NHC precursors

The methodologies described above lead to NHC precnrsors rather limited in terms of substitution at the four- and five-positions as their access is restricted to the accessibility of the appropriate diimine. As snch snbstitntions are of great interest in particular for the design of asymmetric catalysts, rontes to the synthesis of the NHC precursors have more recently been developed. Some of these approaches are described in Scheme 1.4. 

Scheme 1.4 Synthetic pathways to NHC precursors with a substituted backbone (C C )...

Asymmetric versions of this transformation were also developed by using chiral imidazolium pro-ligands as NHC precursors, or silver transmetallation methodology with chiral NHC ligands (Fig. 2.23) [106]. Imidazolium salts with chiral A-substituents (132) or imidazolidinium salts with chirality at the backbone of the heterocycle (133) gave quantitative conversions at -78°C with good ee (58% and 70% respectively). 

Some other enantioselective approaches have been attempted, still with moderate enantioselectivities, by making use of in situ systems containing a chiral NHC precursor. Luo and co-workers reported on the use of the bidentate chiral imidazo-lium salt 16, derived from L-proUne, in combination with [RhCia-COCcod)], leading to an enantiometic excess of around 20% [30]. The use of chiral imidazolium salt 17 in combination with [RhCl(CH2=CHj)j]j by Aoyama afforded slightly better ee (Fig. 7.3) [31 ]. So far, Bohn and co-workers have obtained the best enantioselectivities (up to 38% ee) for the catalytic addition of phenylboronic acid to aromatic aldehydes by using planar chiral imidazolium salts 18, derived from paracyclophane, in combination with [Rh(OAc)2]2 [32]. 

The wide diversity of topologies that can today be found for NHC-precursors, together with the different efficient metallation strategies [6], have provided a large set of Ir—NHC complexes among which monodentate, bis-chelate and chiral... 

Because of their convenient preparation from palladium(II) salts and stable NHC-precursors (vide supra), paUadium(ll) complexes were first examined as potential catalysts for Heck-type reactions. Due to the high thermal stability, temperatures up to 150°C can be used to activate even less reactive substrates, like, e.g., aryl chlorides. Inunobilization of such catalysts has been shown recently (vide infra) ... 

The abihty of ROMP to polymerize even more complex functional monomers was demonstrated by the fact that the cationic NHC precursor 1,3-di( 1 -mesityl)-4- [ (bicyclo [2.2.1 ]hept-5-en-2-ylcarbonyl)oxy]methyl -4,5-di-hydro-lH-imidazol-3-ium tetrafluoroborate can be polymerized using both rutheniiun- and molybdemun-based initiators. Thus, reaction of this monomer with RuCl2(PCy3)2(CHPh) in methylene chloride at 45 °C results in com-... 

Scheme 10 Living polymerization of W-heterocyclic carbene (NHC) precursor, formation of (u-(triethoxysilyl)-telechelic oligomer and immobilization on silica...

Scheme 17 Immobilization of a NHC precursor on a ROMP-derived monolith via in situ grafting...

Unlike phosphines, the coordination of NHCs to metal centers usually requires the activation of a precursor, which makes NHC-based complexes relatively less accessible than the analogous phosphine compounds. There is a variety of methods for forming carbenes, most of them from the corresponding azolium salts, and these have been reviewed [10-14], The methods for preparing NHC-metal complexes can be classified according to the nature of the NHC precursor and to the activation method employed. In this sense, the most widely used strategies are ... 

In 1993, Kuhn reported that cyclic thiourea derivatives like 1,3,4,5-tetramethyl-2(3H)-thione can be used as NHC precursors [62]. In most cases the thione affords an easy access to the free carbenes by treatment with sodium or potassium [62-71]. This method provides an efficient way to prepare unsymmetrically substituted saturated NHCs (Scheme 16) [35,72],... 

Reaction between Ru3(CO)12 and three equivalents of the NHCs ImMes2 and ImDipp2 give quantitative yields of mononuclear Ru(CO)4(NHC), whereas sulfido clusters 39 and 40 are isolated from the reaction with the NHC precursor S=ImMes2. A similar reaction with the smaller ImMe4 (l,3,4,5-tetramethylimidazol-2-ylidene) affords the trinuclear cluster 41, a result that most likely stems from the difference in steric bulk around the nitrogen.32... 

Similar to the Tp family of ligands, the monoanionic HB(RIm)3 Ugands can be deriva-tised by substituting the BH backbone with a CH group [338-340L The result is a neutral HC(RIm)3 ligand. Biffls et al. have used a known tris-benzimidazole compound [416] that becomes a suitable tris-NHC precursor upon triple quartemisation with Meerwein s salt [390] (see Figure 3.133). 

This facile solution for catalyst immobilisation follows a more complex approach reported by Mayr et al. [246], This research group attached the imidazolium salt to a nor-bomene unit that was then subjected to a ring opening metathesis polymerisation (ROMP) reaction to form the polymeric NHC precursor (see Figure 4.77). The ROMP reaction had to be carried out with a molybdenum based Schrock catalyst because the ruthenium based Grubbs catalyst did not provide an endgroup that could be quantitatively capped with a suitable final endgroup. 

Figure 6.29 Synthesis of a carboxylic acid functionalised NHC precursor (the glycine fragment is highlighted in bold).

Truscott BJ, Klein R, Kaye PT (2010) Expeditious synthesis of NO-substituted N-mesitylimidazolium salts as NHC precursors. Tetrahedron Lett 51 5041-5043... 

NHC precursors 47a and 47b may be used to generate the corresponding free carbene because an alcohol or chloroform readily eliminates from carbon (equation 10.20). Chemists can synthesize and isolate these precursors before allowing them to react with metal complexes or simply generate them in situ in the presence of the metal complex. 

NHC precursor was generated in situ from the corresponding imidazolium salt.39... 

Chiral N heterocyclic carbenes (NHCs), as Lewis basic organocatalysts, have been synthesized and applied to enantioselective organocatalytic reactions in recent years. Encouraged by Sheehan and Hunneman s first report of chiral thiazolium salts as NHC precursors for organocatalytic reactions [37], Leeper, Enders, Rovis, Glorius, Herrmann, and others have synthesized series of novel chiral NHCs with mono cyclic, bicyclic, or tricyclic backbones [38]. Recently, a series of bifunctional NHCs were synthesized and applied to aza BMH reaction of cyclopent 2 enone with... 

In order to generate sufficient porosity, monoliths with a suitable microporosity (40 %) and microglobule diameter (1.5 0.5 pm) were synthesized. Consecutive in-situ derivatization was successfully accomplished using a mixture of norborn-2-ene and the corresponding NHC-precursor in methylene chloride (Scheme 1). The use of norborn-2-ene significantly enhances grafting yields for the functional monomer. Using this setup. 

Metathesis-based grafting techniques have already been successfully applied to the synthesis of other silica-based catalytic supports, e.g. those for heterogeneous ATRP[7, 18] as well as for heterogeneous Heck-type reactions[19]. This tempted us to investigate as to which extent these grafting techniques might be applied to the synthesis of silica-immobilized NHC-precursors. The x-ray structure of such a polymerizable NHC-precursor is shown in Fig. 2. 

Scheme 3. Synthesis of a triethoxysilyl-telechelic, oligomeric NHC precursor.

The use of bulky NHC precursor IPr-HCl in conjunction with KO Bu as base, a palladium source, and 1,4-dioxane as solvent permits the catalytic C-N coupling of aryl iodides and bromides at room temperature and of aryl chlorides at elevated temperature. High conversions were achieved with primary and secondary, cyclic and acyclic amines with various aryl halides. 4-Chlorotoluene and ort/zo-substituted aryl halides were aminated in good to excellent yields. The effective coupling of 4-chloroanisole with sterically unhindered amines makes this one of the most effective catalytic systems to date (Scheme 21) [75]. 

An alternative solution to the same problem uses mixed vinylalanes that contain silicon in the a-position. Since these derive from a diisobutylaluminum (DIBAL)-based hydroalumination of silylalkynes, the resulting species are diisobutyl(alkenyl)-alanes. These undergo transmetalation in the presence of an NHC-Cu complex, derived from CuCb and, importantly, a bidentate, dimeric silver NHC precursor (illustrated below). Silyl moieties can be TMS or TBS, although the latter, bulkier group in the starting alane requires room temperature for 1,4-addition to ensue. Both 5- and 6-membered enones can be used representative examples are shown below. The resulting vinylsilane in each product can be easily converted to alternative functionality, such as a ketone via oxidation with MCPBA), a halide e.g., an iodide, with NIS), and an alkene yia protodesilylation with TFA). ... 

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