1,5-Cyclooctadienyl alcohols and ketones generate a new class of COD Pt complexes

Article abstract of DOI:10.1039/c8dt00075a

A variety of new racemic alcohol and ketone cyclooctadiene derivatives was prepared for their complexation with platinum to generate a new class of platinum(ii) complexes.

Full text of DOI:10.1039/c8dt00075a

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1,5-Cyclooctadienyl alcohols and ketones generate a new class of
COD Pt complexes
Angela. E. E. Wandlera, Martin R. M. Koosa, Martin Niegerb, Burkhard Luya and Stefan Bräse *a,c
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A variety of new racemic alcohol and ketone cyclooctadiene (Scheme 1).
O
O
OH
OH
derivatives was prepared for their complexation with platinum to
Me
generate a new class of platinum(II) complexes.
TMS
2aA, 53%
3aB, 67%
2dA, 78%
3dB, 9%
Platinum(II)1-6 and other metal7-9 complexes with
2bA, 94%
2cA
, 15%
unsubstituted 1,5-cyclooctadiene (COD) are very common as
O
O
O
building blocks for the creation of other mono- and
polynuclear platinum(II) complexes.10-16 Besides that platinum
Br
compounds have been used in catalysis17-19 and material
2gA, 63%
3gB, 85%
3gC, 12%
2eA
3eB, 76%
3eC, 55%
2fA
3fB, 69%
3fC, 24%
TMS
, 65%
, 69%
science,20,
they also have shown interesting cytotoxic
6, 22-24
Recently we have discovered new
21
properties.3,
O
O
O
O
O
PPh2
organometallic platinum(II) compounds with monosubstituted
1,5-cyclooctadiene ligands and performed their detailed NMR
characterization and toxicological studies.12 However, there
are virtually no reports on the effect of additional coordinating
groups, so there is still plenty of room for investigation.
In this work we elaborate the synthesis of oxygen-
functionalized cyclooctadienyl derivatives inspired by the work
of Matier et al.25 (Scheme 1) and the discovery of new
platinum complexes with monosubstituted 1,5-cyclooctadiene
units. Recently, we disclosed a route using palladium-catalyzed
lithium cross-coupling reactions using cyclooctadienyl lithium
as the building block of choice.
N
O
2jA
2kA
, 45%
3kB, 51%
2hA, 40%
3hC, 9%
2iA, 33%
3iB, 8%
, 55%
3jB, 80%
O
OH
O
Fe
2lA, 52%
A
2m , 43%
3nC, 46%
Me
OH
N
Me
3lB, 89%
O
O
O
Cl
O
3oC
3pC
3qC
, 24%
, 54%
, 45%
OH
O
1) tBuLi, Et O, 78 - 0°C
MnO2
−
2
Br
R
R
CH2Cl2, 24h, rt
2) RCHO
= alcohol and ketone were isolated
A
B
Figure 1: Synthesized COD derivatives. (A: yield of the alcohol; B: yield
of the ketone via Method B; C: yield of the ketone via Method C;
isolated yields)
1
2
3
1) tBuLi, Et O, 78 - 0°C
−
2
C
2) RCOOH
Scheme 1: Synthesis of 1,5-cyclooctadienyl alcohols 2 and ketones 3.
Herein we presented the optimization of the lithiation of COD
(see SI). This step expresses the most crucial step for the work
we describe in this paper.26 In order to obtain the desired
building blocks, two pathways turned out to be feasible
The two-step method A/B started from the lithiated species
which was treated with the corresponding aldehydes to form
the alcohols 2a-2m and then oxidized with manganese dioxide
to yield compounds 3a
structure of 3f, see SI).
, 3d-3g and 3i-3l (for the molecular
Specifically, the alcohol derivatives were isolated in moderate
2i; 33%) to excellent yields (2b; 94%). Alcohol 2c was obtained
(
in a yield of 15%. Over a time-period of a few days the mass of
the starting material could not be detected via GC-MS, that
aggravates the performance of the second step, the oxidation.
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Phosphine 2i was synthesized starting from 2-
(diphenylphosphino)benzaldehyde.
Our motivation was to build up ligands with two interesting
coordination sides for the synthesis of bimetallic complexes.
The COD derivative 2i contains the diene moiety for
coordination of one metal and the phosphine and an alcohol
moiety as bidentate coordination for the second metal.
Unfortunately, it turned out that the phosphorous was easily
oxidized during the reaction, following by the formation of
unknown byproducts, which reduces the yield of the
unexpected but still attractive product.
Scheme 2. Synthesis of platinum (II) complexes 4,5 starting from
alcohol 2 and ketone 3 derivatives, respectively.
Paracyclophane derivative 2h was produced as a single
diastereomer, the relative configuration was assumed to be
RP/S and Rp/R. Terephthaldehyde gave a mixture of meso- and
For 4f the corresponding alcohol 2f is just slightly soluble in all
solvents which can be used for the reaction system. So, the
resulting solid product was isolated as a mixture of the newly
formed complex 4f and the starting material 2f. Also heating
up the reaction mixture for a couple of hours did not change
the conformation turnover. Interestingly, the complex 4e was
insoluble in all commercial available deuterated solvents.
rac-2m
.
Oxidation of the alcohols 2a, 2d-2g and 2i-2l by manganese
dioxide27 delivered the ketones 3a, 3d-3g and 3i-3l in good to
very good yields (51-89%) with two exceptions (3d/9%; 3i/8%).
For the synthesis of compound 3d it is necessary to use
another conditions with stronger oxidative reagents, e.g.
pyridinium chlorochromate in order to increase the reaction
yield.28 On closer examination, the molecule 2b exhibits similar
structural properties like 2d, so stronger oxidative conditions
are necessary to obtain the corresponding ketone in a good
yield, therefore the experiment was not carried out.
Phosphineoxide 3i was isolated in low yields for reasons
described above.
Finally, the ketones 3e-h and 3n-q can be prepared directly in
one step starting from COD-Li and carboxylic acids in low to
moderate yields (9-55%). In general, benzoic acid derivatives
are suitable for this method, while the reaction is not
compatible with enolizable compounds. For example, the
ketone 3d was synthesized via Method B, but could not be
formed by Method C. Lithiated COD acts as a base and
enolates the isobutyric acid, therefore the desired product
cannot be obtained by this method. In summary the two-step
route A/B is more versatile than the direct method supported
by the fact of the use of a high excess of lithiated specie.
Figure 2. First examples for intramolecular COD alkoxide and acyl
platinum(II) complexes; molecular structure of complex 5d
(displacement parameters are drawn at 50% probability level).
For complex 5d we obtained a molecular structure which
Nearly all products were obtained in high yields. The
compounds shown in Figure 1 are unknown, except of 2a and
confirms the proposed conformation (Figure 2). The acyl
complexes
5 show hemi-labile behavior – the mass spectra
3a 25
.
shows the fast release of one chloride ion (see SI).
With these new substances in hand we performed the
synthesis of platinum(II) complexes starting from these novel
ligand classes. Platinum(II) complexes were synthesized based
on the protocols which were reported by us previously12
following the procedure developed by Wen29 and Clark.30
Using Clark`s protocol, we were able to isolate monometallic
platinum(II) complexes starting from our newly synthesized
alcohols and ketones (Scheme 2, Figure 2).
The performance of the synthesis of the complexes starting
from the alcohols is a lot easier to realize. Most of the alcohols
are oils which are soluble in npropanol. The handling of
paracyclophanes can be difficult. Using Method
C gave
cyclooctadiene 3h in a low yield of 9%. So, we decided to focus
on the formation of the complex 4h. Further, we developed
the synthesis of compound 2m because of our high interest to
yield directly a bimetallic Pt-complex. Unfortunately, the
reaction was not successful.
Complexes 4d, 4h, 5d and 5e were obtained in good yields
(Figure 2). The gross formula of complexes 4f and 4e were
corroborated by EI-Mass and HRMS but the structure could
not fully investigated via NMR spectroscopy (vide infra).
These complexes
4 and 5 represent a new class of platinum(II)
complexes. We showed that a 1-substituted cyclooctadiene
derivative can be used to coordinate a metal-atom with its two
coordination sides: two double bonds and its donor functional
group. In case of the complexes with the ketone as a ligand it is
quite remarkable that it was possible to build the
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dichloroplatinum(II) complexes, were the metal center faces
the carbonyl group close-by.
Conflicts of interest
“There are no conflicts to declare”.
Structural analysis of some complexes was performed in detail
by multinuclear Platinum-195 NMR spectroscopy. Chemical
shifts and coupling constant data are summarized in Table 1.
Chemical shifts are in the expected range of Pt(II) complexes
(−5500 to −1500 ppm).31 Compared to the unsubstituted COD
ligand, the residue R increases chemical shift by a small value
(up to 150 ppm). In previous studies using alkane substituents
smaller shift differences were observed.12
Notes and references
CCDC 1812128 (3f) and 1812129 (5e) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
2
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-- -- --
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We acknowledge financial support from the Deutsche
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