It is shown that racemic oxazolones are excellent reagents for the synthesis of chiral quaternary amino acids and its derivatives by the diastereo- and enantioselective nucleophilic addition to alpha,beta-unsaturated aldehydes catalyzed by diarylprolinol silyl ethers. The scope of this new organocatalytic reaction is demonstrated for different oxazolones having aromatic and alkyl groups at the reactive carbon atom and different aromatic and aliphatic substituted alpha,beta-unsaturated aldehydes, for which the stereoselective reaction proceeds with good yield, moderate to good to very high diastereoselectivity, and very high enantioselectivity. The potential of the reaction is shown for the synthesis of optically active alpha,alpha-disubstituted alpha-amino acids, alpha-quaternary proline derivatives, amino alcohols, lactams, and tetrahydropyranes. Furthermore, we have calculated by DFT-methods the transition-state structures that account for both the diastereo- and enantioselectivity observed for the addition of oxazolones to the alpha,beta-unsaturated aldehydes. For one class of compounds, the stereoselectivity is controlled by a hydrogen-bonding interaction of the enolate-form of the oxazolone with an ortho-hydroxy-phenyl substituent of the alpha,beta-unsaturated aldehyde, whereas the benzhydryl-protecting group in the oxazolone determines the diastereo- and enantioselectivity in a more general manner for both aromatic and aliphatic alpha,beta-unsaturated aldehydes.
The first example of catalytic enantioselective nucleophilic aromatic substitution of beta-dicarbonyl compounds is presented. An O-benzoylated cinchona alkaloid derivative catalyst gave a selective C-arylation reaction compared to, e.g., the corresponding benzylated catalyst which provided a 1:1 mixture of the C- and O-arylation products. The reaction proceeds well for various aromatic compounds with different 1,3-dicarbonyl compounds, and the optically active products are obtained in very high yields and with up to 92% ee. One further scope of the organocatalytic enantioselective nucleophilic aromatic substitution reaction is demonstrated by the synthesis of the optically active spiro-pyrrolidone-3,3'-oxoindole structure.
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