Synthesis Of Novel Quaternary Ammonium Salts Derived From Amino Acids With Sterically Hindered Group And Application In Asymmetric Mannich Reaction

Commerically available amino acids with bifunctional groups of amino and carboxyl,as well as chiral skeletons,have become one of the most valuable chiral pool of organo catalysts.In recent years,many of researchers draw more attention to the application of chiral ammonium as phase transfer catalysts in asymmetric reaction.Our group has designed and synthesized a series of chiral cation bifunctional organo catalysts(ammonium and phosphonium)derived from amino acids and applied on catalyzing asymmetric reactions.Mannich reaction is a typical reaction,which is commonly used to forming C-C bond or C-N bond and widely employed in the synthesis of natural products and pharmaceutical compounds.Among these reactions,the direct Mannich reaction of a Glycine Schiff bases or ?-amino acid derivatives with imines is a straightforward method to stereoselectively obtain ?,?-diamino acid derivatives.In this thesis,we designed and synthesized a series of novel quaternary ammonium salt catalysts derived from chiral ?-amino acid and applyed to stereo-selectively catalyze asymmetric Mannich reaction of glycine Schiff bases with N-Boc-Imines.We have optimized this reaction conditions,including the different structure of catalyst,reaction solvent,base,equivalent amount of base and reaction temperature.Then,the scope of substrates were tested with the optimization of this reaction.The corresponding products could be obtained in excellent yields with good diastereo-and enantioselectivities(up to 95% yield,dr > 20 : 1,> 90% ee).After the screening of N-Boc-imines with different aryl substituents,the substituent effect of aryl group is found: poor diastereoselectivities and enantioselectivities of the products are obtained for ortho-substituted substrates.As for the meta-substituted or para-substituted N-Boc-imines,products could be obtained with good diastereoselectivities and enantioselectivities.Meanwhile,good yields and stereoselectivities of products are also got for heteroaromatic substitutedN-Boc-imines.In summary,this Mannich reaction is carried out to prove the developed catalysts with an excellent catalytic activity under mild conditions.