A novel fluorinated gold(I) N-heterocyclic carbene complex: Exploiting fluorine stereoelectronic effects to control molecular topology

Article abstract of DOI:10.1021/om100789n

The synthesis of a novel fluorinated Au(I) N-heterocyclic carbene is disclosed together with solid-state and solution-phase conformational analysis. The potential of the fluorine gauche effect [σ_C-H → σ*_C-F] for controlling the topology of catalytically relevant architectures is showcased by a representative NHC in which the C-F bond is β to the triazolium moiety.

Full text of DOI:10.1021/om100789n

4424 Organometallics 2010, 29, 4424–4427
DOI: 10.1021/om100789n
A Novel Fluorinated Gold(I) N-Heterocyclic Carbene Complex:
Exploiting Fluorine Stereoelectronic Effects To Control
Molecular Topology
Susann Paul, W. Bernd Schweizer, Marc-Olivier Ebert, and Ryan Gilmour*
€
Laboratory for Organic Chemistry, ETH Zurich, Honggerberg, Wolfgang-Pauli-Strasse 10,
8093 Zurich, Switzerland
Received August 13, 2010
Summary: The synthesis of a novel fluorinated Au(I) N-hetero-
cyclic carbene is disclosed together with solid-state and solution-
phase conformational analysis. The potential of the fluorine
gauche effect [σC-H f σ*C-F] for controlling the topology of
catalytically relevant architectures is showcased by a representa-
tive NHC in which the C-F bond is β to the triazolium moiety.
The highly polarized nature of the C-F bond, attributable
to the electronegativity of fluorine (χF ≈ 4), often elicits
intriguing physical and electronic properties.1 Importantly,
the low-lying σ*C-F antibonding orbital can readily interact
with adjacent, vicinal σ-bonds and nonbonding electron
pairs, resulting in the rich diversity of stereoelectronic effects
that are associated with organofluorine compounds.2-4
These stereoelectronic effects are necessarily accompanied
by conformational changes which, if used appropriately,
provide the foundations for effective preorganization stra-
tegies. Moreover, the small van der Waals radius of fluorine
coupled with its high bond strength to carbon (105.4 kcal
mol-1) render it an excellent, chemically inert steering group
for controlling molecular topology. However, of the numer-
ous fluorine conformational effects that are known, rela-
tively few have been consciously employed in the design of
catalytically relevant scaffolds with a view to modulating
reactivity (Figure 1).3-5 Early examples from this laboratory
include a dynamic gauche effect that is induced when chiral
secondary β-fluoroamines are condensed with R,β-unsatu-
rated aldehydes to form iminium ions, a concept that has
been successfully applied in enantioselective epoxidation
reactions,3 and the development of novel, conformationally
restricted surface modifiers for the asymmetric heteroge-
neous platinum-catalyzed hydrogenation of R-keto esters.4
Figure 1. Examples of the C-F bond being used in catalyst
design.3,4,5b
Scheme 1. Synthesis of 11 from Pyroglutamic Acid (5)
In order to expand the repertoire of this design approach, a
study of other catalyst architectures that might benefit from
having a β-fluoroamine-derived conformational restraint
embedded in the structure was initiated. N-heterocyclic
carbenes (NHCs) are excellent candidates, owing to their
synthetic versatility as both nucleophilic organocatalysts6
and ancillary ligands for an array of metals.7 In particular,
recent advances in gold catalysis have challenged our pre-
conceptions of the synthetic potential of this noble metal.8
The Lewis acidity of cationic Au(I) complexes, the associated
relativistic effects (expanded 5d and contracted 6s orbitals),
and its resistance to oxidation endow gold complexes with
unique reactivity. Furthermore, gold chemistry can often be
performed in the presence of oxygen without detrimental
effects, and concerns pertaining to oxidation state shuttling
[Au(I) T Au(III)] can be largely dismissed. Recently, Rovis
*To whom correspondence should be addressed. E-mail: ryan.gilmour@
org.chem.ethz.ch. Tel: þ41 44 632 79 34.
(1) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308.
(2) For selected examples see: (a) O’Hagan, D.; Bilton, C.; Howard,
J. A. K.; Knight, L.; Tozer, D. J. J. Chem. Soc., Perkin Trans. 2 2000,
605. (b) Briggs, C. R. S.; O'Hagan, D.; Howard, J. A. K.; Yufit, D. S. J.
Fluorine Chem. 2003, 119, 9. (c) Briggs, C. R. S.; Allen, M. J.; O'Hagan, D.;
Tozer, D. J.; Slawin, A. M. Z.; Goeta, A. E.; Howard, J. A. K. Org. Biomol.
Chem. 2004, 2, 740. (d) Gooseman, N. E. J.; O'Hagan, D.; Slawin, A. M. Z.;
Teale, A. M.; Tozer, D. J.; Young, R. J. Chem. Commun. 2006, 3190.
(e) Gooseman, N. E. J.; O'Hagan, D.; Peach, M. J. G.; Slawin, A. M. Z.; Tozer,
D. J.; Young, R. J. Angew. Chem., Int. Ed. 2007, 46, 5904.
(3) Sparr, C.; Schweizer, W. B.; Senn, H. M.; Gilmour, R. Angew.
Chem., Int. Ed. 2009, 48, 3065.
(4) Mondelli, C.; Bucher, C.; Baiker, A; Gilmour, R. J. Mol. Catal. A:
Chem. 2010, 327, 87. Also see: Bucher, C.; Sparr, C.; Schweizer, W. B.;
Gilmour, R. Chem. Eur. J. 2009, 15, 7637.
(5) (a) Marson, C. M.; Melling, R. C. J. Org. Chem. 2005, 70, 9771.
(b) DiRocco, D. A.; Oberg, K. M.; Dalton, D. M.; Rovis, T. J. Am. Chem.
Soc. 2009, 131, 10872.
(6) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534. Marion,
N.; Díez-Gonzalez, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988.
Enders, D.; Niemeier, O.; Henseller, A. Chem. Rev. 2007, 107, 5606.
(7) See the themed issue on “N-Heterocyclic Carbenes” in Dalton
Trans. 2009, 35, 6873-7316. Raubenheimer, H. G.; Cronje, S. Chem.
Soc. Rev. 2008, 37, 1998.
ꢀ
r
pubs.acs.org/Organometallics
Published on Web 09/22/2010
2010 American Chemical Society

Communication
Organometallics, Vol. 29, No. 20, 2010 4425
Table 1. Selected X-ray Data for Compounds 8, 11, 16, and 13
a Dimeric species. Pentane was omitted for clarity. b Only one of the two symmetry-independent molecules in the unit cell is shown for clarity.
reported on the enhanced performance of NHC-based
Stetter organocatalysts upon fluorination of the bicyclic
core (Figure 1, lower).5b In contrast, we sought to probe the
utility of the C-F bond in restricting the relative conforma-
tional freedom of a model Au(I) NHC bearing a pendant
(diphenylfluoro)methyl moiety (Figure 1, right). Key to our
design was the installment of a C-F bond in a vicinal relation-
ship to the azolium nitrogen atom at the ring junction. We
envisaged that the fluorine would adopt an antiperiplanar
alignment to the vicinal C-H bond such that hyperconjugative

4426 Organometallics, Vol. 29, No. 20, 2010
Paul et al.
electron donation of the type [σC-H f σ*C-F] would be
operational, thus rigidifying the ancilliary ligand sphere and
efficiently shielding one face of the Au center. To test this
hypothesis, the NHC precursor 11 was prepared in a concise
six-step sequence from pyroglutamic acid (5) (Scheme 1).
The synthetic sequence began with esterification of the
starting acid 5 to form the methyl ester 6 (81% yield),
followed by the chemoselective double addition of phenyl-
magnesium bromide to generate carbinol 7.9 Deoxyfluorina-
tion of the tertiary alcohol using (diethylamino)sulfur
trifluoride (DAST) in CH2Cl2 at 0 ꢀC furnished the expected
β-fluoroamide derivative 8 as a solid. Gratifyingly, it was
possible to grow crystals of the fluoride that were suitable
for X-ray analysis, ultimately allowing the torsion angle
j
NCCF = -60.4ꢀ to be measured (Table 1).2a
Subsequent alkylation with the Meerwein salt followed by
successive treatment with phenylhydrazine and then methyl
orthoformate furnished the desired NHC precursor 11 in
excellent overall yield (47% over three steps). X-ray analysis
of this salt revealed a clear gauche orientation between the
C-F bond and the vicinal C-N bond (jNCCF = -54.0ꢀ,
Table 1), indicating that the delocalized positive charge of
the triazolium ring system is sufficient to induce structural
rigidification. Conversion of the tetrafluoroborate salt 11 to
the desired Au(I) NHC began with formation of the inter-
mediate silver complex 12 by treatment with Ag2O in
CH2Cl2. It should be noted that the formation of the bis-
NHC structure 12 is consistent with the findings of Wang
and Lin on related Ag(I)-carbene transfer agents.10 Finally,
transmetalation using AuCl(SMe2)11 furnished the desired
Au(I) species as a mixture of the mono- and bis-NHC species
13 and 14 (1.33:1). Interestingly, by simple counterion
exchange from the tetrafluoroborate (11) to the chloride
(15), it was possible to suppress formation of the bis-NHC
Ag(I) species 12 with the mono-NHC compound 16 being
isolated exclusively. This material was then smoothly pro-
cessed to give the Au(I)-NHC species 13 in 71% overall
yield (Scheme 2). Gratifyingly, it was possible to unambigu-
ously establish the molecular connectivities of both the Ag
and Au complexes (16 and 13, respectively) by single-crystal
diffraction analysis. The Ag(I) complex 16 crystallizes in the
orthorhombic space group P212121 with two symmetry-
independent molecules in the asymmetric unit cell. An
Figure 2. X-ray structures of complexes 16 (top) and 13 (bottom),
=
˚
3.31 A).
˚
showing the metallophilic interactions (dAg-Ag =3.12 A;dAu-Au
Scheme 2. Synthesis of Complex 13
˚
interatomic Ag-Ag distance of 3.12 A was measured, which
is indicative of a metallotropic interaction. Furthermore, the
NCCF dihedral angles in the solid state are jNCCF = -64.4
and -52.4ꢀ, as was predicted at the outset of this study.
Similarly, the Au(I) species 13 crystallizes in the same
orthorhombic space group as complex 16 (P212121) with
(8) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed. 2006,
45, 7896. F€urstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410.
Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395. Hashmi, A. S. K. Chem.
Rev. 2007, 107, 3180. Bongers, N.; Krause, N. Angew. Chem., Int. Ed.
2008, 47, 2178. Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev. 2008, 37,
1766. Marion, N.; Nolan, S. Chem. Soc. Rev. 2008, 37, 1776. Jimenez-
Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326, 3266. Gorin,
D. J.; Sherry, B. B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
Widenhoefer, R. A. Chem. Eur. J. 2008, 14, 5382. F€urstner, A. Chem.
Soc. Rev. 2009, 38, 3208. Shapiro, N. D.; Toste, F. D. Synlett 2010, 5, 675.
Sengupta, S.; Shi, X. ChemCatChem 2010, 2, 1. Hashmi, A. S. K.; Hengst,
T.; Lothsch€utz, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 1315.
(9) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett. 2008,
10, 277.
two symmetry-independent molecules in the asymmetric unit
cell. As in the case of the Ag(I) precursor, the X-ray analysis
revealed a relatively short Au-Au contact of 3.31 A and a clear
˚
gauche orientation of the fluorine with respect to the triazolium
ring system (jNCCF = -61.9 and -48.6ꢀ). The CR-Au-Cl
angles in the dimeric solid-state structure were found to be 175.8
and 177.0ꢀ, confirming the expected linear, binuclear coordina-
tion geometry of the gold center. Comparison of the CR-M
bond lengths in the Ag and Au complexes revealed only a slight
(10) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972.
ꢀ
(11) De Fremont, P.; Scott, N. M.; Stevens, E. D.; Nolan, S. P.
˚
difference (ΔAg-Au ≈ 0.1 A). It is noteworthy that the aurophilic
Organometallics 2005, 24, 2411.

Communication
Organometallics, Vol. 29, No. 20, 2010 4427
relationship can be calculated with15
xt ¼ ðÆJæ - JgÞ=ðJa - JgÞ
ð2Þ
For 3JCF consensus values of 1.2 Hz (Jg) and 11.2 Hz (Ja) are
3
reported in the literature.16 For JHF the corresponding
coupling constants were calculated to be 7.6 and 36 Hz,
respectively, using a modified Karplus relation.17 Indepen-
dently inserting the experimentally determined coupling
constants of 29 Hz (3JHF) and 2.6 Hz (3JCF) in eq 2 yields
populations of conformation I and II (Figure 3) of 75% and
14%, respectively. Recently a modified Karplus relation
based on DFT calculations was reported for vicinal coupling
constants between 1H and 13C.18 In the case of the substitution
pattern present in 13 this equation predicts significant deviation
of 3JCH from symmetry around jHCCC = 0ꢀ (Jþg = 0.3 Hz,
J-g = 2.7Hz, Ja= 4.2 Hz). Resorting to eq 1 and inserting 3JC1H
and 3JC2H, which are equal within the assumed error limits and
thus render stereoselective assignment dispensible, in a system of
two equations yields populations of 80% (I), 10% (II), and 10%
(III). These values are in good agreement with the populations
derived from JHF and JCF. The coupling constants for the
individual rotamers derived from Karplus equations are a known
source of systematic error.19 We therefore treat these results as a
qualitative finding, nevertheless clearly identifying rotamer I as
the dominant conformation in solution (jNCCF = 60ꢀ).
In summary, we have disclosed the synthesis and confor-
mational analysis of a novel fluorinated Au(I) NHC. By
inserting a C-F bond in a vicinal relationship to the triazo-
lium nitrogen atom at the ring junction, it has been possible
to control the relative molecular topology of the flanking
diphenylfluoromethyl group and the core scaffold by means
of a stabilizing hyperconjugative interaction.
Figure 3. Conformational analysis of 13 in the solution phase.
interaction that is observed in the solid-state analysis of complex
˚
13 (dAu-Au =3.31A) is frequently observed in closed-shell Au(I)
systems (5d10) and other transition-metal complexes.12 Intrigu-
ingly, the interatomic distance is marginally longer than that of
˚
the Ag(I) precursor (dAg-Ag = 3.12 A), which also displays a
clear interaction between the metal centers (Figure 2). This
shorter argentophilic interaction as compared to the aurophilic
interaction is consistent with a recent report from Ghosh and co-
workers, who observed similar differences in metallophilicity
when comparing dimeric Au and Ag N-heterocyclic carbenes.13
To complement the crystallographic investigation, we then
performed a solution-phase conformational analysis of 13 by
NMR spectroscopy. Initial studies revealed a low-field 13C-
{1H} NMR shift of the carbenic carbon at 171.3 ppm (100
MHz, CDCl3) and a 19F NMR signal at -168.2 ppm (376
MHz, CDCl3). Assuming that only staggered conformations
are significantly populated in solution, the observed
vicinal coupling constant ÆJ æ between two nuclei sitting at
tetrahedral carbons flanking a rotatable bond can be de-
scribed by
3
3
ÆJæ ¼ x1J1 þ x2J2 þ x3J3
ð1Þ
where Ji values are the individual couplings of the three
rotamers and xi values are their molar fractions. If the Ji
values are known independently and at least two vicinal
coupling constants can be measured, then the rotamer
populations can be determined. Very often, however, the
function relating the dihedral angle between two nuclei to the
corresponding coupling constant is approximately sym-
metric around zero.14 Assuming that the three rotamers
can be described by dihedral angles of 60ꢀ (þgauche), -60ꢀ
(-gauche), and 180ꢀ (anti) then the following expression
holds, Jþg = J-g = Jg. In this case the molar fraction xa of
the conformer in which these two nuclei are in an anti
Acknowledgment. We gratefully acknowledge generous
financial support from the Alfred Werner Foundation
€
(assistant professorship to R.G.) and the ETH Zurich.
Supporting Information Available: Text, figures, tables and
CIF files giving synthetic and spectroscopic data for compounds
6, 7, 8, 11, 12, 13, 15, and 16, crystallographic data for 8, 11, 13,
and 16 and a detailed solution-phase NMR analysis of 13. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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