Research And Application Of The Asymmetric Reactions Promoted By The Organocatalysts Derived From Amino Acid

Due to the environmental and economic benefits, organic catalysts derived from amino acid have various applications in recent years. In this article, several different types of reaction were investigated for the application of organiccatalysts derived from amino acid.1) We developed an asymmetric method for the Michael addition between β-nitro enamine and a,β-unsaturated aldehydes. Treatment of a,β-unsaturated aldehydes with nitro-methylene imidazole can afford products through Michael reaction and sebesquent acetal-amination. Good yield and moderate to excellent stereoselectivities (up to 10:1 dr and 95 ee) were obtained when diphenylprolinol silyl ether was used as catalyst. This catalytic system shows good flexibility when aliphatic unsaturated aldehydes are employed. Enlarging the reaction scale to gram has no effect on enantioselectivity. Commercialized insecticide Paichongding with optical activity was obtained by simple etherification.This was the first attempt of chiral neonicotinoid insecticides synthesis by direct asymmetric organocatalysis.2) General asymmetric phosphine catalysis system was limited to reactions involving electron-deficient alkenes, allenes, or alkynes. In this article, we have developed a new asymmetric dual reagent catalyst system consisting of a bifunctional thioureaphosphine derived from amino acids and methyl acrylate as the additive. This catalyst system can efficiently catalyze the direct Mannich-type reaction of β-ketoesters with N-Boc-aldimines at low temperature in a short time to afford the desired products in good yields and high diastereo-and enantioselectivities. The reaction proceeded efficiently with electron-rich, electron-deficient, and heteroaromatic groups. The catalytic system was also suitable for the Mannich reaction of a variety of cyclic β-ketoester substrates. The practicality of this method was also demonstrated by transforming one of the products into a novel P-amino alcohol and a spiro-lactam.With the success of the employment of dual reagent catalytic system to the asymmetric Mannich reaction, we tried to catalyze the Henry reaction of nitromethane to carbonyl compounds by using this novel catalytic system. Unfortunately, although the reaction catalyst, additive, temperature, solvent and substrate were screened and the change of meticulously, we still did not get the good stereoselectivity of this Henry reaction. We expected the low stereoselectivity may be due to strong basicity of the zwitter ionic intermediates generated form chiral phosphorus and acrylate, the retro Henry reaction was too fast so that the racemization was occurred by the background reaction. The following work will focus on the modification of substrate to inhibit the retro-Henry reactions, and application of the dual reagent catalytic system to other types of reaction.3) The quinolizidine skeleton is found in a large number of naturally occurring compounds and these alkaloids. In order to combine both reaction activity and functionalization, N-(2-(1H-indol-3-yl)ethyl)-2-(phenylsulfonyl)acetamide was employed in the Michael/Pictet-Spengler reaction with α,β-unsaturated aldehydes. The preliminary study of asymmetric phase transfer catalysis Michael/Pictet-Spengler reaction didn’t give a good stereoselectivity. We still focus on this tandem reaction as a racemate. The reaction proceeded efficiently with arylsubstituted α,β-unsaturated aldehydes, having both electron-rich, and electron-deficient aryl groups, as well as heteroaryl and alkyl substituted groups. The sulfone group of quinolizidine can be gently removed undergo a single electron reduction.