Suzuki-miyaura cross-coupling of 1,8-diaminonaphthalene (dan)-protected arylboronic acids

Article abstract of DOI:10.1021/acscatal.9b03667

We report a Suzuki-Miyaura cross-coupling reaction of 1,8-diaminonaphthalene (dan)-protected arylboronic acids in the presence of KOt-Bu, which does not require the removal of the dan moiety. Notably, the use of aryl-B(dan) in the Suzuki-Miyaura reaction provides a complementary solution to the protodeboronation problems. The base KOt-Bu plays a crucial role for the promotion of these cross-coupling reactions as it enables the formation of a borate salt. This reaction protocol was extended to the one-pot sequential Suzuki-Miyaura cross-coupling reaction of 4-[(pin)B]C₆H₄-B(dan), wherein the "less reactive" aryl-B(dan) moiety was cross-coupled preferentially.

Full text of DOI:10.1021/acscatal.9b03667

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Letter
Suzuki–Miyaura Cross-Coupling of 1,8-
Diaminonaphthalene (dan)-Protected Arylboronic Acids
Yuichiro Mutoh, Kensuke Yamamoto, and Shinichi Saito
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b03667 • Publication Date (Web): 11 Oct 2019
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ACS Catalysis
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Suzuki−Miyaura Cross-Coupling of 1,8-Diaminonaphthalene (dan)-
Protected Arylboronic Acids
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Yuichiro Mutoh,* Kensuke Yamamoto, and Shinichi Saito*
Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo
162-8601, Japan.
ABSTRACT: We report a Suzuki−Miyaura cross-coupling reaction of 1,8-diaminonaphthalene (dan)-protected
arylboronic acids in the presence of KOt-Bu, which does not require the removal of the dan moiety. Notably, the use of
aryl-B(dan) in the Suzuki−Miyaura reaction provides a complementary solution to the protodeboronation problems. The
base KOt-Bu plays a crucial role for the promotion of these cross-coupling reactions as it enables the formation of a
borate salt. This reaction protocol was extended to the one-pot sequential Suzuki−Miyaura cross-coupling reaction of 4-
[(pin)B]C6H4−B(dan), wherein the "less reactive" aryl-B(dan) moiety was cross-coupled preferentially.
KEYWORDS: B(dan), borate, boronic acid, cross-coupling, palladium, Suzuki−Miyaura
Suzuki−Miyaura cross-coupling reactions between
organoboronic acids and aryl halides represent one of the
most useful and straightforward methods to synthesize
biaryl compounds.1 Given the utility of B-protected
(masked) boronic acids in iterative Suzuki−Miyaura
reactions,2 it is not surprising that substantial research
efforts have been devoted to the development of a diverse
range of effective protecting (masking) groups.2 Among
these, much attention has been focused on nitrogen-
containing protective groups,2a−c particularly the
naphthalene-1,8-diaminato (dan) group,3,4 as aryl-B(dan)
derivatives are stable toward protodeboronation under
aqueous basic conditions.4−6 Yet the removal of the dan
group from Ar−B(dan) under acidic conditions is
necessary to provide the latent boronic acids that engage
in the subsequent Suzuki−Miyaura reaction.2,4a,b,e
Initially, we examined the impact of various bases on
the reaction of Ph−B(dan) (1a) and 4-iodoanisole (2a) in
the presence of Pd-PEPPSI-IPr13 at 70 °C in toluene
(Table 1). When KOt-Bu was used as the base, the cross-
coupled product (3aa) was obtained in 95% yield (entry
1). When NaOt-Bu or LiOt-Bu were used, the cross-
coupling of 1a and 2a did not proceed (entries 2 and 3).
Other basic potassium salts were also examined, but only
KOt-Bu promoted the desired reaction in high yield
(entries 4−6). Subsequently, we varied the amount of
KOt-Bu and discovered that 2.5 equiv of the base was
optimal for this reaction (entries 7−9). The addition of
water, which is essential to promote the Suzuki−Miyaura
cross-coupling of R−B(pin) (pin = pinacolato), inhibited
the reaction (entry 10).
Table 1. Impact of the Nature of the Base on the
Palladium-Catalyzed Cross-Coupling of 1a and 2aa
The direct use of Ar−B(dan) derivatives in
Suzuki−Miyaura cross-coupling reactions would thus be
highly desirable in terms of step- and atom-economy,7
which would help to streamline the synthesis of complex
molecules. Moreover, it would contribute to a significant
broadening of the utility of Ar−B(dan) derivatives, which
could provide
protodeboronation
a
complementary solution to the
problems known as the
entry base
equiv
3.0
yield (%)b
“polyfluorophenyl8 and 2-pyridyl9 problems”. Although
palladium- or copper-catalyzed reactions of alkynyl-
B(dan), RC≡C−B(dan), with aryl halides have been
reported,10 examples of the formation of carbon−carbon
bonds via direct cross-coupling reactions of Ar−B(dan)
derivatives remain elusive.11 Herein, we report
Suzuki−Miyaura cross-coupling reaction of Ar−B(dan)
derivatives with aryl halides, where the removal of the dan
moiety is not required.12 The key to the success of these
cross-coupling reactions is the use of KOt-Bu as the base,
as KOt-Bu enables the formation of an active borate,
which was characterized by NMR spectroscopy and
single-crystal X-ray diffraction analysis.
1
1.0 M KOt-Bu/THF
95
2
1.0 M NaOt-Bu/THF
1.0 M LiOt-Bu/THF
KOt-Bu
3.0
trace
3
3.0
no reaction
4
3.0
95
5
KOEt
3.0
28
6
KF
3.0
no reaction
7
1.0 M KOt-Bu/THF
1.0 M KOt-Bu/THF
1.0 M KOt-Bu/THF
1.0 M KOt-Bu/THF
3.75
2.5
99
8
99
9
10c
1.25
2.5
40
trace
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aGeneral reaction conditions: 1a (1.25 equiv), 2a (1.0 equiv),
Pd-PEPPSI-IPr (2.0 mol %), toluene ([2a]0 = 0.05 M).
bIsolated yield. cA mixture of toluene/H2O (5:1, v/v) was used
as the solvent.
were obtained regardless of the position of the bromine
atom on the benzene ring. These results suggest that the
products should be readily amenable to further
functionalization of the C(sp2)−Br bond. Sterically
demanding 2,4,6-trimethylphenyl-B(dan) (1j) reacted with
2a using XPhos as the ligand, and 3ja was isolated in 75%
yield.
1
2
3
4
5
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7
8
Subsequently, we briefly screened various palladium
complexes for the Suzuki−Miyaura cross-coupling of 1a
and 2a in the presence of KOt-Bu in toluene (Table 2).
The use of Pd-PEPPSI-IPr as the catalyst is not
mandatory. When other palladium(II) complexes such as
[PdCl2(dppf)]·CH2Cl2 and [PdCl2(PPh3)2] were employed,
the cross-coupling reaction proceeded smoothly (entries
1−3). A combination of [Pd(OAc)2] and XPhos14 also
provided 3aa in high yield (entry 4). The cross-coupling
reaction also proceeded in the presence of common
palladium(0) complexes such as [Pd2(dba)3]·CHCl3/PPh3
and [Pd(PPh3)4] (entries 5 and 6). These results
demonstrate that common palladium-based catalyst
systems can be used for the cross-coupling of Ar−B(dan).
To investigate the “polyfluorophenyl and 2-pyridyl
problems” in these Suzuki−Miyaura cross-coupling
reactions, polyfluorophenyl-B(dan) derivatives 1k and 1l
and a 2-pyridyl-B(dan) derivative 1m,4c which are stable
and can be easily purified by column chromatography,
were subjected to the established cross-coupling protocol.
When the reactions of 1k and 1l were carried out in the
presence of a reduced amount (1.25 equiv) of KOt-Bu, the
corresponding polyfluorobiaryls 3ka and 3la were isolated
in high yield. The reaction of 1m with 2a provided coupling
product 3ma in 92% yield. These results indicate that the
cross-coupling using 1k−m complements the previous
solutions15−18 for the “polyfluorophenyl and 2-pyridyl
problems”.
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Table 2. Screening of Palladium Complexes for the
Cross-Coupling of 1a and 2a in the Presence of KOt-
Bua
Table 3. Substrate Scope of the Suzuki−Miyaura
Cross-Coupling Reaction Between Ar−B(dan) (1) and
ArX (2).
entry [Pd] complex
additive
yield (%)b
1c
2
3
4
5
6
Pd-PEPPSI-IPr
[PdCl2(dppf)]·CH2Cl2
[PdCl2(PPh3)2]
[Pd(OAc)2]
−
99
95
91
97
97
94
−
−
XPhosd
d
[Pd2(dba)3]·CHCl3
[Pd(PPh3)4]e
PPh3
−
aGeneral reaction conditions: 1a (1.25 equiv), 2a (1.0 equiv),
[Pd] (2.0 mol %), KOt-Bu (2.5 equiv), toluene ([2a]0 = 0.05
M). bIsolated yield. cTaken from entry 8 in Table 1. d4 mol %
of the additive were used. ePurified by recrystallization prior
to use.
Then, we investigated the substrate scope of this
Suzuki−Miyaura cross-coupling reaction under the
established optimal conditions (Table 3). When 4-
substituted phenyl-B(dan) (1b−f) and 4-iodoanisole (2a)
were used, the corresponding biaryls (3ba−fa) were
obtained in high yield. Notably, the cross-coupling of the
B(dan) group in benzenediboronic acid derivative 1e
proceeded selectively to afford 3ea in 89% yield, which
shows that the B(pin) group in 1e remains unaffected
under the established cross-coupling conditions, and that
3ea should be susceptible to further functionalization of
the
C(sp2)−B(pin)
bond
under
conventional
Suzuki−Miyaura coupling conditions. Although the
reactivity of Ar−B(dan) derivatives with silylether and
cyclic ether moieties (1f and 1g) are low, biaryls 3fa and
3ga were obtained in high yield when XPhos was used as
the ligand. Moreover, the bromo functionality in Ar−B(dan)
substrates 1h and 1i is tolerated in this cross-coupling
reaction, and the corresponding products (3ha and 3ia)
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ACS Catalysis
(a) Control experiments
Pd-PEPPSI-IPr (2.0 mol %)
1
2
3
1.0 M KOt-Bu/THF (2.5 equiv)
+
1a
2a
3aa
toluene
70 °C, 24 h
(1.25 equiv)
(1.0 equiv)
with TEMPO (1.0 equiv): 56%
with 1,4-benzoquinone (1.0 equiv): 34%
without Pd-PEPPSI-IPr: no reaction
4
5
6
7
8
9
(b) Effect of the addition of 18-crown-6
[Pd2(dba)3]·CHCl3 (2 mol%)
PPh3 (4 mol %)
1.0 M KOt-Bu/THF (2.5 equiv)
18-crown-6 (0 or 2.5 equiv)
+
3aa
0 equiv: 80%
2.5 equiv: 25%
1a
2a
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(1.25 equiv)
(1.0 equiv)
THF
70 °C, 24 h
(c) Formation and molecular structurea of the borate K[1a(Ot-Bu)]
H
H
N
N
t-Bu
1.0 M KOt-Bu/THF (1.0 equiv)
B
O B
K+
N
H
N
toluene
rt, 10 min
H
1a
K[1a(Ot-Bu)]
11B: – 1.9 ppm
(1.0 equiv)
11B: 29.0 ppm
δ
δ
O
K
H
O
N
B
N
H
(d) Stoichiometric reaction of K[1a(Ot-Bu)] with [PdI(4-MeOC6H4)(PPh3)2]
OMe
aGeneral reaction conditions: 1 (1.25 equiv), 2a (1.0 equiv),
[Pd2(dba)3]·CHCl3 (2.0 mol %), PPh3 (4.0 mol %), KOt-Bu
(2.5 equiv), toluene ([2a]0 = 0.05 M). bTHF was used as the
solvent. cXPhos (4.0 mol %) was used instead of PPh3. dThe
reaction was carried out at 110 °C. e1.25 equiv of KOt-Bu was
used.
H
N
B
t-Bu
PPh3 (0.2 equiv)
Ph3P
I
O
3aa
K+
Pd
+
N
toluene
70 °C, 4 h
H
92%
PPh3
(1 equiv)
K[1a(Ot-Bu)]
(1 equiv)
We also briefly explored the scope with respect to aryl
halides (2) in these cross-coupling reactions. Various
substituted iodobenzene derivatives (2b−e) were tested,
and, as expected, the corresponding coupling products
(3ab−ae) were obtained in high yield, regardless of the
substituents and their positions on the benzene ring.
Finally, 4-bromo- and 4-chloroanisole were used in the
cross-coupling of 1a, which afforded 3aa, albeit slightly
modified reaction conditions were required.
aFor clarity, only one of the repeat units of the one-
dimensional coordination polymer of {[K(thf)][1a(Ot-Bu)]} is
shown. Thermal ellipsoids are shown at 50% probability and
only selected atoms are labeled.
the presence of radical scavengers such as TEMPO and
1,4-benzoquinone afforded 3aa in moderate yields, while
the reaction in the absence of a palladium complex did not
proceed,
which
renders
single-electron-transfer
To gain insight into the mechanism underlying the
Suzuki−Miyaura cross-coupling of Ar−B(dan), we carried
out several control experiments (Scheme 1). The cross-
coupling of 1a and 2a in
pathways19 unlikely (Scheme 1a). Moreover, in the
presence of 18-crown-6, the reaction of 1a and 2a
afforded 3aa only in 25% yield (Scheme 1b),20 indicating
that the potassium ion is of crucial importance for this
reaction.21 Subsequently, we examined the chemical
species present in the reaction mixture. When a toluene
solution of 1a was treated for 10 min at room temperature
Scheme 1. Preliminary Mechanistic Studies
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