Imidazolium salts chiral

Gade and Bellemin-Laponnaz have reported the synthesis, in good yields, of chiral oxazoline-imidazoliums salts 10a (Scheme 8) obtained by reaction of 2-bromo-4(S)-t-butyl oxazoline with several mono-N-substituted imidazoles [16]. Similaly an imidazolium salt 10b bearing a paracyclophane substituent was prepared by Bolm [17]. 

The synthesis of the unsymmetrical imidazolium salt 11 bearing a planar-chiral ferrocene was described by Bolm starting from (Rp)-[2-(trimethysilyl)-ferrocenyl] methanol 12 which afforded the salt in good yield after reaction with Ar,M-carbonyl diimidazole and methylation (Scheme 9) [18]. 

RajanBabu reported the first preparation of a bis-imidazolium salt 15 bearing a chiral linker (Scheme 11). The starting material was the enantiomerically pure (S)-l,l -bi-2-naphtol bis(trifluoromethanesulfonate) which was transformed in two steps into the dibromomethyl derivative 16 and then into the bis-imidazole. Quaternarization of this compound afforded 15 [20]. 

Herrmann et al. reported for the first time in 1996 the use of chiral NHC complexes in asymmetric hydrosilylation [12]. An achiral version of this reaction with diaminocarbene rhodium complexes was previously reported by Lappert et al. in 1984 [40]. The Rh(I) complexes 53a-b were obtained in 71-79% yield by reaction of the free chiral carbene with 0.5 equiv of [Rh(cod)Cl]2 in THF (Scheme 30). The carbene was not isolated but generated in solution by deprotonation of the corresponding imidazolium salt by sodium hydride in liquid ammonia and THF at - 33 °C. The rhodium complexes 53 are stable in air both as a solid and in solution, and their thermal stability is also remarkable. The hydrosilylation of acetophenone in the presence of 1% mol of catalyst 53b gave almost quantitative conversions and optical inductions up to 32%. These complexes are active in hydrosilylation without an induction period even at low temperatures (- 34 °C). The optical induction is clearly temperature-dependent it decreases at higher temperatures. No significant solvent dependence could be observed. In spite of moderate ee values, this first report on asymmetric hydrosilylation demonstrated the advantage of such rhodium carbene complexes in terms of stability. No dissociation of the ligand was observed in the course of the reaction. 

Chiral diaminocarbene complexes of copper were used in asymmetric conjugate addition of diethylzinc to Michael acceptors. Achiral copper carbene complexes derived from imidazolium salts were synthesized and characterized for the first time by Arduengo in 1993 [43]. In 2001, Woodward reported the use of such Arduengo-type carbene in copper-catalyzed conjugate addition and showed their strong accelerating effect [44]. The same year, Alex-... 

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]. 

Nair and co-workers have demonstrated NHC-catalysed formation of spirocyclic diketones 173 from a,P-unsaturated aldehydes 174 and snbstitnted dibenzylidine-cyclopentanones 175. Where chalcones and dibenzylidene cyclohexanones give only cyclopentene products (as a result of P-lactone formation then decarboxylation), cyclopentanones 175 give only the spirocychc diketone prodncts 173 [73]. Of particular note is the formation of an all-carbon quaternary centre and the excellent level of diastereoselectivity observed in the reaction. An asymmetric variant of this reaction has been demonstrated by Bode using chiral imidazolium salt 176, obtaining the desymmetrised product with good diastereo- and enantioselectivity, though in modest yield (Scheme 12.38) [74],... 

Asymmetric homogeneous catalysis generally requires chiral ligands. Approaches to chiral NHCs have focused on the generation of chiral centers either in the 4- and 5-position of imidazolidinium salts 71 or in the a-position of the nitrogen substituents for imidazolium salts 72. 

Recently, the oxidative addition of C2-S bond to Pd has been described. Methyl levamisolium triflate reacts with [Pd(dba)2] to give the cationic palladium complex 35 bearing a chiral bidentate imidazolidin-2-ylidene ligand [120]. The oxidative addition of the levamisolium cation to triruthenium or triosmium carbonyl compounds proceeds also readily to yield the carbene complexes [121], The oxidative addition of imidazolium salts is not limited to or d transition metals but has also been observed in main group chemistry. The reaction of a 1,3-dimesitylimidazolium salt with an anionic gallium(I) heterocycle proceeds under formation of the gaUium(III) hydrido complex 36 (Fig. 12) [122]. 

Also the use of moisture stable ionic liquids as solvents in the Diels-Alder reaction has been carried out, and in all examples an enhanced reaction rate was observed [182,183]. The application of pyridinium-based ionic liquids allowed the utilization of isoprene as diene [184]. The chiral ionic liquid [bmim][L-lactate] was used as a solvent and accelerated the reaction of cyclopentadiene and ethyl acrylate, however, no enantiomeric excess was observed [183]. In addition several amino acid based ionic liquids have been recently tested in the Diels-Alder reaction. Similar exo. endo ratios were found but the product was obtained as racemate. The ionic liquids were prepared by the addition of equimolar amounts of HNO3 to the amino acids [185]. Furthermore, an enantiopure imidazolium salt incorporating a camphor motive was tested in the Diels-Alder reaction. No enantiomeric excess was found [186]. 

The formation of a quaternary stereocenter could be achieved with a,a,a-trifluoroacetone as electrophile. An enantioselective procedure for this novel carbon-carbon bond-forming process has not been reported to date, the first results with a chiral imidazolium salt as precatalyst developed by Glorius et al. resulted in only low enantiomeric excesses (12-25% ee). 

Alternatively, a chiral imidazolium salt generates a chiral-activated ester which allows for the kinetic resolution of chiral secondary alcohols. Chan and Scheidt described this reaction of racemic 1-phenylethanol and cinnamaldehyde [62]. The enantiodiscrimination was explained by the chiral intermediate formed between the chiral imidazolium salt and cinnamaldehyde, which has sufficient facial selectivity to react preferentially with the (R)-stereoisomer of 1-phenylethanol. 

Suzuki et al. [74] and Maruoka and colleagues [75] made further progress in the enantioselective acylation of secondary alcohols 93. Suzuki et al. reported moderate enantiomeric excesses (up to 51% ee) when employing Ci symmetric chiral imidazolium salts 94 as precatalysts and vinyl acetate as acylation agent. How-... 

The first chiral NHCs of this type were developed by Herrmann and En-ders in 1996. Herrmann s group [6] synthesized a symmetric imidazolium salt 1 (as carbene precursor), starting from an enantiopure chiral amine which was readily converted to the heterocycle using a multi-component reaction previously developed by Arduengo [7]. After coordination to a rhodium(I) complex precursor (Scheme 1), this ligand was tested in the hydrosilylation of acetophenone. 

Chung et al. reported the enantioselective synthesis of chiral NHCs, such as 6, using a chiral ferrocene derivative (Scheme 8) [28]. The nucleophilic substitution of the hydroxy function by an imidazole in an acidic medium gives the imidazolium salt with retention of the configuration at the chiral C-atom. 

Fig. 6 A chiral bis(imidazolium) salt with a cyclohexane-1,2-diamine backbone...

Finally, Fiirstner et al. published the synthesis of the enantiopure chiral palladium(II) complex 29, in which the NHC, contains a trans-1,2-cyclohexanediamine backbone (Scheme 22), although no application of this system in catalysis has been reported to date [60,61]. The N-heterocyclic car-bene palladium complex is obtained by oxidative addition of Pd(PPh3)4 to 2-chloro-l,3-disubstituted imidazolium salts that are easily accessible. 

In 2000, Rajanbabu et al. published the synthesis and coordination chemistry of the first chiral NHC containing a l.T-binaphthyl unit as the chiral element (Scheme 24) [69]. It contains two imidazolium rings linked to the l,T-binaphlhyl backbone in the 2 and 2 position through methylene bridges. This linkage was achieved by nucleophilic substitution and the imidazolium salts subsequently generated in an N-quaternization step with methyl iodide. 

Scheme 33 Coordination chemistry of chiral ferrocenyl phosphine/sulfide-imidazolium salts...

Scheme 36 Design of a chiral bis(ferrocenyl)imidazolium salt...

Finally, two chiral monodentate N-heterocyclic carbene ligands that contain an oxazoline unit have been reported. Glorius et al. reported the synthesis of the imidazolium salts 76 by cyclizing the corresponding bisoxazolines 75 (Scheme 50) [133]. 

Building on the success of Woodward s use of an achiral NHC to catalyze the conjugate addition of dialkyl zincs, Alexakis and Roland simultaneously reported the use of chiral NHCs to achieve the asymmetric addition into enones. In Alexakis s system, the catalyst was generated in situ by addition of BuLi to a suspension of imidazolium salt 19, Cu(OTf)2, and enone in toluene followed by addition of Et2Zn (Eq. 28) [63]. While conversions and yields were found to be nearly quantitative, ee values were moderate with 51% being the highest reported. 

Glorius F, Altenhoff G, Goddard R, Lehmann C (2002) Oxazolines as chiral building blocks for imidazolium salts and N-heterocyclic carbene ligands. Chem Comm 2002 2704-2705... 

Figure 3.29 Synthesis of an oxazoline functionalised chiral imidazolium salt from serine.

Figure 3.50 Synthesis of a chiral amino functionalised NHC ligand by reduction of a chiral imino functionalised imidazolium salt using NaBH. ...

Note The racemic hydroxyl functionalised imidazolium salt can be purified (isolation of one enantiomer only) by standard chiral resolution techniques, i.e. via the tartrate. 

Figure 3.80 Stepwise introduction of a phosphino group and an imidazolium salt on a chiral paracyclophane.

The 2-chloro-imidazolium salt is accessible from the corresponding thione that can be synthesised by Kuhn s method [260] from the diamine. Using a chiral 1,2-diamino-cyclohexane scaffold produces a chiral samrated carbene. 

Phosphino functionalised carbenes do not need to be used in situ or the carbene complexes generated without the formation of the free carbene. Danopoulos et al. have isolated and structurally characterised a phosphino functionahsed carbene after deprotonation of the corresponding imidazoUum salt with KNfSiMej) [280], a feat repeated by Hodgson and Douthwaite using a chiral imidazolium salt [243]. 

A totally different approach to bis-carbene ligands on a cyclic scaffold comes from Burgess and coworkers [351], They start from AA -dimethyl-l,2-diaminocyclohexane and acetylate this compound with chloroacetic acid chloride. Addition of an N-substituted imidazole yields the chiral bis-imidazolium salt (see Figure 3.110). Reaction with silver(I) oxide and carbene transfer to palladium(II) completes the reaction sequence. 

A third example comes from Clyne et al. [358] and concerns the axial chiral binaphthyl backbone [359,360], itself known from phosphorus chemistry [361]. The synthesis starts from the trifluoromethylsulfonato substituted binaphthyl with a Kumada coupling reaction [291,292] with methytmagnesiumbromide. Oxidation with NBS yields the methyl brominated derivative that can be attached to the imidazole ring. Subsequent methylation results in the bis-imidazolium salt that is deprotonated to the bis-carbene and coordinated to the transition metal halide (Pd, Ni), a rather straightforward reaction sequence (see Figure 3.113). The overall yield for the four-step reaction to the bis-imidazolium salt is surprisingly good (65%). 

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