Effective modulation of the donor properties of n-heterocyclic carbene ligands by "Through-space" communication within a planar chiral scaffold

Article abstract of DOI:10.1021/ja076028t

A high yielding approach to planar chiral carbene ligands is described, in which an imidazo[1,5-a]pyridine-3-ylidene unit is embedded into a cyclophane scaffold. As evident from the IR data of the corresponding rhodium complex 18 as the parent member of this family, these new ligands turned out to be exceptionally strong electron donors, rivaling or even outperforming the other diamino-stabilized five-membered N-heterocyclic carbenes (NHC) known to date. If the remote ring of the cyclophane is substituted by four fluorine atoms, however, the donor capacity is significantly reduced by the through-space interaction of the tetrafluorobenzene moiety with the underneath carbene entity. Since X-ray data suggest that the steric demand of the fluorinated and the nonfluorinated cyclophane-2-ylidenes are virtually identical, these results illustrate that the electronic properties of an NHC ligand can be tuned over a wide range without the need to change its constitution or steric attributes. The synthesis route leading to the planar chiral imidazopyridinium salts serving as the immediate carbene precursors involves a previously unrecognized 6π-electrocyclic ring opening reaction upon exposure of the pyridine-N-oxide 12 to N,N-dimethyl-carbamoyl chloride and TMSCN, as evident from the crystal structure analysis of the resulting azatriene adduct 13. Copyright

Full text of DOI:10.1021/ja076028t

Published on Web 10/02/2007
Effective Modulation of the Donor Properties of N-Heterocyclic Carbene
Ligands by “Through-Space” Communication within a Planar Chiral Scaffold
Alois Fu¨rstner,* Manuel Alcarazo, Helga Krause, and Christian W. Lehmann
Max-Planck-Institut fu¨r Kohlenforschung, D-45470 Mu¨lheim/Ruhr, Germany
Received August 10, 2007; E-mail: fuerstner@mpi-muelheim.mpg.de
Scheme 1. Donor Capacity of Selected NHC Ligandsa
The tremendous success of N-heterocyclic carbenes (NHC) as
organocatalysts and as ancillary ligands for transition-metal catalysis
is innately linked to their powerful two-electron donor capacity.1
If one takes the stretching frequency of the CO ligand in complexes
of type 1 as an estimate for the donor strength of the trans-disposed
ligand L,2 NHC’s are distinctly more electron releasing than even
the most basic trialkylphosphines.
In contrast to the phosphine series, however, where substantial
electronic tuning can be easily accomplished, the dispersion of the
donor capacities among the commonly used NHC’s is exceedingly
narrow (Scheme 1).2c In the extreme, it was even possible to alter
the steric properties of a given type of NHC over a wide range
without any noticeable effect on the donor ability.3 Serious
electronic modulations require constitutional redesign (acyclic
a For data concerning other carbenes, see the Supporting Information.2c
Scheme 2 a
carbenes,4 different size of the backbone,5 donor atoms other than
nitrogen,6 one rather than two heteroatoms in the ring,7 etc.),1,2c
with the only important exception being the six-membered, boron
containing NHC’s 8 pioneered by Bertrand.8 These ligands are
designed such that variations of the substituents R1 and R2 on boron
enable electronic modulations within a quasi-constant steric envi-
ronment (Scheme 1). Outlined below is an alternative concept that
allows uncoupling of the electronic and structural parameters. This
goal was reached by embedding the NHC into a planar chiral
cyclophane scaffold that enjoys an effective electronic cross-talk
between its layers.9
The preparation of the new type of ligand starts from the known
N-oxide 12 which was readily prepared by following a literature
route (Scheme 2).10 O-Acylation with Me2NC(O)Cl followed by
reaction with TMSCN11 furnished azatriene 13 rather than the
expected 2-cyanopyridine 14, as unambiguously proven by X-ray
crystal structure analysis (Figure 1, left).12 This previously unrec-
ognized opening of the pyridine nucleus is deemed to reflect the
strain of the cyclophane framework.
a Conditions: (a) KOtBu, EtOH, 79%; (b) hν, P(OMe)3, 64%; (c)
mCPBA, CH2Cl2, 76%; (d) (i) N,N-dimethylcarbamoyl chloride, CH2Cl2;
(ii) TMSCN, room temp; (e) 1,2-dichloroethane, reflux, 54% (over three
steps); (f) H2, Pd/C catalyst, HOAc, quantitative; (g) HC(O)OMe, Et3N,
reflux, 68%; (h) POCl3, toluene, 80 °C, 61%; (i) MeI, THF, 60 °C, 87%;
(j) Ag2O, CH2Cl2; (k) [(cod)RhCl]2, 71%; (l) CO, THF, 92%.
Gratifyingly, however, 13 underwent a thermal 6π-electro-
cyclization/elimination process when refluxed in 1,2-dichloro-
ethane, thus furnishing 14 in respectable overall yield.10 Routine
operations then allowed us to elaborate this compound into 16, a
planar chiral analogue of the known imidazo[1,5-a]pyridinium salts
5.13 Reaction of 16 with Ag2O followed by transmetallation with
[RhCl(cod)]2 readily gave the planar chiral rhodium complex 17
(Figure 1, right).
To assess the donor properties of the new carbene, 17 was
converted to the corresponding carbonyl complex 18. The stretching
frequency of its trans-CO ligand at ν˜ ) 1989 cm-1 indicates that
the donor capacity of this novel planar chiral ligand rivals or even
exceeds that of all other diamino-stabilized, five-membered NHC’s
known to date.2c Equally striking is the fact that the incremental
gain in donor strength, expressed as ∆ν˜, in going from 5 to 18 is
substantially higher than the effect of ring-annulation upon formal
conversion of the parent compound 4 into imidazopyridin-ylidene
5. By virtue of the through-space interaction between the carbene
Figure 1. Molecular structures of 13 and 17 in the solid state.
unit and the aromatic lid of the cyclophane in juxtaposition, the
new ligand actually resembles the more basic carbenes with 6-
membered or acyclic skeletons in electronic terms (cf. Scheme 1).2c
Next, we set out to probe whether remote electronic variations
can be transmitted within the cyclophane scaffold. To this end, we
prepared the tetramethoxy and the tetrafluoro analogues 19 and 22
by adaptation of the synthesis pursued en route to 18.12 As might
be expected from literature data,14 the donor ability of the
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10.1021/ja076028t CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
appropriate substituent R1 on top of the bound metal center as shown
in the generic structure 27, such that the chiral binding pocket is
clearly defined. Work in this laboratory is ongoing to exploit these
structural features. Thereby, the basic nitrogen in, e.g., 14 or 15
provides opportunities for the separation of the enantiomers by
conventional means. Moreover, we were able to obtain the
imidazolium salt 16 in optically pure form by preparative HPLC.12,17
Chart 1. Tetramethoxycarbene-Rh Complex 19 and
Conformational Preference of the Related Cyclophane 2014
Chart 2. Fluorinated Planar Chiral Rh-Carbene Complexes and
Overlay of the Molecular Crystal Structure of the Fluorinated
Carbene Part of 21 (Yellow) and its Non-fluorinated Counterpart in
17 (Blue)12
Acknowledgment. Financial support by the DFG, the Fonds
der Chemischen Industrie, and the Spanish Ministerio de Educacio´n
y Ciencia (fellowship to M.A.) is gratefully acknowledged.
Supporting Information Available: Additional reference data,
Experimental Section, and copies of the NMR spectra. This material
is available free of charge via the Internet at http://pubs.acs.org.
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22 is very significantly shifted (ν˜ ) 2004 cm-1), thus revealing
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of the carbene underneath. The remote fluorination overcompensates
the effects induced by ring annulation as well as cyclophane
formation, rendering the carbene unit in 22 even less electron-
donating than the parent compound 5. Since fluorine closely mimics
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In addition to the remote control over the donor abilities, the
planar chiral structure of the NHC ligands presented herein deserves
further comment. Although a host of chiral NHC’s has been
presented in the literature,1,15 planar chiral ones are scarce and
limited to cases such as 23-26 in which an NHC is merely attached
to a planar chiral entity (Chart 3).16 In contrast to such a tangling
arrangement, the NHC in 17-22 constitutes an integral part of the
stereogenic unit, which largely consists of π-bonds and is hence
distinctly more rigid and conformationally preorganized. Further-
more, the new ligand design allows one to precisely position an
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