Asymmetric chiral cation

The lipophilicity of the TRISPHAT anion 8 also confers to its salts an affinity for organic solvents and, once dissolved, the ion pairs do not partition in aqueous layers. This rather uncommon property was used by Lacour s group to develop a simple and practical resolution procedure of chiral cationic coordination complexes by asymmetric extraction [134,135]. Selectivity ratios as high as 35 1 were measured for the enantiomers of ruthenium(II) trisdiimine complexes, demonstrating without ambiguity the efficiency of the resolution procedure [134]. 

Collins and co-workers have performed studies in the area of catalytic enantioselective Diels—Alder reactions, in which ansa-metallocenes (107, Eq. 6.17) were utilized as chiral catalysts [100], The cycloadditions were typically efficient (-90% yield), but proceeded with modest stereoselectivities (26—52% ee). The group IV metal catalyst used in the asymmetric Diels—Alder reaction was the cationic zirconocene complex (ebthi)Zr(OtBu)-THF (106, Eq. 6.17). Treatment of the dimethylzirconocene [101] 106 with one equivalent of t-butanol, followed by protonation with one equivalent of HEt3N -BPh4, resulted in the formation of the requisite chiral cationic complex (107),... 

However, in the presence of Lewis acids such as AlBr3, without the presence of the CpFe(CO)2+ Lewis acid the [3 + 2[-cycloaddition process was more effective, giving the product in 45% yield. The application of a chiral cationic CpFe(diphosphine) complex as the catalyst (Scheme 9.37) for the asymmetric [3 + 2]-cycloaddition of nitrones to acrolein derivatives was described by Kiindig and coworkers [95],... 

S. Oi, E. Terada, K. Ohuchi, T. Kato, Y. Tachibana, and Y. Inoue, Asymmetric hetero Diels-Alder reaction catalyzed by chiral cationic palladium(II) and platinum(II) complexes, J. Org. Chem., 64 (1999) 8660-8667. 

In cathodic reactions, adsorption effects would be expected to arise predominantly from adsorbed cations. Perhaps the most interesting phenomenon ascribable to adsorption of cations is the asymmetric induction observed when cathodic reduction of a prochiral substrate is performed in the presence of a chiral cation (Gourley et al., 1967 Homer and Degner, 1948). Table 18 summarizes a few selected cases of this reaction type (for reviews see Homer et al., 1972 Eberson and Homer, 1973) just to illustrate the scope of the reaction. The structural variables affecting the optical yield are unfortunately too complex to cover here. 

Characteristic of this process is the low concentration of chiral cation necessary to induce optical activity (10% of the substrate concentration is sufficient) and that the chiral salt is recovered mostly unchanged (except for no. 3). Quaternary ammonium ions work as well as substituted ammonium ions, thereby making less probable the mechanism first suggested (Gourley et al., 1967, 1970), namely, hydrogen atom transfer from an ammonium radical R3NH to the substrate. Today it seems reasonably well established that adsorption of the chiral cation, possibly as a complex with an intermediate is connected with the asymmetric induction observed (Horner et al., 1972 Kariv et al., 1973a). 

Asymmetric Induction during Cathodic Reduction of Prochiral Compounds in the Presence of Chiral Cations... 

Although efficient asymmetric catalytic transformations involving anionic intermediates with chiral, cationic catalysts have been realized (for several reviews, see Houk and List 2004), analogous versions of inverted polarity with reasonable enantioselectivity, despite attempts, have been illusive (Scheme 22 Eqs. 39 10 for a review, see Lacour and Hebbe-Viton 2003 see also Llewellyn and Arndtsen 2005 Dorta et al. 2004 Carter et al. 2003). 

Some attempts have been made towards asymmetric Diels-Alder reactions by using chiral ionic liquids. However, neither with a chiral cation, viz. A r.A r-di(2. S -2 -mcthylbutaiic)imida/olium.1116 nor a chiral anion, viz. /.-lactate, 117 could any significant chiral induction be observed. However, substantial chiral induction was achieved with a chiral organic catalyst immobilised in either [C4Ciim][PF6] or [C4Ciim][SbF6], as shown in Scheme... 

In the reaction between cyclohexadiene and acrylate, ees as high as 93% could be observed. An ionic liquid composed of a structurally related chiral cation is thus likely to promote asymmetric Diels-Alder reactions. 

A number of CSPs have been developed that are based on optically active synthetic helices formed by the asymmetric polymerization of methacrylate monomers. These polymers have been formed using either chiral monomers such as (S)-acryloylphenyl-alanine (73) and N-methylacryloyl-(S)-cyclohexylethylamine (73), or achiral monomers such as triphenyl methacrylate (74) and diphenyl-2-pyridyl-methyl methacrylate (74). In the latter case, the polymers were prepared using chiral cation catalysts including (—)-spartene-butyllithium and (+)-6-benzylsparteine-butyllithium complexes (74). The commercially available forms of these CSPs are listed in Table 3. 

Chiral cationic Pd-complexes with phosphinooxazolidine (POZ) represent another choice of catalyst for asymmetric Diels-Alder reaction [59]. Polymer-supported cationic POZ catalyst 107 effectively catalyzed the Diels-Alder reaction of cyclopentadiene 104 and acryloyl-1,3-oxazolidin-2-one 108 (Scheme 3.30). 

In 2008, Fan and Xu developed an air stable and phosphine free Ir catalyst for the asymmetric hydrogenation of quinolines [20]. They used chiral cationic Cp Ir(OTf) (CF3TSDPEN) complex as catalyst ]21]. The reaction proceeded smoothly in unde gassed methanol with no need for inert gas protection and afforded the 1,2,3,4 tetrahydroquinoline derivatives in up to 99% ee (Table 10.3). The counterion of iridium catalyst is very important, OTf gave high reactivity and enantioselectivity, and no reactivity was observed for chloride. It is noted that it is one ofthe best results of asymmetric hydrogenation of quinolines. 

The above catalytic systems for the asymmetric hydrogenation of quinolines are mainly iridium catalysts. In 2008, Fan and coworkers developed recyclable phos phine free chiral cationic ruthenium catalyzed asymmetric hydrogenation of qui nolines [23]. They found that the phosphine free cationic Ru/TsDPEN catalyst exhibited unprecedented reactivity and high enantioselectivity in the hydrogenation of quinolines in neat ionic liquid. The results were very excellent and enantioselec... 

Nakai and a coworker achieved a conceptually different protonation of silyl enol ethers using a chiral cationic palladium complex 40 developed by Shibasaki and his colleagues [61] as a chiral catalyst and water as an achiral proton source [62]. This reaction was hypothesized to progress via a chiral palladium enolate which was diastereoselectively protonated by water to provide the optically active ketone and the chiral Pd catalyst regenerated. A small amount of diisopropylamine was indispensable to accomplish a high level of asymmetric induction and the best enantioselectivity (79% ee) was observed for trimethylsilyl enol ether of 2-methyl-l-tetralone 52 (Scheme 11). 

Asymmetric oxidative alkylation of free tetrahydroisoquinolines 9 was recently described by Sodeoka and co-workers (Scheme 6) [22, 23]. Through the use of a chiral cationic palladium(II) species 10, The enantiopure alkylated BOC protected amines 11 were obtained with good yields and enantioselectivity. The alkylation is believed to occur through the initial protection of the amine with (Boc O, followed... 

An asymmetric lithium halogen exchange is possible by the reaction of metalated bislactim ether with electrophiles. The diastereoselectivity of this transformation is high in many cases176 and the resulting chlorides are useful synthons for chiral cationic amino acids. 

Ionic liquids containing chiral cations and which can be prepared enantiomerically pure on a kg scale, have also been developed with the potential for applications as solvents in asymmetric synthesis and catalysis. Two examples are... 

The enantioselective synthesis of (-i-)-shikimic acid and (-i-)-5-ep/-shikimic acid by an asymmetric Diels-Alder reaction of (5)-a-sulfmylacrylates with furan was reported. In the Diels-Alder reaction between acryloyloxazolidinone and furan catalyzed by a chiral cationic Cu(II) complex a high enantioselectivity was observed <97TL57>. The synthesis of ubiquinones-3 specifically labelled with C at the C(5)- or C(6)-positions starting with 2,5-bis(trimethylsilyloxy)-3-methylfuran and (2- C)-2-bromo-l,2-dichloroethene was reported <97T2505>. Diels-Alder reactions of 5-triisopropylsilyl-2-vinylfuran and 2-triethylsilyl-4-vinylfuran with acetylenic and olefinic dienophiles occur with high site specificity in the extraannular mode to produce trialkylsilylbenzofuran derivatives <97H(45)1795>. 

As one of the most important methodologies for carbon-carbon bond construction, asymmetric ene reactions catalyzed by chiral Lewis acids have received great attention in recent years [172-175]. An effective chiral cationic... 

I Ls containing a chiral cation ora chiral anion have been reported and are thought to play an important role for asymmetric synthesis or for chiral separation (6-9) [32-37]. A chiral IL based on l-((-)-menthoxycarbonylmethylene)-3-mefhylimida-zolium) hexafluorophosphate has been applied in stereospecific free-radical polymerization of vinyl monomers. The asymmetric environment of chiral ILs is believed to have some effect on the stereostructure of polymers [38]. 

Similarly, a [Pd2(dba)3]/dppb catalyst in toluene at 100 °C isomerizes PhC(O)—C=C—Bu into the dienone PhC(0)CH=CH—CH=CHEt in good yields. A variety of dienones has been prepared in this way. " There can be little doubt that all these reactions proceed via Pd Tr-allyl intermediates. The asymmetric isomerization of 4-hydroxycyclopent-2-en-l-one is catalyzed by [(R)-BINAP)Rh(MeOH)2] and gives 4-hydroxycyclopent-3-en-l-one as the primary product. With racemic starting material, the 5 enantiomer is consumed faster, to give a 5 1 enantiomeric discrimination. The primary product can tautomerize to 1,3-cyclopentadione. The same chiral cationic rhodium catalyst is also effective in the asymmetric isomerization of allylamines. Water impurities deactivate the catalyst. One such deactivation product is the air-stable trinuclear cluster (20), which was characterized by X-ray diffreaction. "" ... 

Following on from the pioneering strategy of applying chiral solvents in asymmetric synthesis, developed by Seebaeh and Oei, chiral ILs have also been applied in the enantioseleetive MBH reaction. Vo-Thanh et al. first reported the asymmetrie induetion eaused by a chiral IL 309 as the only source of chirality in an asymmetric reaction. In the DABCO-catalyzed MBH reactions of aldehydes and methyl acrylate, they obtained enantioselectivities up to 44% ee by using an IL 309 with chiral cations derived from (-)-A-methyl-ephedrine as reaction media (Scheme 1.122). Importantly, the presence of the hydroxyl function on chiral ILs 309 is propitious for the transfer of chirality. 

The asymmetric counteranion directed organocatalysis has been also applied to the enantioselective transfer hydrogenation of a,f)-unsaturated ketones employing catalyst 11, which involves a chiral cation such as a valine ester anunonium salt and a chiral binaphthol derived phosphate [23]. This combination, in the presence of the Hantzsch ester 4, is a very active and enantioselective system for the transfer hydrogenation of a variety of cyclic a,P-unsaturated ketones (Scheme 2.5). Acyclic ketones are also reduced but with slightly lower enantioselectivities. 

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