One-pot synthesis of an enantiopure N,N,O scorpionate ligand derived from (+)-camphor

Article abstract of DOI:10.1002/ejic.200700827

A one-pot synthesis of the new enantiopure heteroscorpionate ligand HOPhbpm^3cam (3) was described. Ligand 3 was obtained in a pyridine-catalysed Peterson rearrangement starting from camphorpyrazole, thionyl chloride, and salicylaldehyde. κ²- and κ³- coordination of the ligand was observed, and the ligand was shown to form a tetrahedral zinc complex [Zn-κ³-(OPhbpm^3cam)CH ₃] (4) as well as an octahedral rhenium complex [Re- κ³-(OPhbpm^3cam)(CO)₃] (6). Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejic.200700827

SHORT COMMUNICATION
DOI: 10.1002/ejic.200700827
One-Pot Synthesis of an Enantiopure N,N,O Scorpionate Ligand Derived from
(+)-Camphor
Johannes Elflein,[a] Florian Platzmann,[a] and Nicolai Burzlaff*[a]
Dedicated to Professor Horst Kisch on the occasion of his 65th birthday
Keywords: Chiral pool / Ligand design / Zinc / Rhenium / Camphor
A one-pot synthesis of the new enantiopure heteroscorpion-
ate ligand HOPhbpm3cam (3) was described. Ligand 3 was
obtained in a pyridine-catalysed Peterson rearrangement
starting from camphorpyrazole, thionyl chloride, and salicyl-
aldehyde. κ2- and κ3-coordination of the ligand was ob-
served, and the ligand was shown to form a tetrahedral zinc
complex [Zn-κ3-(OPhbpm3cam)CH3] (4) as well as an octahe-
dral rhenium complex [Re-κ3-(OPhbpm3cam)(CO)3] (6).
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
carbon atom. Any additional group, Z, at this atom will
form a prochiral centre rather than an additional stereocen-
tre (Figure 1).[11]
Introduction
During the last decade, various bis(pyrazolyl)methane-
based “heteroscorpionate” ligands have been recognised as
very versatile ligands for bioinorganic chemistry and orga-
nometallics.[1–3] Specifically, several achiral tripodal N,N,O
and N,N,S ligands were reported by Carrano and coworkers
that can be obtained from 1,1Ј-carbonylbis(pyrazole) and
functionalised aldehydes.[3–5] This cobalt-catalysed reaction,
in which CO2 is released, is based on some early reports
from the 1970s by Peterson and Thè[6] and was recently
modified by Reger to involve aldehyde and 1,1Ј-sulfinylbis-
(pyrazole).[7] First applications of group 4 metal complexes
bearing these tridentate heteroscorpionate ligands consist
of catalytic ethylene and propylene polymerisation.[8]
Figure 1. Prochirality in the enantiopure ligands Hbpa4cam and
Hbpa4menth [9]
.
So far, two examples of enantiopure N,N,O tripod li-
gands based on this concept were published by our group,
namely, bis(camphorpyrazol-1-yl)acetic acid Hbpa4cam and
bis(menthylpyrazol-1-yl)acetic acid Hbpa4menth (Fig-
ure 1).[9] Other bis(pyrazolyl)methane-derived enantiopure
tripod ligands were reported by Otero and coworkers re-
cently.[12] Here we report on a one-step synthesis of an
enantiopure N,N,O scorpionate ligand HOPhbpm3cam (3)
derived from (+)-camphor by using a modified version of
the Peterson cobalt rearrangement that does not require the
cobalt catalyst.
Results and Discussion
Recently, we reported on a rather simple concept based
on prochirality that allows us to synthesise enantiopure fa-
cially binding tripod ligands from C2 symmetric precursors
without any additional separation of enantiomers or dia-
stereomers.[9] C2 symmetry is a feature often used in
enantiopure bidentate chelating ligands.[10] In many of
these, two identical enantiopure donor groups, Y*, are con-
nected by a tetrahedral bridging atom, for example, an sp3
Camphorpyrazole 1 [i.e. (4S,7R)-7,8,8-trimethyl-4,5,6,7-
tetrahydro-4,7-methano-1(2)H-indazole] is an enantiopure
pyrazole derived from the chiral pool that can be obtained
easily and in high yield in a two-step synthesis starting from
(+)-camphor.[13] Reaction of 1 with phosgene to afford 2,2Ј-
carbonylbis(camphorpyrazole) (2b) was previously de-
scribed in a footnote by Rebek and coworkers.[14]
[a] Institut für Anorganische Chemie und Interdisciplinary Centre
for Molecular Materials (ICMM), Universität Erlangen-
Nürnberg,
Egerlandstrasse 1, 91058 Erlangen, Germany
Fax: +49-9131-85-27387
E-mail: burzlaff@chemie.uni-erlangen.de
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
Eur. J. Inorg. Chem. 2007, 5173–5176
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J. Elflein, F. Platzmann, N. Burzlaff
SHORT COMMUNICATION
According to a very recent report by Artaud, phosgene
can be replaced in such carbonylbis(pyrazole) syntheses by
triphosgene.[15] We now found that reaction of 1 with tri-
phosgene and triethylamine first gives the C1 symmetrical
isomer of 1,2Ј-carbonylbis(camphorpyrazole) (2a), which is
transformed into the C2 symmetrical 2,2Ј-carbonylbis(cam-
phorpyrazole) (2b) upon standing in solution within some
days (Scheme 1).
Figure 2. Molecular structure of 2,2Ј-carbonylbis(camphorpyra-
zole) (2b); thermal ellipsoids are drawn at the 50% probability level;
hydrogen atoms are omitted for better clarity. Selected bond lengths
[Å] and angles [°]: C1–O1 1.204(2), C1–N32 1.392(3), C1–N12
1.402(3), O1–C1–N32 123.93(19), O1–C1–N12 121.0(2), N32–C1–
N12 115.07(18).
made by various other groups who used the Peterson re-
arrangement for their syntheses. We thus developed an al-
ternative procedure for this reaction to which we were in-
spired by a publication of Canty and coworkers.[17] They
reported on a coupling of 1,1Ј-carbonylbis(3,5-dimethylpyr-
azole) and pyridine-2-aldehyde without any cobalt cata-
lyst.[17] Indeed, a similar reaction of 2b, pyridine and salicyl-
aldehyde yields the ligand (o-hydroxyphenyl)bis(camphor-
pyrazol-1-yl)methane HOPhbpm3cam (3) in reproducible
yields up to 70% (Scheme 1) without the use of the cobalt
catalyst. The synthetic procedure was modified further by
us according to the version of Reger for the Peterson re-
arrangement, which we mentioned above, involving the al-
dehyde and 1,1Ј-sulfinylbispyrazole. Thereby, we finally de-
veloped a one-pot synthesis for (o-hydroxyphenyl)bis(cam-
phorpyrazol-1-yl)methane HOPhbpm3cam (3) starting with
the reaction of camphorpyrazole (1) with sodium hydride
and thionyl chloride. Without any further purification, pyr-
idine and salicylaldehyde were added to the resulting 2,2Ј-
sulfinylbis(camphorpyrazole) to yield ligand 3 in yields up
to 60%. After the reaction was scaled up, we were able to
obtain up to 7 g of enantiopure ligand 3 in one run. Be-
cause of the loss of C2 symmetry, the two pyrazole donors
are no longer spectroscopically equivalent and two sets of
1
signals in the H and 13C NMR spectra are exhibited.
Scheme 1. Synthesis of homochiral heteroscorpionato complexes.
Treatment of ligand 3 with dimethylzinc resulted in very
pure monomethylzinc complex [Zn(OPhbpm3cam)CH3] (4)
A reaction under reflux in toluene or benzene gives only and methane without any formation of bis(ligand) complex
the desired C2 symmetrical 2,2Ј-carbonylbis(camphorpyr- [Zn(OPhbpm3cam)2]. In the NMR spectra, the methyl group
azole) (2b) in very high yield (Scheme 1). An X-ray struc- in 4 (1H NMR: δ = –0.60 ppm; 13C NMR: δ = –14.6 ppm)
ture determination of isomer 2b (Figure 2) allows doubtless is observed at high field. This agrees well with the complex
[Zn(bpaMe ,tBu )CH3] reported recently by us and with the
2
2
differentiation between the two isomers.
Furthermore, only one set of camphorpyrazole signals is sterically hindered (o-hydroxyphenyl)bis(pyrazol-1-yl)meth-
1
observed in the H and 13C NMR spectra of 2b, as to be ane zinc complex published by Carrano and cowork-
expected for a C2 symmetric compound, which is in con- ers.[4d,18]
trast to the two sets of signals observed in the spectra of
In an attempt to synthesise the chlorido complex [Zn(κ3-
N,N,O-OPhbpm3cam)Cl], colourless crystals of [Zn(κ2-N,N-
2a.
To test our concept of “prochirality-based” ligands with HOPhbpm3cam)(Cl)2] (5) were obtained from an acetonitrile
a new N,N,O tripod ligand, we then synthesised (o-hydro- solution.
xyphenyl)bis(camphorpyrazol-1-yl)methane HOPhbpm3cam
The molecular structure (Figure 3) clearly shows κ2-coor-
(3) by applying the cobalt-catalysed Peterson rearrange- dination of the ligand, similar to the achiral complex
ment of 2b with salicylaldehyde.[16] Unfortunately, the yield [Zn(κ2-N,N-HOPhbdmpzm)(I)2] [HOPhbdmpzm: ortho-
of this reaction was quite erratic; this observation was also (hydroxyphenyl)bis(dimethylpyrazol-1-yl)methane] recently
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Eur. J. Inorg. Chem. 2007, 5173–5176

Enantiopure N,N,O Scorpionate Ligand Derived from (+)-Camphor
reported by Carrano and coworkers.[4d] The molecular
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HOPhbpm3cam ligand (3). It has to be emphasised that in
this new ligand the chiral camphorpyrazolyl donors are
pointing towards the zinc centre. This is different from our
former ligands and makes this ligand a promising candidate
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Figure 3. Molecular structure of [Zn(κ2-N,N-HOPhbpm3cam)(Cl)2]
(5); thermal ellipsoids are drawn at the 50% probability level; most
hydrogen atoms are omitted for better clarity. Selected bond lengths
[Å] and angles [°]: Zn–Cl1 2.2267(8), Zn–Cl2 2.2293(7), Zn–N11
2.053(2), Zn–N31 2.089(2), Zn–N31–N32 111.92(16), Zn–N11–
N12 122.78(17), N11–Zn–N31 94.20(9), N11–Zn–Cl2 108.64(7),
N31–Zn–Cl2 119.39(6), N11–Zn–Cl1 112.42(7), N31–Zn–Cl1
107.79(6), Cl2–Zn–Cl1 113.01(3).
Reaction of K[OPhbpm3cam] with [ReBr(CO)5] resulted
in a complex [Re(OPhbpm3cam)(CO)3] (6). Elemental analy-
sis, FAB MS [M + H]+ peak and, pursuant to C1 symmetry,
three class A carbonyl vibrations at 2018, 1910 and
1881 cm–1 indicate κ3-coordination of the ligand and for-
mation of an octahedral complex.
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[10]
[11]
[12]
Conclusions
Chiral modification of the well-established (2-hydroxy-
phenyl)bis(pyrazol-1-yl)methane ligands leads to the new
enantiopure heteroscorpionate ligand (2-hydroxyphenyl)-
bis(camphorpyrazol-1-yl)methane HOPhbpm3cam (3). This
ligand provides similar coordination properties as its achiral
analogues, which was proven by the synthesis of a tetrahe-
dral monomethylzinc complex and an octahedral tricarbon-
ylrhenium complex. The simple one-pot synthesis, starting
from camphorpyrazole, thionyl chloride and salicylalde-
hyde, should allow broad application of this and related li-
gands in coordination chemistry, especially because the
achiral analogues have already shown their potential for
catalytic processes. Furthermore, it is obvious that in the
future a broad spectrum of similar homochiral tripod li-
gands should be accessible by variations of this one-pot
synthesis.
[13]
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[15]
[16]
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To avoid extraordinarily long abbreviations, the abbreviation
system for Tp and benzopyrazolylborate TpBo ligands intro-
duced by Trofimenko was transferred to this manuscript. A
superscript of 3 preceding “cam” indicates a 3,4-fusion of the
camphor group to the pyrazole. This results in the abbreviation
HOPhbpm3cam (3). For further details see: S. Trofimenko, Scor-
pionates – The Coordination Chemistry of Polypyrazolylborate
Ligands, Imperial College Press, London, 1999, p. 5.
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Crystallographic data for 2 (C23H30N4O): crystal dimensions
0.50ϫ0.40ϫ0.30 mm3, monoclinic space group P21, a =
6.7212(13) Å, b = 12.544(3) Å, c = 25.060(5) Å, β = 90.32(3)°,
V = 2112.7(8) Å3, Z = 4, ρcalcd. = 1.190 gcm–3, 2Θmax = 58.5°,
Mo-Kα radiation, λ = 0.71073 Å, T = 100 K, 28855 reflections
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and X-ray data for 2b and 5.[19]
[17]
[18]
[19]
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(BU 1223/2–1 and SFB 583). We thank Dr. F. Heinemann for col-
lecting an X-ray data set.
Eur. J. Inorg. Chem. 2007, 5173–5176
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5175

J. Elflein, F. Platzmann, N. Burzlaff
SHORT COMMUNICATION
collected, 5896 independent reflections (Rint = 0.0834), 5474
reflections used with I Ͼ 2σ, R = 0.0459, wR = 0.1150. Crystal-
lographic data for 5 (C29H36Cl2N4OZn·2CH3CN): crystal di-
mensions 0.23ϫ0.22ϫ0.18 mm3, triclinic space group P1, a =
phenol proton (5) was found and its coordinates were refined
isotropically. Pictures were prepared with the program Dia-
mond 2.1e.[21] CCDC-651140 (for 2b) and -651141 (for 5) con-
tain 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.
7.7111(3) Å,
b = 14.5669(15) Å, c = 15.577(2) Å, α =
80.438(8)°, β = 87.859(6)°, γ = 80.738(5)°, V = 1702.8(3) Å3, Z
= 2, ρcalcd. = 1.316 gcm–3, 2Θmax = 59.0°, Mo-Kα radiation,
λ = 0.71073 Å, T = 100 K, 44677 reflections collected, 17289
independent reflections (Rint = 0.0358), 14660 reflections used
with I Ͼ 2σ, R = 0.0334, wR = 0.0734, Flack parameter:
0.020(6). The structures were solved by using direct methods
and refined with full-matrix least-squares against F2 (Siemens
SHELX-97).[20] A weighting scheme was applied in the last
steps of the refinement with w = 1/[σ2(Fo2) + (aP)2 + bP] and
P = [2Fc2 + max(Fo2,0)]/3. Most hydrogen atoms were included
in their calculated positions and refined in a riding model. The
[20] G. M. Sheldrick, SHELX-97: Programs for Crystal Structure
Analysis, University of Göttingen, Göttingen, 1997.
[21] K. Brandenburg, M. Berndt, Diamond-Visual Crystal Structure
Information System, Crystal Impact GbR, Bonn, 1999; see
also: W. T. Pennington, J. Appl. Crystallogr. 1999, 32, 1028–
1029.
Received: August 6, 2007
Published Online: October 11, 2007
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Eur. J. Inorg. Chem. 2007, 5173–5176