Carbonyl cinchona-catalyzed nucleophilic

Cinchona-Catalyzed Nucleophilic a-Substitution of Carbonyl Derivatives... 

Cinchona-catalyzed nucleophilic a-substitution of carbonyl derivatives... 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

The tetrahedral intermediate is generated by a nucleophilic attack on the carbonyl carbon atom of the activated nucleophile, which in the case of chymotrypsin and trypsin is the catalytic Serl95. The mechanism of chymotrypsin can be compared to that of Song catalyst 77 that catalyzes the nucleophilic ring opening of acid anhydrides. The role of the sulfonamide group is played by the oxyanion hole amide NH groups, and the role of the cinchona alkaloid-derived base is played by the Asp-His-(Ser) dyad/triad. 

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