Benzylquininium chloride

The addition of nitromethane to chalcones has been studied using N-benzylquininium chloride as the chiral phase-transfer catalyst and fluoride ion as the base (46). The enantiomeric excess was moderate (up to 26%). No conclusions were drawn from this study. 

In general, cydohexenones fail to give optically active products under phase-transfer, hydrogen peroxide, benzylquininium chloride, and basic reaction conditions (77). In fact, it appears that the starting material decomposes, since only water-soluble products are formed. Of several cydohexenones tried, only one, namely 4,4-diphenylcyclohexenone, furnished an optically active epoxide. 

Successful asymmetric epoxidation of 2-cyclohexen-l-one was achieved using /-butyl hydroperoxide, toluene, solid sodium hydroxide, and benzylquininium chloride. Cyclohexenone epoxide obtained in this manner has an e.e. of 20% ([ ] = -39°). 

Attempts to produce chiral cyanhydrins under phase-transfer catalytic conditions (3.3.9) using ephedrinium or cinchoninium catalysts has been singularly unsuccessful [21,22]. Optical purities varying from 0 to 60% have been recorded [22], but verification of the reproducibility of the higher values is needed. Similarly, nucleophilic attack on a carbonyl group by the trichloromethyl anion under phase-transfer catalytic conditions (see Section 7.4) in the presence of benzylquininium chloride produces a chiral product, but only with an enantiomeric excess of 5.7% [23]. The veracity of this observation has also been questioned [24],... 

Stereoselective ring cleavage and monoesterification of chiral Meldrum s acid derivatives has been achieved in high yield with a 34% enantiomeric excess under phase-transfer catalytic conditions in the presence of A-benzylquininium chloride [29]. A similar asymmetric ring-opening of prochiral (meso) acid anhydrides with... 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

Method C ( Bu02H in PhMe (80%, 10 ml) is added with stirring at room temperature to the alkene (15 mmol) and W-benzylquininium chloride (0.5 g, 1.1 mmol) in PhMe (10 ml). The mixture is stirred for 5 h, Et20 (25 ml) is added, and the mixture is extracted with H20 (4 x 50 ml). The dried (MgS04) organic phase is evaporated to yield the oxirane. Method D Aqueous NaOCl (115 g, 1.2 ml) is added to the alkene (1 mmol) and chiral catalyst (0.1 mmol) in PhMe (10 ml) at 250 C. The mixture is stirred for 24-48h and H20 (5 ml) is then added. The aqueous phase is separated, extracted with EtOAc (10 ml), and the combined organic solutions are dried (Na2S04) and evaporated to yield the chiral oxirane. 

Basic solid liquid two-phase conditions with f-butyl peroxide and N-benzylquininium chloride convert cyclohex-2-enone preferentially into the 2(S),3(S)-oxirane (20% ee) which, upon purification and treatment with hydrazine, yields (S)-cyclohex-2-enol [7]. This reaction contrasts with the direct reduction of cyclohex-2-enone to the /J-isomer by lithium aluminium hydride in the presence of quinine [20]. 

The stepwise formation of epoxides through the reaction of alkenes with sodium hypochlorite with, or without, the isolation of the intermediate chlorohydrin has been subjected to catalysis with (V-benzylquininium chloride under liquiddiquid two-... 

CMral tpoxyiutphthoquinones. Pluim and Wynberg1 have prepared a number of Optically active epoxides of 2-alkyl- and 2,3-dialkyl-l,4-naphthoquinones by Oxidation with 30% H202, aqueous NaOH, and benzylquininium chloride. Enantiomeric excesses of 43% can be realized, and these can be improved by Oiyitallization. The authors also report that the most satisfactory method for preparation of 2-alkyl-1,4-naphthoquinones is that of Jacobsen (5, 17 8, 18). 

Asymmetric epoxidathn (7, 311 8, 430) Optically active epoxides of cyclohexenones can be obtained by epoxidation with /-butyl hydroperoxide in toluene with solid NaOH and (-)-benzylquininium chloride as the chiral catalyst. In the case of a cyclohexenone the chemical yield is 60% and the optical yield is 20 3%. ... 

I.POXIDATION, ASYMMETRIC (--)-Benzylquininium chloride. f-Butyl hydroperoxide-Vanadyl acetoacetate. Hydrogen peroxide-1,1,3,3-Tetrachloro-aceione. (SM2-Hydroxy-N,N-diinethyl-propanamidc-OtO )oxodiperoxymolyb-denum(VI). 

NaOCl, cat chiral Mn(IH)-salen, N-benzylquininium chloride (enantioselective, cis-alkene to trans-epoxide)... 

Compared with boranes, borohydrides are inexpensive and easy to handle. As early as 1978 Colonna and Fornasier reported that aryl alkyl ketones such as acetophenone can be reduced asymmetrically by sodium borohydride by use of an aqueous-organic two-phase system and chiral phase transfer catalysts [20], In this study, the best enantiomeric excess (32%) was achieved when pivalophenone (11) was reduced in the presence of 5 mol% benzylquininium chloride (12) (Scheme 11.4) [20]. Other chiral phase-transfer catalysts, for example ephedrinium salts, proved less effective. 

The combined use of catalytic amounts of N-benzylquininium chloride (1) with hydroxide bases (NaOH or KOH) has been explored for a variety of phase transfer reactions, including epoxidations, alkylations, and Michael reactions. The degree of stereoselectivity in product formation induced by the reagent can vary widely. ... 

Benzylquininium chloride has shown good to excellent selectivity in the epoxidation of a,p-unsaturated ketones. Oxidation of quinone (2) in the presence of (1) with aqueous t-Butyl Hydroperoxide and Sodium Hydroxide in toluene gave rise to a 95% chemical yield of epoxide (3) in 78% ee (eq 1). Recrystallization improved the ee to 100% with 63% mass recovery. Aqueous Hydrogen Peroxide decreased both the yield (89%) and enantioselectivity (50% ee). 

Benzylquininium chloride has been studied as a catalyst for the asymmetric Michael reaction. Reaction of amidoma-lonate (5) and chalcone (4) with catalytic base and a variety of chiral, nonracemic ammonium salts in the absence of solvent produced (6) in yields of 41-68% and 20-68% ee (eq 2). The quinine-derived salt (1) was of intermediate effectiveness (38% ee, 47% yield) when compared to ephedrine-based catalysts. Although (1) was not specifically tested with regard to solvation effects, it is suggested that increased aggregation of reactive species under solid-liquid PTC conditions leads to enhanced organization and selec-... 

In 1978, Colonna and coworkers first demonstrated that in the presence of cinchona-derived PTCs, alkyl aryl ketones can be reduced asymmetrically with the inexpensive and easily handled sodium borohydride under aqueous-organic biphasic conditions. However, the enantiomeric excess of the corresponding alcohols was very disappointing. The best ee obtained in their study was 32% when pivalophenone was reduced in the presence of 5 mol% of benzylquininium chloride 1 (Scheme 5.28) [34]. Variants of this procedure were tried later by several research groups, but in all cases the enantioselectivities were too low for synthetic applications [35]. 

Chiral epoxides. (- )-Benzylquininium chloride (1) can introduce a considerable degree of asymmetry in several methods for preparation of epoxides. Actually the earlier method (enone and H2O2, 7, 311) is still the most effective an enantiomeric excess of 557 has since been achieved by carrying out the epoxida-tion at 3° for 90 hours. ... 

Asymmetric borohydride reduction. Colonna and Fornasier have examined the reduction of ketones with sodium borohydride under phase-transfer conditions in the presence of optically active ammonium salts containing at least one hydroxyl group. Of the seven catalysts tested (-)-benzylquininium chloride (1) (7, 311) was the most effective for asymmetric reduction of r-butyl phenyl ketone (pivalo-phenone) to the corresponding carbinol with optical yields as high as 32%. Two factors would appear to be important for this asymmetric reduction the catalyst must be conformationally rigid and the hydroxyl group must be in the 8-position to the onium function. ... 

Na-methoxide in methanol added to a suspension of N-benzylquininium chloride in THF at room temp., stirred for 10 min, added dropwise to a soln. of 5-phenyl-2,2,5-trimethyl-4,6-dioxo-l,3-dioxane in toluene at —50°, stirred for 15 min at —50°, then quenched with 3% citric acid (R)-product. Y 73% (e.e. 34%). The alkoxide forms an ion pair in situ with the chiral reagent. F.e.s. J. Hiratake et al.. Synthesis 1988, 278-80. 

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