Asymmetric quaternization

Takemoto and coworkers extended their palladium-catalyzed asymmetric allylic alkylation strategy using allyl acetate and chiral phase-transfer catalyst to the quaternization of 13 [23b]. A correct choice of the achiral palladium ligand, (PhO P, was again crucial to achieve high enantioselectivity and hence, without chiral phosphine ligand on palladium, the desired allylation product 15 was obtained with 83% ee after hydrolysis of the imine moiety with aqueous citric acid and subsequent benzoylation (Scheme 2.12). 

This powerful quaternization method enabled the catalytic asymmetric synthesis of quaternary isoquinoline derivatives with 42 (R1 = Me) as a substrate. When 42 (R1 = Me) was treated with a,a -dibromo-o-xylene, CsOHH20 and (S,S)-le (1 mol%) in toluene at 0 °C, the transient monoalkylation product was rapidly produced, and subsequently transformed into the desired 44 (64%, 88% ee) during the work-up procedure. Catalytic asymmetric alkylation of 42 (R1 = Me) with functionalized benzyl bromide 45, followed by the sequential treatment with 1 M HC1 and then excess NaHC03, furnished the corresponding dihydroisoquinoline derivative 46 in 87% with 94% ee (Scheme 5.23) [25]. 

The quaternization method is also highlighted by the short asymmetric synthesis of cell adhesion molecule BIRT-377 (Scheme 5.24), which is a potent inhibitor of the interaction between intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) [16]. Thus, asymmetricp-bromobenzylation of the alanine derivative 42 (R1 = Me) with (S)-18 under similar phase-transfer conditions as described above gave rise to p-bromobenzylalanine ester 10 in 97% ee (83% yield). A similar asymmetric p-bromobenzylation of alanine ethyl ester 42 (R1 = Me, R= Et) gave the amino ester 47 (R= Et) in 90% ee (86% yield). The amino ester 47 (R = t-Bu or Et) was treated with 3,5-dichlorophenyl isocyanate in the presence of sodium carbonate in dimethylsulfoxide (DMSO) to furnish the hydantoin 48 in 86%... 

A new C3-symmetric chiral phase-transfer catalyst that offers multipoint inteaction with a nucleophile has been described (Scheme 7.6) [23]. Thus, various quaternary ammonium salts were prepared through the ring opening of optically active epoxides, followed by quaternization of the resulting amines. Asymmetric benzylation of Schiff s base 20 in the presence of catalyst 24—26 yielded (S)-21 with moderate enantioselectivity. As expected, the C3-symmetric catalyst R,R,R)-26a provided... 

The PDMAEMA stars are weak cationic polyelectrolytes. But they can be easily transformed into strong cationic polyelectrolytes poly [2-(methacryloyloxy)ethyl] trimethylammonium iodide] (PMETAI) stars by quaternization with methyl iodide. Asymmetric field flow fractionation (AFFF) measurements showed that the silsesquioxane core remained intact. The PMETAI brushes were also subjected to... 

The salt is prepared by quaternization of (-)-ephedrine with methyl bromide. Asymmetric oxirane synthesis. Japanese chemists have reported asymmetric synthesis of 2-phenyloxirane from benzaldehyde and dimethylsulfonium methylide generated from tiimethylsulfonium iodide in 50% NaOH with the chiral phase-transfer catalyst (-)-N,N-dimethylephedrinium bromide (1). 

Numerous creative solutions for asymmetric bond installation have been unveiled as a result of experimental efforts directed toward quaternization of oxindole C3. Examples in this section have been broadly categorized on the basis of the nature of the functionality that has been installed at C3 (i.e., C3-carbon, C3-oxygen, or C3-nitrogen bond construction). 

Enantioselective Phase-Transfer Catalyzed Reactions. TAA salts are readily available as single enantiomers via quaternization of trialkylamines containing chiral substituents, most often alkaloids. One could therefore expect that use of chiral TAA salts as PT catalysts would result in enantiodifferentia-tion in reactions of prochiral educts, thus affording asymmetric synthesis. A priori... 

A variety of chiral phase-transfer catalysts have been developed and successfully used in asymmetric syntheses of a-amino acids [19. 23, 24]. In 1984, researchers at Merck described the methylation of indanone 74 in the presence of the quaternized cinchona salt 75 as a chiral phase-transfer catalyst (Scheme 10.12) [66]. The alkylation product 76 was isolated in 92% ee and 95 % yield and subsequently elaborated into (-H)-indacrinone (77), which had previously only been prepared by resolution techniques. 

Researchers at Merck documented that the N-benzylated cinchonidinium derivative 112 was an excellent phase-transfer catalyst in the Michael addition of 2-propylindanone 111 to 74 (Scheme 12.14) [108]. The reaction is conducted in a biphasic medium (50% aq. NaOH/toluene) with substoichio-metric quantities of the quaternized cinchonidinium salt 112 [109]. The adduct 113 was isolated in 95 % yield and 80 % ee and served as a key intermediate en route to an asymmetric synthesis of the drug candidate 114 [108]. 

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