Asymmetric Catalytic Synthesis Of Five And Three-Membered Heterocycles

Chiral heterocyclic molecules are core structural element present in numerous natural products, biological active molecules and mutifuctional material, as well as important building blocks in organic synthesis. Catalytic asymmetric methods to access these compounds would be hihyly valuable and had attracted organic chemists' great interest. In this manuscript, we have developed two new approaches for catalytical asymmetric synthesis of optically active imidazolidines and cis-glycidic amides, respectively.Optically active imidazolidines are important intermediates with broad applications to organic synthesis. The 1,3-dipolar cycloaddition of azomethine ylides to imines with concomitant creation of multiple stereogenic centers represents an efficient and atom-economic method for the manufacture of these compounds. However, to date, the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides to imines has not yet appeared and therefore remains an important challenge. In this manuscript, we have described the first Br(?)nsted acid catalyzed asymmetric 1, 3-dipolar cycloaddition between azomethine ylides and imines that directly assembles aldehydes, amino esters, and anilines into synthetically useful chiral imidazolidines with high levels of stereoselectivity. The negative NLE revealed two molecules of chiral phosphoric acids participated in the catalysis by the activation of both azomethine ylides and imines. This reaction has further demonstrated that the chiral Br(?)nsted acid-activated dipoles are versatile intermediates for the creation of new enantioselective 1,3-dipolar cycloadditions.The optically active glycidic esters and amides have.been one of the most of important classes of chiral molecules. The well established methods to access these optical compounds include asymmetric catalytic epoxidation ofα,β-unsaturated carbonyl compounds and Darzens reaction. Despite these elegant advances, relatively few protocols have been available for accessing either the cis-glycidic esters or amides. We have described a highly diastereo-and enantioselective Darzens reaction of aldehydes with diazoacetamides catalyzed by a chiral titanium complex formed in situ from commercially available Ti(O-i-Pr)4 and (R)-binaphthol, solely giving cis-glycidic amides with excellent enantiomeric purity. The protocol tolerated a broad scope of structurally diverse aldehydes, including aromatic, heteroatomatic, unsaturated, and aliphatic aldehydes. This new method has high potential in the enantioselective synthesis of biologically active substances as demonstrated by the preparation of the side chains of taxol and the chiral building block of (-)-bestatin.