Cinchonidinium

Although several noble-metal nanoparticles have been investigated for the enantiomeric catalysis of prochiral substrates, platinum colloids remain the most widely studied. PVP-stabilized platinum modified with cinchonidine showed ee-values >95%. Several stabilizers have been also investigated such as surfactants, cinchonidinium salts and solvents, and promising ee-values have been observed. Details of a comparison of various catalytic systems are listed in Table 9.16 in one case, the colloid suspension was reused without any loss in enantioselectiv-ity. Clearly, the development of convenient two-phase liquid-liquid systems for the recycling of chiral colloids remains a future challenge. 

The N-anthracenylmethyl cinchonidinium catalyst 12 (R=PhCH2, X=HF2) was applied to the aldol reaction of the silyl ether 43 derived from the... 

The epoxidation of the dienone 92 proceeded to give the epoxide 93 using the cinchonidinium catalyst 9 (R=H, X=C1) with tert-butyl hydroperoxide.1701... 

The stereospecific C-alkylation of a range of benzylic ketones, such as tetralones, 2-phenylcyclohexanones and cycloheptanones, and 2-phenyl-y-lactones, has also been described [8]. For example, Af-(4-trifiuoromethylbenzyl)cinchonidinium bromide catalyses the reaction of 1,5-dibromopentane with 7-methoxy-l-methyl-2-tetralone to yield the (R)-l-(5-bromopentyl) derivative (75% yield with 60% ee). 

The aldehyde (3.38 mmol) and the cinchonidinium catalyst (40 mg, 16.9 imol) in CH2C12 (0.8 ml) are added to the O-silyl ketene acetal (0.676 mmol), derived from... 

The Robinson annulation reaction of 7-methoxy-l-methyl-2-tetralone with methyl vinyl ketone in the presence of A,-(4-trifluoromethylbenzyl)cinchonidinium bromide produces the S-isomer of the tricyclic compound (Scheme 12.10) with an 81% conversion (81% ee) [8]. 

Diastereomeric excesses of up 56% have been claimed for the preparation of a-amino-P-hydroxy acids via the aldol condensation of aldehydes with f-butyl N-(diphenylmethylene)glycinate [63]. It might be expected that there would be thermodynamic control of the C-C bond formation influenced by the steric requirements of the substituents, but the use of cinchoninium and cinchonidinium salts lead to essentially the same diastereoselectivity. The failure of both tetra-n-butylammo-nium and benzyltriethylammonium chloride to catalyse the reaction is curious. 

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. 

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. 

Phase-transfer catalysed oxidation of ketones with dioxygen under basic conditions in the presence of triethyl phosphite and a cinchonium salt produces a-hydroxy-ketones (Schemes 12.14 and 12.15, Table 12.9) in good overall yield (-95%) and with a high enantiomeric excess [>70% ee using N-(4-trifluoromethyIbenzyl)cincho-nium bromide] [29], Lower asymmetric induction is observed with ephedrinium salts, polymer-supported salts and, surprisingly, by cinchonidinium salts. 

This asymmetric phase-transfer method has been applied to enantio-selective Robinson annelation as shown in Scheme 14 (41). First, alkylation of a 1-indanone derivative with the Wichtetie reagent as a methyl vinyl ketone equivalent in the presence of p-CF3BCNB gives the S-alkylation product in 92% ee and 99% yield. With 1 -(p-trifluoro-methylbenzyl)cinchonidinium bromide, a pseudo-enantiomeric diaste-reomer of p-CF3BCNB, as catalyst, the -alkylation product is obtained in 78% ee and 99% yield. These products are readily convertible to the... 

Enantioselective Robinson annelation Alkylation of indanone 2 with 1,3-dichloro-2-butene (E/Z = 4 1) catalyzed by 1 gives (S)-3 in 92% ee. The enantiomer, (R)-3, is obtained by the same alkylation but catalyzed by N-(/ -trifluoro-methylbenzyl)cinchonidinium bromide in 78% ee and 99% yield. Optically pure 3 undergoes hydrolysis and cyclization in high yield. Demethylation and alkylation provides the desired tricyclic enone 4 in 83% overall yield from (R)-3. 

N-(p-Trifluoromethylbenzyl)-cinchonidinium bromide, 325 N-(p-Trifluoromethylbenzyl)-cinchoninium bromide, 325 Tris[2-(2-methoxyethoxy)ethyl]amine, 336... 

Subsequent generations of catalyst (Scheme 10.4 and Tables 2 and 3) have led to increased product enantioselectivity. In the second generation, the A-benzyl-O-allyl cinchonidinium... 

Toda, F., Tanaka, K., Stein, Z., and Goldberg, I. (1994) Optical Resolution of Binaphthol and Biphenanthryl Diols by Inclusion Crystallization with V-Alkyl- cinchonidinium Halides. Structural Characterization of the Resolved Materials, J. Org. Chem., 59, 5748-5751. 

The enolate derived from the Schiff base 3 has been added to a,/ -unsaturated esters and ketones with a high level of enantioselectivity. For example, in the presence of 10 mol% lb, the enolate of the glycine derivative 3 was added to cyclohexenone with excellent diastereo-selectivity to give the ketoester 20 with >99% ee (Scheme 7) [15]. Promising results have also been obtained in the Michael additions of malonates to chalcone deriviatives [16], The novel cinchonidinium bromide lg was found to be the most effective catalyst for this transformation, yielding the Michael adduct 21 with 70% ee (Scheme 8). 

Two different epoxidation reactions have been studied using chiral phase transfer catalysts. The salts 22 and 23 have been used to catalyse the nucleophilic epoxidation of enones (e.g. 24) to give either enantiomer of epoxides such as 25 (Scheme 9) [17]. Once again, the large 9-anthracenylmethyl substituent is thought to have a profound effect on the enantio selectivity of the process. A similar process has been exploited by Taylor in his approach to the Manumycin antibiotics (e.g. Manumycin C, 26) [18]. Nucleophilic epoxidation of the quinone derivative 27 with tert-butyl hydroperoxide anion, mediated by the cinchonidinium salt la, gave the tx,/ -epoxy ketone 28 in >99.5% ee (Scheme 10). 

Corey studied the X-ray crystal structures of cinchonidinium salts and has formulated a model which explains the highly enantioselective alkylation of the enolate of 3 [3]. This model accounts for the sense of asymmetric induction in this process and the importance of the size of the R1 substituent in the salts 1 and 2 the model can be used to rationalise other phase transfer catalysed processes involving similar catalysts. The enolate 37 is thought to be in close contact with the least hindered face of the tetrahedron formed by the four atoms surrounding the quaternary nitrogen atom (the rear face of this tetrahedron is blocked by the bulky 9-anthracenylmethyl group). Alkylation of the less hindered face of 37 leads to the observed enantiomer of the product (see Figure 1). 

The advantages of PTC reactions are moderate reaction conditions, practically no formation of by-products, a simple work-up procedure (the organic product is exclusively found in the organic phase), and the use of inexpensive solvents without a need for anhydrous reaction conditions. PTC reactions have been widely adopted, including in industrial processes, for substitution, displacement, condensation, oxidation and reduction, as well as polymerization reactions. The application of chiral ammonium salts such as A-(9-anthracenylmethyl)cinchonium and -cinchonidinium salts as PT catalysts even allows enantioselective alkylation reactions with ee values up to 80-90% see reference [883] for a review. Crown ethers, cryptands, and polyethylene glycol (PEG) dialkyl ethers have also been used as PT catalysts, particularly for solid-liquid PTC reactions cf. Eqs. (5-127) to (5-130) in Section 5.5.4. 

Asymmetric Alkylation. 7Y-[4-(Trifluoromethyl)benzyl]-cinchoninium bromide (1) has been used as chiral phase-transfer catalyst in the alkylation of indanones (eq 1). For the alkylation of a-aryl-substituted carbonyl compounds the diastere-omeric 7Y-[4-(trifluoromethyl)benzyl]cinchonidinium bromide (2) was used to obtain the opposite stereochemistry (eqs 2 and 3). The asymmetric alkylation of oxindoles was used as the key step in an asymmetric synthesis of (—)-physostigmine (eq 4). ... 

PREPARATION OF 0-ALLYL-N-(9-ANTHRACENYLMETHYL) CINCHONIDINIUM BROMIDE AS A PHASE TRANSFER CATALYST FOR THE ENANTIOSELECTIVE ALKYLATION OF GLYCINE BENZOPHENONE IMINE tert-BUTYL ESTER (4S)-2-(BENZHYDRYLIDENAMINO)PENTANEDIOIC ACID, 1-tert-BUTYL ESTER-5-METHYL ESTER... 

B. 0-Allyl-N-(9-Anthracenylmethyl)cinchonidinium bromide. A 1-L, three-necked flask, equipped with an overhead stirrer and nitrogen inlet, is charged with 49.5 g (80.7 mmol) of N-(9-anthracenyhnethyl)cinchonidinium chloride-toluene solvate, 400 mL of methylene chloride (CHjClj), 25 mL of allyl bromide (35.0 g, 289 mmol) (Note 6) and 50 mL of 50% aqueous potassium hydroxide (Note 7). The mixture is stirred vigorously for 4 hr, then diluted with 400 mL of water and stirred for 5 min. After separation of the phases, the organic phase is washed with a solution of 25 g of sodium... 

Allyl bromide (99%) was purchased from the Aldrich Chemical Co., Inc. and used as received. Excess reagent is used, as hydrolysis of the allyl bromide is competitive with the 0-alkylation of N-(9-anthracenylmethyl)cinchonidinium chloride. 

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