C 2-Symmetric S/C/S ligands based on N-heterocyclic carbenes: A new ligand architecture for asymmetric catalysis

Article abstract of DOI:10.1039/b910846g

Neutral, C₂-symmetric S/C/S ligands based on N-heterocyclic carbenes and thioether functionalities were incorporated into transition metal complexes characterised by two direct metal-stereogenic sulfur bonds. This new ligand design was applied

Full text of DOI:10.1039/b910846g

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C2-Symmetric S/C/S ligands based on N-heterocyclic carbenes: a new ligand
architecture for asymmetric catalysis†
a
b
a
b
b
b
´
Javier Iglesias-Sigu¨enza, Abel Ros, Elena D´ıez, Antonio Magriz, Arcadio Va´zquez, Eleuterio Alvarez,
Rosario Ferna´ndez*a and Jose´ M. Lassaletta*b
Received 2nd June 2009, Accepted 30th July 2009
First published as an Advance Article on the web 28th August 2009
DOI: 10.1039/b910846g
Neutral, C2-symmetric S/C/S ligands based on N-heterocyclic
carbenes and thioether functionalities were incorporated into
transition metal complexes characterised by two direct metal-
stereogenic sulfur bonds. This new ligand design was applied
to 1,3-dipolar cycloadditions as the first example of the use
silver of carbenes in asymmetric catalysis.
stereogenic centres upon coordination to the metal centre. In
view of our recent interest in new N-heterocyclic carbene (NHC)
architectures,4,5 we have recently reported the synthesis and
applications of Pd and Rh complexes containing heterobiden-
tate C/S ligands based on NHCs and thioether functionalities
(Fig. 2).6 In these complexes, the configuration of the sulfur
atom is controlled by a neighbour stereogenic centre that forces
a relative trans configuration in the chelate to avoid severe steric
interactions.
The design of new types of ligands has been the central strat-
egy that enabled the formidable development of homogeneous
catalysis over the past decades. This statement particularly applies
to asymmetric catalysis, where the construction of suitable chiral
environments around the active centres is essential to discriminate
diastereomeric transition states. After the seminal work by Dang
and Kagan,1 one of the most successful catalyst designs exploits
the geometrical simplicity associated with a C2-symmetry that
reduces the number of possible transition states. Though it has
been rationalised how and why C1-symmetric catalysts provide a
better performance in some cases,2 there is still a high proportion of
C2-symmetric ligands (BOX, PyBOX, BINAP, BINOL, SALEN,
TADDOL, DUPHOS, etc.) which have a wide applicability (the
so called “privileged ligands”).3
In most cases, the asymmetric environment is provided by
chiral elements (stereogenic centres, chiral axes, etc.) separated
by at least two bonds from the active centre. Taking transition
metal–bis-oxazoline BOX or PyBOX complexes as representative
examples, the stereogenic centres on the oxazoline ring are placed
Fig. 2 NHC–thioether heterobidentate chiral ligands.
˚
˚
at typical distances of ca. 3.0–3.2 A and 3.3–3.5 A from the metal,
respectively (Fig. 1).
On this basis, we designed C2-symmetric complexes of structure
I (Scheme 1), based on a tridentate S/NHC/S ligand that
combines the stabilising properties of the imidazol-2-ylidene or
its benzimidazole analogue with two directly bonded stereogenic
sulfur atoms. In this communication, we wish to report on the
successful development of catalysts based on this new S/C/
S-ligand class and the first application of silver NHC carbenes
in asymmetric catalysis.
Fig. 1 Metal complexes of bidentate BOX and tridentate PyBOX ligands.
A closer asymmetric environment can be provided by ligands
bearing heteroatoms (N, P or S) that are able to become stable
aDepartamento de Qu´ımica Orga´nica, Univ. de Sevilla, Apdo. de Correos
1203, 41071 Seville, Spain. E-mail: ffernan@us.es; Fax: +34 954624960
bInstituto de Investigaciones Qu´ımicas (CSIC-US), Ame´rico Vespucio 49,
41092 Seville, Spain. E-mail: jmlassa@iiq.csic.es; Fax: +34 95 4460565
† Electronic supplementary information (ESI) available: Experimental
procedures. CCDC reference number 712595. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b910846g
Scheme 1 Retrosynthetic analysis to C2-symmetric S/C/S-complexes I.
Dalton Trans., 2009, 8485–8488 | 8485
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Scheme 2 Synthesis of S/C/S pincer ligands and complexes thereof.
The very simple retrosynthetic analysis of compounds I suggests
their synthesis from imidazolium(benzimidazolium) salts II, which
in turn should be easily accessible by alkylation (twice) of the free
heterocycles with appropriate reagents III.
As deduced from previous structural studies on heterobidentate
ligands,6 the isopropyl group appears to be big enough to control
the relative configuration of the neighbour S stereogenic cen-
tre created upon coordination. Thus, (1-bromo-3-methylbutan-
2-yl)[alkyl(aryl)]sulfanes 2a–d (Scheme 2) were chosen as the
reagents. Their synthesis was readily accomplished in good yields
by treatment of alcohols 1a–d‡7,8,9 with CBr4 and PPh3.
The akylation of imidazole with bromides 2a–d afforded the
desired products 3a–d, that were further alkylated with the same
bromides 2 to afford the required imidazolium salts 4a–d§ in
moderate yields. Stepwise alkylation of benzimidazole with 2a
afforded 5 and 6 in a similar manner. Treatment of bromides 4a–d
and 6 with Ag2O afforded the corresponding silver carbenes 7a–d
and 8, respectively, in excellent yields.
Fig. 3 Ortep drawing of the cationic Pd(II) complex 10. Thermal ellipsoids
are drawn at the 50% probability level. Chloride counteranion and
H-atoms are omitted for clarity.
C(1) = 67.30◦] with absolute S configuration at the sulfur atoms
˚
and Pd–S distances of 2.3060(12) and 2.3215(11) A.
Silver N-heterocyclic carbenes, commonly used as transfer
agents to other transition metals,10 have received little attention
as potential catalysts,11 probably due to its lability. However,
the expected stabilising capability of the pincer S/C/S ligands
prompted us to explore the possibility of using silver complexes 7
and 8 as catalysts. Taking into account the well established use of
silver complexes in asymmetric 1,3-dipolar cycloadditions,12 the
reaction of imino esters 11–16 with t-butyl acrylate was chosen as
a model system (Scheme 3). Previously reported silver complexes
with heterobidentate C/S ligands 17–216 were incorporated in the
preliminary experiments. From these screenings, it was concluded
that catalyst 7a based on the new tridentate S/C/S ligands affords
a higher selectivity (ee 55%, Table 1, entry 6) than complexes 17–21
from bidentate ligands (ee’s up to 35% at rt, entries 1–5). These
results are tentatively explained by assuming a hemilabile behavior
of the ligand 7.13 Surprisingly, the benzimidazole derivative 8 was
not an active catalysts in the model reaction (entry 7).
In addition, the cationic palladium complex 10 was obtained in
86% yield by a direct reaction of the azolium chloride 9, [obtained
R
by exchange from 4a with resin Dowexꢀ 22 (chloride form)] with
PdCl2 in DMF.¶ Alternatively, the same product was obtained
in near quantitative yield by the reaction of the same azolium 9
with Ag2O and in situ transmetallation with [PdCl2(CH3CN)2].
Suitable crystals for X-ray diffraction analysis were obtained by
slow diffusion of hexane into a solution of 10 in CH2Cl2 (Fig. 3).ꢀ
The structure exhibits the expected square-planar geometry with
nearly no distortion [C(1)–Pd(1)–S(1) 90.05(14)◦, C(1)–Pd(1)–S(2)
88.39(14)◦], with the palladium atom being part of two boat-
like constrained metallacycles, with a relatively short Pd–C
˚
bond of 1.947(5) A. The two isopropyl groups are arranged
in pseudo-equatorial positions, forcing the cyclohexyl groups to
accommodate in relative trans pseudo axial positions [torsional
angles C(14)–S(1)–Pd(1)–C(1) = 82.97◦ and C(20)–S(2)–Pd(1)–
8486 | Dalton Trans., 2009, 8485–8488
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Table 1 Enantioselective 1,3-dipolar cycloaddition of azomethine ylides (from imino esters 11–16) with tert-butyl acrylatea
Entry
Imine
Ar
Cat.
Solvent
T/◦C
t/h
Prod.
Yieldb
eec
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
11
11
11
11
11
11
11
11
12
12
12
12
13
14
15
16
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
17
18
19
20
21
7a
8
7a
7a
7b
7c
7d
7a
7a
7a
7a
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Et2O
Et2O
Et2O
Et2O
Et2O
25
25
25
25
25
25
25
-25
-25
-25
-25
-25
-10d
-25
-25
-25
8
8
8
8
8
22
22
22
22
22
22
—
22
23
23
23
23
24
25
26
27
70
62
33
50
85
75
—
52
89
84
90
85
62
93
70
66
30
33
10
0
35
55
—
74
76
48
26
6
8
48
84
84
84
84
84
84
84
84
84
2-Tolyl
2-Tolyl
2-Tolyl
2-Tolyl
4-Methoxyphenyl
4-Bromophenyl
4-Chlorophenyl
2-Naphthyl
Et2O
Et2O
Et2O
Et2O
70
76
80
74
a Reactions were performed with 1.2 equiv. of t-butyl acrylate on a 0.15 mmol scale. b Isolated yields of pure endo isomers. Endo/exo ratios ≥ 95 : 5 were
determined by H NMR of crude reaction mixtures in all cases. c Determined by HPLC on chiral stationary phases. d Reaction carried out at -25 ◦C
1
afforded < 10% of product after prolonged reaction times.
Notes and references
‡ 1a and 1d were prepared according to literature procedures: see ref. 6
and 7. 1b was prepared from (R)-tert-butyl tert-butanethiosulfinate by
the reaction with i-BuMgCl according to the procedure described in ref.
8. The resulting sulfoxide was transformed into 1b by the reaction with
chloromethyl benzyl ether according to the procedure described in ref. 6.
1c was prepared by organocatalytic a-sulfenylation of isovaleraldehyde
and subsequent reduction (see ref. 7); the product had spectroscopical and
analytical data in agreement with those reported in ref. 6.
§ The direct alkylation of imidazole with two equivalents of bromides
2 afforded lower yields of products 4. Moreover, compounds 3 are
interesting intermediates that could also be used to build asymmetric salts
by alkylation with different reagents.
¶ The same treatment from bromide 4a afforded a similar product, but its
X-ray analysis revealed the presence of a mixture of chloride and bromide
anions.
ꢀ Crystal data for 10: C51H94Cl6N4O2Pd2S4 [2(C25H44ClN2PdS2), CH2Cl2,
˚
2(H2O), 2(Cl)], triclinic, space group P1, Z = 1, a = 10.2385(4) A, b =
◦
◦
˚
˚
25.066(9) A, c = 17.2053(7) A, a = 84.804(2) , b = 82.038(2) , g =
◦
3
-1
Scheme 3 1,3-Dipolar cycloaddition of azomethine ylides from imino
esters 11–16 with tert-butyl acrylate.
˚
61.151(1) , V = 1568.82(11) A , m(Mo Ka) = 1.001 mm , T = 100(2)
K, 57 350 reflections measured, 12 767 unique (Rint = 0.039) which were
used in all calculations. R1(F2) = 0.0414 [for 11 768 reflections with Fo
>
4s(Fo)], wR = 0.0977 for all data, GOF = 1.027. CCDC 712595. Flack
parameter: -0.01(2).
◦
Under optimized conditions (-25 C, Et2O as the solvent and
1 T. P. Dang and H. B. Kagan, J. Chem. Soc. D, 1971, 481.
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catalysts loading of 5 mol%), complex 7a proved to be a better
catalyst than its analogues 7b–d (entries 10–12), affording cy-
cloadducts 22–27 with excellent endo selectivities and enantios-
electivities up to 80% (Table 1, entries 8–9, 13–16).
In summary, pincer type, C2-symmetric S/C(NHC)/S neutral
ligands provide an unprecedented geometry characterised by a
direct bonding of two stereogenic S atoms to the metal centre. As
a first application for this ligand topology, their silver complexes
were successfully used as catalysts in the asymmetric 1,3-dipolar
cycloaddition of imino glycinates. The development of different
applications in asymmetric catalysis is a current object of study in
our laboratories.
We thank the Spanish “Ministerio de Ciencia y Tecnolog´ıa”
(grants CTQ2007-61915 and CTQ2007-60244) and the Junta
de Andaluc´ıa (grants 2005/FQM-658 and 2008/FQM-3833) for
financial support. J. I.-S. and A. V. thank the Ministerio de Ciencia
e Innovacio´n for predoctoral fellowships.
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8488 | Dalton Trans., 2009, 8485–8488
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