Quininium salts

As is the case in all other quinine-catalyzed reactions, the quininium-salt-catalyzed phase-transfer reactions are subject to strong solvent effects (Table 8) (81). The fact that, in the presence of water, polar solvents lower the e.e., whereas apolar solvents raise the e.e., indicates that these are true phase-transfer reactions in which the ion pairs within the organic layer are responsible for the asymmetric induction. 

Modifications in the benzyl portion of the molecule are significant. The nitro group in the benzyl portion of the molecule apparently increases the local polarity of the transition state. The influence on the chemical and enantiomeric yield of variations in the benzyl portion of the quininium salt was dramatically confirmed recently by the work of Dolling and coworkers on the phase-transfer alkylation of a hydrindanone (83). 

Stability of ephedrinium and quininium salts under phase-transfer catalytic conditions Catalyst Reaction conditions % decomposition... 

Asymmetric alkylation of a-substituted benzyl cyanides has been achieved using A-benzylquininium and cinchonium salts using procedures analogous to those described in 6.2.2 [19, 20], Analogous reactions catalysed by l-alkyl-3-hydroxy-quinuclidinium salts are less effective than those catalysed by quininium salts [20], whereas 1 -methyl-1 -diphenylmethyleneimino-2(5)-hydroxymethylpyrroli-dinium iodide is a more effective catalyst (>70% ee) [18]. 

The use of quininium salts can add to the high stereoselectivity (65-80% ee) that can be achieved under phase-transfer catalytic conditions in the synthesis of oxiranes by the Darzens reaction (Section 12.1) from chloromethylsulphones and aromatic aldehydes [6],... 

C-alkylated Meldrum s acid derivatives are cleaved asymmetrically by alkoxide anions in the presence of quininium salts to yield chiral half esters (9.2.2) [11]. Thus, benzylquininium and cinchonidinium salts produce fl-hemi-esters and the cincho-nium and quinidinium salts produce the S-hemi-esters from, for example, 2,2,5-trimethyl-5-pheny 1-1,3-dioxane-4,6-dione. 

Method B The quininium salt (0.05 mmol) and LiOH (47.9 mg) are added to the alkene (1 mmol) in CHClj (3 ml) and aqueous H202 (30%, 1 ml) at -10°C and the mixture is stirred for ca. 5 h at-10C. Aqueous HCI (1M, 3 ml) is added and the mixture is extracted with Et20 (3x15 ml) and washed with brine (20 ml). Evaporation of the dried (Na2S04) organic phase yields the chiral oxirane. ( Optimum ee was obtained using the N-(a-naphthyl) salt.)... 

In thorough work of related interest, the resolution of the arsonthious ester 2-p-carboxyphenyl-5-methyl-l 3-dithia-2-arsindane (141) was described by the fractional crystallization of the (+)-a-methylbenzylammonium and the ( —)-quininium salts the former yielded the (—)-acid, [a]i, —8.7° (CHCI3) the latter the (+)-acid, [a]D + 8.9° (CHCl3) . The optical stability of the compound was unaffected by crystallization from boiling ethanol, but in pyridine the rotation of the (—)-acid reached half-value within 6 weeks. The compound racemized more rapidly in 0.1 N sodium hydroxide, which was attributed to fission of the arsenic-sulphur bonds. 

The foregoing approach to the aza-Henry reaction can be also classified as an example of chiral phase transfer catalysis. A more recent example of chiral phase transfer catalysis in water was made possible by a careful molecular design aiming at incorporating into the same species both a water soluble frame in the form of a long PEG chain and two catalytically active quininium salt moieties. The synthetic plan is shown in Figure 13 The... 

The enantiomeric excess of 7 can be improved by recrystalhzation of its quinine salt, using the following procedure to a solution of 7 (74% ee, 5.12 g, 30.1 mmol, lequiv) in MeOH (36 ml) was added a solution of quinine (12.4 g in 12.8 ml of MeOH, 38.2 mmol, 1.3 equiv) and the solution was stirred at 40°C for 10min. Then, the solvent was evaporated, the residue redissolved in AcOEt (25 ml) and heated under reflux for 10 min. After coohng to room temperature, the mixture was filtered to eliminate the excess of quinine. The filtrate was evaporated and the solid (15.65 g) crystallized from MeOH (about 20 ml) to obtain the quininium salt as a white sohd. 

To recover the acid, the quininium salt was dissolved in a 10% HCl solution in water (500ml) and extracted with AcOEt (3x 240ml). The combined organic phases were washed with 10% HCl (2 x 50 ml), brine (2x 40 ml), and H2O (40 ml). The organic phase was dried with Naj SO4 and the solvent was evaporated to obtain the enantiomerically pure (lS,2S)-diacid 7 (3.7g, 82%). Quinine was recovered by treatment of the acidic water solution with NaOH. The sohd was filtered and washed with HtO. 

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