Phase transfer catalysts, chiral solid

These observations showed that the reaction can be simplified by preformation of the indanone enolate in toluene/50% NaOH and subsequent addition of catalyst and CH3CI (Figure 12). This eliminates the "induction period and most importantly the high sensitivity of rate and ee to the catalyst/indanone ratio. Detailed kinetic measurements on this preformed enolate methylation in toluene/50% NaOH determined that the reaction is 0.55 order in catalyst. This is consistent with our finding that the catalyst goes into solution as a dimer which must dissociate prior to com-plexation with the indanone anion. If the rate has a first order dependence on the monomer, the amount of monomer is very small, and the equilibration between dimer and monomer is fast, then the order in catalyst is expected to be 0.5. The 0.5 order in catalyst is not due to the preformation of solid sodium indanone enolate but is a peculiarity of this type of chiral catalyst. Vlhen Aliquat 336 is used as catalyst in this identical system the order in catalyst is 1. Finally, in the absence of a phase transfer catalyst less than 2% methylation was observed in 95 hours. 

Taddol has been widely used as a chiral auxiliary or chiral ligand in asymmetric catalysis [17], and in 1997 Belokon first showed that it could also function as an effective solid-liquid phase-transfer catalyst [18]. The initial reaction studied by Belokon was the asymmetric Michael addition of nickel complex 11a to methyl methacrylate to give y-methyl glutamate precursors 12 and 13 (Scheme 8.7). It was found that only the disodium salt of Taddol 14 acted as a catalyst, and both the enantio- and diastereos-electivity were modest [20% ee and 65% diastereomeric excess (de) in favor of 12 when 10 mol % of Taddol was used]. The enantioselectivity could be increased (to 28%) by using a stoichiometric amount of Taddol, but the diastereoselectivity decreased (to 40%) under these conditions due to deprotonation of the remaining acidic proton in products 12 and 13. Nevertheless, diastereomers 12 and 13 could be separated and the ee-value of complex 12 increased to >85% by recrystallization, thus providing enantiomerically enriched (2S, 4i )-y-methyl glutamic add 15. 

The aim of this book is to provide a concise and comprehensive treatment of this continuously growing field of catalysis, focusing not only on the design of the various types of chiral phase-transfer catalyst but also on the synthetic aspects of this chemistry. In addition, the aim is to promote the synthetic applications of these asymmetric phase-transfer reactions by giving solid synthetic evidence. Clearly, despite recent spectacular advances in this area, there is still plenty of room for further continuous development in asymmetric phase-transfer catalysis. 

Whereas the results summarized in Scheme 4.32 were achieved under homogeneous reaction conditions, Colonna et al. reported the use of chiral phase-transfer catalysts for asymmetric addition of benzyl mercaptan and thiophenols to cyclohexenone and derivatives [55b], The best result was 85% yield and 36% enantiomeric excess in the addition of thiophenol to cyclohexenone, catalyzed by ca 0.4 mol% N-(o-nitrobenzyl)quininium chloride at 25 °C. In this experiment, CCI4 served as solvent and solid KF as the base. Finally, Aida et al. reported in 1996 that chiral... 

In an attempt to develop a PEG-supported version of a chiral phase-transfer catalyst the Cinchona alkaloid-derived ammonium salt 15 used by Corey and Lygo in the stereoselective alkylation of amino acid precursors was immobilized on a modified PEG similar to that used in the case of 13. The behaviour of the catalyst obtained 16, however, fell short of the expectations (Danelli et al. 2003). Indeed, while this catalyst (10 mol%) showed good catalytic activity promoting the benzy-lation of the benzophenone imine derived from tert-butyl glycinate in 92% yield (solid CsOH, DCM, -78 to 23 °C, 22 h), the observed ee was only 30%. Even if this was increased to 64% by maintaining the reac-... 

The reaction between ( )-2-bromoalkanoates and potassium phthalimide under solid-liquid phase transfer conditions using either (—)- or (-l-)-l-benzyl-cinchonidinium chloride as a chiral phase transfer catalyst gives optically active 2-phthalimido esters. ... 

Instead of using chloramine-T (pKa 13.5), the employment of more nucleophilic chloramine salt, A-chloro-A-sodiobenzyloxycarbamate (pKa 15.3), allows for an efficient aziridination of electron-deficient olefins (Michael acceptors) in the presence of a solid-liquid phase-transfer catalyst (Scheme 2.38) [57]. The reaction would involve an ionic pathway where the Michael-addition of chloramine salt to alkenes and the following back-attack of the resulting enolate at the electrophilic N-center to cyclize. This reaction was successfully extended to the asymmetric aziridination of the enones that have an auxiliary, to produce chiral aziridines with good enantioselectivities up to 87% ee. Another option to aziridinate electron-deficient alkenes is the utilization of... 

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

The unsubstituted catalyst (3) was also used in an asymmetric Gabriel synthesis of a-amino acids via solid-liquid chiral phase-transfer alkylation of potassium phthalimide with 2-bromocarboxylates. ... 

Alkylation of phthalimide anion can be carried out under solid-liquid phase-transfer conditions, using phosphonium salts or ammonium salts. In the reaction systems using hexadecyltributylphosphonium bromide, alkyl bromides and alkyl methanesulfonate are more reactive than alkyl chlorides. Octyl iodide is less reactive than the corresponding bromide and chloride. ( )-2-Octyl methanesulfonate was converted into (S)-2-octylamine with 92.5% inversion. Kinetic resolution of racemic ethyl 2-bromopro-pionate by the use of a chiral quaternary ammonium salt catalyst has been reported. Under liquid-liquid phase-transfer conditions, A -alkylation of phthalimide has been reported to give poor results. ... 

Enantioselective introduction of a side chain to glycine involves alkylation of 14, of 15, and a bomanesultam derivative under solid-liquid phase transfer catalysis conditions. Chiral catalysts serving in the alkylation of iV-protected glycine esters include the quatemized cinchona alkaloid 16. Another method involves alkylation of 17 (both enantiomers are available). 

A -Aroyl-A -substituted thiourea derivatives have been prepared from reaction of aroyl isothiocyanate with amines under solid-liquid phase transfer catalysis condition using polyethylene glycol-400 (PEG-400) as catalyst. Reaction of isothiocyanates with lithiated chiral secondary amines has provided chiral thioureas (Scheme 40). °... 

The importance of chiral epoxy-ketones is becoming increasingly recognized as physiologically active natural products, as metabolic intermediates, and as chiral synthons. Cyclohex-2-enones (1) have been transformed into optically active epoxycyclohexanones (2) using t-butylhydroperoxide in toluene, to which catalytic quantities of solid sodium hydroxide and the chiral catalyst quininium benzyl chloride were added, under phase-transfer conditions. In the unsubstituted case the yield is 60% with enantiomeric excess of 20% as determined by n.m.r. Substituents at C(2), C(3), and C(4) block the epoxidation reaction but compounds with gem-dimethyl groups at C(5) and C(6) are readily converted. 

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