Amino acid derivatives cinchona-based catalysts

Asymmetric synthesis of unnatural j8-amino acids derivatives based on azide chemistry is known. Enantioselective desymmetrization of mera-anhydride 293 mediated by cinchona alkaloids gives optically active monomethylester 294. This compound was converted into the acyl azide, which underwent Curtius degradation followed by alcoholysis of the intermediate isocyanate affording 8-amino acid derivative 295 in high enantiomeric excess. The authors observed that Grubbs catalyst was able to polymerize norbomene-type monomer 295 affording the corresponding polymer 296 in quantitative yield (Scheme 3.45). 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

The intramolecular alkylation of the enolate derived from phenylalanine derivatives 22a,b to form P-lactams 23a,b has also been achieved using Taddol as a chiral phase-transfer catalyst (Scheme 8.11) [23]. In this process, the stereocenter within enantiomerically pure starting material 22 is first destroyed and then regenerated, so that the Taddol acts as a chiral memory relay. Taddol was found to be superior to other phase-transfer catalysts (cinchona alkaloids, binol, etc.) in this reaction, and under optimal conditions (50 mol % Taddol in acetonitrile with BTPP as base), P-lactam 23b could be obtained with 82% et. The use of other amino acids was also studied, and the... 

Considering that the a-proton-exchange of racemic azlactones occurred rapidly in the presence of a tertiary amine base. Song and coworkers demonstrated enan-tioselective synthesis of a-deuterated a-amino acids via dynamic kinetic resolution (DKR) of azlactones with EtOD using cinchona-derived dimeric squaramide catalyst 33 (Scheme 10.34) [112]. The authors noted that by increasing the amount of EtOD, the level of deuterium incorporation increased, whereas the enantioselectivity decreased. By using 50 equivalents of EtOD, the products were obtained with... 

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