Photochemical Generation of Chiral N,B,X-Heterocycles by Heteroaromatic C?X Bond Scission (X=S, O) and Boron Insertion

Article abstract of DOI:10.1002/anie.201803760

Chiral organoboron compounds with a chelate backbone and mesityl/heterocycle substituents (thienyl, furyl, and derivatives thereof) undergo a quantitative phototransformation that yields rare, chiral N,B,X-containing heterocycles, such as base-stabilized

Full text of DOI:10.1002/anie.201803760

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Accepted Article
Title: Photochemical Generation of Chiral N,B,X-Heterocycles via
Heteroaromatic C-X Bond Scission (X = S, O) and Boron
Insertion
Authors: Soren K Mellerup, Cally Li, Julian Radtke, Xiang Wang, Quan-
song Li, and Suning Wang
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201803760
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Photochemical Generation of Chiral N,B,X-Heterocycles via
Heteroaromatic C–X Bond Scission (X = S, O) and Boron Insertion
Soren K. Mellerup,[a] Cally Li,[a] Julian Radtke,[b] Xiang Wang,[a] Quan-Song Li,[c]* and Suning Wang[a],[c]
*
Abstract: Chiral organoboron compounds with a chelate backbone
and mesityl/heterocycle substituents (thienyl, furyl and derivatives)
undergo a quantitative phototransformation yielding rare, chiral
N,B,X-embedded heterocycles (b) (e.g. base-stabilized 1,2-
thiaborinines and 1,2-oxaborinines). Boriranes (a) were observed as
intermediates in some of these transformations. The oxaborinines
display further reactivity, generating 4a,12b-dihydro-benzo[h][1,2]-
systems such as azaboratabisnorcaradienes (B),[10a,b] B,N-1,4,6-
cyclooctatrienes,[10c] azaborabenzotropilidenes,[10d] and 4bH-
azaborepins (C),[10e,f] each of which possesses interesting
properties and would be very difficult to prepare by traditional
synthetic protocols. In many of these examples, the photo-
generated boriranes B act as reactive intermediates, enabling
subsequent transformations to more stable isomers. Based on
this idea of “storing” energy within boriranes to encourage new
reactivity, we hypothesized that by pre-organizing appropriate
functionalities near the three-membered boracycle, it may be
possible to tune their reactivity towards specific, desirable
transformations involving both borirane and installed
functionality.
oxaborinino-[4,3-f]quinolones through
a
sequential conrotatory
electrocyclization and [1,5]-H shift. Compounds b display strong
blue-green to orange-red emission in the solid state. Combined
DFT//CASP2T calculations suggest that
a common biradical
intermediate is responsible for the formation of a and b, as well as a
to b conversion in the excited state.
The selective manipulation of specific chemical bonds
within molecular frameworks has been of a longstanding interest
to synthetic chemists both from a practical[1] and fundamental[2]
perspective. Much like transition metal complexes, which were
recognized to be highly effective in bond activation and catalysis
decades ago,[3] recent advances in main-group chemistry have
revealed great promise/potential for p-block element enabled
chemical transformations.[4] Nevertheless, there still remain
many substrates that are routinely handled by transition metals,
e.g. C–X bonds (X = S, O, or N) in heteroaromatic systems,[5]
most of which have yet to be established for main-group
analogues.[6,7]
The key facet of main-group systems that allows them to
activate various chemical bonds is their possession of
“unquenched reactivity” imposed by specific electronic and steric
constraints.[8] Aside from designing systems with the necessary
features to yield these types of reactive systems, one promising
alternative is the use of light to bring molecules into their excited
state(s) such that bond activation can be performed via these
higher energy species.[9] This methodology has several
advantages, with the most prominent being access to reactive
intermediates from easily prepared and often air stable starting
materials. Using this approach, we have recently unveiled a
number of photo-initiated transformations available to N,C-
chelate boron compounds (e.g. A, Scheme 1), wherein readily
accessible precursors are converted to novel B,N-embedded
Scheme 1. Reactivity of chiral boron systems (a) and (b).
To this end, we designed a series of chiral, chelate boron
systems bearing two different aryl groups at boron, consisting of
the necessary mesityl anchor,[10e] various chelate units, and a
range of 2-heterocycles (1 – 10, 1 in Scheme 2). The
anticipated regioselective borirane formation[10e] on the
heterocycles would place their C2–X bonds in close proximity to
the borirane ring (a) and potentially facilitate C–X bond
activation through either photochemical borylene insertion[11] or
heterocycle rearrangement.[12] In this way, a variety of base-
stabilized X-borinines (X = O, S; b) could be conveniently
prepared. It is known that replacing aromatic C=C bonds with B–
N bonds leads to significant changes in molecular properties,
lending such species to a variety of new applications including
optoelectronic materials and medicines.[13] As a result, synthetic
methodologies for accessing azaborinines are well developed.
By comparison, oxa- and thiaborinines remain rare and
underdeveloped,[14] which furthers the need for new methods to
prepare such systems. Indeed, the new chiral boron compounds
undergo the targeted phototransformation, yielding rare, chiral
N,B,X-heterocycles (b) with interesting photophysical properties.
[a]
[b]
[c]
S. K. Mellerup, C. Li, Dr. X. Wang, Prof. Dr. S. Wang
Department of Chemistry, Queen’s University
Kingston, Ontario, Canada, K7L 3N6
E-mail: sw17@queensu.ca
J. Radtke
Institut für Anorganische und Analytische Chemie
Goethe-Universität Frankfurt
D-60438, Frankfurt (Main), Germany
Prof. Dr. Q. -S. Li, Prof. Dr. S. Wang
Beijing Key Laboratory of Photoelectronic/Electrophotonic
Conversion Materials, School of Chemistry
Beijing Institute of Technology, Beijing, 10081, P. R. China
Email: liquansong@bit.edu.cn
Supporting information for this article is given via a link at the end of
the document.
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Labile BN bonding in 1,2-(benzo)oxaborinines allows further
photoisomerization, resulting in N,B,O-embedded 4a,12b-
dihydrotriphenylene derivatives. CASPT2 calculations suggest
that heterocycle ring-opening/migration is responsible for the
formation of the N,B,X-heterocycles, as well as implicate a
common biradical intermediate connecting the excited-state
reaction pathways leading to a and b. The details of this rare
phototransformation and mechanistic insight are presented
herein.
air-stable, with its structure first established by 2D NMR (see SI)
and subsequently confirmed by x-ray crystallography (Figure 2).
The chiral boron compounds 1 – 10 were prepared in low
to moderate yields (~5-50%) by a modified procedure,[10e]
employing B(R)(Ar)Mes and lithiated chelating ligands (see
Scheme 2 and Supporting Information). In addition, compound 1,
an isomer of 1, was also prepared. All compounds were fully
characterized by 1H, 13C, and 11B NMR and HRMS
spectroscopic analyses. The crystal structures of 2, 5, 6, and 1
were determined by single crystal x-ray diffraction analysis and
have bond lengths around the B atom similar to those of A (see
SI).[10e,f] These compounds all have strong and broad absorption
bands ranging from 300-405 nm (ε = 8000 – 20000 cm-1 L-1 mol),
and fluoresce weakly in the visible region (λem = 400 – 570 nm,
Φfl = ~ 0.05 – 0.30) due to their charge transfer (CT) S1 transition
from heterocycle (, HOMO) to chelate backbone (*, LUMO).[10]
Figure 1. 1H NMR spectra showing the conversion of 2 to 2b (20 mg in 0.4 mL
of C6D6) with irradiation at 365 nm.
Figure 2. Crystal structures of 2b, 4b, and 5b with 35% thermal ellipsoids.
The crystal structure of 2b confirms the chiral boron atom,
which has formally inserted into the C–S bond of
benzothiophene. Coordination of the py group decreases the
B1–S1 and B1–C1 bonds of 1,2-benzothiaborinine (1.920(2) and
1.590(2) Å, respectively) relative to base-free 1,2-
thiaborinines.[14c] To the best of our knowledge, 2b represents
the first example of heteroaromatic C–S bond activation by a
main-group system, as well as a previously unknown 1,2-
benzothiaborinine derivative. Compound 1 undergoes a similar
structural change as does 2, however, continued irradiation
leads to the decomposition of 1b (see Figure S3C). Control
experiments established that the 1/2 to 1b/2b transformation
occurs via the excited state of 1/2, and is not a thermal process
(see SI). Due to concomitant formation of two photoproducts,
quantum yields of isomerization could not be determined. The
importance of boron and C2–S bond proximity in 1/1a and 2/2a
Scheme 2. Synthesis of compounds 1 – 10 and 1’.
Irradiation of 1 or 2 with 365 nm light initiates a two-step
phototransformation as illustrated by the 1H NMR tracking
experiment of 2 shown in Figure 1. As 2 is consumed, two sets
of new resonances appear. From the singlet at ~1.2 ppm, it is
clear that one of the products is 2a, where regioselective
borirane formation has occurred on the 2-benzothienyl ring.
Notably, 2a is only detected as the minor product after each
irradiation interval, with the major product being the base-
stabilized 1,2-benzothiaborinine 2b. Further irradiation converts
all of the remaining 2 and 2a to 2b cleanly and quantitatively.
The 11B chemical shift (1.8 ppm) of 2b is similar to that of 2 (2.6
ppm), indicating a tetrahedral environment around boron. 2b is
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was confirmed by the photoreaction of 1‘ (Scheme 3), which
follows that of A → C in Scheme 1.[10e,f] Therefore, the C2–B
connectivity in 1/1a and 2/2a plays a critical role in facilitating the
photogeneration of 1b and 2b, which is elucidated in the
computed reaction pathway for 1 to 1b.
f]quinoline by 2D NMR experiments (see SI), where the two
inner H-atoms have a trans-configuration and large J coupling
3
constant (~18 Hz). Control experiments indicated that 7f is
generated via a photo- process (see Figure S3ZW), likely
according to the sequence shown in Scheme 4. 7b exhibits
weak BN coordination (11B = ~20 ppm) due to O-atom lone
pair delocalization with boron, causing the unbound form (7d) to
be more stable (based on DFT calculated energies). 7d
structurally resembles o-terphenyl derivatives which are known
to undergo conrotatory photocyclization.[15] The photocyclized
product trans-4a,4b-dihydrotriphenylene 7e is unstable[15] and
undergoes an H-shift forming the more stable 4a,12b-
dihydrotriphenylene isomer 7f, clearly driven by the re-
aromatization of py and ph. The retained trans-configuration of
the inner H-atoms in 7f is consistent with a suprafacial [1,5]-H
shift as per the Woodward-Hoffman rules.
Scheme 3. Reactivity of 1’ and 5, and the structure of 6c.
To establish the scope of this new photoreaction,
compounds 3 – 5 bearing a 2-(5-phenyl)thienyl or 2-benzothieyl
substituent and different chelate backbones were studied.
Similar to 1 and 2, irradiation of 3 at 365 nm yields 3b
quantitatively (see Figures S3S –S3W), establishing that
substituted 1,2-thiaborinine derivatives can be prepared by this
approach. Unlike 1b, compound 3b is stable towards irradiation,
allowing its quantitative isolation. The benzimidazole and NHC
functionalized 4 and 5 convert to their respective products 4b
and 5b quantitatively, which were both characterized by NMR
and x-ray diffraction (see SI and Figure 2). While 4b shares
structural features with 2b, the connectivity in 5b is unusual in
that the C2 atom of benzothienyl is bound to the carbon atom of
the NHC with a C–C bond length of 1.449(4) Å. This implies that
the initial C–C bond formation in the phototransformation occurs
regioselectively at the NHC instead of phenyl, which leads to the
product 5b shown in Scheme 3, and is contrary to our previous
observations in related B(NHC-Ph)Mes2 systems where C–C
bond formation is selective for the phenyl ring.[11] Although the
origin of this discrimination is not understood, the resulting
bonding arrangement in 5b is rather unique, as it contains a 1,4-
azaborinine unit and has a more pronounced zwitterionic
character compared to 2b and 4b (e.g. its B–C/B–S bonds are
considerably longer). Attempts to decouple the internal donor
from its 1,2-benzothiaborinine by utilizing a weaker donor (6)
gave 6c after irradiation (Scheme 3, see SI) due to the low
aromaticity of the thiazolyl ring.[10c] Furthermore, reactions of 2b
Scheme 4. Reactivity of 7/8 and the relative DFT computed energies
(kcal/mol) of 7–7f (B3LYP/6-31G*).
In contrast to 7f, which was generated and isolated as a
pure substance, compound 8 yields a mixture of 8a, 8b, 8c
(analogue of 1c), and 8f, attributable to the slow photo-
conversion of 8a to 8b and the relatively high internal reaction
temperature caused by long UV exposure times.[10e] Attempts to
obtain the fully aromatized N,B,O-triphenylene analogues via
oxidative dehydrogenation using air or I2 were unsuccessful,[15]
resulting in a variety of unidentifiable decomposition products. N-
heterocycle substituted 9 and 10 show the least photoreactivity
of the entire series, with 9 being completely inert. 10 does show
evidence for regioselective borirane formation on the indole
substituent (see SI), however, prolonged irradiation results
predominantly in decomposition. Photoproducts 2b – 5b all
display strong emission in the solid state (blue-green to orange-
red, see Table S5A) due to CT from HOMO (π-thiaborinine) to
LUMO (π*-chelate), indicating the tunable photophysical
properties of such systems.
with external Lewis or Brønsted acids (BF3 or [(Et2O)2H][BArF ])
4
were unsuccessful, perhaps due to strong BN coordination
(see Figure S3M for V.T. 11B NMR).
The possibility of activating other aromatic C–X bonds (X =
O or N) was also explored with 2-furyl (7), 2-benzofuryl (8), N-
methyl-2-pyrrolyl (9), and N-methyl-2-indolyl (10) at boron.
Compound 7 behaves similar to 1 and 2 when irradiated at 365
nm, initially forming its dark isomer 7a and base-stabilized 1,2-
oxaborinine 7b. Addtionally, a third new species appears with
time (7f, Scheme 4) and was isolated quantitatively. 7f was
determined to be 4a,12b-dihydro-benzo[h][1,2]-oxaborinino[4,3-
To gain a better understanding of the dynamics following
excitation at 365 nm, ab initio calculations combining the
CASPT2//CASSCF method with DFT and TD-DFT were
employed to study the phototransformation of 1 (see Figure 3
and SI). Excitation of 1 at 365 nm populates its S1 state, which is
of π-thienyl (HOMO)
 π*-(ppy) (LUMO) CT character.
Comparing S0 and S1 minimum structures at the CAM-B3LYP
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level of theory, the B–CPh bond is weakened (1.62 vs. 1.66 Å;
see SI).
cyclization and [1,5]-H migration. Mechanistic excited-state
calculations indicate that biradical species are key intermediates
in the photogeneration of thiaborinines and boriranes. These
results provide a promising strategy for the activation of
chemical bonds via reactive excited state intermediates, and
pave the way for new developments in organoboron
photochemistry.
Acknowledgements
The authors thank the Natural Science and Engineering
Research Council of Canada (RGPIN1193993-2013) and the
Natural Science Foundation of China for financial support
(grants 21571017 and 21773007). S.K.M. thanks the Canadian
Government for the Vanier CGS.
Conflict of interest
The authors declare no conflict of interest.
Figure 3. Computed reaction pathways of the 1 to 1b transformation based on
CASPT2 energies. IM = intermediate; CI = conical intersection.
Keywords: Photochemistry • Photoisomerization • C–X Bond
Cleavage • Boron Insertion • Boron chemistry
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In summary, we have demonstrated that appropriate
functionalization of chiral chelate boron systems can lead to
photoactive molecules capable of undergoing specific chemical
bond activation. The resulting products represent the first
examples of base-stabilized 1,2-(benzo)thiaborinines and 1,2-
(benzo)oxaborinines, with the former displaying interesting solid
state emission properties. The labile nature of BN coordination
in oxaborinines allows for the photogeneration of 4a,12b-
dihydro-benzo[h][1,2]-oxaborinino[4,3-f]quinolines via electro-
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Table of Contents
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S. K. Mellerup, C. Li, J. Radtke, X.
Wang, Q.-S. Li,* and S. Wang*
h
Ar1: NHC
Ar1: py, bzm
Ar2: Ph
Ar1: py
X: O
Ar2: Ph
Page No. – Page No.
X: S, O
X: S
Photochemical Generation of N,B,X-
Heterocycles via Heteroaromatic C–X
Bond Scission (X = S, O) and Boron
Insertion
Photoisomerization of chiral chelate boron compounds generates rare chiral
N,B,X-heterocycles quantitatively via boron insertion into a C-X bond.
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