Organocatalysts quinidine

A series of quinidine-derived organocatalysts, solvents, and temperatures for the asymmetric allylic 5 2 reaction between 0-Boc-protected Morita-Baylis-Hillman adducts and carbamates or tosylcarbamates were tested. The best results were 0 obtained using the catalyst (2) in THF at 20 C. Most of the yields obtained using a variety of substrates were >80%, with >80% ee. 

In addition, the tertiary amine-catalysed asymmetric aldolisation of hydroxy-acetone with a variety of aromatic aldehydes was investigated by Mlynarski et al. in the presence of quinidine as the organocatalyst. " Although the corresponding products were formed in reasonable yields (10-96%), the moderate enantioselectivities (<47% ee) remained to be improved. Finally, Huang et al. 

After initial reports that natural alkaloids like quinidine (QD-1) can be applied as bifimctional chiral organocatalysts, several synthetically modified catalysts were prepared (Scheme 3.9) for the enhancement of their catalytic activity and enantioselectivity. - ... 

Cinchona-based organocatalysts with a guanidine functionality were studied by Lu and coworkers [93] and by the group of Park [94]. In the former study, several guanidines derived from quinidine were synthesized and observed to catalyze the asymmetric amination reaction of a-fluorinated ji-ketoesters (Scheme 6.44). 

The asymmetric reaction of nitromethane with aldehydes as well as activated ketones (e.g., trifluoroacetophenone and a-ketoesters) is possible with various chiral metallic complexes or organocatalysts under atmospheric pressure with good yield and enantioselectivity. However, the Henry reaction of aryl alkyl ketones still remains problematic and challenging. Matsumoto s group also tested the very difficult reaction of acetophenone and nitromethane with quinidine. No product was observed under Ibar and only traces at 7 kbar, but application of 10 kbar resulted in a significant improvement in yield (31%) -unfortunately, no enantioselectivity was detected (Scheme 21.3). 

Quinine 84 and quinidine 85 are well-known medicinally important alkaloids as well as mother structures for organocatalysts. Hatakeyama and co-workers reported on organocatalytic asymmetric synthesis of a key intermediate for these alkaloids. They performed the intramolecular direct aldol reaction of bis aldehyde 79 in the presence of L-proline 57. After reduction of the ketone, syn-diol 80 and anti-diol 81 were obtained with high enantiose-lectivity (Scheme 27.14). The mixture was converted into the common intermediate 83 for quinine 84 and quinidine 85 via ketone 82. Quinine 84 and quinidine 85 were... 

An efficient method for enantioselective synthesis of (3-nitroalkylphos-phonates (549) in good ee values (up to 84% ec), ia the Michael addition of diphenyl phosphite (547) to nitroalkenes (548), using the readily available quinidine thiourea organocatalyst (550), has been developed Zhao and coworkers (Scheme 136). ... 

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