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Journal ArticleDOI

Beyond Conventional N-Heterocyclic Carbenes: Abnormal, Remote, and Other Classes of NHC Ligands with Reduced Heteroatom Stabilization

30 Mar 2009-Chemical Reviews (American Chemical Society)-Vol. 109, Iss: 8, pp 3445-3478
TL;DR: The present account is mainly directed toward the impact of these still unusual metal-carbene bonding modes on the electronic properties and on the new catalytic applications that have been realized by employing such new carbene complexes.
Abstract: N atom, thus providing carbenes derived from pyrazolium, isothiazolium, and even quinolinium salts that contain a stabilizing heteroatom in a remote position (G-J in Figure 1). Recently, carbenes such as K, which are comprised of only one heteroatom and lack delocalization through the heterocycle, have been discovered as versatile ligands, thus constituting another important class of carbenes with low heteroatom stabilization. Both the synthesis of the organometallic complexes of these ligands as well as the (catalytic) properties of the coordinated metal centers generally show distinct differences, compared to the more classical NHC complexes, such as C2-metallated imidazolylidenes. This review intends to describe such differences and highlights the chemical peculiarities of these types of N-heterocyclic carbene complexes. It introduces, in a qualitative manner, the synthetic routes that have been established for the preparation of such complexes, covering the literature from the very beginning of activities in this area up to 2008. While specialized reviews on some aspects of the present topic have recently appeared,7 a comprehensive overview of the subject has not been available thus far. Rather than just being descriptive, the present account is mainly directed toward the impact of these still unusual metal-carbene bonding modes on the electronic properties and on the new catalytic applications that have been realized by employing such new carbene complexes. As a consequence of our focus on complexes with less-stabilized heterocyclic ligands, systems comprising acyclic carbenes have not been included, and the interested reader is, instead, referred to the pioneering and

Summary (8 min read)

1. Introduction

  • The organometallic chemistry of N-heterocyclic carbenes (NHCs) has experienced explosive development during the last few years, and the topic remains the main focus of many outstanding research programs.
  • Rather dormant in the beginning of the new millennium, the concept of heterocyclic carbene ligands that are not stabilized by two adjacent heteroatoms, as in Arduengo-type carbenes, and also not necessarily with heteroatoms placed in a position R to the carbene carbon was revived by a serendipitous discovery of C4 bonding in imidazolylidenes.
  • Terms such as "wrong way", "abnormal", "unusual", or "nonclassical" have been used to describe C4/C5-bound imidazolylidenes (B). 11 A final preliminary remark concerns the controversial classification of all these ligands as "carbenes".
  • When bonded, this negative charge is obviously transferred to the metal in one canonical form.

2. Methods of Ligand Complexation

  • A variety of different methods have been established for the complexation of less-heteroatom-stabilized NHC ligands.
  • Some of these methods are very similar to those yielding normal C2-bound imidazolylidene complexes, while others are unique to a particular subclass of NHC ligands.
  • Further details are provided in this section, which has been organized according to the different ligand systems involved, rather than according to the methods used.

2.1.1. C-H Bond Activation of Unsubstituted 2H-Imidazolium Salts

  • The coordination mode was deduced from NMR spectroscopy and was unambiguously confirmed by X-ray crystallographic analysis.
  • Hence, product formation seems to be kinetically controlled.
  • 19 Such mechanistic proposals were further supported by experimental data, which demonstrate that product distributionsand, thus, the site of metallationsis strongly anion-dependent.
  • Notably, chelation of the pyridine moiety is not essential and similar selectivities in C-H bond activation have been observed with simple imidazolium salts upon reaction with [IrH 5 (PPh 3 ) 2 ] in the presence of pyridine.
  • The trans orientation of the two carbene ligands seems to play a decisive role for C4 bonding.

2.1.2. C-H Bond Activation of C2-Substituted Imidazolium Salts

  • Which may be particularly relevant for in situ complex formation, unprotected imidazolium salts are primarily metallated at the C2position.
  • The C4-bound carbene is significantly more prone to reductive elimination than the C2-bound IMes ligand, leading to the exclusive formation of the imidazolium salt 16 and C4-bound carbene metal complexes can also be made by transmetallation from the corresponding silver complexes.
  • IR spectroscopy of this dicarbonyl complex allows for an estimation of the electron-donating ability of such C4-bound carbenes.
  • 33, 34 While yields are generally low, product formation at room temperature indicates that the stability of the Ag complex may be sufficiently high to provide access to the desired product.
  • 39 The metallation, using [Rh(cod)Cl] 2 , proceeded considerably better when the reaction was performed in the presence of air and potassium iodide (KI) as well as acetate.

2.1.3. Coordination to Free Carbenes

  • Normal C2-bound imidazolylidene metal complexes are often synthesized by a stepwise procedure that first includes the generation of a free carbene from the azolium salt with a strong base and subsequent metal coordination.
  • In most instances, C4 metallation has been an unexpected result and rational protocols are not available.
  • Copper complexes that contain nonclassical C4-bound carbene ligands have been isolated from the reaction of copper(I) salts with the tripodal carbene ligand 43 (see Scheme 16).
  • The steric bulk imposed by the nitrogen substituents has been identified as a major driving force for this carbene rearrangement.

2.1.4. Oxidative Addition

  • As early as 1973, Stone and co-workers introduced the oxidative addition of thiazolium salts to low-valence metal fragments as a route to carbene complexes.
  • Accordingly, the oxidative addition of 4-haloimidazolium salts also represents a rational access to C4-metallated carbenes.
  • The potentially chelating ligand precursors 54 were prepared by sequential regioselective H-substitution and N-alkylation of iodoimidazole.
  • Oxidative addition to zerovalent Pd(dba) 2 then afforded the corresponding complexes 55 that carry abnormal carbenes (see Scheme 21).

2.2. Triazolylidene Complexes

  • The formation of carbene ligands with reduced neighboring heteroatom stabilization has recently been demonstrated when 1,2,3-triazolium salts were used as ligand precursors.
  • Nitrogen alkylation of the 1,4-disubstituted triazols 56 at the N3-position gives compounds 57 as precursors for abnormal carbene bonding (while N2-alkylation would provide normal carbene precursors; see Scheme 22).
  • Metallation of triazolium salts (57) via C-H bond activation using Pd(OAc) 2 or Ag 2 O, and subsequent transmetallation of the silver carbene complex with ruthenium(II), iridium(I), and rhodium(I) has been demonstrated.
  • A preliminary assessment of the donor strength of these 1,2,3-triazolylidene ligands has been accomplished, based on the ν CO stretching frequences of the iridium dicarbonyl complex 59a.
  • The resulting Tolman electronic parameter 29, 53 compares well with those of the most basic normal carbenes (cf. also 19b; recall Scheme 7).

2.3. Pyrazolylidene and Isothiazolylidene Complexes

  • Similar to imidazolium-derived carbenes, pyrazolium metallation may give either normal or abnormal carbene ligands.
  • In normal C3-bound carbenes, a single N atom is located adjacent to the carbene carbon, which may increase the donor properties of these ligands, compared to normal C2-imidazolylidenes.
  • In abnormal C4-bound carbenes, only remotely located heteroatoms are available for carbene stabilization .
  • Different routes to normal C3-bound pyrazolyidenes have been disclosed.
  • The properties of the corresponding complexes reveal that this type of ligand indeed is complementary in many respects to its imidazolylidene counterpart.

2.3.1. C-H Bond Activation

  • The pyrazolylidene complexes 64 were made via thermolysis of the pyrazolium salt of the decacarbonyl dimetallates 63 (see Scheme 23).
  • N-dimethylimidazol-2-ylidene (IMe) ligand, cis-(IMe) 2 Mo(CO) 4 , readily undergoes photochemical trans isomerization, complex 65 is inert toward such a rearrangement.
  • This may be a consequence of the larger trans effect exhibited by the carbene ligand in 65.
  • The trans influence is similar, i.e., the crystallographically determined metal-carbonyl bonds in the Cr complex 64b and (IMe)Cr(CO) 5 are of equal length (Cr-CO trans ) 1.86 and 1.87 Å, respectively).
  • The complexes are prepared via in situ deprotonation of the corresponding azolium salts by a metal complex that contains a basic ligand and the subsequent introduction of carbon monoxide, as illustrated in the synthesis of complex 67b (see Scheme 24).

2.3.2. Transmetallation

  • Transmetallation methods are rather unexplored in pyrazolylidene chemistry.
  • Without isolation of the presumed silver carbene complex, successful ruthenation afforded the complexes 69 and 70 (see Scheme 25).
  • 34 The stoichiometry of the reactants could be utilized to access either the mono 69 (0.5 mol equiv ruthenium dimer, with respect to pyrazolium salt) or the bis complex 70 (0.25 mol equiv).

2.3.3. Oxidative Addition

  • The low CH acidity of pyrazolium salts has restricted their metallation by C-H bond activation to only few metal precursors thus far.
  • Oxidative addition provides an alternative approach (e.g., for the preparation of palladium complexes 72 from the 3-chloropyrazolium salt 71; see Scheme 26).
  • At elevated temperatures, displacement of a phosphine ligand by the nucleophilic Clanion is observed, yielding the neutral cis isomer 73.
  • The carbene in the trifluoroacetate complex 75b appeared at unusually high field (δ C ) 113.8), thus representing one of the most shielded carbene-type resonances known.

2.3.4. Nitrogen Functionalization of Metallated Pyrazolyl Ligands

  • Another approach to preparing less-stabilized NHC complexes involves first installing the metal on the heterocycle (R), followed by protonation or alkylation of the heteroatom to induce carbene-type bonding (S) (see Scheme 28).
  • This approach has been successfully applied to the preparation of a variety of carbene complexes with different metals.
  • 59 Typically, metallation has been performed via lithiation of the azole-ligand precursor, followed by transmetallation and protonation or alkylation.
  • 62 A significant downfield shift of the metal-bound carbon resonance (Δδ ) 25) occurs upon quaternization, and the carbonyl stretching frequencies again shifted to higher energies, presumably reflecting the formation of a metal-carbene bond.
  • This fact might explain the protonation at carbon to form the coordination complex 86.

2.3.5. Cycloaddition to Fischer Carbene Complexes

  • Cycloaddition of dinucleophiles to unsaturated Fischertype carbenes represents an alternative route to N-heterocyclic carbenes.
  • 65 For example, the pyrazolylidene complex 90 has been obtained upon addition of dimethylhydrazine to the alkynyl carbene 89 or to the allenylidene 91 (see Scheme 34).
  • This synthetic route is particularly useful for the introduction of specific substitution variations into heterocyclic carbenes; yet, the yields for the cyclization step are typically low.
  • Recently, it has been shown that the pyrazolylidene in complex 90 is readily transferred to late transition metals.

2.4. Pyridylidene Complexes

  • Pyridinium salts represent a subclass of carbene precursors that are remarkable in their own right.
  • First, deprotonation of a ring carbon formally produces six-membered Nheterocyclic carbenes that are stabilized by one heteroatom, viz, the pyridylidene isomers U, V, and W (see Scheme 36).
  • 68, 69 A recent computational study suggests that free 2-pyridylidenes may be stable if the heterocycle is extensively substituted by electron-donating amino groups.
  • 70 Second, metal coordination at the ortho, meta, and para positions may provide normal, abnormal, and remote carbene complexes.
  • Regioselectivity is obviously relevant, and electronic as well as steric influences might be involved.

2.4.1. Oxidative Addition

  • The first pyridylidene-type transition-metal complexes were prepared in 1974, via the oxidative addition of pyridinium salts to low-valent metal centers.
  • This result, together with the increased ν CO , has been the basis for proposing carbene complex formation.
  • 81 Taking into account the absence of steric differentiation between the 2-position and the 4-position in the protonated pyridinium salt 113a, these results indicate that electronic considerations predominantly determine the regioselectivity of metallation.
  • 86 Both the σand π-contributions to the M-C bond have been calculated to be larger in pyridinium-derived NHC complexes than in the corresponding 2-imidazolylidene systems.
  • Cyclometallation of pyridinium derivatives via C-H bond oxidative addition has been successfully utilized for the synthesis of normal and remote pyridylidene iridium(III) complexes.

2.4.2. Nitrogen Functionalization of Metallated Pyridyl Ligands

  • This conclusion was corroborated by results of 1 H NMR studies, which revealed a hindered rotation about the M-C bond in 2-pyridylidene complexes prepared by protonation, such as 124a.
  • Finally, the observed high-frequency shift of the M-Br stretching vibration upon protonation was attributed to a decreased trans influence of the carbene, compared to the anionic pyridyl ligand.
  • Subsequent alkylation of the pyridyl nitrogen in 143 yields the corresponding carbene complexes 144.

2.4.3. C-H Bond Activation

  • The exact binding mode of that ligand raised a controversy, 103 which was finally clarified by a single crystal structure determination .
  • The structure demonstrated that this complex contains the first, initially unrecognized, abnormal pyridylidene ligand.
  • In a more rational approach, Wimmer and co-workers demonstrated the successful cyclometallation of monoalkylated 2-pyridyl and 4-pyridyl pyridinium salts 147, using tetrachloropalladate and tetrachloroplatinate precursors.
  • The initially formed coordination complexes 148 were isolated and converted to the corresponding metallacycles upon heating in aqueous solutions or in the solid state (see Scheme 49).
  • Analysis of the resulting abnormal 3-pyridylidene complexes 149 was hampered by their poor solubility in common solvents, and, perhaps as a consequence.

Scheme 49

  • //doc.rero.ch of the lack of conclusive data, the carbenoid character of the metal-carbon bond in these complexes has not been discussed, also known as http.
  • In contrast, cyclometallation of 3-pyridyl pyridinium salts such as 150 may afford normal or remote pyridylidene complexes.
  • This model is consistent with a change from ionic pyridyl-type coordination in 152 toward neutral carbene-like pyridylidene donation of the ligand in 153.
  • Accordingly, the Pt-C bond is significantly longer than that in 154a (2.011(2) Å), and the aromatic C-C bonds of the NMe 2 substituted ring alternate in length.
  • The exchange rate for the carbene complex 154a is ∼3 orders of magnitude higher than for its neutral 2-phenyl pyridine analogue.

Scheme 52 Scheme 53

  • Deuterium labeling experiments provide evidence that the iridium-bound mesityl substituents of the IrTp′ fragment are involved in the proton shift process, possibly acting as hydrogen reservoirs.
  • Moreover, the observed depletion of the deuterium content at the pyridine C3-and C4-positions suggests that carbene formation at these C atoms is also occurring.
  • 69 Hence, in N-alkylated pyridylidenes, F-strain 83 may well be a relevant driving force for remote NHC formation (i.e., for the high regioselectivity to metallate the C4-position).
  • In an attempt to cyclometallate the potentially C,Nbidentate chelating ligand precursor 175 with IrCl 3 , complex 176 has unexpectedly been isolated, along with several other products (see Scheme 59).

2.4.5. Cycloaddition to Fischer Carbene Complexes

  • Pyridylidene complexes can be synthesized by modifying existing coordinated carbenes.
  • The carbene carbon NMR resonance typically shifts ∼50 ppm upfield upon cyclization, because of a significant π-electron contribution from the aromatic pyridylium resonance form.
  • The dichotomy in representing complexes, makes a consistent representation of the formulas in this review impossible.

2.5.1. Coordination to Free Cyclic (Amino)(Alkyl)Carbenes

  • Based on the successful preparation of free carbenes (AACs), 9 Bertrand and co-workers pursued the synthesis of stable cyclic carbenes and their transition-metal complexes.
  • Based on CO stretching frequencies in the corresponding RhCl(CO) 2 complexes, these CAACs are stronger donors than classical NHCs, yet weaker than C4-bound abnormal imidazolylidenes.
  • Flexible substituents such as the cyclohexyl group in 186b provide facile access to bis complexes of gold via homoleptic rearrangement from (CAAC)AuCl to [(CAAC) 2 Au] + and [AuCl 2 ] -. 134 A similar rearrangement can be prevented using bulky ligands such as 186a or 186c, which comprise an adamantyl-derived motif to stabilize the gold complex 189.

2.5.2. Oxidative Addition

  • In analogy to other less-stabilized NHC complexation procedures (Vide supra), oxidative addition was also successfully applied for the preparation of a CAAC complex.
  • Starting from the chloride salt precursor 195, oxidative addition to Pd 0 occurred smoothly and afforded the neutral complex 196 (see Scheme 67).

2.5.3. C-H Bond Activation

  • Direct C-H bond activation has been explored little in the synthesis of carbene complexes that comprise saturated heterocycles.
  • Interestingly, piperidine undergoes a similar double dehydrogenation only with the osmium analogue of 197, OsHCl(PiPr 3 ) 2 , but not with the Ru complex itself.
  • Apparently, subtle steric differences in the heterocycle have a pronounced influence on this reaction.
  • Double sequential R C-H bond activations in 199 produce the carbene complex 201 (see Scheme 69).
  • Such solvent-induced toggeling between carbene and alkyl bonding modes may provide access to useful applications, perhaps involving hydrogentransfer reactions.

2.5.4. Cycloaddition to Fischer Carbene Complexes

  • Heterocyclic ring formation from Fischer-type allenylidene complexes provides a versatile pathway for the synthesis of nonconjugated heterocyclic carbene complexes.
  • This route is related to the method used in the preparation of pyrazolylidene complexes (cf. Scheme 34).
  • According to the CO stretching vibrations, pyrazolylidenes are slightly weaker donors than their unsaturated pyrazolylidene analogs (cf. 90 in Scheme 34), yet they are stronger than the corresponding isoxazolinylidene ligand in 204, although the differences are small.
  • Cyclic carbene complexes related to 204 and 205 have been synthesized via various different methods, including CdO activation in lactames, ation of coordinated isocyanides, and heteroatom substitution in oxacycloidene complexes of chromium with an NH unit.
  • Representative products of these reactions are shown in Figure 10 (206-208).

2.5.5. (Amino)(Ylide)Carbenes

  • Recently, an important variation within NHC chemistry was revitalized by incorporating heteroatom stabilization by virtue of an exocyclic ylide residue.
  • Further investigations are warranted to transform these isolated observations into clear and useful trends.
  • The concept of AYCs has recently been expanded to include chelating ligands by resorting to the base sensitivity of the ylide moiety in the free carbenes.

2.6. Miscellaneous N-Heterocyclic Carbenes with Low Heteroatom Stabilization

  • Seven-membered heterocyclic carbenes with only one stabilizing heteroatom adjacent to the carbene carbon have been prepared by cycloaddition of a diamine or an aminothiol to the allenylidene 91, thus affording complexes 225 and 226, respectively (Scheme 76).
  • Furthermore, related absorption data for complexes 225 and 226 suggest that the type of heteroatom has only a minor influence on the donor properties of these ligands.
  • The six-membered analog of the heterocyclic carbene in 225 has been prepared via an unusual rearrangement in the pyrazolylidene complex 90 (see Scheme 77).
  • Subsequent protonation or alkylation yielded complex 227.
  • Remarkably, the NMR shift of the metal-bound carbon barely changes upon deprotonation (Δδ C ≈ 6), despite the significant rehybridization and conformational changes that are associated with this reaction.

3. Carbenes or Zwitterionic Ligands?

  • The question of carbene (or carbenoid) character in socalled metal carbene complexes and, more particularly, the importanceofM-C carbene π-interactionhasbeenaddressedsalbeit not always satisfactorilyssince the characterization of the first Fischer-type carbene complexes.
  • Bercaw and co-workers indicated that such changes can be evoked by providing competing possibilities for diminishing the positive charge on the carbene C atom.
  • Factors such as the position of the heteroatom(s), the substitution pattern, contribution from aromaticity, steric constraints, or the nature of cis-positioned ligands affect the chemical shift substantially and limit the use of NMR data for bondingmode analysis.
  • 37 All studies consistently indicate that the ligands belonging to these classes are pre-eminently very strong σ-donors and weaker π-acceptors than their normal isomers, and these complexes also exhibit significantly lower 13 C chemical shifts than the 2-imidazolylidenes.

4. Donor Properties of the Ligands

  • The overall donor ability of ligands has generally been characterized according to two complementary scales: Tolman's electronic parameters (TEPs) 29 and Lever's electronic parameters (LEPs).
  • Specifically, it has been shown that the associated TEP of ligands L in complexes of general formula IrCl(CO) 2 (L) can be determined by using linear regression methods.
  • 53 Hence, the CO stretching frequency, taken as an average of the asymmetric and the symmetric vibration, offers a direct probe for the donor ability of the corresponding ligand.
  • This method has been extensively used in NHC chemistry, and pertinent data are available also for many abnormal carbene ligands.

5. Catalytic Applications

  • The activity of transition-metal complexes in homogeneous catalysis is, by and large, a function of the ligands that are attached to the metal center.
  • The influence and electronic impact of nonclassical carbene ligands on metal centers has been investigated in many situations, which are summarized in Table 5 .
  • Not unexpectedly, Pd complexes have received the most attention, although, lately, also catalytic applications of Ni, Rh, and Ru complexes have been reported.

5.1. Carbon-Carbon Cross-Coupling Reactions

  • Palladium carbene complexes have been used in a variety of C-C bond-forming reactions.
  • Along these lines, 49 A marked decrease in catalyst activity was noted, which indicates a mechanism that involves, at least in part, heterogeneous palladium.
  • An appreciable 37% conversion of aryl chlorides was recorded, which may be further improved by suitable ligand tuning and catalyst optimization.

5.2. Hydrogenation and Hydrosilylation Reactions

  • Apart from C-C bond-forming reactions, certain NHCmetal complexes are also useful catalysts for hydrogenation reactions.
  • 39 While activities are acceptable (TOF values at 50% conversion are >200 h -1 ), it is noteworthy that the corresponding C2-bound Rh complexes are virtually inactive in catalyzing such hydrogen-transfer reactions.
  • The observed conversions suggest that strong σ-donation, which is inherent to abnormal carbenes and also to pyrazolylidenes, enhances the catalytic activity of the system.
  • 7c,170 The catalyst system based on the 2H-imidazolium salt 244 is the most active one and gives predominantly the hydrosilylated product 241 from the reaction of styrene with HSiEt 3 (see Scheme 91).

6. Conclusions

  • For a long time, the transition-metal chemistry of lessstabilized N-heterocyclic carbenes (NHCs) has been a rather neglected area of study.
  • Various preparative routes are now available to make such compounds (cf. Table 1 ).
  • In such instances, systematic solid-state structural as well as theoretical studies have been undertaken.
  • In particular, pyrazolylidenes and C4-bound imidazolylidenes seem to be extraordinary strong donors.
  • Initial catalytic screenings of complexes that contain abnormal, remote, and other classes of NHC ligands with reduced heteroatom stabilization have been performed, and they reveal, indeed, in certain instances, a catalytic scope beyond that which has been observed for phosphine or even classical NHC complexes.

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Figures (14)

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theme are found via the replacement or displacement of one
N atom, thus providing carbenes derived from pyrazolium,
isothiazolium, and even quinolinium salts that contain a
stabilizing heteroatom in a remote position (G-J in Figure
1). Recently, carbenes such as K, which are comprised of
only one heteroatom and lack delocalization through the
heterocycle, have been discovered as versatile ligands, thus
constituting another important class of carbenes with low
heteroatom stabilization. Both the synthesis of the organo-
metallic complexes of these ligands as well as the (catalytic)
properties of the coordinated metal centers generally show
distinct differences, compared to the more classical NHC
complexes, such as C2-metallated imidazolylidenes. This
review intends to describe such differences and highlights
the chemical peculiarities of these types of N-heterocyclic
carbene complexes. It introduces, in a qualitative manner,
the synthetic routes that have been established for the
preparation of such complexes, covering the literature from
the very beginning of activities in this area up to 2008. While
specialized reviews on some aspects of the present topic have
recently appeared,
7
a comprehensive overview of the subject
has not been available thus far. Rather than just being
descriptive, the present account is mainly directed toward
the impact of these still unusual metal-carbene bonding
modes on the electronic properties and on the new catalytic
applications that have been realized by employing such new
carbene complexes. As a consequence of our focus on
complexes with less-stabilized heterocyclic ligands, systems
comprising acyclic carbenes have not been included, and the
interested reader is, instead, referred to the pioneering and
1. Introduction
The organometallic chemistry of N-heterocyclic carbenes
(NHCs) has experienced explosive development during the
last few years, and the topic remains the main focus of many
outstanding research programs.
1
The ongoing popularity of
this research area is certainly due to the development of
extremely active catalyst systems comprising such carbene
ligands. This is perhaps most clearly illustrated by the
second-generation olefin metathesis catalysts developed by
Grubbs and Nolan,
2
or by the cross-coupling catalysts
introduced by Organ and currently commercialized by
Aldrich.
3
The potential of NHCs as ligands for transition metals has
been pioneered, in particular, by the independent work of
O
¨
fele and Wanzlick, and, later, also by Lappert and Stone
in the 1960s and early 1970s.
4
Despite the considerable
progress achieved by these groups, the topic did not attract
widespread attention until Arduengo reported on the isolation
and stability of free N-heterocyclic carbenes.
5
This discovery
marked a watershed in carbene complex chemistry, and these
ligands became available from convenient and inexpensive
precursors such as imidazolium salts. A key factor in the
remarkable stability of Arduengo-type free carbenes lies in
the almost-excessive heteroatom stabilization, because of the
presence of two heteroatoms, at least one of which is
typically a nitrogen in a position R to the carbene carbon (A
in Figure 1).
5
The chemistrysand, specifically, the coordina-
tion behaviorsof these “classical” heterocyclic carbenes has
been reviewed extensively: monographs as well as special
issues have dwelled on this topic.
1
Rather dormant in the beginning of the new millennium,
the concept of heterocyclic carbene ligands that are not
stabilized by two adjacent heteroatoms, as in Arduengo-type
carbenes, and also not necessarily with heteroatoms placed
in a position R to the carbene carbon was revived by a
serendipitous discovery of C4 bonding in imidazolylidenes.
6
The large class of heterocyclic carbenes that can be grouped
together under the title of this review include, in particular,
imidazolium-derived ligands that bind the metal via the C4
or C5 carbon (B and C in Figure 1) as well as the
pyridylidene family with only one heteroatom present in the
heterocyclic skeleton (D-F in Figure 1). Variations on this
Beyond Conventional N-Heterocyclic Carbenes: Abnormal, Remote, and Other
Classes of NHC Ligands with Reduced Heteroatom Stabilization
Oliver Schuster,*
,†
Liangru Yang,
Helgard G. Raubenheimer,
and Martin Albrecht*
,‡
Department of Chemistry, University of Stellenbosch, Private Bag X1, 7602 Matieland, Stellenbosch, South Africa, and Department of Chemistry,
University of Fribourg, Ch. du Musée 9, CH-1700 Fribourg, Switzerland
Published in "Chemical Review 109(8): 3445–3478, 2009"
which should be cited to refer to this work.
http://doc.rero.ch
1

ongoing work of Bertrand and co-workers.
8,9
Similarly,
heteroatom-free cyclic carbenes are not further detailed
here.
10
In the literature, different terms have been coined to
describe the bonding of such less-stabilized carbenes to metal
fragments. For example, terms such as “wrong way”,
“abnormal”, “unusual”, or “nonclassical” have been used to
describe C4/C5-bound imidazolylidenes (B). Throughout this
review, we refer to “abnormal” carbenes as those NHC
ligands for which a canonical valence bond representation
requires the introduction of additional formal charges on
some nuclei (e.g., B, C, E,orI in Figure 1). The term
“remote” carbene indicates that no heteroatom is located in
a position R to the carbene carbon (e.g., E, F, H, I in Figure
1); it may be possible to write uncharged contributing
resonance structures for the free ligand.
11
A final preliminary remark concerns the controversial
classification of all these ligands as “carbenes”. While this
classification implies that the ligand is a neutral donor, in
all instances, a zwitterionic canonical representation consist-
ing of a carbanionic and a cationic iminium center may be
similarly appropriate and even necessary. When bonded, this
negative charge is obviously transferred to the metal in one
canonical form. Clearly, the borderline between the two
limiting representations is continuous, and the issue of
whether a ligand is, in reality, a carbene or not may become
semantic. In the case of the C2-bound imidazolylidenes,
experimental and theoretical studies are in agreement with
a relatively small π-contribution to the M-C bond only (M
) electron-rich metal center),
12-14
and, hence, the M -C
interaction is typically represented by a single bond. How-
ever, detailed studies involving less-stabilized N-heterocyclic
carbenes are still rare. Often, crystallographic and NMR
spectroscopic arguments have been put forward to support
one resonance form or the other. Despite the fact that the
metal-carbon bonds in Fischer carbenes and in N-hetero-
cyclic carbenes are very much related, different means of
representation have evolved in the literature. In this review,
single bonds are used to represent M-C
carbene
interactions,
which is consistent with the accepted representations of
conventional NHC-metal bonds and even other metal-ligand
bonds that are known to comprise significant π-character
(e.g., the M-CO bond in carbonyl complexes). Classical
Fischer-type carbene complexes are written with an M)C
double bond, in agreement with a different convention
developed in the 1960s. A more complete discussion of these
Table 1. Available Methods for NHC Metallation
metallation method ligand system
via free carbene 2-imidazolylidenes and related ligands
a
4-imidazolylidenes (via 2-imidazolylidene rearrangement)
cyclic (amino)(alkyl)carbenes (CAACs)
and (amino)(ylide)carbenes (AYCs)
C-H bond activation 2-imidazolylidenes and related ligands
a
4-imidazolylidenes
4-triazolylidenes
3-pyrazolylidenes
2-, 3-, 4-pyridylidenes
CAACs and AYCs
C-E bond activation 2-imidazolylidenes (E ) CH
3
: activation with Ag
I
; E ) CO
2
-
:
activation with d
8
metals; CdC activation of enetetramines)
2-pyridylidenes (E ) PR
2
: activation with Pd
II
)
C-X oxidative addition 2-imidazolylidenes and related ligands
a
4-imidazolylidenes
3- and 4-pyrazolylidenes
2-, 3-, 4-pyridylidenes
CAACs
transmetallation 2-imidazolylidenes (predominantly from Ag complexes)
3-pyrazolylidenes (from Ag, Cr)
4-imidazolylidenes
4-triazolylidenes
2-pyridylidenes (from Cr)
heteroatom alkylation 3-pyrazolylidenes
2-, 3-, 4-pyridylidenes
cycloaddition to Fischer carbenes 2-imidazolylidenes and related ligands
a
3-pyrazolylidene
2- and 4-pyridylidene
expanded ring NHCs
a
Includes NHCs with two different stabilizing heteroatoms in a position R to the carbene.
Figure 1. N-heterocyclic carbenes, including the “classical” NHC
representative (A) and representatives of subclasses comprising
reduced heteroatom stabilization (B-K); all are shown in their
carbene form.
http://doc.rero.ch
2

considerations is provided in Section 3, after synthetic
strategies have been introduced. The review concludes with
applications of such carbene complexes in catalysis.
2. Methods of Ligand Complexation
A variety of different methods have been established for
the complexation of less-heteroatom-stabilized NHC ligands.
Some of these methods are very similar to those yielding
normal C2-bound imidazolylidene complexes, while others
are unique to a particular subclass of NHC ligands. The
different methods of NHC ligand complexation are compiled
in Table 1. Further details are provided in this section, which
has been organized according to the different ligand systems
involved, rather than according to the methods used.
2.1. Complexes with C4-Bound Imidazolylidenes
2.1.1. C-H Bond Activation of Unsubstituted
2H-Imidazolium Salts
Crabtree and co-workers
15
were the first to observe
abnormal C4 metallation of imidazolium salts a few years
ago (Figure 2). The reaction of pyridine-functionalized
imidazolium salt 1 with the iridium polyhydride IrH
5
(PPh
3
)
2
also afforded the iridium (III) complex 2, which is comprised
of a carbene that is abnormally bound through C4 rather than
C2 (see Scheme 1). The coordination mode was deduced
from NMR spectroscopy and was unambiguously confirmed
by X-ray crystallographic analysis. No interconversion to the
presumably more-stable normal carbene complex 3 was
detected. Hence, product formation seems to be kinetically
controlled. These results indicated, for the first time, that it
may not always be safe to assume C2 bonding when
preparing NHC complexes in situ from imidazolium salts
and a metal precursor.
The activation of the C4-H bond in imidazolium salts
such as 1 is remarkable when considering the acidity
difference between the two types of heterocyclic protons.
The acidity of the proton attached to C2 has been determined
experimentally and by calculation (pK
a
) 24 ( 1).
16
This
value is 9 pK
a
units lower than that calculated for the C4-
bound proton (pK
a
) 33).
17
The difference suggests that
aspects other than the acidity of the protons control the
regioselectivity of metallation.
The selective formation of C4- or C2-bound carbene
complexes with iridium hydrides seems to be dependent on
multiple factors.
18
Calculations suggest that C2 bonding and
C4 bonding proceed via distinctly different reaction pathways
involving either C2-H heterolytic bond cleavage or C4-H
oxidative addition, implicating an iridium(V) species (see
Scheme 2).
19
Such mechanistic proposals were further
supported by experimental data, which demonstrate that
product distributionsand, thus, the site of metallationsis
strongly anion-dependent. Large anions such as BF
4
-
typi-
cally are only weak partners for hydrogen bonding and effect
small changes in charge distribution. Consequently, such
anions favor an oxidative addition pathway, leading to
carbene C4 bonding. In contrast, smaller counterions such
as Br
-
accelerate heterolytic C-H bond cleavage through
hydrogen bonding, thus supporting a proton migration from
the imidazolium moiety to the metal-bound hydride. Ac-
cordingly, such anions preferentially yield C2-bound car-
benes. Time-dependent NMR analysis of the formation of 2
has revealed the intermediate formation of a hydrogenated
imidazolinylidene species 4.
15
This result is consistent with
an oxidative addition pathway that is comprised of an [IrH
4
]
+
species, which may reversibly transfer H
2
from the metal
center to the imidazolylidene heterocycle. Notably, chelation
of the pyridine moiety is not essential and similar selectivities
in C-H bond activation have been observed with simple
imidazolium salts upon reaction with [IrH
5
(PPh
3
)
2
]inthe
presence of pyridine.
20
Recent studies by Esteruelas et al. on the metallation of
imidazolium salts such as 1 with the osmium hydride
precursor [OsH
6
(PiPr
3
)
2
] have confirmed the relevance of the
counteranion for the regioselectivity of metallation.
21
Met-
allation at the C4 position is again favored with large and
unpolarized [BPh
4
]
-
anions, whereas imidazolium bromides
afford, almost exclusively, the C2-metallated carbene. Time-
dependent analysis of carbene formation indicated that kinetic
factors are more relevant for C4 coordination than for C2
coordination. In addition, isomerization of the C4-bound
carbene to its thermodynamically favored C2-bound isomer
has been accomplished under strongly acidic conditions in
the presence of HBF
4
.
The regioselectivity of metallation is further influenced
by the wingtip substituents on the imidazolium salt.
22
A
mesityl substituent promotes C4 bonding to the Os center 6,
while the corresponding benzyl-substituted imidazole gives
the C2-bound carbene complex 7 in high yields (see Scheme
3). The outcome of this reaction can be explained by
invoking steric hindrance between the isopropyl groups of
the phosphines and the imidazolium wingtip groups, which
is more pronounced for mesityl than for the comparatively
flexible benzyl substituent.
A driving force different from counterion effects and
steric discrimination is required to rationalize the selective
C4 metallation of the imidazolium salt 8, which is
comprised of a chelating phosphine wingtip group to give
complex 10 (see Scheme 4).
23
With [Ir(cod)Cl]
2
(where cod
) 1,5-cyclooctadiene), initial phosphine coordination and
formation of 9 has been observed. Subsequent C-H bond
activation occurs exclusively at the C4-position and is
reversible with ethylene-linked bidentate ligands, yet slow
and irreversible with the analogous methylene-bridged
derivative 9a. Base-mediated reductive elimination affords
the corresponding iridium(I) complexes 11. Furthermore,
neither a small wingtip group nor a hard chloride counterion
(not shown) succeeds in promoting C2-H bond activation.
Perhaps the affinity of iridium(I) for olefinic CdC bonds
Figure 2. Metal complexes comprising normal (L) and abnormal
(M) imidazolylidene ligands bound at the C2 and the C4 position,
respectively.
Scheme 1
http://doc.rero.ch
3

might also play a role in the regioselectivity of iridation. In
addition, the constrained bulk of the coordinated phosphine
ligand could increase the steric sensitivity of the Ir
center.
Additives also have a distinct influence on the regiose-
lectivity of imidazolium palladation. Metallation of the
hydrochloride adduct of N,N-dimesitylimidazol-2-ylidene
(IMes · HCl) with Pd(OAc)
2
, in the presence of Cs
2
CO
3
as a
base, occurs selectively at the C2-position, thus affording
the normal bis(carbene) complex 12 (see Scheme 5).
24
In
the absence of Cs
2
CO
3
, however, the heteroleptic complex
13 is formed. It is comprised of one C2-bound NHC ligand
and one carbene that is bound abnormally at C4 to the
palladium center (see Scheme 5). Interestingly, an X-ray
structure analysis shows that the two different Pd-C bond
lengths are identical within experimental error (Pd-C )
2.019(13) and 2.021(11) Å for the normal and abnormal
carbene, respectively). According to the mechanistic model
used for iridium metallation (Vide supra), the CO
3
2-
anion
may promote heterolysis of the most acidic C-H bond, thus
favoring formation of C2-bound complexes. In the absence
of a base, the C4-H bond is activated, probably by oxidative
addition, to give 13. The trans orientation of the two carbene
ligands seems to play a decisive role for C4 bonding. In
rigidly cis coordinating, chelating bis(carbene) complexes,
exclusive C2 bonding is observed under identical base-free
metallation conditions.
25,26
2.1.2. C-H Bond Activation of C2-Substituted
Imidazolium Salts
Although the previous section illustrates the feasibility of
C4 bonding with 2H-imidazolium salts, which may be
particularly relevant for in situ complex formation, unpro-
tected imidazolium salts are primarily metallated at the C2-
position. A rational route toward C4-bound carbenes there-
fore includes the selective protection of the most acidic C2-
position, e.g., by incorporating alkyl or aryl substitutents.
Thus, oxidative addition of the C4-H bond of the tetra-
alkylated C2-blocked imidazolium salt 14 to zerovalent
Pt(norbornene)
3
, in the presence of equimolar amounts of
the free carbene IMes, yields the platinum hydride complex
15 with the mixed C2- and C5-bound carbenes both attached
to platinum (see Scheme 6).
27
The formation of this complex
has been proposed to occur stepwise. Initial coordination of
the basic IMes provides the necessary electron density at
the central metal to allow for subsequent oxidative addition
of the imidazolium C4-H bond. A similar reaction sequence
may apply to the formation of the abnormal/normal
[Pd(IMes)
2
Cl
2
] complex 13 (Vide supra). When using the
asymmetrically 1,2,3-trialkylated imidazolium precursor 16,
a mixture of C4- and C5-bound isomers 17a and 17b is
formed in a 3:1 ratio. This product distribution might reflect
a moderate steric preference in the transition state of the
oxidative addition.
Complexes 17 are unstable in the presence of certain
alkenes, such as styrene, and undergo reductive elimination.
The C4-bound carbene is significantly more prone to
reductive elimination than the C2-bound IMes ligand, leading
to the exclusive formation of the imidazolium salt 16 and
Scheme 2
Scheme 3
http://doc.rero.ch
4

the Pt
0
complex, Pt(IMes)(diolefin). No products resulting
from reductive elimination of the normal C2-bound carbene
nor from alkene insertion into the Pt-H bond are observed.
Both, electronic and steric reasons may account for the
observed reaction outcome, and further investigations are
clearly desirable.
C4-bound carbene metal complexes can also be made by
transmetallation from the corresponding silver complexes.
Precursor Ag-NHC complexes are typically generated from
silver oxide (Ag
2
O) and imidazolium salts.
28
To achieve
selective metallation, it is necessary to protect both the C2-
and C5-positions. For example, the disubstituted imidazolium
salt 18 undergoes clean deprotonation in the presence of
Ag
2
O.
20
Subsequent transmetallation of the presumably
formed silver complex with [Ir(cod)Cl]
2
yields the Ir
+
complex 19a, and after the exchange of spectator ligands
(cod for CO) complex 19b (see Scheme 7). IR spectroscopy
of this dicarbonyl complex allows for an estimation of the
electron-donating ability of such C4-bound carbenes. From
the observed stretching frequencies (ν
CO
) 2045, 1961 cm
-1
),
a Tolman electronic parameter (TEP)
29
of ν ) 2039 cm
-1
has been estimated. This value is considerably lower than
for analogous C2-bound carbenes (ν 2050 cm
-1
) or basic
phosphines (cf. PCy
3
, ν ) 2056 cm
-1
). Hence, such C4-
bound carbenes are among the best neutral donors known.
Complex 19a has been demonstrated to be a useful metal
precursor for transmetallation. In the presence of a Ag-
triazolylidene, swift formation of the normal/abnormal bis-
(carbene) complex 20 is observed.
30
Complexes such as 20
generally exist as multiple diastereoisomers, since rotation
about the Ir-C
carbene
bonds is hampered by the two cis-
coordinated carbene ligands. Initial attempts to separate the
diastereoisomers of 20 by recrystallization have been unsuc-
cessful; yet, this may become an attractive methodology for
application in asymmetric catalysis.
Notably, the formation of stable abnormal silver carbene
complexes for transmetallation is often limited to imidazo-
lium salts with aryl substituents at the C2-position, because
primary or secondary alkyl groups have been found to be
unreliable protecting groups.
31
Reaction of Ag
2
O with
2-methylated or 2-benzylated imidazolium salts 21 initiates
an unexpected C-C bond activation process, thus yielding
the normal Ag-carbene complex 22 (see Scheme 8). A
detailed analysis of the course of reaction reveals that Ag
2
O
is gradually oxidizing the carbon that is attached to C2 to
yield acyl imidazolium salts and metallic silver. In the
presence of water that is formed during this redox reaction,
acyl functionalities seem to be good leaving groups and,
hence, promote metallation at the C2 carbon. Consistent with
this mechanistic scheme, the highest yields are obtained when
a large excess of silver salt is used. A similar oxidation is
effectively suppressed when a quaternary carbon (e.g. a
phenyl group) is attached to C2.
A transmetallation protocol has been applied for the
synthesis of a series of complexes 24 that are comprised of
abnormally bound imidazolylidene-derived ligands (see
Scheme 4
Scheme 5
Scheme 6
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