Cinchona alkaloids oxindole derivatives

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

Chen and coworkers employed the cinchona alkaloid-derived catalyst 26 to direct Mannich additions of 3-methyloxindole 24 to the A-tosylimine 25 to afford the all-carbon quaternary center of oxindole 27 with good enantioselectivity (84% ee) [22]. The outcome of this Mannich reaction is notable in that it provided very good selectivity for the anti diastereomer (anti/syn 94 6). The mechanism of asymmetric induction has been suggested to involve a hydrogen bonding network between the cinchona alkaloid 26, the oxindole enolate of 24, and the imine electrophile 25 (Scheme 7). Asymmetric allylic alkylation of oxindoles with Morita-Baylis-Hillman carbonates has been reported by the same group [23]. 

C-alkylation of indanone derivatives and oxindoles using cinchona alkaloids... 

S. Oxindole Derivatives. Most recently, Curti et al. [140] disclosed the first example of a direct, organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindole to nitroalkenes. Bifunctional cinchona alkaloid/thiourea catalyst 69 could effectively promote the reaction, solely aHbrding the 7-substituted 3-alkylidene oxindoles 146 with excellent regio-, diastereo-, and enantioselectivities (Scheme 5.71). Importantly, both aromatic and aliphatic substituted nitroalkenes were applicable for such a reaction. 

Later, an enantioselective one-pot tandem Mannich-hydroamination reaction was reported by Liu and co-workers on the basis of a sequential organo- and gold catalysis.The proeess involved propargylated malonitrile and oxindole imine derivatives as substrates and employed a chiral cinchona alkaloid, such as a quinidine phenol derivative, to induce the enantioselective Mannich reaction and a gold catalyst, such as XPhosAuNTfa... 

The ease of preparation and generality of fluorination make the [N-F] class of reagents an excellent choice for enantioselective electrophilic fluorination. Advantageously, enantioselective electrophilic fluorination was also achieved with silyl enol ethers and oxindoles as substrates using a catalytic amount of bis-cinchona alkaloids and NFSI in the presence of excess base (Scheme 44.14). Applications of these [N-F] reagents include the enantioselective syntheses of a-fluoro-a-amino acid derivatives (Scheme 44.15), a potent opener of maxi-K channels (BMS-204352, MaxiPost Xi an Unique Electronics Chemical Co., Ltd, Xi an, P.R. China), and 20-deoxy-20-fluorocamptothecin (see section 3). 

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