Carbenes stabilized by ylides: Pushing the limits

Article abstract of DOI:10.1002/anie.200803200

(Chemical Equation Presented) Being neighborly: The concept of placing two reactive intermediates next to each other to gain stability is borne out in amino(ylide)carbenes (AYCs). Different kinds of ylides stabilize an adjacent singlet carbene by donation

Full text of DOI:10.1002/anie.200803200

Communications
DOI: 10.1002/anie.200803200
Carbenes
Carbenes Stabilized by Ylides: Pushing the Limits**
Alois Fꢀrstner,* Manuel Alcarazo, Karin Radkowski, and Christian W. Lehmann
Dedicated to Professor Manfred T. Reetz on the occasion of his 65th birthday
The most successful strategies for taming carbenes consist of
coordination to a transition-metal fragment and/or the
attachment of heteroatoms to their formally divalent carbon
atom.[1] The latter concept was particularly successful for
nitrogen as the heteroelement and has resulted in the
numerous variants of (di)aminostabilized carbenes with
cyclic and acyclic backbones known to date.[2] It is the overlap
of the lone pair of electrons on the nitrogen atom with the
empty p orbital of the carbene which is essential for stabiliz-
ing the reactive site (Figure 1).[2]
In fact, metal complexes containing such (amino)-
(ylide)carbene (AYC) ligands have been known for a long
time, but have had little impact compared with their
(di)aminostabilized relatives.[3,4] Such AYC ligands were
prepared by base-induced cyclization of transition-metal
isocyanide complexes B bearing a latent phosphorus ylide in
the vicinity (Scheme 1).[4] However, this method invariably
Scheme 1. Known entries into metal–AYC complexes: a) M=[PtCl2-
(PR3)], Et3N (excess), R=H; or M=[W(CO)5], Na[N(SiMe3)2], R=H;
b) M=[Rh(cod)Cl], mesityllithium, R=Me; or M=[PdI(allyl)], tBuOK,
R=Me. cod=1,5-cyclooctadiene.
delivered AYCs with an indole skeleton featuring an unpro-
tected NH group (A, R = H), and the efficiency of cyclization
was found to be strongly dependent on the nature of the
involved metal fragment. Importantly, Kawashima and co-
workers reported earlier this year that deprotonation of a
suitable phosphonium salt precursor C provides a comple-
mentary route to metal–AYC complexes, even though it was
again an indole nucleus which served as proof of principle (A,
R = Me).[5] We report herein a generalizion of the underlying
concept.[3–6] Moreover, we demonstrate the remarkable donor
ability of such ligands and show for the first time that
uncomplexed AYCs can be sufficiently stable to be observed
as discrete entities in solution.
Since all the AYCs reported to date incorporate a
phosphorus ylide motif,[3–5] we first investigated if other
types of ylides are also capable of stabilizing an adjacent
carbene center. To this end, N-methylindole (1) was treated
with diphenylsulfoxide and trifluoroacetic acid anhydride to
give sulfonium salt 2[7] as a crystalline compound after
exchange of the counterion for BF4ꢀ (Scheme 2). Subsequent
deprotonation with KHMDS in the presence of [{RhCl-
(cod)}2] furnished the desired AYC–rhodium complex 3
embodying a sulfur ylide motif.[8] Complex 3 was then
transformed into the carbonyl analogue 4 under standard
conditions.
Figure 1. Basic structure of an N-heterocyclic carbene (NHC) as a
prototype singlet carbene stabilized by two flanking amino groups
(X=CH, N; R=alkyl, aryl). The formal replacement of one NR unit by
an ylide leads to an archetype (amine)(ylide)carbene (AYC) species.
Under this premise, other chemical entities with a lone
pair of electrons disposed in an orbital of appropriate
symmetry might serve the exact same purpose. The polarized
p bonds of ylides are suitable candidates in this regard. Thus,
the formal replacement of one (or both) N atoms of a
prototype N-heterocyclic carbene (NHC) by ylide moieties
leads to constructs which owe their stability to a combination
of two very reactive sites (Figure 1). As the p-donating
capacity of an ylide, however, arguably exceeds that of a
nitrogen atom while the inductive effect should be smaller,
one might expect such compounds to exhibit particularly
pronounced electron-releasing capacities and hence to be of
considerable interest as ancillary ligands for homogeneous
catalysis.
[*] Prof. A. Fꢀrstner, Dr. M. Alcarazo, K. Radkowski, Dr. C. W. Lehmann
Max-Planck-Institut fꢀr Kohlenforschung
45470 Mꢀlheim an der Ruhr (Germany)
Fax: (+49)208-306-2994
The structures of the carbene precursor 2 (Figure 2) and
the rhodium complex 3 (Figure 3) are highly instructive.[9]
Specifically, the analysis of the bond lengths in 2 reveals a
significant degree of charge delocalization of the sulfonium
moiety into the heterocyclic ring. This is expressed in the
E-mail: fuerstner@mpi-muelheim.mpg.de
[**] Generous financial support from the MPG, the Spanish Ministerio
de Educaciꢁn y Ciencia (fellowship for M.A.), and the Fonds der
Chemischen Industrie is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803200.
ꢀ
ꢀ
lengthening of the C1 C2 bond and the shortening of the N1
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Figure 3. Structure of complex 3 in the solid state.[9]
complexes 5 and 6, respectively, synthesized by Kawashima
and co-workers.[5]
Scheme 2. Preparation and structural characteristics of an AYC incor-
To further generalize the concept, we investigated if
backbones other than indoles are also able to contain ylide-
stabilized carbenes.[5b] To this end, the readily available
vinamidinium salt 9[13] was treated with two different mono-
substituted hydrazines to give compounds 11a,b in good
yields (Scheme 3).[14,15] The structure of 11a (R = Ph) in the
solid state (Figure 4), however, suggests that the mesomeric
extreme 11a’ gains importance, wherein the positive charge
largely resides on the lateral phosphonium entity. Even
though this fact might argue against deprotonation at the
carbon atom, treatment of 11a with KHMDS at ꢀ788C
furnished the corresponding AYC 12 (R = Ph) which is
sufficiently stable for direct observation. This fact is remark-
able in view of the unsuccessful attempts of Kawashima and
co-workers to observe the analogous AYC derived from
indolic precursors of type C.[5] The most indicative spectro-
scopic features are the loss of the saltꢀs acidic proton (d =
8.91 ppm) and the appearance of the characteristic 13C
resonance of the resulting carbene center at d = 218 ppm
(JC,P = 51.2 Hz).
porating a sulfur ylide. Reagents and conditions: a) 1. trifluoroacetic
=
acid anhydride, Ph2S O, CH2Cl2, ꢀ308C!RT; 2. aq sat. NaBF4, 44%;
b) KHMDS, [{RhCl(cod)}2], THF, ꢀ788C!RT, 18%; c) CO (1 atm),
THF, 52%.
Figure 2. Structure of 2 in the solid state.[9]
The fact that 12 reacts with sulfur to give thioamide 13
provides chemical evidence for its carbene character
(Scheme 3). Moreover, 12 can be intercepted with [{RhCl-
(cod)}2] in high yield. The structural attributes of the resulting
complex 14a (R = Ph) are again consistent with the view that
the ligand constitutes an amino(ylide)carbene (Figure 5 and
Scheme 3).[9] Since the N-methylated salt 11b converted
similarly well into complex 14b (R = Me), it is clear that steric
shielding by a bulky N substituent plays only a subordinate
role, if any, in the stabilization of a transient AYC of this type.
The exceptional donor qualities of 12 are highlighted by
comparison with the otherwise closely related triazole-2-
ylidene ligand commonly employed in organic and organo-
metallic catalysis.[2,16] Specifically, the unsymmetrical stretch-
ing mode of the CO groups of the rhodium complex 15
appears at a frequency no less than 44 cmꢀ1 lower than that of
the triazolyl-2-ylidene complex 16, which indicates that the
formal replacement of a single N atom in the heterocycle by
C1 bond relative to those in the parent compound indole.[10]
The substantial contribution of the mesomeric form 2’
(Scheme 2) to the ground-state structure is also visible in
ꢀ
the C2 S1 distance, which is much shorter than the corre-
sponding bonds between the sulfur atom and the equally sp2-
hybridized ipso-C atoms of the phenyl substituents. This
substantial transmission of charge into the ring predisposes
the salt for deprotonation at C1.
The carbene character of the resulting AYC transpires
from the structural features of its rhodium complex 3
(Figure 3 and Scheme 2) In addition to the distinctive pattern
of bond lengths in the heterocyclic segment, the diminished
N1-C1-C2 angle of only 105.238 (compared to 109.178 in 2)
constitutes a particularly characteristic feature.[11] Overall, the
available X-ray diffraction data and spectroscopic proper-
ties[12] illustrate that 3 and 4 are close relatives of AYC
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Figure 5. Structure of complex 14a (R=Ph) in the solid state.[9]
tionally strong electron-releasing ligands, unmistakably sur-
passing the traditional NHCs in this regard.
=
Next, it was probed if polarized C C bonds also lend
themselves to the stabilization of vicinal carbene
a
(Scheme 4). In recognition of the ylidic character innate to
Scheme 3. Reagents and conditions: a) HC(NMe2)(OEt)2, reflux, 92%;
b) DMF, POCl3, then aq sat. NaBF4, 708C, 81%; c) PhNHNH2, MeCN,
reflux, 68%; d) MeCN, 1808C (microwaves), 88% (11a, R=Ph); or
MeNHNH2, MeCN, reflux, 68% (9!11b, R=Me); e) KHMDS, THF,
ꢀ788C; f) S8, THF, ꢀ788C!RT, 65%; g) [{RhCl(cod)}2], THF,
ꢀ788C!RT, 88% (R=Ph), 92% (R=Me); h) CO (1 atm), THF, 79%
(R=Ph).
Scheme 4. Reagents and conditions: a) HC(NMe2)(OEt)2, reflux, 94%;
b) 1. DMF, POCl3 708C; 2. aq sat. NaBF4, 73%; c) PhNHNH2, MeCN,
1808C, microwaves, 81%; d) KHMDS, S8, THF, ꢀ788C!RT, 55%.
ene-1,1-diamines,[17] compound 20 was designed as a potential
progenitor. Even though its structure in the solid state
(Figure 6)[9] suggests the imidazolium resonance form 20’ to
be the dominant mesomeric extreme (see, for example, the
ꢀ
long C1 C7 bond (1.454(3) ꢁ)), the fact that the two rings are
Figure 4. Structure of 11a in the solid state.[9]
close to coplanarity (N1-C1-C7-C6 = 26.358) might allow for
sufficient electronic cross-talk to render deprotonation at C6
feasible. In fact, treatment of 20 with KHMDS in THF
generates a reactive intermediate that shows its carbene
nature upon reaction with admixed sulfur to give thioamide
22. Attempts to trap the transient carbene 21 with [{RhCl-
(cod)}2], however, were only partly successful. Although MS
inspection of the crude product indicated formation of the
the phosphorus ylide has tremendous electronic implications.
This fact is fully appreciated if one recalls that even
substantial structural variations of conventional five-mem-
bered NHCs engender only minor spectroscopic changes.[12]
Overall, the recorded IR data characterize AYCs as excep-
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[1] Carbene Chemistry. From Fleeting Intermediates to Powerful
Reagents (Ed.: G. Bertrand), Dekker, New York, 2002.
[2] a) A. J. Arduengo, Acc. Chem. Res. 1999, 32, 913 – 921; b) D.
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[3] In a formal sense, carbenes stabilized by a phosphorus ylide were
first prepared by reaction of [M(CO)6] (M = Cr, Mo, W) or
Figure 6. Structure of the complex cation of 20 in the solid state (only
one of the two crystallographically independent molecules in the unit
cell is depicted); the BF4ꢀ counterion is omitted for clarity.[9]
=
related carbonyl complexes with R3P CH2 followed by O-
desired complex, we were not able to obtain this rather
sensitive product in analytically pure form.
alkylation(silylation) of the resulting intermediates. However,
all available spectroscopic and structural data show that these
products must not be interpreted as (phosphorus ylide)carbene
complexes I, but constitute phosphoniovinyl metal complexes II.
In an attempt to stabilize such a metal–AYC complex
containing a “carbon ylide”, the corresponding N-pyridyl
derivative 23 was treated with [Pd(acac)2].[18] Much to our
delight, the resulting chelate complex 24 could be isolated in
appreciable yield by flash chromatography (Scheme 5).
For pioneering studies, see the following and literature cited
therein: a) W. C. Kaska, D. K. Mitchell, R. F. Reichelderfer,
W. D. Korte, J. Am. Chem. Soc. 1974, 96, 2847 – 2854; b) S.
Voran, H. Blau, W. Malisch, U. Schubert, J. Organomet. Chem.
1982, 232, c33 – c40; c) N. E. Kolobova, L. L. Ivanov, O. S.
Zhvanko, I. N. Chechulina, A. S. Batsanov, Y. T. Struchkov, J.
Organomet. Chem. 1982, 238, 223 – 229; d) W. Malisch, H. Blau,
U. Schubert, Chem. Ber. 1983, 116, 690 – 709.
Scheme 5. Reagents and conditions: a) 2-pyridyl-NHNH2, MeCN,
1808C (microwaves), 76%; b) [Pd(acac)2], C6H5Cl, 1608C, 58%.
acac=acetylacetonoate.
[4] a) G. Facchin, R. Campostrini, R. A. Michelin, J. Organomet.
Chem. 1985, 294, c21 – c25; b) R. A. Michelin, G. Facchin, D.
Braga, P. Sabatino, Organometallics 1986, 5, 2265 – 2274;
c) R. A. Michelin, M. Mozzon, G. Facchin, D. Braga, P. Sabatino,
J. Chem. Soc. Dalton Trans. 1988, 1803 – 1811; d) G. Facchin, M.
Mozzon, R. A. Michelin, M. T. A. Ribeiro, A. J. L. Pombeiro, J.
Chem. Soc. Dalton Trans. 1992, 2827 – 2835; e) M. Tamm, F. E.
Hahn, Coord. Chem. Rev. 1999, 182, 175 – 209.
Importantly, this example also showcases that the widely
practiced method for the preparation of metal–NHC com-
plexes by reaction of a precursor salt with a suitable metal
reagent carrying (weakly) basic counterions[2] also pertains to
the AYC arena. It is expected that this gentle way of
generating transient carbenes will foster systematic explora-
tions of this emerging class of ligands.
[5] a) S. Nakafuji, J. Kobayashi, T. Kawashima, Angew. Chem. 2008,
120, 1157 – 1160; Angew. Chem. Int. Ed. 2008, 47, 1141 – 1144;
b) for
a recent extension to a pyrrole-based (amino)bis-
In summary, carbenes stabilized by one nitrogen atom and
one ylide (AYCs) constitute a promising class of neutral two-
electron donor ligands. They can be generated by an opera-
tionally simple deprotonation route and are available in many
different structural formats. Since various kinds of ylides and
heterocyclic scaffolds were shown to be effective, further
studies into the conceivable structural space are promising.
Applications of AYCs in catalysis also deserve scrutiny, given
their outstanding donor abilities compared with the com-
monly used NHC counterparts.
(ylide)carbene, see: M. Asay, B. Donnadieu, A. Baceiredo, M.
Soleilhavoup, G. Bertrand, Inorg. Chem. 2008, 47, 3949 – 3951.
[6] In a formal sense, AYCs are a subtype of the cyclic (alkyl)ami-
nocarbenes (CAACs), which are also strong donors, see: a) V.
Lavallo, Y. Canac, C. Prꢄsang, B. Donnadieu, G. Bertrand,
Angew. Chem. 2005, 117, 5851 – 5855; Angew. Chem. Int. Ed.
2005, 44, 5705 – 5709; b) V. Lavallo, Y. Canac, A. DeHope, B.
Donnadieu, G. Bertrand, Angew. Chem. 2005, 117, 7402 – 7405;
Angew. Chem. Int. Ed. 2005, 44, 7236 – 7239; c) J. Vignolle, H.
Gornitzka, B. Donnadieu, D. Bourissou, G. Bertrand, Angew.
Chem. 2008, 120, 2303 – 2306; Angew. Chem. Int. Ed. 2008, 47,
2271 – 2274; d) V. Lavallo, G. D. Frey, B. Donnadieu, M.
Soleilhavoup, G. Bertrand, Angew. Chem. 2008, 120, 5302 –
5306; Angew. Chem. Int. Ed. 2008, 47, 5224 – 5228.
Received: July 2, 2008
Published online: September 22, 2008
[7] Prepared according to: K. Hartke, D. Teuber, H.-D. Gerber,
Tetrahedron 1988, 44, 3261 – 3270.
[8] The rather low yield is due, in part, to the limited stability of the
complex during flash chromatography.
Keywords: carbenes · heterocycles · ligands · rhodium · ylides
.
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[9] Anisotropic displacement parameters are drawn at the 50%
[12] For a discussion of the different “scales” commonly used to
assess the donor properties of ligands and a compilation of IR
data for complexes of type [RhL(CO)2Cl], see: A. Fꢃrstner, M.
Alcarazo, H. Krause, C. W. Lehmann, J. Am. Chem. Soc. 2007,
129, 12676 – 12677 and its Supporting Information .
[13] R. Gompper, E. Kujath, H.-U. Wagner, Angew. Chem. 1982, 94,
559 – 560; Angew. Chem. Int. Ed. Engl 1982, 21, 543 – 544.
[14] Hydrazones 10 can, but need not, be isolated. For the structure
of compound 10a in the solid state, see the Supporting
Information.
[15] Whereas the reaction with MeNHNH2 in refluxing MeCN is
highly efficient, the condensation with PhNHNH2 is best carried
out under microwave irradiation. Under these conditions, the
conversion of 9 into 11a (R = Ph) can be performed in one pot.
[16] D. Enders, K. Breuer, G. Raabe, J. Runsink, J. H. Teles, J.-P.
Melder, K. Ebel, S. Brode, Angew. Chem. 1995, 107, 1119 – 1122;
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[17] A. Fꢃrstner, M. Alcarazo, R. Goddard, C. W. Lehmann, Angew.
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probability level, hydrogen atoms have been omitted for clarity.
CCDC 692803 (2), 692804 (3), 692800 (10a), 692801 (11), 692805
(14), and 692802 (20) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. The structure of 10a in
the solid state as well as short summaries of the crystallographic
data can be found in the Supporting Information of this paper.
[10] Reference bond lengths: F. H. Allen, O. Kennard, D. G. Watson,
L. Brammer, A. G. Orpen, R. Taylor, J. Chem. Soc. Perkin Trans.
2 1987, S1 – S19.
[11] NHCs in free and complexed form are distinguished by small N-
C-N angles, see Ref. [2] for pertinent reviews and the following
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J. R. Goerlich, D. Khasnis, W. J. Marshall, T. K. Prakasha, J. Am.
Chem. Soc. 1997, 119, 12742 – 12749; d) for pertinent examples
from our research group, see: A. Fꢃrstner, H. Krause, L.
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[18] Inspiration was provided by: a) N. A. Piro, J. S. Owen, J. E.
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