Chiral N-heterocyclic carbene ligands based on a biisoquinoline template

Article abstract of DOI:10.1039/b611647g

New chiral imidazolinium salts with tunable steric features, based on a biisoquinoline template, have been developed and structurally characterised using single crystal X-ray crystallography. The trans PdI₂(NHC) ₂ complex was prepared by reaction of the parent H₄ imidazolinium salt with Pd(OAc)₂ in the presence of NaI, and the solid state structure determined by X-ray crystallography. The rigid, chiral, biisoquinoline geometry of the H₄ imidazolinium salt was found to be maintained upon ligand complexation. The sterically unencumbered parent biisoquinoline ligand has been found to give high conversion with modest enantioselectivity in the copper-catalysed asymmetric addition of diethylzinc to cyclohexenone. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b611647g

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PAPER
www.rsc.org/dalton | Dalton Transactions
Chiral N-heterocyclic carbene ligands based on a biisoquinoline template
Kingsley J. Cavell,* Mark C. Elliott,* David J. Nielsen and James S. Paine
Received 3rd July 2006, Accepted 11th August 2006
First published as an Advance Article on the web 30th August 2006
DOI: 10.1039/b611647g
New chiral imidazolinium salts with tunable steric features, based on a biisoquinoline template, have
been developed and structurally characterised using single crystal X-ray crystallography. The trans
PdI
the presence of NaI, and the solid state structure determined by X-ray crystallography. The rigid, chiral,
biisoquinoline geometry of the H imidazolinium salt was found to be maintained upon ligand
2
(NHC)
2
complex was prepared by reaction of the parent H
4
imidazolinium salt with Pd(OAc)
2
in
4
complexation. The sterically unencumbered parent biisoquinoline ligand has been found to give high
conversion with modest enantioselectivity in the copper-catalysed asymmetric addition of diethylzinc to
cyclohexenone.
Introduction
Results and discussion
The application of N-heterocyclic carbenes (NHCs) in catalysis
The synthesis of enantiomerically pure diamine 1 was accom-
plished by the previously reported method. The tetramethyl-
1
11
was first described by Lappert and coworkers, and Hill and
2
3
4
Nile, then more recently by Herrmann and others. As these
studies on NHCs progressed it became evident that carbenes,
when compared to the ubiquitous phosphines, frequently show
unique chemical behaviour, which may have a significant impact
substituted diamine 3 was prepared following similar methodol-
ogy, as described below. Diamines 1 and 3 reacted smoothly with
triethylorthoformate in the presence of ammonium tetrafluorob-
orate to give the “parent” imidazolinium salt 2 and the new salt 4,
respectively, as shown in Scheme 1.
5–8
on their application in catalysis. Early on in the study of NHCs
as ligands, the design of new chiral carbene ligand systems for
9
asymmetric catalysis developed as an important target. Numer-
ous approaches have been investigated, which have met with mixed
10
success.
As part of our studies on the fundamental reaction behaviour
of NHC complexes and their role in catalysis we commenced
a study on the design of chiral ligands, both monodentate
and chelating, with varying structural motifs with a view to
relating fundamental ligand structure to catalytic performance. A
structural motif of particular interest comprises a monodentate
NHC in which the chiral information is built into the ligand
backbone. Concurrent studies within our group had provided
11
geometrically-constrained diamines of general structure 1, which
are readily converted to imidazolinium salts such as 2. We
initially reported the application of compound 2 in homogeneous
catalysis (non-enantioselective telomerization); complexation and
12
structural studies followed. Subsequent to these initial reports,
Herrmann et al. described the coordination of the NHC derived
from 2 to Rh and Ir; asymmetric hydrosilylation and the transfer
hydrogenation of acetophenone catalysed by the enantiopure
3 4 4
Scheme 1 Reagents and conditions (i) (EtO) CH, NH BF , reflux, 3 h.
Imidazolinium salts 2 and 4 precipitated from their reaction
solutions giving crystals suitable for single crystal X-ray diffraction
studies. The structures of these compounds are shown in Fig. 1
and Fig. 2, respectively. In each case, the constrained geometry
engendered by the biisoquinoline unit results in a considerable
twisting of the ligand backbone (C11–C2–C3–C19 dihedral angle
13
complexes were also described.
We now report the synthesis and X-ray structure of imida-
zolinium salt 2 and the related, sterically hindered 4, together
with the palladium complex 5. We also report preliminary
results of the application of 2 in asymmetric conjugate addition
reactions.
◦
of approximately 127 in compound 2 and a corresponding C11–
◦
C2–C3–C21 dihedral angle of 109 in compound 4). In particular,
ꢀ
the hydrogen atoms/methyl groups at the biisoquinoline 3- and 3 -
School of Chemistry, Cardiff University, Main College Building, Park Place,
Cardiff, UK CF10 3AT. E-mail: cavellkj@cardiff.ac.uk; Fax: +44 (0)29
positions are in non-equivalent environments. The key structural
change in the formation of compound 2 compared to a simple
2
0874030; Tel: +44 (0)29 20875899
4
922 | Dalton Trans., 2006, 4922–4925
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Scheme 2
diffraction study yielded the solid-state structure of the complex,
as shown in Fig. 3. The structure of the ligand is essentially
unchanged upon complexation, with the substantial twist of the
NHC ligand maintained, although the two NHC ligands are not
Fig. 1 Projection along the H1–C1 bond of the cation of 2, showing the
atom labelling scheme.
◦
precisely equivalent (C9–C10–C11–C12 dihedral angle 124.0(6) ;
◦
C28–C29–C30–C31 dihedral angle 127.9(6) ; C1–Pd1 bond length
˚
˚
2
.041(6) A; C20–Pd1 bond length 2.017(6) A). In the solid state
the NHC rings are aligned roughly perpendicular to the Pd
◦
◦
coordination plane (making angles of 85.7(6) and 76.7(6) for
the NHC rings containing C1 and C20, respectively), but deviate
◦
somewhat from coplanarity (17.6(9) ). Significantly, an identical
reaction sequence to that shown in Scheme 2, but employing the
sterically demanding imidazolinium salt 4, leads to considerable
difficulty in generating complexes of the type PdI
2
(NHC) . Indeed,
2
metal complexes derived from 4 appear to be less stable than the
analogues derived from 2, and have thus far failed to provide
crystals suitable for analysis. This result may be rationalised given
the extremely hindered environment around C1 as shown in the
crystal structure of the imidazolinium salt 4, Fig. 2. However, 4
is active in the in situ telomerization reaction of butadiene and
methanol (TON 700), albeit with reduced activity compared to 2
12
(
TON 3500).
Fig. 2 Projections a) along the H1–C1 bond; and b) normal to the
N1–C1–N2 fragment of the cation of 4, showing the atom labelling scheme.
1
,2-diphenylethane-1,2-diamine is the tethering of the N-
substituents to the aromatic rings. This feature provides increased
rigidity in the ligand, and could be expected to lead to higher levels
of enantioselectivity.
Palladium complex 5 was prepared by the reaction of racemic
imidazolinium salt 2 with palladium acetate and sodium iodide in
Fig. 3 Oblique projection of complex 5 (solvent molecules omitted),
showing the atom labelling scheme. Selected bond distances and an-
gles: Pd1–C1 2.041(6), Pd1–C20 2.017(6), Pd1–I1 2.5933(6), Pd1–I2
DMSO, Scheme 2. The initial product of this reaction, as shown
.5924(6) A; C1–Pd1–C20 176.6(3) , I1–Pd1–I2 176.72(3) , N1–C1–N2
˚
07.8(5) , N3–C20–N4 107.9(5) .
◦
◦
2
1
1
◦
◦
by H NMR spectroscopy, is a mixture of isomeric PdI
2
(NHC)
O yields trans
complex 5 as a yellow solid. Vapour diffusion of Et O into
2
complexes, but recrystallisation from THF–Et
2
2
Following our earlier report on the application of 2 in telom-
12
THF yielded a crystalline sample of 5; a single crystal X-ray
erization catalysis, optically pure imidazolinium salt 2 was
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Dalton Trans., 2006, 4922–4925 | 4923

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evaluated as a ligand for the copper-catalysed conjugate addition
of diethylzinc to cyclohexenone. We were attracted to this process,
since Alexakis et al. have previously used imidazolinium salt 6
in the reaction, obtaining the conjugate addition product with
diamine 1 (200 mg, 0.76 mmol) and ammonium tetrafluoroborate
(80 mg, 0.76 mmol) in triethyl orthoformate (1 ml) was heated
under reflux for 3 h. After removal of the solvent under reduced
pressure, the residue was triturated with aqueous ethanol to give
14
4% ee. In compound 6, the chiral influence of the ligand is
the title compound (260 mg, 95%) as a colourless solid. Mp 253–
◦
relatively distant from the metal centre, whereas in the featured
biisoquinoline derived ligands, tethering the imidazolinium ring
to the aromatic ring gives a pseudo-BINAP twist that translates
directly to the metal coordination sphere. This may be expected
to improve the enantioselectivity of these ligands when applied to
asymmetric catalysis.
The conjugate addition reaction using ligand 2 proceeds with
excellent conversion (100% conversion, and 88% isolated yield
compared to 32% conversion, 17% isolated yield with compound
256 C (dec.). d
H
(400 MHz; d
6
-DMSO) 8.83 (1H, s, N=CH–N),
7.52–7.42 (6H, m, aromatic CH), 7.37 (2H, d, J = 7.4 Hz, aromatic
CH), 5.75 (2H, s, 2 × CH), 4.17 (2H, ddd, J = 13.1, 6.6 and 3.1 Hz,
2 × CH), 3.35 (2H, ddd, J = 13.1, 10.3 and 5.4 Hz, 2 × CH), 3.25–
3.19 (2H, ddd, J = 22.9, 10.3 and 6.6 Hz, 2 × CH), 3.10–3.05 (2H,
ddd, J = 22.9, 5.4 and 3.1 Hz, 2 × CH). Racemic compound 2
was similarly prepared.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(1RS,1 RS)-3,3,3 ,3 -Tetramethyl-1,1 ,2 ,3,3 ,4,4 -octahydro-1,1 -
biisoquinoline (3). Prepared from known compound 8 as
6
). The product, 7, was obtained in 10% ee (Scheme 3). This
14
16
represents a small improvement over the results of Alexakis et al.;
described below.
however, it indicates that the tethering in compound 2 may offer
potential benefits in the application of this ligand in asymmetric
catalysis.
1
,2-Dibromoethane (0.1 mL, 1.2 mmol) was added to a suspen-
sion of zinc dust (2.55 g, 39 mmol) in acetonitrile (50 ml). The
suspension was heated to reflux for 30 min, then cooled to room
temperature and chlorotrimethylsilane (0.2 mL, 1.6 mmol) added.
After stirring for 45 min, compound 8 (5.2 g, 33 mmol) was added
followed by chlorotrimethylsilane (6.2 mL, 49 mmol) at such a
Scheme 3 Reagents and conditions: (i) a solution of (R,R)-2 (4 mol%
with respect to cyclohexenone) and n-BuLi in THF was allowed to
◦
◦
warm from −78 C to 25 C, then added to CuOTf
2
in toluene at
Zn (1.5 eq., 1.0 M
◦
rate to keep the temperature below 40 C. The temperature was
◦
−
20 C. Cyclohexenone was added, followed by Et
2
◦
◦
maintained at 40 C for 3 h, then the reaction was cooled to 0 C
and quenched with saturated aqueous NH Cl (25 ml) and aqueous
NH (25 ml). The residual zinc was removed by filtration and the
layers separated. The aqueous layer was extracted with CH Cl
2 × 50 ml) and the combined organic layers washed with brine
50 ml), dried over Na SO , and the solvent removed in vacuo to
15
in hexanes) according to a published procedure.
4
3
Chiral imidazolinium salt 4 has been designed to provide added
steric control and improved chiral influence at the metal centre,
compared to the parent biisoquinoline-based imidazolinium salt
2
2
(
(
2
4
2, by discriminating more strongly between reaction quadrants.
give compound 3 together with the corresponding meso isomer
as a pale yellow oil (5.56 g). The hydrobromide salt was formed
by addition of 48% HBr (5 ml) followed by removal of water in
vacuo. Aqueous 10% HBr (50 ml) was added to the residue, and
The X-ray structure of compound 4 shows the significant impact
that the additional methyl groups will have on the coordination
sphere of the metal in subsequent complexes. We are currently
undertaking further catalytic testing with ligands 2 and 4, and with
other derivatives of the parent species, 2; these will be reported in
due course.
◦
the suspension heated to 100 C. After filtration, the pure (± )-
isomer was deposited, from which compound 3 was liberated by
partitioning between aqueous NaOH and CH
2
Cl
2
. Yield: 1.63 g,
◦
3
1%. Mp 118–120 C. d
H
(400 MHz; CDCl
3
) 7.35 (2H, d, J =
Experimental
7.7 Hz, aromatic CH), 7.28 (2H, apparent t, J = 7.4 Hz, aromatic
CH), 7.11 (2H, apparent t, J = 7.4 Hz, aromatic CH), 6.97 (2H,
d, J = 7.6 Hz, aromatic CH), 4.63 (2H, s, 2 × CH), 3.67 (2H, d,
J = 15.4 Hz, 2 × CHH), 2.39 (2H, d, J = 15.4 Hz, 2 × CHH),
General comments
Procedures involving metal complexes were performed in dry,
deoxygenated solvents using standard Schlenk techniques, all
other reagents were used as received. NMR spectra were recorded
at 295 K on a Bruker Avance DPX 400 MHz spectrometer, with
chemical shifts reported in ppm relative to the residual proton
signals of the deuterated solvent. ESI-MS was performed in DCM
on a Micromass LCT Premier XE TOF spectrometer using a
1
.06 (6H, s, 2 × CH
CDCl
1.8, 24.3.
3
), 0.88 (6H, s, 2 × CH
3
). d (100 MHz;
C
3
) 136.7, 136.2, 129.5, 126.2, 126.1, 125.0, 58.0, 48.8, 42.9,
3
(
13bRS,13cRS)-6,6,8,8-Tetramethyl-5,6,8,9,13b,13c-hexahy-
dro-7a-aza-6a-azonia-dibenzo[c,g]fluorene tetrafluoroborate (4).
◦
Prepared in an analogous manner to compound 2. Mp 224–
source temperature of 80 C and capillary voltage of 2000 V.
◦
2
(
(
28 C. d
H
(400 MHz; CDCl
3
) 8.61 (1H, s, N=CH–N), 7.40–7.32
4H, m, aromatic CH), 7.27–7.20 (4H, m, aromatic CH), 5.57
Preparation of compounds
2H, s, 2 × CH), 3.05 (2H, d, J = 16.0 Hz, 2 × CH), 2.88 (2H, d,
(
13bR,13cR)-5,6,8,9,13b,13c-Hexahydro-7a-aza-6a-azonia-di-
J = 16.0 Hz, 2 × CH), 1.57 (6H, s, 2 × CH ), 1.51 (6H, s, 2 ×
3
benzo[c,g]fluorene tetrafluoroborate (2). A mixture of (R,R)-
CH ).
3
4
924 | Dalton Trans., 2006, 4922–4925
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Complex 5. Palladium acetate (0.032 g, 0.14 mmol), racemic 2
¯
(
M
r
1018.87), triclinic, P1, a = 12.4100(3), b = 12.7960(3), c =
◦
(
0.100 g, 0.28 mmol), and NaI (0.042 g, 0.28 mmol) were heated
˚
1
2
3
5.1290(4) A, a = 100.433(1), b = 99.417(1), c = 111.286(1) , Z =
3 −3
◦ ◦
c
◦
in DMSO (4 ml) at 60 C for 16 h, then the temperature was
˚
, V = 2131.48(9) A , D
= 1.586 g cm , 2.91 ≤ 2H ≤ 27.485 .
◦
gradually raised to 120 C over a period of 8 h, after which time
2768 reflections were collected of which 8678 were unique. 8678
the dark red-brown solution had become pale brown. The solution
was filtered to remove Pd black, the solvent removed in vacuo, and
the residue washed with methanol (3 × 5 ml) then extracted with
THF to separate unreacted, insoluble, 2. The crude product (a
mixture of several isomers) was precipitated by the addition of
reflections having I > 2.0r(I) were used for refinement (449
parameters), converging to R = 0.0524 and R = 0.1310.
W
CCDC reference numbers 611607–611609 for 2, 4 and 5,
respectively.
For crystallographic data in CIF format see DOI:
Et
2
O and further recrystallised from THF–Et
(400 MHz; CDCl
.35 (16H, m, aromatic CH), 5.17 (4H, s), 4.67–4.75 (4H, m),
2
O to yield 5 as a
1
0.1039/b611647g
yellow powder. Yield: 0.30 g, 23%. d
H
3
) 7.20–
7
3
Acknowledgements
.66–3.78 (4H, m), 3.54–3.66 (4H, m), 2.86 (4H, d (J = 16 Hz) of
+
poorly resolved t). HRMS (ESI, [M + H] ): m/z = 909.0099 Da
We are extremely grateful to Drs Li Ling Ooi and Andreas Stasch
for the crystal structure determinations, to the EPSRC/Crystal
Faraday and Cardiff University for financial support, and to
Johnson Matthey for a loan of Pd salts.
(
−4.8 ppm from calc.).
X-Ray crystallography
All structures were collected at 150 K on a Bruker/Nonius
Kappa CCD diffractometer using graphite monochromated Mo-
References
˚
Ka radiation (k = 0.71073 A). Structure refinement and final
geometrical calculations were carried out with the SHELX-97
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13bRS,13cRS)-5,6,8,9,13b,13c-Hexahydro-7a-aza-6a-azonia-
6
D. S. McGuinness, B. F. Yates and K. J. Cavell, J. Am. Chem. Soc.,
dibenzo[c,g]fluorene tetrafluoroborate (2). Colourless crystals
2
001, 123, 8317.
3
(
0.30 × 0.12 × 0.10 mm ) of 2 (racemic) were grown from a
7 K. J. Cavell and D. S. McGuinness, Coord. Chem. Rev., 2004, 248,
6
71.
mixture of ethanol and diethyl ether: C19
¯
H
19BF
4
N
2
(M
r
362.17),
˚
8
9
C. M. Crudden and D. P. Allen, Coord. Chem. Rev., 2004, 248, 2247.
triclinic, P1, a = 7.5518(15), b = 8.1740(16), c = 14.052(3) A, a =
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◦
3
˚
1
D
00.08(3), b = 101.81(3), c = 96.24(3) , Z = 2, V = 826.5(3) A ,
1
996, 129, 1483.
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−
3
◦
◦
c
= 1.455 g cm , 3.02 ≤ 2H ≤ 27.00 . 6741 reflections were
3
collected of which 3588 were unique. 3588 reflections having I >
.0r(I) were used for refinement (235 parameters), converging to
R = 0.0721 and R = 0.1828.
1
2
W
13bRS,13cRS)-6,6,8,8-Tetramethyl-5,6,8,9,13b,13c-hexahydro-
1
7
a-aza-6a-azonia-dibenzo[c,g]fluorene tetrafluoroborate (4).
3
Colourless crystals (0.20 × 0.15 × 0.15 mm ) of 4 were grown
¯
from ethanol: C23
H
27BF
4
N
2
(M
r
418.28), triclinic, P1, a =
˚
8
.0210(16), b = 10.697(2), c = 12.929(3) A, a = 71.95(3),
◦
3
˚
b = 86.98(3), c = 74.82(3) , Z = 2, V = 1017.4(4) A , D =
c
−
3
◦
◦
1
.365 g cm , 3.03 ≤ 2H ≤ 26.99 . 7948 reflections were collected
1
1
3 W. A. Herrmann, D. Baskakov, E. Herdtweck, S. D. Hoffmann, T.
Bunlaksananusorn, F. Rampf and L. Rodefeld, Organometallics, 2006,
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were used for refinement (275 parameters), converging to R =
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0
.0529 and R
W
= 0.1179.
2
001, 12, 2083.
3
Complex 5. A pale yellow crystal (0.20 × 0.15 × 0.15 mm )
15 P. K. Fraser and S. Woodward, Tetrahedron Lett., 2001, 42, 2747.
1
1
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equivalents of diethyl ether) was grown by vapour diffusion of di-
ethyl ether into a THF solution of the complex: C44
H
49
I
2
N
4
O1.5Pd
18 L. J. Farrugia, J. Appl. Crystallogr., 1997, 30, 565.
This journal is © The Royal Society of Chemistry 2006
Dalton Trans., 2006, 4922–4925 | 4925