Carbenes N-heterocyclic

N-heterocyclic carbene (NHC) catalysed reactions have greatly increased in popularity since 2004, when several groups reported reactions other than the 

The diamino enol formed after reaction of a NHC with simple aldehydes (Breslow intermediate) can react with other aldehydes or imines to aehieve the benzoin or azabenzoin condensation, and the Stetter reaction when reacting with electron-poor alkenes. 

1 Benzoin, Cross-benzoin and Aza-cross-benzoin Reaction 

Recently, there has heen some work dealing with the cross-henzoin condensation to afford nonsymmetrical products chemoselectively. In this case, the Breslow intermediate has to he formed predominantly with only one of the aldehydes and react selectively with the other one. Kuhl and Glorius have succeeded in this area developing a selective hydro gmiethylation of aldehydes.With a different approach, it is also possible to use hindered ortho-substituted aldehydes to inhibit the retro-benzoin reaction and the attack of the As an extension, the cross-benzoin reaction has been 

Scheidt et al. proved that acyl silanes can react in the same way as aldehydes in the so-called sila-Stetter reaction to eventually form 1,4-dicarbonyls in up to 75% The first intramolecular Stetter reaction was re- 

Other NHCs, such as 11.20,11.21,11.22, and 11.23, are readily accessible by similar routes, starting from the corresponding azoles 11.20, deriving from 1,2,4-triazole, and 11.21, from thiazole. 11.23 is an abnormal 

The commonest route goes via the free NHC, 11.16, formed via deprotonation of the parent imidazohum salt with a strong base, such as BuLi (Eq. 11.38). Bulky R groups such as mesityl prevent the free carbene from dimerizing to 11.19, but the need for BuLi forbids the presence of functional groups with labile protons in the NHC structure. These limitations have led to the development of milder routes that avoid the free carbene. 

Simplest among these is direct oxidative addition (Eq. 11.39), where the outcome can be complicated by subsequent reactions of the hydride formed in the oxidative addition step. Direct metallation can be assisted by weak bases such as acetate because agostic binding of C(2)-H makes it easier to deprotonate the imidazolium ion. A very useful method is the initial formation of a silver carbene 11.21 from Ag20, followed by transmetallation to give the final product (Eq. 11.50). NHC carboxylate 11.22 and its esters are also useful NHC transfer agents (Eq. 11.51).  

In an example that shows the strong donor character of NHCs, the tripodal polydentate NHC ligand in 11.26 stabilizes Fe(V) as an organo-metallic nitride. Not all potentially chelating bis-NHC ligands in fact form chelates, however, even when the chelate would be thermodynamically favored. Each NHC often binds to a separate metal in a 2 1 complex as kinetic product because, unlike M-PR3, M-NHC bond formation is not reversible, so the error cannot be remedied by reversible dissociation (Eq. 11.42). 

There are numerous catalytic applications of NHC complexes (hydrogenation, hydrosilation, metathesis, coupling chemistry, etc.) in which they show advantages over phosphines. Rates can be faster, and the catalysts usually do not need protection from air during catalysis. Imidazoles are also more readily synthesized in a variety of structural modifications, although subsequent formation of the M-C bond can be somewhat more difficult than in the case of PR3. Ruthenium NHCs can even be stable under intensely oxidative and acidic conditions in catalytic water oxidation driven by Ce(IV). Since free NHCs would be easily oxidized, this emphasizes the kinetic inertness of M-NHC bonds and contrasts with the ease of oxidation of many M-PR3 to give 0=PR3. 

A study of the ROP of D,L-lactide catalyzed by the IMes carbene revealed a preference for isotactic enchainment, such that conducting the polymerization at -20 °C resulted in a PLA with a probability of isotactic enchainment (Pm) of 0.75 [19]. Further studies revealed that, at -70 °C, the Pm could be increased to 0.83 [20]. The application of a more sterically hindered carbene at -70 C further enhanced the isotacticity of the polymer to Pm = 0.90. Interestingly, the appUcation of sterically hindered chiral carbenes did not further enhance the stereocontrol of the ROP process, which suggested that a chain-end-controlled process was dominating the stereoselectivity. 

In the absence of protic initiators, Waymouth and coworkers showed that it is possible to synthesize cyclic polymers [22, 23]. In THF solution, the ROP of lactide was shown to produce cycHc polymers with PDI 1.3 (less than 90% monomer 

Further studies conducted by Jeong, Hedrick and Waymouth showed that the appHcation of l,3-dimesitylimidazoHn-2-yhdene efficiently mediated the ROP of P-butyrolactone and P-propiolactone to form cycHc polymers, and with good control over the molecular weight and polydispersities 1.3 [23]. A kinetic analysis showed the ROP to be first order with respect to both monomer and carbene concentrations. The integrity of the iititiation step was confirmed by the isolation of the spiro imidazoHdine compound formed by the equimolar reaction of P-butyrolactone and carbene. 

This catalyst system was also appHed to the synthesis of a wide range of functional, block and dendritic star copolymers [25, 28]. Further investigations into the 

In a related study, Hedrick, Waymouth and coworkers reported that NHCs were also able to act as catalysts for the ROP of trimethylene carbonate (target DP 50) [31]. The appHcation of l,3-bis(2,6diisopropylphenyl)-imidazol-2-ylidene resulted in 99% monomer conversion within 30 min, producing polymers with predictable molecular weights and a narrow PDl (1.06). However, the less-hindered and more basic l,3-diisopropyl-4,5-dimethylimidazol-2-ylidene produced polymers with much broader polydispersities ( 2), albeit within a few seconds. 

---

The surprising stability of N-heterocyclic carbenes was of interest to organometallic chemists who started to explore the metal complexes of these new ligands. The first examples of this class had been synthesized as early as 1968 by Wanzlick [9] and Ofele [10], only 4 years after the first Fischer-type carbene complex was synthesized [2,3] and 6 years before the first report of a Schrock-type carbene complex [11]. Once the N-heterocyclic ligands are attached to a metal they show a completely different reaction pattern compared to the electrophilic Fischer- and nucleophilic Schrock-type carbene complexes. 

During the last decade N-heterocyclic carbene complexes of transition metals have been developed for catalytic applications for many different or-... 

Ruthenium Precatalysts with N-Heterocyclic Carbene Ligands.238... 

The search for even more active and recyclable ruthenium-based metathesis catalysts has recently led to the development of phosphine-free complexes by combining the concept of ligation with N-heterocyclic carbenes and benzyli-denes bearing a coordinating isopropoxy ligand. The latter was exemplified for Hoveyda s monophosphine complex 13 in Scheme 5 [12]. Pioneering studies in this field have been conducted by the groups of Hoveyda [49a] and Blechert [49b], who described the phosphine-free precatalyst 71a. Compound 71a is prepared either from 56d [49a] or from 13 [49b], as illustrated in Scheme 16. 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

Synthesis of Chiral N-heterocyclic Carbenes and of Their Complexes... 

Nolan SP, Viciu MS (2005) The Use of N-Heterocyclic Carbenes as Ligands in Palladium Mediated Catalysis. 14 241-278... 

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

Glorius F (ed) (2007) N-heterocyclic carbenes in transition metal catalysis. Springer, Hamburg... 

C. S. J. Cazin (ed.), N-Heterocyclic Carbenes in Transition Metal Catalysis and Organocatalysis, Catalysis by Metal Complexes 32,... 

Fig. 1.1 Number of publications N-heterocyclic carbene as research topic)...

Nielsen DJ, Cavell KJ (2006) Pd-NHC complexes as catalysts in telomerization and aryl amination reactions. In Nolan SP (ed) N-Heterocyclic carbenes in synthesis. WUey-VCH, Weinheim, pp 73-102... 

---