylation, for convenient
synthesis of 3-iodo-2-naphthaleneboronic acids from
naphthalenes.
Takeshi Yamamoto, Aoi Ishibashi, Masashi Koyanagi,
Hideki Ihara, Nils Eichenauer, and Michinori
Suginome*
An outline of the transformation of naphthalenes (2) to
3-iodo-2-naphthylboronic acid derivatives (1) is shown in
Scheme 1. A B(pin) group is introduced by Ir-catalyzed C–H
borylation.9 The borylation is expected to take place
selectively at the 2-position of the unsubstituted benzene ring.
After replacing the pinacol ligand with an anthranilamide
(AAM) ligand, a silyl group is introduced to the 3-position by
Ru-catalyzed C–H silylation directed by the AAM group.8 The
Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto University, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received
January
18,
2017;
E-mail:
suginome@sbchem.kyoto-u.ac.jp
product
is
iododesilylated
to
give
Oligo(naphthalene-2,3-diyl)s were synthesized by
iterative cross-coupling of 1,8-diaminonaphthalene-
modified 3-iodo-2-naphthylboronic acids prepared from
3-iodo-2-naphthaleneboronic acids. The AAM ligand on the
boron atom is replaced by a 1,8-diaminonaphthalene (DAN)
ligand to use these naphthalene derivatives in iterative SMC.3b
The o-directed silylation has already been established by our
group using AAM or PZA (2-pirazolyl-3-aniline)10 as a
temporarily attached directing group.
naphthalenes
via
Ir-catalyzed
C–H
borylation,
Ru-catalyzed ortho-C–H silylation directed by an
anthranilamide-modified boronyl group, and subsequent
iododesilylation. The introduction of a chiral diol to the
retained terminal boronyl group allowed selective induction
of P- or M-helical conformations.
The Suzuki–Miyaura coupling (SMC) provides one of the
most reliable accesses to conjugated polymers.1 The
cross-coupling synthesis of polyarenes is classified mainly
into two systems from the viewpoint of monomer structures:
an AA/BB coupling system, where two bifunctional
monomers are polymerized, and an AB system, where a single
monomer bearing both boronyl and leaving groups is
employed.2 The latter system is advantageous in avoiding
accurate adjustment of the molar equivalent of two monomers
and applicability to iterative cross-coupling synthesis of
sequence-defined oligoarenes.3 However, the AB system is
significantly hampered by the difficulty in synthesizing
requisite monomers bearing both the boronyl and the leaving
group. It is therefore highly desirable to establish a general
and efficient synthesis of arylboronic acids bearing a leaving
group.
Among the various conjugated polyarenes, particular
attention has been focused on ortho-linked polyarenes
adopting helical structures.4 However, since early reports on
the synthesis of poly(o-phenylene)s, not much progress has
been made, probably because of the lack of suitable synthetic
access. Meanwhile, we have reported helical structures and
new functions of poly(quinoxaline-2,3-diyl)s,5 which are
Scheme 1. Outline of the conversion of naphthalene to
3-iodo-2-naphthylboronic acids
1,4-Dimethylnaphthalene was initially subjected to the
protocol (Scheme 2). According to a previous report,8
Ir-catalyzed C–H borylation was conducted with
bis(pinacolato)diboron (2 equiv) in cyclohexane at 80 °C in
the presence of [Ir(OMe)(cod)]2 (1.0 mol%), giving a pinacol
ester of 2-naphthylboronic acid (3a) in 98% yield. The ester
3a was converted into the corresponding naphthylboronic acid
and condensed with AAM, giving AAM-modified
naphthylboronic acid 5a in good yield. Its reaction with
PhMe2SiH in the presence of RuH2(CO)(PPh3)3 along with
norbornene allowed the introduction of a silyl group at the
3-position.11 The silyl group was replaced by an iodine group
using ICl at –78 °C. The AAM group was replaced by a DAN
group to attain more robustness during the coupling process.
accessible
by
living
polymerization
of
1,2-diisocyanobenzenes.6 The study clearly indicates that the
helical architectures of o-linked polyarenes lead to new
In
a
similar
manner,

2
Bull Chem. Soc. Jpn., Template for Short Articles
1,4-dimethyl-2,3-di(propoxymethyl)naphthalene (2b) was
converted into the corresponding 3-iodo-2-naphthaleneboronic
acid 1b. We note that, in these C–H borylations of
naphthalenes 2a and 2b bearing substituents on one of the two
rings, monoborylation took place at the -position of the
unsubstituted ring regioselectively without using excess
amounts of the naphthalenic starting materials, although an
excess amount of naphthalene (2c, 4 equiv) was used in the
synthesis of 3c.
The iterative coupling protocol was applicable to the
synthesis of sterically more demanding
oligo(5,8-dimethylnaphthalene-2,3-diyl)s (Scheme 4). Starting
from 5,8-dimethyl-2-naphthaleneboronic acid, bi-, ter-, and
quarternaphthalenes 11–13 were obtained by iterative SMC
using 1a as the sole building block.
Combined use of the coupling building blocks 1a–c in the
iterative SMC process allowed us to synthesize
oligo(naphthalene-2,3-diyl)s in which the three different
monomers are assembled in a sequence-selective manner
(Scheme 5). Starting from 7, which was obtained through
coupling of 1c (Scheme 3), 14 and 15 were obtained by
sequential coupling with 1a and 1b.
Scheme 4. Synthesis of
oligo(5,8-dimethylnaphthalene-2,3-diyl)s
Scheme 2. Synthesis of cross-coupling monomers
With the cross-coupling monomers 1a–c in hand,
quinquenaphthalene 10 was synthesized using an iterative
SMC protocol (Scheme 3). 6-Ethoxy-2-naphthylboronic acid
was cross-coupled with 1c to afford DAN-masked
binaphthaleneboronic acid 7 in high yield.3b After deprotection
of the DAN group under acidic conditions, subsequent
coupling was conducted, again using 1c as the coupling
building block, giving 8 in high yield. Repetition of the
two-step process afforded the quarternaphthalene 9 and
quinquenaphthalene 10, which retained the terminal boronyl
group protected by DAN. This demonstrates that the iterative
SMC using 1 as a building block provides a straightforward
route to oligonaphthalene derivatives.
Scheme 5. Sequence-selective synthesis of quarternaphthalene
Oligo(naphthalene-2,3-diyl)s thus obtained generally have
a terminal boronyl group protected by a DAN group. To gain
insight into their helical conformation, a chiral diol was
introduced to the terminal boronyl group in anticipation of
induction of helical chirality (eq. 1).5c Bi-, ter-, quarter-, and
quinquenaphthalenes 7–10 were treated with HCl to remove
the DAN-masking group. Oligonaphthaleneboronic acids (n =
1–4) thus obtained were reacted with chiral diol (R,R)-16 in
the presence of MgSO4, giving the corresponding
oligonaphthalenes (R,R)-17–20 (n
=
1–4). Although
1
binaphthalene (R,R)-17 (n = 1) showed a simple H NMR
spectrum at room temperature, larger oligomers (R,R)-18–20
(n = 2–4) showed complicated spectra resulting from slow
interconversion of conformers on the NMR time scale (see SI).
For example, two benzylic protons at the chiral centers
exhibited two or more singlet peaks around 5 ppm. In NMR
experiments conducted at variable temperatures, these
conformer peaks were coalesced into single broad peaks at
80–100 °C in DMSO-d6. It is interesting to note that
binaphthalene (R,R)-17 (n = 1) and ternaphthalene (R,R)-18 (n
Scheme 3. Synthesis of oligo(naphthalene-2,3-diyl)s

= 2) showed only a weak circular dichroism (CD) signal,
whereas (R,R)-19 (n = 3) and (R,R)-20 (n = 4) showed intense
CD signals with a clear Cotton effect in acetonitrile (Fig. 1).
In addition, (S,S)-19 (n = 3) obtained with (S,S)-16 showed
mirror-image CD spectra. These results suggested that helical
conformation is preferred in higher oligomers, probably
because steric repulsion of the naphthalene rings becomes
more pronounced.
6b (70 mg, 94%).
[Cross-coupling] A mixture of 7 (1.63 g, 3.5 mmol), THF (35
mL), and aqueous HCl (6 M, 3.5 mL) was stirred at 80 °C for
3 h. After extraction with Et2O, the organic phase was dried
over MgSO4. Filtration and evaporation gave the
corresponding arylboronic acid. A mixture of the arylboronic
acid, Pd(OAc)2 (0.18 mmol), K3PO4 (7.0 mmol) and water
(35 mmol) in THF (7 mL) was stirred for 15 h at 60 °C. The
mixture was diluted with water and extracted with CH2Cl2.
The combined extracts were washed with water and brine,
dried over MgSO4, filtered with pad of Celite®, and
concentrated to dryness by evaporation. Product 8 (1.90 g,
92%) was isolated by washing with hexane.
References
(1)
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Figure 1. CD spectra of chiral oligomers in acetonitrile at
20 °C.
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For
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In summary, we have described a convenient synthesis of
3-iodo-2-naphthaleneboronic acid derivatives via nondirected
Ir-catalyzed C–H borylation and Ru-catalyzed C–H silylation
directed by an AAM-modified boronyl group. They serve as
building blocks for the iterative SMC for the synthesis of
oligo(naphthalene-2,3-diyl)s, whose helical structures were
proven by deracemization experiments using a chiral diol as
the chiral modifier at the terminal boronyl group.
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Typical Experimental Procedures
[Ir-catalyzed
C–H
borylation]
A
mixture
of
[Ir(COD)(OMe)]2 (8.7 mol), 4,4'-di-t-butyl-2,2'-bipyridine
(0.017 mmol), bis(pinacolato)diboron (1.9 mmol), and 2b
(512 mg, 1.7 mmol) in cyclohexane (1.7 mL) was heated for
18 h at 80 °C. After cooling to room temperature, the solvent
was evaporated in vacuo. The product 3b was isolated by
silica gel column chromatography (593 mg, 81%).
[Ru-catalyzed o-C–H silylation] A mixture of 5b (117 mg,
0.263 mmol), RuH2(CO)(PPh3)3 (0.053 mmol), norbornene
(1.3 mmol), and hydrosilane (1.3 mmol) in toluene (0.13 mL)
was heated in a sealed glass tube at 135 °C for 20 h. The
mixture was subjected to column chromatography on Florisil®,
giving 4b (73 mg, 48%).
[Iododesilylation] To a solution of 4b (75.5 mg, 0.13 mmol)
in CH2Cl2 (6.5 mL) was added ICl (0.26 mmol) at –78 °C.
After stirring for 18 h, 2-methyl-2-butene (0.9 mmol) was
added, and the mixture was stirred for 5 min at room
temperature. The precipitate was washed with hexane, giving
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H. Noguchi, M. Murakami, Chem. Lett. 2007, 36, 1036. c) S.
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8 a) H. Ihara, M. Koyanagi, M. Suginome, Org. Lett. 2011, 13,
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Bull Chem. Soc. Jpn., Template for Short Articles
11 The conversions of 5c and a into 6c and a, respectively,
has been reported in the previous communication (ref. 8).

1,8-Diaminonaphthalene (DAN)-masked 3-iodo-2-naphthylboronic acids were prepared from their
corresponding naphthalenes via Ir-catalyzed nondirected C–H borylation, Ru-catalyzed ortho-C–H silylation
directed by an anthranilamide (AAM)-modified boronyl group, and iododesilylation followed by replacement of
the AAM group with DAN. Iterative Suzuki–Miyaura cross-coupling of the DAN-masked
3-iodo-2-naphthylboronic acids afforded helical oligo(naphthalene-2,3-diyl)s bearing a convertible terminal
boronyl group.