1,1-Hydroboration of Fused Azole-Isoindole Analogues as an Approach for Construction of B,N-Heterocycles and Azole-Fused B,N-Naphthalenes

Article abstract of DOI:10.1021/acs.orglett.6b00485

Three isoelectronic analogues of pyrido[2,1-a]isoindole have been found to undergo a facile 1,1-hydroboration with HBMes₂ borane, which provides a new and convenient method for the synthesis of B,N-heterocycles 1a-3a in high yields. Compounds 1a-3a can undergo photoelimination upon irradiation at 300 nm, generating heterocycle-fused B,N-naphthalene molecules 1b-3b, which display distinct yellow-green and blue fluorescent colors, respectively. Compound 1a undergoes thermal elimination, producing 1b at 280°C, while compound 2a only undergoes partial elimination, forming 2b at 320°C. Compound 3a is thermally stable up to 320°C.

Full text of DOI:10.1021/acs.orglett.6b00485

Letter
pubs.acs.org/OrgLett
1
,1-Hydroboration of Fused Azole−Isoindole Analogues as an
Approach for Construction of B,N‑Heterocycles and Azole-Fused
B,N‑Naphthalenes
†
,§
‡,§
‡
†
†
,†,‡
Yong-gang Shi, Deng-Tao Yang, Soren K. Mellerup, Nan Wang, Tai Peng, and Suning Wang*
†Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry, Beijing Institute of
Technology, Beijing 100081, P. R. China
‡
Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6, Canada
*
S Supporting Information
ABSTRACT: Three isoelectronic analogues of pyrido[2,1-
a]isoindole have been found to undergo a facile 1,1-
hydroboration with HBMes borane, which provides a new
2
and convenient method for the synthesis of B,N-heterocycles
1
a−3a in high yields. Compounds 1a−3a can undergo
photoelimination upon irradiation at 300 nm, generating
heterocycle-fused B,N-naphthalene molecules 1b−3b, which display distinct yellow-green and blue fluorescent colors,
respectively. Compound 1a undergoes thermal elimination, producing 1b at 280 °C, while compound 2a only undergoes partial
elimination, forming 2b at 320 °C. Compound 3a is thermally stable up to 320 °C.
yrido[2,1-a]isoindole (isocarb, Figure 1) and its isoelec-
tronic analogues such as pyrrolo[1,2-a]pyridine are known
by demonstrating its viability with various isoelectronic
analogues of isocarb. Three fused azole−isoindole molecules,
benzo[4,5]thiazolo[2,3-a]isoindole (1), 5-methyl-5H-benzo
P
[4,5]imidazo[2,1-a]isoindole (2), and 1-methyl-2-phenyl-1H-
1,2,4]triazolo[5,1-a]isoindole (3), shown in Figure 1 were
[
chosen as representative examples for our investigation.
The possibility that compounds 1−3 may undergo 1,1-
hydroboration in the same manner as isocarb was first
supported by the results of DFT computational study, which
revealed that the electronic structures of 1−3 are in fact similar
to those of isocarb. As can be seen in Figure 1, the unique
carbon atom of each species has a significant contribution to
the HOMO level much like isocarb, suggesting that they
should all possess similar nucleophilic character. Additionally,
the HOMO level is either similar in energy or destabilized
relative to that of isocarb, which indicates that the basicity/
nucleophilicity of compounds 1−3 should either be similar or
greater than that of isocarb. Indeed, our experimental work has
confirmed that compounds 1−3 are also capable of facile 1,1-
hydroboration, which provides a new, simple, and highly
efficient synthetic route to B,N-heterocycles based on hetero-
cycle-fused isoindoles. The details are presented herein.
Figure 1. DFT calculated HOMO and LUMO energies and orbital
diagrams of isocarb and its isoelectronic analogues.
to be reactive heterocycles that can readily undergo 1,3-dipolar
cycloadditions with alkynes to generate a variety of interesting
1
π-conjugated systems. This is facilitated by the unique C6
atom of isocarb (and its familial equivalents), which is highly
nucleophilic and easily reacts with electrophiles such as acyl
2
Compound 1 was prepared directly according to a modified
groups to form C−C-coupled products. Recently, we
11
literature procedure. The precursor compounds 11H-benzo-
discovered that isocarb can undergo unprecedented and
[4,5]imidazo[2,1-a]isoindole (pre-2) and 2-phenyl-5H-[1,2,4]-
unusual 1,1-hydroboration reactions with a variety of HBR2
3
triazolo[5,1-a]isoindole (pre-3) for 2 and 3, respectively, were
boranes, leading to the convenient synthesis of B,N-
prepared according to literature procedures (see the Supporting
heterocyclic compounds that are known precursors to a class
2
,12
4
Information).
Compounds pre-2 and pre-3 were converted
of rare and highly emissive B,N-phenanthrenes. Given the
in good yields to their methylated salts, [pre-2-Me]I and [pre-
potential applications of and tremendous current research
5
6−9
interest in B,N-heterocycles and azaborinines, as well as the
3
,10
underdeveloped nature of 1,1-hydroboration chemistry,
we
Received: February 19, 2016
set out to expand the scope of our 1,1-hydroboration protocol
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00485
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
-Me]I, respectively, by first reacting with dimethyl sulfate
Letter
13
3
prepared and reacted with t-BuLi/BMes F, resulting in a 16%
2
followed by the addition of 30% aqueous KI solution.
Deprotonation [pre-2-Me]I and [pre-3-Me]I using bases
such as NaOH or Na CO were unsuccessful due to the
isolated yield of 2a (see the SI).
Compounds 1a, 2a, and 3a were fully characterized by NMR
and HRMS analyses. All three molecules display a B chemical
shift (3.70, 1.80, and 1.80 ppm, respectively) that is
characteristic of four-coordinated boron. In addition, the
crystal structures of 1a and 3a were established by single-crystal
X-ray diffraction analysis. The B−C bond lengths in both
molecules are similar and comparable to those of 2-(o-
1
1
2
3
formation of ring-opened products in the presence of
1
2
t
3,4
hydroxide. Use of a non-nucleophilic base such as KO Bu
in toluene did give the desired products 2 and 3; however,
attempts to purify these heterocycles proved problematic due
to their extremely high sensitivity to air, which always led to
contamination by the decomposition products. Therefore, we
designed a one-pot procedure for the generation of 2 and 3 and
their borylated counterparts 2a and 3a. In this procedure
4
tolyl)pyridine-BMes and derivatives. The B−N bond in 3a
2
(1.636(2) Å) is however significantly shorter than that in 1a
(
1.669(2) Å) and 2-(o-tolyl)pyridine-BMes2 (1.666(2) Å),
(Scheme 1), [pre-2-Me]I and [pre-3-Me]I were reacted with
which could be attributed to the reduced congestion around the
boron center in 3a (Figure 2). All three compounds are stable
in solution and in the solid state under ambient conditions.
Scheme 1. 1,1-Hydroboration of 1 and Analogous One-Pot
Procedure for 2 and 3
Figure 2. Crystal structure of 3a. Important bond lengths (Å) and
angles (deg): B(1)−N(1) 1.636(2), B(1)−C(1) 1.654(2), B(1)−
C(17) 1.666(2), B(1)−C(26) 1.655(2); C(1)−B(1)−N(1)
97.04(11), C(1)−B(1)−C(17) 106.76(12), C(1)−B(1)−C(26)
119.37(13), N(1)−B(1)−C(17) 111.83(12), N(1)−B(1)−C(26)
107.93(11), C(17)−B(1)−C(26) 112.88(12).
t
excess KO Bu in toluene at ambient temperature. After the
t
removal of KI and excess KO Bu by filtration under nitrogen,
the filtrates were used directly for the hydroboration reaction.
To establish if compounds 1a−3a can act as precursors for
the generation of azaborinine derivatives, their photoreactivity
Surprisingly, the addition of HBMes (Mes = mesityl) to the
2
solution of in situ generated 2 or 3 in benzene or toluene at
ambient temperature resulted in the formation of the
corresponding borylated products 2a and 3a in good yields
was examined. Compounds 1a−3a have low energy absorption
bands with λ = ∼ 295, 310, and 310 nm, respectively (see the
max
SI) and are not fluorescent in solution. However, as the
solutions of 1a−3a are irradiated with 300 nm UV light, they
become brightly fluorescent and display distinct fluorescent
(
70% and 72%, respectively, after purification and isolation by
column chromatography). Compound 1 reacted with HBMes2
at 80 °C to produce the borylated product 1a in high yield
−5
colors. For example, THF solutions (∼10 M) of 1a and 2a
changed from nonfluorescent to yellow-green and green
fluorescent, respectively, following irradiation, with new
absorption peaks appearing at λmax = 450 nm (1b) and 445
nm (2b) in their UV−vis spectra (Figure 3). Accompanying
this change in absorptions are new emission peaks with well-
(
90%). The successful synthesis of compounds 1a−3a
demonstrates that 1,1-hydroboration is a general reactivity of
fused azole-isoindole derivatives and can be used to build
heteroatom-doped polycyclic organoboron compounds.
This new, one-pot 1,1-hydroboration protocol of isocarb
analogues is an extremely useful synthetic method, as it is the
only viable approach of achieving borylated compounds such as
resolved vibrational features at λmax = 520 nm (1b, Φ
=
FL
0.022) and 495 nm (2b, Φ = 0.47) in their fluorescence
FL
1
a, 2a, and 3a in high yield. Our previously established
spectra. For 3a, its solution produced intense sky-blue
fluorescence after irradiation with a new absorption peak at
procedure for achieving the BMes -chelated 2-(o-tolyl)pyridine
2
species involved the use of n-BuLi at −78 °C, which is prone to
λmax = 405 nm and a broad, featureless emission peak at λmax =
the generation of side products such as ortho-metalation at the
478 nm (Φ = 0.13) in the UV−vis and the fluorescence
FL
2
3
4
sp -phenyl carbon rather than the desired sp -methyl. These
undesired deprotonations become even more likely upon the
introduction of additional heteroatoms into the chelating
framework, such as 1-methyl-2-(o-tolyl)-1H-benzo[d]imidazole
and 4-methyl-3-phenyl-5-(o-tolyl)-4H-1,2,4-triazole, which
would be the required substrates for the preparation of 2a
and 3a, respectively, under such conditions. To compare these
two methods, 1-methyl-2-(o-tolyl)-1H-benzo[d]imidazole was
spectra, respectively. NMR and HRMS analyses confirmed that
the new fluorescent species are heterocycle-fused B,N-
naphthalenes 1b, 2b, and 3b, respectively (Scheme 2) and
that the photochemical conversion of 1a−3a to 1b−3b is clean
11
(see the SI). The B chemical shifts of 1b−3b (36.3, 34.1, and
3
,4
33.6 ppm, respectively) are consistent with azaborinines.
Compound 1b is similar to a BMes -chelate molecule we
2
4
reported recently, while compounds 2b and 3b are new
B
DOI: 10.1021/acs.orglett.6b00485
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Organic Letters
Letter
Figure 3. Absorption (dotted lines) and fluorescence spectra (solid
−5
line) of 1b−3b in THF (∼1 × 10 M). The fluorescence spectra were
recorded at λ of absorption. Inset: photographs showing the
max
emission colors of 1b−3b.
Figure 4. (Top) TD-DFT calculated S → S transition energies,
0
1
oscillator strength, and orbital diagrams for 1b−3b. (Bottom) H and L
energy level change from isoindole heterocycles to B,N-arenes.
Scheme 2. Photo- and Thermal Reactivity of 1a−3a
corresponding B,N-arenes have the same number of π electrons
in their respective conjugated units. However, the insertion of a
B-Mes unit into the isoindole ring significantly stabilizes both H
and L levels of the molecule (H is lowered by 0.23, 0.36, and
0
4
.27 eV, respectively from 1−3 to 1b−3b) as shown in Figure
. The stabilization of the HOMO level leads to an enhanced
stability of the B,N-arenes toward oxygen relative to the
isoindole heterocycles and a narrowing of the H−L gap with
respect to 1 and 2 (see the SI for details).
Previously, we have shown that BMes -chelated isocarb
2
compounds can display either retro-1,1-hydroboration (debor-
3
ylation) or mesitylene elimination upon heating. To determine
members of the B,N-arene family. Efforts to grow single crystals
of 2b and 3b for X-ray diffraction analysis were unsuccessful.
The successful synthesis of 1b−3b via photoelimination of the
chelate precursors 1a−3a demonstrates that this transformation
is a general reactivity for B,N-heterocycles possessing an azole-
fused backbone. The distinct emission colors of 1b−3b indicate
that the fused benzazole ring of the B,N-naphthalenes has a
significant influence on the photophysical properties of this
class of compounds and may therefore be used as a convenient
approach to tune the emission color of B,N-arenes.
if BMes -chelate compounds based on isocarb analogues
2
display similar reactivities, we examined the thermal reaction
of compounds 1a−3a. Compound 1a was found to undergo a
clean thermal elimination upon heating at 280 °C, producing
1b nearly quantitatively. Compound 2a is stable at 280 °C and
undergoes partial conversion to 2b along with the formation of
unidentified products at 320 °C. In contrast, 3a is thermally
stable and shows no change at temperatures between 280 and
3
20 °C. On the basis of these findings, it is clear that the
To gain insight into the impact of the fused benzazole unit
on compounds 1b−3b, TD-DFT calculations were performed
at the cam-B3LYP/6-31g(d) level of theory. The general trend
of absorption and fluorescence spectra of 1b−3b is
corroborated by TD-DFT data as shown in Figure 4. For 1b
and 2b, the transition to the first excited state primarily involves
HOMO (H) → LUMO (L) (96%) with large oscillator
strength. For 3b, the transition to the first excited state is from
H to L (57%) and LUMO+1 (L + 1, 38%), also with large
oscillator strength. The H orbital for all three compounds is a π
orbital concentrated primarily on the B,N-naphthalene portion
of the molecule, while the L orbital for 1b and 2b is a π* orbital
involving the entire conjugated unit. For 3b, L and L+1 orbitals
have significant contributions from the phenyl substituent on
the triazole ring. The nonrestricted rotation of this phenyl ring
in 3b is believed to be responsible for the broad and featureless
emission band and the relatively large Stokes shift of 3b. It is
noteworthy that the fused azole−isoindole molecules 1−3 and
conjugated heterocyclic backbone has an impact not only on
the electronic structure of the corresponding B,N-arenes but
also on the stability/reactivity of the chelate compounds. The
fact that no deborylation products were observed in any of the
thermal reactions indicates that deborylation is likely a
thermodynamically disfavored process.
In summary, we have established that the 1,1-hydroboration
of isoindole derivatives is a general reactivity available to this
class of molecules and can be used as a simple and effective
method of preparing B,N-heterocycles. Further, we have shown
that this new synthetic protocol can be implemented in tandem
with our previously described photo- and thermal reactivity to
afford a wide variety of unexplored B,N-arenes. Ongoing
research efforts are focused on exploiting the generality of these
transformations with the aim of creating larger and more
complex B,N-doped nanographenes.
C
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Letter
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ASSOCIATED CONTENT
Supporting Information
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AUTHOR INFORMATION
Corresponding Author
(8) (a) Hatakeyama, T.; Hashimoto, S.; Seki, S.; Nakamura, M. J. Am.
Chem. Soc. 2011, 133, 18614−18617. (b) Wang, X.-Y.; Zhuang, F.-D.;
Wang, R.-B.; Wang, X.-C.; Cao, X.-Y.; Wang, J.-Y.; Pei, J. J. Am. Chem.
Soc. 2014, 136, 3764−3767. (c) Wang, X.-Y.; Wang, J.-Y; Pei, J. Chem.
■
*
E-mail: wangs@chem.queensu.ca.
Author Contributions
-
Eur. J. 2015, 21, 3528−3539.
§
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T. S.; Parvez, M. Angew. Chem., Int. Ed. 2007, 46, 4940−4943.
Y.-g.S. and D.-T.Y. contributed equally to this work.
Notes
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c) Bosdet, M. J. D.; Piers, W. E. Can. J. Chem. 2009, 87, 8−29.
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
Y.-g.S., N.W., T.P., and S.W. thank the Beijing Institute of
Technology for financial support. D.-T.Y., S.K.M., and S.W.
thank the Natural Sciences and Engineering Research Council
of Canada for financial support and the High Performance
Computing Virtual Laboratory at Queen’s University for
computational facilities.
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