Transition metal-free B(dan)-installing reaction (dan: naphthalene-1,8-diaminato): H-B(dan) as a B(dan) electrophile

Article abstract of DOI:10.1039/d0cc02560g

H-B(dan) was demonstrated to serve as a B(dan) electrophile, despite its highly diminished boron-Lewis acidity, leading to direct and transition metal-free approach to R-B(dan) of high synthetic utility upon treatment with Grignard reagents. Iterative cross-coupling of 5-bromo-2-pyridyl-B(dan), synthesized by the present method, was also achieved.

Full text of DOI:10.1039/d0cc02560g

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Transition metal-free B(dan)-installing reaction (dan:
naphthalene-1,8-diaminato): H–B(dan) as a B(dan) electrophile
Jialun Li,a Michinari Seki,a Shintaro Kamioa and Hiroto Yoshidab*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
H–B(dan) was demonstrated to serve as a B(dan) electrophile,
despite its highly diminished boron-Lewis acidity, leading to direct
and transition metal-free approach to R–B(dan) of high synthetic
utility upon treatment with Grignard reagents. Iterative cross-
coupling of 5-bromo-2-pyridyl–B(dan), synthesized by the present
method, was also achieved.
A. “Protected” B(dan) in SMC
NaOH, K3PO4, CsF
HN
B
Ar’–X
Pd cat.
B(dan) =
Ar B(dan)
HN
t-BuOK
Ar Ar’
B. B(dan) in direct SMC
Lewis acidity of organoboron compounds having a naphthalene-
1,8-diaminato substituent on the boron center, R–B(dan), is
highly diminished, owing to the effective electron-donation
from the adjacent nitrogen atoms and the nearly ideal B(sp2)-
hybridized orbital arising from the planar six-membered ring
structure.1 This feature is well illustrated by boron-masking
strategy in iterative Suzuki–Miyaura coupling (SMC) with Ar–
B(dan), where they become inert toward transmetalation even
with commonly used bases such as NaOH, K3PO4 and CsF (Fig.
1A).2 We have recently reported, on the other hand, that the
“protected” B(dan) moiety can be readily activated by t-BuOK
to generate the respective borate species, which serves as a key
intermediate in the actual direct SMC with Ar–B(dan) (Fig. 1B).3,4
In view of the synthetic significance derived from their base-
dependent inactive/active modifiable character toward SMC,
the development of a convenient and direct method of
accessing Ar–B(dan) would be an important subject in synthetic
organic chemistry. Previously, they have been synthesized by
dehydrative condensation of Ar–B(OH)2 with 1,8-
diaminonaphthalene (danH2) (Fig. 2A),2a,5 and by Cu6- or Pd7-
catalyzed Miyaura–Ishiyama-type coupling of aryl halides with
(pin)B–B(dan)8 (Fig. 2B); the use of H–B(dan) as a B(dan)-
installing reagent in Ir-catalyzed dehydrogenative coupling with
Ar–H is another option for preparing them (Fig. 2C).9 Based on
our results that the B(dan) moiety can smoothly accept
nucleophilic attack by t-BuOK, despite the diminished Lewis
Fig. 1 Suzuki-Miyaura coupling with Ar–B(dan).
A. Dehydrative condensation
Ar B(OH)2
+
danH2
B. Cu or Pd-catalyzed Miyaura–Ishiyama coupling
Cu or Pd cat.
+
X
(pin)B B(dan)
Ar
Ar B(dan)
C. Ir-catalyzed dehydrogenative coupling
Ir cat.
+
H
H
B(dan)
Ar
D. This work
Ar MgBr +
H
B(dan)
transition metal-free
Fig. 2 Synthesis of Ar–B(dan).
acidity, we envisaged that a B(dan) reagent having a suitable
leaving group should react with carbon nucleophiles, leading to
transition metal-free B(dan)-installing reaction into organic
frameworks.10,11 Herein we report that H–B(dan) serves as a
convenient B(dan) electrophile12,13 in the reaction with various
aryl Grignard reagents, which provides a direct way of
a. Applied Chemistry Program, Graduate School of Advanced Science and Engineering,
Hiroshima University, Higashi-Hiroshima 739-8527, Japan.
b. Basic Chemistry Program, Graduate School of Advanced Science and Engineering,
Hiroshima University, Higashi-Hiroshima 739-8526, Japan.
† Electronic Supplementary Information (ESI) available: Experimental procedures and
characterization data. See DOI: 10.1039/x0xx00000x
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Table 1 Optimization of reaction conditions.a
N
N
View Article Online
HN
i-PrMgCl•LiCl (1.5 eq)
H–B(dan) (1 eq)
DOIR: 10.1039B/D0CC02560G
R
Br
p-xylene
rt, 3 h
p-xylene
rt, 3 h
HN
Conditions
H–B(dan) (1 eq)
HN
B
Mg (1.68 eq)
1
3
Br
MgBr
THF
THF
rt, 3 h
1.4 eq
HN
rt, 1 h
1a
2a
3a
B(dan)
B(dan)
B(dan)
N
1.4 eq
N
Entry
Changes from Standard Conditions
Yield (%)b
N
1
2
3
4
5
none
0 °C
50 °C
Ether
Toluene
93 (87c)
3r: 52%a
3s: 71%
3t: 74%a
59
40
37
0
B(dan)
B(dan)
B(dan)
N
N
N
a Standard conditions: 1a (1.40 mmol), Mg (1.68 mmol), THF (2 mL), H–B(dan) (1.00
mmol), rt. b GC yield. c Isolated yield.
Br
3u: 69%
3v: 34%
3w: 53%
synthesizing diverse Ar–B(dan) derivatives (Fig. 2D). Other
Grignard reagents with alkyl, allyl, ethynyl or vinyl groups have
also proven to be efficient nucleophiles in this reaction.
Fig. 4 Synthesis of pyridyl–B(dan) with Turbo Grignard reagent. a Pyridyl–Br (1 eq), Turbo
Grignard reagent (1.4 eq).
We first carried out the reaction of H–B(dan) with
phenylmagnesium bromide (2a), generated in situ from phenyl
bromide (1a) and magnesium, in THF at room temperature, and
found that H–B(dan) served as a B(dan) electrophile for
capturing 2a to afford Ph–B(dan) (3a) in 93% yield (Table 1,
Entry 1). Lowering (0 °C) or raising (50 °C) the reaction
temperature resulted in decrease in the yield (Entries 2 and 3)
and the use of diethyl ether or toluene as a solvent was not
effective for the formation of 3a (Entries 4 and 5).
With the optimized reaction conditions in hand, we next
investigated the B(dan)-installing reaction with various aryl
Grignard reagents (Fig. 3). The substrate scope has turned out
to be sufficiently broad: arylmagnesium bromides bearing an
electron-donating (3b–3g) or -withdrawing substituent (3h and
3i) were readily convertible into the respective Ar–B(dan) in
high yields within 3 hours. In addition, halogen-substituted Ar–
B(dan) (3j–3l) could be synthesized by the present reaction,
being utilizable for the iterative SMC.2 The reaction was also
applicable to polycyclic- and sterically bulky arylmagnesium
HN
bromides to furnish 3m–3p, and 2-thienylmagnesium bromide
H
B(dan)
1 eq
Ar
Ar
MgBr
+
B
could be transformed into 2-thienyl–B(dan) (3q) in 84% yield.14
The versatility of the present method was further enhanced
by its application to pyridyl bromides (Fig. 4). Thus, treatment
of 3-pyridyl or 2-pyridyl bromides with Turbo Grignard reagent
(i-PrMgCl•LiCl)15 and H–B(dan) was found to provide the
THF, rt, 3 h
HN
2
3
1.4 eq
B(dan)
B(dan)
B(dan)
B(dan)
B(dan)
iPr
respective pyridyl–B(dan) (3r–3w) in good yields. It should be
noted that the resulting 2-pyridyl–B(dan) are enough stable to
be isolated even by silica gel column chromatography,3,6,7 being
in stark contrast to the strong propensity of their B(OH)2/B(pin)
counterparts to decompose by protodeborylation.16 As
compared with the existing synthesis of 2-pyridyl–B(dan) by use
of (dan)B–B(pin) and a transition metal catalyst,6,7 the present
reaction has proven to be superior in efficacy and substrate
scope;17 its combination with our direct SMC would provide a
promising option for “2-pyridyl problem” (see also Scheme 1).18
As shown in Fig. 5, a variety of primary (Me, n-Bu, i-Bu,
neopentyl), secondary (i-Pr, cyclopropyl) and tertiary (t-Bu) alkyl
Grignard reagents could facilely be coupled with H–B(dan) to
3a: 87%
3b: 93%
3c: 92%
3d: 94%
3e: 91%
B(dan)
B(dan)
B(dan)
B(dan)
B(dan)
CF3
CF3
OMe
NMe2
CF3
Br
3f: 81%
3g: 90%
3h: 90%
3i: 71%
3j: 40%
B(dan)
B(dan)
B(dan)
B(dan)
B(dan)
Cl
Ph
Cl
3k 88%
3l: 57%
3m: 84%
3n: 83%
3o: 52%
produce the corresponding alkyl–B(dan)
straightforward manner, and furthermore vinyl– (4h), ethynyl–
4i and 3-hydroxypropyl–B(dan) 4j were also readily
accessible under the present reaction conditions. Moreover,
allyl bromide was efficiently transformable into allyl–B(dan) (4k
in 95% yield by employing Barbier-type conditions, whereas the
(4a–4g) in a
B(dan)
B(dan)
(
)
( )
S
)
3p: 90%
3q: 84%a
reaction of crotyl bromide (E:Z = 85:15) gave a mixture of α- (4l
and γ-adducts (4’l) in 42:58 ratio.
)
a
Fig. 3 Substrate scope on aryl Grignard reagents. 2-Thienylmagnesium bromide was
prepared at reflux temperature.
2
| J. Name., 2012, 00, 1-3
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A. H2 Trapping Experiment
Ph
B
View Article Online
DOI: 10.1039/D0CC02560G
HN
B
R
MgX
2 eq
H
B(dan)
1 eq
+
R
HN
N
THF, rt, 24 h
HN
X = Cl, Br
4
1. Mg (3.36 mmol), 1 h
2. H–B(dan) (2 mmol), 3 h
H+
Ph B(dan)
Ph Br
and/or
Ph
THF, rt
2.8 mmol
3a: 87%
B(dan)
B(dan)
B(dan)
B(dan)
Me
4a: 49%a
B
N
N
4b: 96%
4c: 83%
4d: 55%a
B(dan)
B(dan)
B(dan)
+
B(dan)
4e: 86%
H2
4h: 73%a
4g: 66%
4f: 72%
H
B(dan)
5% Pd/C (1 mol % of Pd)
THF, rt, 16 h
Ph
Ph
Ph
Ph
B(dan)
4i: 46%a
+
H
HO
B(dan)
B(dan)
4k: 95%b
0.5 mmol
88%
4j: 85%b
B(dan)
4l+4'l: 67% (42:58)b
B. Quenching with Me–OTs
Exp. 1
a
1. Mg (1.68 eq), 1 h
2. H–B(dan) (1 eq), 3 h
Fig. 5 Substrate scope of other Grignard reagents. Commercially available Grignard
Ph
B
Ph
B
b
reagents were used. The reaction was conducted according to modified procedures.
Me
Me
Me
(2 eq), 24 h
3. Me OTs
N
NH
N
N
See ESI for details.
Ph Br
1.4 eq
3a
+
+
THF, rt
During the course of the reaction, we observed vigorous
evolution of gas from the reaction mixture.19 On the assumption
that the gas would be hydrogen, generated from a leaving group,
a hydride (H–MgX) and a proton (H–N on the B(dan)), we carried
out its trapping experiment by using trans-stilbene as a
hydrogen accepter in the presence of a palladium catalyst (Fig.
6A). A reduced product, 1,2-diphenylethane, was found to form
in 88% yield, which verifies the evolved gas is indeed hydrogen.
Moreover, this result implies that R–B(dan) would exist as their
anionic forms in the reaction mixture before aqueous work-up;
quenching the reaction with methyl tosylate afforded a mixture
of N-methylated (3’a) and N,N’-dimethylated (3”a) products (Fig.
6B, Exp. 1), while N-methylation of isolated 3a did not occur at
all under similar conditions (Fig. 6B, Exp. 2). In addition, the
reaction with D2O-quenching gave deuterated 3a (Fig. 6C).
Based upon these, a plausible pathway for the B(dan)-installing
reaction, where a hydride serves as a good leaving group,20 is
depicted in Scheme 1. First, a Grignard reagent of enough
nucleophilicity attacks the boron center of H–B(dan) to lead to
3’a
29%
3”a
12%
55%
Exp. 2
(2 eq)
Me OTs
3a 100% recovery
3a
THF, rt, 24 h
C. Quenching with D2O
1. Mg (1.68 eq), 1 h
2. H–B(dan) (1 eq), 3 h
Ph
B
(H or)
(or H)
D
D
(2 eq), 24 h
3.
D
OD
N
N
Ph Br
1.4 eq
THF, rt
3a + 3a-d1 + 3a-d2
75%, D incorporation ratio = 40%
Fig. 6 Mechanic studies.
R
B
R
MgX
HN
NH
R
H
H
MgX
+
+
B(dan) MgX
H
B(dan)
intermediary formation of a borate species (5). Subsequent
5
elimination of H–MgX, which promptly reacts with the H–N on
the B(dan) moiety to evolve H2, followed by aqueous work-up
finally gave the product.
R
B
R
B
H2
H+
HN
N
XMg
N
N
MgX
MgX
R
B(dan)
+
The synthetic utility of the present reaction was well
demonstrated by the iterative SMC with 3w (Scheme 2); the
chemoselective SMC at the Br moiety of 3w with p-TolB(OH)2
Scheme 1 A plausible pathway for the B(dan)-installing reaction.
offered
bond. The resulting
iodobenzotrifluoride under our direct SMC conditions to furnish
oligoarene in 52% yield.
6
in 45% yield without damaging the 2-pyridyl–B(dan)
6
was then cross-coupled with 4-
sp3)–B(dan) of high synthetic utility under the transition metal-
free conditions. Moreover, the reaction pathway has been
found to include the evolution of H2 via the deprotonation of
the H–N on the B(dan) moiety with H–MgX. Further studies on
the B(dan)-installing reactions by utilizing H–B(dan) as a B(dan)
electrophile and the direct SMC of R–B(dan) therefrom are in
progress.
7
In conclusion, we have demonstrated that H–B(dan) can
serve as a promising B(dan) electrophile for capturing such
carbon nucleophiles as diverse Grignard reagents, leading to the
convenient and practical method for synthesizing C(sp, sp2 and
This journal is © The Royal Society of Chemistry 20xx
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p-TolB(OH)2 (2 eq)
Pd(Pt-Bu3)2 (2 mol %)
CsF (2 eq)
Org. Chem., 2014, 3, 1204; (c) H. Yoshida, Y. TakVeiemwoAtrtoiclaenOdnliKne.
Takaki, Chem. Commun., 2015, 51, 6297; (d) I. Kageyuki, I.
Osaka, K. Takaki and H. Yoshida, Org. DLOetIt:.1,02.1001379/,D109C,C803205;6(0eG)
H. Yoshida, S. Kamio and I. Osaka, Chem. Lett., 2018, 47, 957;
(f) H. Yoshida, Y. Murashige and I. Osaka, Adv. Synth. Catal.,
2019, 361, 2286.
N
B(dan)
N
B(dan)
THF, 70 °C, 4 h
Br
3w
6
selective SMC at Ar–Br
45%
12 Synthesis of R–B(pin) by the reaction of Grignard reagents
with H–B(pin) was reported. See: J. Clary, T. Rettenmaier, R.
Snelling, W. Bryks, J. Banwell, W. Wipke and B. Singaram, J.
Org. Chem., 2011, 76, 9602.
CF3
F3CC6H4I (1 eq)
Pd(PPh3)4 (5 mol %)
t-BuOK (1.5 eq)
N
1,4-dioxane, 100 °C, 4 h
13 For catalytic B(dan)-installing reactions, whose elementary
steps include electrophilic behavior of H–B(dan), see: (a) W. J.
Jang, W. L. Lee, J. H. Monn, J. Y. Lee and J. Yun, Org. Lett., 2016,
18, 1390; (b) W. J. Jang, B.-N. Kang, J. H. Lee, Y. M. Choi, C.-H.
Kim and J. Yun, Org. Biomol. Chem., 2019, 17, 5249; (c) T.
Tsuchimoto, H. Utsugi, T. Sugiura and S. Horio, Adv. Synth.
Catal., 2015, 357, 77; (d) T. Tani, Y. Sawatsugawa, Y. Sano, Y.
Hirataka, N. Takahashi, S. Hashimoto, T. Sugiura and T.
Tsuchimoto, Adv. Synth. Catal., 2019, 361, 1815.
7
direct SMC at 2-Py–B(dan)
52%
Scheme 2 Iterative SMC with 5-bromo-2-pyridyl–B(dan).
We thank Prof. Teruhisa Tsuchimoto (Meiji University,
Japan) for lending a special Schlenk flask used in the H2 trapping
experiment.
14 We have also tried the reaction of 4-bromoacetophenone (or
2-bromobenzonitrile)-derived aryl Grignard reagents using
Turbo Grignard reagent, however, the respective aryl–B(dan)
was not formed at all in each case.
15 A. Krasovskiy and P. Knochel, Angew. Chem. Int. Ed., 2004, 43,
3333.
16 P. A. Cox, A. G. Leach, A. D. Campbell and G. C. Lloyd-Jones, J.
Am. Chem. Soc., 2016, 138, 9145.
17 Because the Pd method was found to be inapplicable to the
synthesis of 2-pyridyl–B(dan) (3s) and 6-methyl-2-pyridyl–
B(dan) (3v), they were thus far available only by the Cu
method, albeit in lower yields (57% and 32%, respectively).
See also ref. 3.
18 G. R. Dick, E. M. Woerly and M. D. Burke, Angew. Chem. Int.
Ed., 2012, 51, 2667.
19 See ESI for video recorded the gas evolution.
20 Singaram has already disclosed that a hydride serves as a good
leaving group in a similar reaction with Grignard reagents and
H–B(pin). See ref. 12.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1
Boron-Lewis acidity decreases as a boron center adopts ideal
B(sp2) geometry (bond angle and planarity). See: (a) A. Zhou,
A. Wakamiya, T. Kushida and S. Yamaguchi, J. Am. Chem. Soc.,
2012, 134, 4529; (b) A. Adamczyk-Woźniak, M. Jakubczyk, P.
Jankowski, A. Sporzyński and P. M. Urbański, J. Phys. Org.
Chem., 2013, 26, 415.
2
3
(a) H. Noguchi, K. Hojo and M. Suginome, J. Am. Chem. Soc.,
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Suginome, Org. Lett., 2008, 10, 377; (c) N. Iwadate and M.
Suginome, Org. Lett., 2009, 11, 1899; (d) N. Iwadate, N and M.
Suginome, Chem. Lett., 2010, 39, 558.
H. Yoshida, M. Seki, S. Kamio, H. Tanaka, Y. Izumi, J. Li, I. Osaka,
M. Abe, H. Andoh, T. Yajima, T. Tani and T. Tsuchimoto, ACS
Catal., 2020, 10, 346.
4
5
For similar direct SMC with Ar–B(dan), see: Y. Mutoh, K.
Yamamoto and S. Saito, ACS Catal., 2020, 10, 352.
(a) G. Kaupp, M. R. Naimi-Jamal and V. Stepanenko, Chem. Eur.
J., 2003, 9, 4156; (b) S. Maruyama and Y. Kawanishi, J. Mater.
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H. Yoshida, Y. Takemoto, S. Kamio, I. Osaka and K. Takaki, Org.
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L. Xu and P. Li, Chem. Commun., 2015, 51, 5656.
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2018, 95, 218.
N. Iwadate and M. Suginome, J. Organomet. Chem., 2009, 694,
1713.
6
7
8
9
10 For transition metal-free B(dan)-installing reactions with
(pin)B–B(dan), see: (a) J. Cid, J. J. Carbó and E. Fernández,
Chem. Eur. J., 2014, 20, 3616; (b) N. Miralles, J. Cid, A. B.
Cuenca, J. J. Carbó and E. Fernández, Chem. Commun., 2015,
51, 1693; (c) K. Chen, S. Zhang, P. He and P. Li, Chem. Sci., 2016,
7, 3676; (d) A. Verma, R. F. Snead, Y. Dai, C. Slebodnick, Y. Yang,
H. Yu, F. Yao and W. L. Santos, Angew. Chem. Int. Ed., 2017,
56, 5111; (e) S. Peng, G. Liu and Z. Huang, Org. Lett., 2018, 20,
7363. (f) X. Liu, W. Ming, X. Luo, A. Friedrich, J. Maier, U.
Radius, W. L. Santos and T. B. Marder, Eur. J. Org. Chem., 2020,
1.
11 For our studies on the B(dan)-installing reactions, see: (a) H.
Yoshida, Y. Takemoto and K. Takaki, Chem. Commun., 2014,
50, 8299; (b) H. Yoshida, Y. Takemoto and K. Takaki, Asian J.
4
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