Asymmetric lithium(I) and copper(II) alkoxy-N-heterocyclic carbene complexes; crystallographic characterisation and Lewis acid catalysis

Article abstract of DOI:10.1039/b404614e

A one-pot synthesis of a wide range of bidentate, alkoxide-N-heterocyclic carbene ligands provides new lithium alkoxy-carbenes and a range of covalently bound organometallic Cu(II) carbene complexes, which are catalytically active, in some cases enantiose

Full text of DOI:10.1039/b404614e

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Asymmetric lithium(
I) and copper(II) alkoxy-N-heterocyclic carbene
complexes; crystallographic characterisation and Lewis acid catalysis†
Polly L. Arnold,* Mark Rodden, Kate M. Davis, Andrew C. Scarisbrick, Alexander J. Blake and
Claire Wilson
School of Chemistry, University of Nottingham, University Park, Nottingham, UK NG7 2RD.
E-mail: polly.arnold@nottingham.ac.uk; Fax: +44 115 9513563; Tel: +44 115 9513437
Received (in Cambridge, UK) 30th March 2004, Accepted 18th May 2004
First published as an Advance Article on the web 17th June 2004
A one-pot synthesis of a wide range of bidentate, alkoxide-N-
heterocyclic carbene ligands provides new lithium alkoxy-
from a racemate, the crystal is homochiral. The structure is a dimer
of LiL, with stoichiometric incorporated LiI, which forms a
tetrameric butterfly of lithium cations. The Li–Ccarbene distance of
2.135 Å is the shortest yet reported.7 Despite this, the Li–NHC
fragment is distorted; the NHC–Ccarbene–Li angle is 152.3° rather
than 180°. The two iodides each cap a Li3 unit, but are not close
enough to suggest any I…I bond (4.14 Å).
carbenes and a range of covalently bound organometallic Cu(II
)
carbene complexes, which are catalytically active, in some cases
enantioselectively, for conjugate addition reactions.
Nucleophilic N,NA-disubstituted imidazol-2-ylidenes, or N-hetero-
cyclic carbenes (NHCs), are strong s-Lewis bases. As such they
have already found use as LAC (ligand accelerated catalysis)
additives that can improve the activity of Lewis acid metal catalyst
systems. For example, the ring opening of meso-epoxides by
triethylaluminium is catalysed by 5 mol% of [:C{(NAr)CH2}2], or
the complex [AlEt3(:C{(NAr)CH2}2)] (Ar = 2,6-Pri2–C6H3); the
latter is a superior catalyst (the imidazolinium-catalysed reaction
also generates other by-products).1 The copper-catalysed conjugate
addition (Michael addition) of diethyl zinc to cyclohexenone has
also been improved by the addition of an in situ generated NHC,
[:C{(NR)CH}2] (R = mesityl), or the silver carbene [Ag(:C{(N-
Me)CHBut}2)];2 the latter is assumed to form a copper carbene
catalyst in situ. Despite much recent interest in NHC-derived
catalysts, there are still few applications in asymmetric synthe-
sis.3
The lithium salts 2 react with half or one equivalent of copper(II
)
chloride or copper(II) triflate to afford mono- or bis-substituted
Cu(II) alkoxy-carbene complexes, isolated as lithium iodide
adducts,
Scheme
1,
3
[Cu{OCR1R2CH2(1-
and [Cu{OCR1R2CH2(1-
C{NCHCHNR3})}Cl(thf)(LiI)]
C{NCHCHNR3})}2(LiI)2] 4 respectively, after recrystallisation
from toluene or thf.¶ The paramagnetism of the complexes
precludes 13C NMR spectroscopic identification of the carbene;
unsurprisingly we were unable to detect a hyperfine coupling to the
carbene by X-band EPR.† Complexes 4 are sufficiently air stable to
show the parent ion in electrospray MS. This makes their potential
for use as homogeneous Lewis acid catalysts most promising.8
We have been studying polydentate ligands that combine the
NHC group with an anionic functional group, to stabilise higher
oxidation state, and Lewis acidic metal catalysts.4 There are many
Cu(
) complexes of neutral, soft NHCs.5 Despite the use of in situ
I
generated mixtures of NHCs and Cu(II) salts in Lewis acid
catalysed reactions such as conjugate addition, only one isolated
divalent copper-NHC complex has been reported, stabilised by the
use of an encapsulating tris(NHC) ligand.6 It is proposed that a high
oxidation state Cu(III)-enolate intermediate forms in copper-
catalysed conjugate addition reactions, so an NHC ligand that
stabilises higher oxidation state complexes should provide a LAC
effect in such a catalysed reaction.
Herein, we report one-pot syntheses of asymmetric alkoxy-
functionalised NHCs that are capable of stabilising Cu(II) carbene
complexes, the synthesis and catalytic reactivity of lithium and
copper complexes, and the first crystallographically characterised
copper(II) carbene.
The reaction of 2-tert-butyl epoxide with imidazole in acetoni-
trile, then with isopropyl iodide yields the imidazolium iodide
[HOCMe2CH2(1-HC{NCHCHNPri})]I [H2LI] 1a, in excellent
yield (see ESI†). This reaction is general; Scheme 1. Sterically
more demanding N-substituents can be incorporated by the use of
preformed alkyl imidazoles; an alternative route forms, for
Scheme 1
example,
the
zwitterionic
1c
[HOCMePhCH2(1-
HC{NCHCHNBut})] [HL]. Single crystal X-ray diffraction studies
of ligands 1a, 1c·HCl, and 1d show the protonated alcohol and
imidazolium groups of the proligand (see ESI†)‡.
Deprotonation of 1 with two equivalents of lithium n-butyl or
LiHMDS (one for 1c) affords the colourless crystalline lithium
alkoxide-carbenes [LiOCR1R2CH2(1-C{NCHCHNR3})], LiL, 2,
recrystallised with an equivalent of the lithium halide by-product
(for iodide), in excellent yields, Scheme 1. Single crystals of 2b·LiI
were grown from a diethyl ether solution, Fig. 1.§ Although grown
Fig. 1 Thermal ellipsoid drawing of 2b. H and coordinated solvent C
omitted. Distances (Å) and angles (°): Li(1)–O(2) 1.888(6), Li(2)–O(2)
1.893(5), Li(1)–Li(2) 2.831(8), Li(1)–I(1) 2.838(6), Li(2)–I(1) 2.904(5),
O(2)–C(6) 1.404(4), N(1)–C(1) 1.358(4), O(2)–Li(2)–O(2)_2, 98.2(2).
† Electronic supplementary information (ESI) available: full synthetic and
structural details. See http://www.rsc.org/suppdata/cc/b4/b404614e/
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C h e m . C o m m u n . , 2 0 0 4 , 1 6 1 2 – 1 6 1 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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The Cu(II)–carbene fragment is interesting in its own right since
it is implicated in so many copper catalysed carbene transfer
reactions, but usually is too reactive to isolate and study.9 Despite
growing a range of crystals of 3 and 4 that appeared optically to be
suitable for single crystal X-ray diffraction, we have been unable to
obtain diffraction patterns from any. However, careful oxidation of
[Cu{OC(Ph)(CH2{1-C[NCHCHNBut]})2}]2 ([CuLo]2) previously
made in our laboratory,4 afforded an orange, highly crystalline,
tetrametallic complex in very low yield, 5%, characterised as [{(m-
O)[CuClLo]2}2] 5, Fig. 2.∑
To the best of our knowledge there is only one other
crystallographically characterised organometallic Cu(II) complex;
the N-confused porphyrin complex [CuII{calix[4]phyrin}] has a
2.007(4) Å Cu–C distance, the average Cu(II)–C distance in 5 is
1.99(3) Å. The Cu centres are slightly distorted square planes with
the alkoxide O atom displaced out of the plane by 0.102 Å.
As well as being rare examples of organometallic Cu(II),10 these
A recent study of catalysts made from copper(II) salts with added
chiral monodentate NHC ligands gave ees of up to 39% at 220 °C
with [:C{(NCH(Ph)Me)CH}2], (but with a yield of 60%), with
improved enantioselectivities at 278 °C over 16 h (to 69% ee), or
with a different test substrate ketone.11
In summary, a range of new anionic, heterobidentate ligands that
combine the strong s-donor N-heterocyclic carbene with an
alkoxide, and the first characterised lithium salts of a bidentate
NHC ligand are easily made. Chiral complexes of rare divalent
copper organometallics have been isolated, these catalyse con-
jugate addition reactions. The first crystal structure of a non-
macrocyclic organometallic copper(II) complex has also been
presented. The insight into the Cu(II)–NHC moiety should aid in
future catalyst, or LAC additive, design.
We thank Dr Simon Woodward, Ms Victoria Albrow, and Mr
Miguel Robredo for help with the catalysis, and to the Royal
Society and the EPSRC for funding (fellowship for PLA,
studentships for MR, ACS).
are the first complexes that tether the NHC group to the copper(II
)
centre by an anionic group, providing an alternative source of
stereocontrol in 3 or 4. NHCs are usually rendered chiral by
incorporation of
a
chiral hydrocarbyl N-substituent e.g.
[:C{(NCH(Ph)Me)CH}2], or by C2 symmetrical 1,2-dialkylation of
the backbone of the saturated NHC analogue, e.g.
[:C{(NR)CHBut}2].
The catalysis of conjugate addition to cyclohexenone, eqn. (1),
by 3 and 4 has been studied. Complex (R)–2b was used to make
enantiomerically pure 3b. All the complexes tested show rapid and
high-yielding catalysis of the substrate, as would be predicted from
the bound NHC donor group, Table 1.
The most efficient catalyst is the N-methylated t-butoxide 3b.
This NHC group is the least sterically encumbered, but makes the
poorest NHC donor. There are no reports of the use of copper
alkoxides as catalysts for conjugate addition reactions, but it is
possible that the alkoxide also contributes to the activity of this
catalyst. The homochiral complex gave an ee of 51%. This
represents good (3 : 1) selectivity, particularly at this relatively high
temperature and short reaction time.
Notes and references
‡ Crystallographic data for all complexes are deposited with the CCDC:
CCDC 235713–235718. See http://www.rsc.org/suppdata/cc/b4/b404614e/
for crystallographic data in .cif or other electronic format.
§ 2b C28 H54 I2 Li4 N4 O4 Mr = 792.31, monoclinic, a = 12.880(2), b =
15.655(2) c = 19.034(2) Å, b = 93.239(2)°,U 3831.8 Å3, T = 150 K, space
group C2/c, Z = 4, dc = 1.373 Mg m23, m(Mo–Ka) = 1.674 mm21 11901
unique reflections (Rint = 0. 031) used in all calculations. Final R1 [4326
reflections with F > 4s(F)] = 0.0362 and wR(all F2) was 0.0854.
¶ 3b: pale green solid, yield 63%. 4a: purple solid, yield 69%. 4b: purple
solid, yield 76%. Anal. calcd. (found) for C20H34CuN4O2·2.5C7H8·2LiI: C,
48.74 (49.05); H, 5.89 (5.27); N, 6.06(6.74).
∑ 5: C48.4 H65.6 Cl4 Cu4 N8 O3.6 Mr = 1215.46, tetragonal, a = b =
14.763(3), c = 27.053(6) Å, U 5896(4) Å3, T = 150(2) K, space group
P41212, Z = 4, dc 1.369 Mg m23, m(Mo–Ka) = 1.649 mm21 7023 unique
reflections (Rint = 0.189) used in all calculations. Final R1 [5208 reflections
with F > 4s(F)] = 0.0645 and wR(all F2) was 0.214.
(1)
1 H. Y. Zhou, E. J. Campbell and S. T. Nguyen, Org. Lett., 2001, 3,
2229.
2 P. K. Fraser and S. Woodward, Tetrahedron Lett., 2001, 42, 2747; J.
Pytkowicz, S. Roland and P. Mangeney, Tetrahedron: Asymmetry,
2001, 12, 2087.
3 (a) S. Lee and J. F. Hartwig, J. Org. Chem., 2001, 66, 3402; (b) J. J. Van
Veldhuizen, S. B. Garber, J. S. Kingsbury and A. H. Hoveyda, J. Am.
Chem. Soc., 2002, 124, 4954; (c) M. C. Perry and K. Burgess,
Tetrahedron: Asymmetry, 2003, 14, 951.
4 (a) P. L. Arnold, A. C. Scarisbrick, A. J. Blake and C. Wilson, Chem.
Commun., 2001, 2340; (b) P. L. Arnold, S. A. Mungur, A. J. Blake and
C. Wilson, Angew. Chem., Int. Ed., 2003, 42, 5981.
5 (a) P. L. Arnold, Heteroatom Chem., 2002, 13, 534; (b) H. Kaur, F. K.
Zinn, E. D. Stevens and S. P. Nolan, Organometallics, 2004, 23, 1157;
(c) A. A. D. Tulloch, A. A. Danopoulos, S. Kleinhenz, M. E. Light, M.
B. Hursthouse and G. Eastham, Organometallics, 2001, 20, 2027.
6 X. L. Hu, I. Castro-Rodriguez and K. Meyer, J. Am. Chem. Soc., 2003,
125, 12237.
7 There are three other Li–NHC crystal structures with a mean of 2.20 Å
including bridging NHC-complexes: Ref. 4b ; A. J. Arduengo, M.
Tamm, J. C. Calabrese, F. Davidson and W. J. Marshall, Chem. Lett.,
1999, 1021; R. Frankell, C. Birg, U. Kernbach, T. Habereder, H. Noth
and W. P. Fehlhammer, Angew. Chem., Int. Ed., 2001, 40, 1907.
8 (a) J. M. Brunel, O. Legrand and G. Buono, C. R. Acad. Sci. Ser. IIC,
1999, 2, 19; (b) M. Gomez, G. Muller and M. Rocamora, Coord. Chem.
Rev., 1999, 195, 769; (c) L. C. Dias, Curr. Org. Chem., 2000, 4, 305.
9 (a) J. M. Fraile, J. I. Garcia, V. Martinez-Merino, J. A. Mayoral and L.
Salvatella, J. Am. Chem. Soc., 2001, 123, 7616; (b) M. P. Doyle and D.
C. Forbes, Chem. Rev., 1998, 98, 911.
Fig. 2 Thermal ellipsoid drawing of 5. Distances (Å) and angles (°): Cu1–
C22 2.008(13), Cu1–O1 1.979(7), Cu1–O2 1.958(6), Cu2–C12 1.971(15),
N1–C12–N2 105.4(14), N1–C12 1.38(2); Cu4 core inset.
Table 1 Results of copper catalysed conjugate additiona
Catalyst conc.
(mol %)
Conversion
(%)
Complex
Time/h
ee (%)
3b
3c
4a
4b
4c
5
5
5
5
5
2
2
2
2
2
100
78
72
98
60
51(S)
—
—
—
—
10 (a) H. Maeda, A. Osuka, Y. Ishikawa, I. Aritome, Y. Hisaeda and H.
Furuta, Org. Lett., 2003, 5, 1293; (b) H. Furuta, H. Maeda and A. Osuka,
Chem. Commun., 2002, 1795.
11 A. Alexakis, C. L. Winn, F. Guillen, J. Pytkowicz, S. Roland and P.
Mangeney, Adv. Synth. Catal., 2003, 345, 345.
a All reactions at 230 °C under purified N2 atmosphere.
C h e m . C o m m u n . , 2 0 0 4 , 1 6 1 2 – 1 6 1 3
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