Direct Access to Axially Substituted Subphthalocyanines from Trimethylsilyl-Protected Nucleophiles

Article abstract of DOI:10.1021/acs.orglett.5b02213

A new synthetic one-step approach to perform the axial ligand exchange reaction in subphthalocyanines that employs trimethylsilyl-protected nucleophiles as starting materials is reported. Theoretical calculations indicate that the exchange reaction procee

Full text of DOI:10.1021/acs.orglett.5b02213

Letter
pubs.acs.org/OrgLett
Direct Access to Axially Substituted Subphthalocyanines from
Trimethylsilyl-Protected Nucleophiles
†
‡
‡
̃
́ ́ ́ ́
Julia Guilleme, Lara Martínez-Fernandez, Ines Corral, Manuel Yanez, David Gonzal
ez-Rodríguez,*,†
‡
,†,§
and Tomas Torres*
†
‡
́ ́
Departamento de Química Organica, and Departamento de Química, Facultad de Ciencias, Universidad Autonoma de Madrid,
E-28049 Madrid, Spain
§
IMDEA Nanociencia, c/Faraday 9, Campus de Cantoblanco, Madrid, 28049, Spain
S Supporting Information
*
ABSTRACT: A new synthetic one-step approach to perform
the axial ligand exchange reaction in subphthalocyanines that
employs trimethylsilyl-protected nucleophiles as starting materi-
als is reported. Theoretical calculations indicate that the
exchange reaction proceeds through a similar 4-centered σ-
bond metathesis transition state as the substitution with phenols.
This direct method allowed us to synthesize new axial derivatives
of singular importance within the chemistry of subphthalocyanines, for which the reactivity and X-ray crystalline structure were
studied.
ubphthalocyanines (SubPcs) are unique nonplanar aro-
matic macrocycles composed of three diiminoisoindoline
B−O bond is being formed. These observations led us to
conclude that in order to perform an axial ligand exchange
reaction, a good nucleophile is not strictly required, but rather
an agent that has some affinity for the axial halogen and hence
can weaken the boron−halogen bond before actual substitu-
tion.
S
N-fused units arranged in a cone-shaped structure. These
molecules are only known as boron complexes, whose
tetrahedral coordination induces the deviation from planarity
1
and thus, their concave nature. Because of their extraordinary
spectral and electronic features, SubPcs are considered
Encouraged by these results, we thought that using alcohols
or other nucleophiles that are “protected” with a trialkylsilyl
competent candidates of increasing interest in different applied
2
fields such as organic light-emitting diodes (OLEDs), organic
group (R Si−Nu) may lead to a similar transition state, since
3
3
4
8
photovoltaic cells (OPVs), or nonlinear optics. For these
reasons, the design of simple and general synthetic routes that
allow the incorporation of SubPcs into more complex systems
still remains an active task.
silanes are well-known halophilic electrophiles. The initial
chlorine atom of the SubPc would be now coordinated to the
halophilic Si center in the transition state promoting the
weakening of the B−Cl bond. Our assumption would be
supported by previous work from Kato et al., who reported in
The reactivity of SubPcs has been addressed by several
1
,5
authors over the last decades, and can be classified in three
2
006 the synthesis of a boron SubPc cation as a salt with a
1
different groups depending on the reactive center: (i) axial
weakly coordinated carborane anion by reaction between
reactivity (central boron atom), (ii) peripheral reactivity
functional groups attached to the aromatic carbons), and
iii) ring-opening reaction (imine-type core of the SubPc).
8c
Et Si(CHB Me Br ) and the corresponding chloro-SubPc.
3
11
5
6
(
(
Moreover, the use of trimethylsilyl-protected reagents presents
several advantages. For instance, the byproduct (Me SiX) that
3
Among them, the axial ligand exchange is by far the most
common approach employed to functionalize subazamacro-
cycles without altering the electronic properties of the
would be generated in this axial ligand exchange would be
volatile in the reaction media, which should shift the
equilibrium toward the products and simplify the purification
step. In addition, their lower nucleophilicity in comparison with
the deprotected nucleophile analogues (Nu-H) should generate
lower amounts of SubPc decomposition products. In this work,
we report on the theoretical and experimental study of a new
synthetic route to axially substituted SubPcs by direct reaction
of chloro-SubPcs and trimethylsilyl (TMS)-protected nucleo-
philes (Scheme 1). We also evaluate the scope of this novel
1
c
macrocycle. Nevertheless, the axial substitution in SubPcs is
slower and tougher than the analogous process in subporphyr-
1b,6
ins, which usually are reported as methoxy-compounds.
Recently, we reported a mechanistic study of the axial ligand
exchange reaction between halo-SubPcs and phenols in which
we determined a second-order reaction rate law for this process,
7
both dependent on SubPc and phenol concentrations. We
proposed that this transformation takes place through a σ-bond
metathesis mechanism involving a bimolecular transition state
in which the phenol assists in the dissociation of the polar
boron−halogen bond by proton coordination, while the new
Received: July 30, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02213
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Organic Letters
Letter
synthetic methodology and its potential to prepare novel SubPc
derivatives that are otherwise not accessible by other methods.
Table 1. TMS Derivatives Employed for the Axial Ligand
Exchange Reaction
Scheme 1. Synthesis of Axially Substituted SubPcs by Direct
Reaction between Chloro-SubPcs and TMS-Nucleophiles
We initiated our studies with a classical, well-known reaction
in SubPc chemistry: the axial ligand exchange with phenol
derivatives. This reaction, as mentioned before, has been
thoroughly studied in our laboratories, both from the
7
a
b
experimental and theoretical perspective. As a proof of
Yields calculated with respect to the starting SubPc. Traces of the
c d
concept and to make a direct comparison with our mechanistic
study, we reacted chloro-SubPc 2 with O-TMS-phenol or
phenol in exactly the same conditions in refluxing toluene. The
desired phenoxy-SubPc 4 was obtained in 89% (entry 1, Table
product were detected. In toluene. In nitrobenzene.
1) using PhOTMS or 85% employing PhOH. This trans-
formation took place in a few hours using an excess of the TMS
derivative, and no decomposition products were observed by
TLC. The reaction with PhOH progressed initially faster but it
took longer to reach completion. We attribute this effect to the
presence of remaining HCl in the reaction media at high
conversion, which can shift the equilibrium toward the starting
chloro-SubPc reagent. As expected, other substituted TMS-
phenols were reactive as well. For instance, the axial ligand
exchange with the (4-bromophenol)trimethylsilane also
proceeded successfully yielding SubPc 5 (entry 2, Table 1).
To investigate the reaction mechanism at a molecular level
for trialkylsilyl protected nucleophiles we have mapped the
ground state potential energy surface for SubPcCl 2 and the
nucleophile O-TMS-phenol by locating the corresponding
stationary points along the axial substitution reaction
coordinate. Figure 1 depicts the potential energy profile as
predicted by density functional theory (DFT) calculations.
Further computational details can be found in the Supporting
Information. Similarly to what was found for unprotected
Figure 1. Reaction profile for the axial ligand substitution reaction as
predicted by DFT calculations. Energies in kcal/mol.
activating the B−Cl bond, which slightly stretches (0.01 Å), and
by simultaneously approaching the O atom of the phenol
nucleophile to the B reaction center. A further respective
reinforcement and weakening of the B−O and B−Cl bonds is
observed at the TS structure, concomitant to the imminent
rupture and formation of the Si−O and Cl−Si bonds, before
the new B−O bond consolidates in the postreaction complex,
where the phenoxySubPc is formed. Interestingly, the
computed barrier is 17 kcal/mol larger than for the reaction
with the unprotected nucleophile. This can be attributed,
among other reasons, to the large size of the silane moiety that
7
phenol nucleophiles, the axial ligand exchange reaction is
facilitated by the interaction of the two reagents (prereaction
complex Reac in Figure 1) and proceeds via a bimolecular
2
transition state to a postreaction complex (Prod in Figure 1),
2
where the leaving Me SiCl group and the phenoxy-SubPc are
3
still interacting.
From the geometric viewpoint, the formation of the
prereaction complex Reac assists the nucleophilic attack by
2
B
DOI: 10.1021/acs.orglett.5b02213
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Organic Letters
Letter
hinders the preparation of nucleophilic attack in the prereaction
complex and the arrangement of the incoming and leaving
nucleophile at the 4-center transition state. This increase in the
energy barrier is consistent with the slower reaction rates
observed for the TMS-protected phenol in comparison with the
unprotected phenol (see above).
any other axial-ligand exchange reaction: electron-rich SubPcs
react faster than electron-poor SubPcs. All new products were
1
13
characterized by H NMR, C NMR, UV−vis, Fourier
transform infrared spectroscopy, mass spectroscopy, and high-
resolution mass spectroscopy. Suitable crystals for X-ray
diffraction analysis were obtained for 7, 8, and 9, and their
resolved structure is shown in Figure 2.
To get further insight into the reactivity of SubPc with
protected nucleophiles, we next examined and compared the
same reaction with aliphatic alcohols. In the case of the reaction
with chloro-SubPcs, aliphatic alcohols are known to produce
lower yields than aromatic alcohols mainly because of SubPc
decomposition, presumably via ring-opening, after prolonged
heating times. However, under the simple standard conditions
employed in this work (see Supporting Information), that
involve the use of only a small excess of the nucleophile, the
reaction did not afford the corresponding axially substituted
SubPcs after 1 day of reaction, either using the TMS-protected
or the unprotected alcohol. More drastic conditions and
additional solvents (refluxing nitrobenzene or benzonitrile)
were also tested but, unfortunately, only traces of SubPc
product were detected in the reaction media. The formation of
the corresponding alkoxy-SubPc 6 could be favored in the
presence of a much larger excess of nucleophile, but we did not
analyze this situation because it is not practical from the
synthetic point of view. On the other hand, the silyl enol ether
Figure 2. Molecular structure of SubPcs 7 (a), 8 (b), and 9 (c) in the
crystal as determined from X-ray diffraction analysis.
(entry 4, Table 1), which can be viewed as a masked ketone,
rapidly provoked the decomposition of the macrocycle.
We then selected different TMS derivatives other than
The new SubPcs 7, 8, 9, and 10 could be regarded as useful
organic synthons to prepare a wide variety of other axially
substituted products. Subsequently, we set out to investigate
the behavior of these common organic functional groups when
attached to the SubPc macrocycle. Triflate-SubPcs (7) have
already demonstrated to be extraordinary activated intermedi-
ates to efficiently substitute the halogen atom with diverse
alcohol nucleophiles, such as the triflate (Me SiOTf) or azide
3
(
Me SiN ). We published a procedure in the past with which
3 3
9
the generation of triflate-SubPcs was carried out successfully.
These interesting derivatives, however, were only produced in
situ as transient activated intermediates for the axial substitution
9
9
with other nucleophiles, but could not be isolated because of
nucleophiles. On the other hand, we tested a set of common
their rapid hydrolysis. A decrease in reactivity could be achieved
by using electron-withdrawing macrocycles, such as 3. The
resulting perfluorinated-triflate-SubPc was much more inert and
could be isolated by standard column chromatography in 62%
yield. In the case of Me SiN , the axial ligand exchange took
chemical transformations of nitriles (nucleophilic addition,
hydrolysis, and reduction reactions) or azides (reductions or
1,3-dipolar cycloadditions). These reactions were considered as
highly valuable, since they could lead to a new family of “exotic”
SubPcs bearing formyl, ketone, or amine functional groups,
among others, at the axial position of SubPcs. However, and
despite all our efforts, which are summarized in the Supporting
Information, these nitrile and azido groups displayed a rather
unusual reactivity, and none of these reactions worked in our
hands. Either the axial functional group did not react under
classical mild conditions or the SubPc macrocycle decomposed
when using harsher conditions. All these premises denote that
these new SubPcs do not present the expected reactivity related
with these common functional groups, probably as a
consequence of the electronic and/or steric effect exerted by
the boron macrocycle.
3
3
place efficiently under the standard conditions (i.e., toluene at
10 °C), and the product, the first example of a SubPc with an
1
axial B−N bond, was perfectly stable.
3
To explore the limits of this new synthetic route for axial
ligand exchange in SubPcs, the reaction was next carried out
with different TMS-carbon nucleophiles. We thought it would
2
be highly interesting to test Csp (phenyl-) and Csp (alkynyl-
or nitrile-) trimethylsilanes (entries 7−9, Table 1), which would
generate novel SubPcs with B−C bonds. However, these
reagents exhibited an evident lack of reactivity and only
decomposition products were observed after days in refluxing
toluene or nitrobenzene. The only exception was the Me SiCN
The only exception was the 1,3-dipolar cycloaddition
reaction to azide-SubPc 8 (Scheme 2). It is known that the
chemistry and reactivity of boryl azides is rare, and so is their
3
reagent, whose nucleophilicity seems to be the actual limit of
this reaction for practical purposes. However, the reaction had
to be carried out in the more polar nitrobenzene solvent in
10
role as 1,3-dipoles in cycloaddition reactions. To the best of
our knowledge only a few examples have been reported in
which electron-rich boryl azides are able to thermally react with
electron-poor alkynes, alkenes, and nitriles to afford the
7
order to increase the reaction rate (see our previous work) and
at temperatures close to its boiling point. In this way, the
valuable cyano-SubPcs 9 and 10 could be obtained in moderate
yields.
On the other hand, the effect of the electronic nature of the
macrocycle was also analyzed. Both SubPcs functionalized with
peripheral electron donating- (entries 2 and 12, Table 1) or
electron-withdrawing groups (entry 5, Table 1) react with these
TMS-nucleophiles. Their reactivity follows the same order as in
10
corresponding cycloaddition adducts. SubPc 8 was subjected
to a copper(I)-catalyzed cycloaddition (CuAAC) with phenyl-
acetylene in THF and the corresponding triazole-SubPc 10 was
obtained in a reasonable 30% yield, despite the absence of
electron-withdrawing groups attached to the acetylene moiety.
The cycloadduct was obtained as a single 1,4-regioisomer due
C
DOI: 10.1021/acs.orglett.5b02213
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Organic Letters
Letter
Scheme 2. Cycloaddition Reaction between SubPc 8 and
Ethynylbenzene
The Centro de Computacion
Auton
allocation of computational time.
́
Cientıfi
́
ca of the Universidad
oma de Madrid is gratefully acknowledged for generous
́
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In conclusion, we have described a new synthetic route to
carry out the axial ligand exchange reaction in SubPcs in one
step that employs TMS-protected nucleophiles as starting
materials. Theoretical calculations indicate that the ligand
exchange reaction proceeds through a similar 4-centered σ-
bond metathesis transition state as the substitution with
phenols, in which the TMS group concomitantly coordinates
to the leaving chlorine atom and initiates the nucleophilic
attack at the boron atom. Although this procedure cannot be
established as a general and practical methodology, it can be
considered as a good alternative to performing the axial
exchange with aromatic alcohols, because the new reactants are
not nucleophiles and a lower amount of decomposition side-
products are detected. This clean method led us to synthesize
three new “exotic” derivatives of singular importance within the
chemistry of SubPcs, the structure of which has been
unambiguously determined by X-ray diffraction.
(
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ASSOCIATED CONTENT
Supporting Information
■
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A. J. Am. Chem. Soc. 2011, 133, 11956−11959. (b) Tsurumaki, E.;
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*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b02213.
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AUTHOR INFORMATION
Corresponding Authors
■
*
9
*
2
(
9) Guilleme, J.; Gonzal
Int. Ed. 2011, 50, 3506.
(10) (a) Merling, E.; Lamm, V.; Geib, S. J.; Laco
Org. Lett. 2012, 14, 2690. (b) Melen, R. L.; Stephan, D. W. Dalton
Trans. 2013, 42, 4795. (c) Muller, M.; Maichle-Mossmer, C.;
Bettinger, H. F. J. Org. Chem. 2014, 79, 5478.
́
ez-Rodríguez, D.; Torres, T. Angew. Chem.,
E-mail: tomas.torres@uam.es. Tel: +34 91 497 4151. Fax: +34
1 497 3966.
E-mail: david.gonzalez.rodriguez@uam.es. Tel: +34 91 497
778. Fax: +34 91 497 3966.
̂
te, E.; Curran, D. P.
̈
̈
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support from the MINECO, Spain (CTQ-2014-
2869-P, T.T.; CTQ2014-57729-P, D.G.-R.), and the Comu-
■
5
nidad de Madrid (S2013/MIT-2841 FOTOCARBON, T.T.) is
acknowledged. The work of J.G. and L.M.F. was funded by
MECD (FPU fellowship). L.M.F., I.C., and M.Y. thank the
MICINN (Spain) for the Project No.CTQ2012-35513-C02-01.
D
DOI: 10.1021/acs.orglett.5b02213
Org. Lett. XXXX, XXX, XXX−XXX