New Approaches to the Use of Amino Acids as Chiral Building Blocks in Organic Synthesis [New Synthetic Methods (85)]

α-Amino acids protected at nitrogen in quite different ways can be transformed without racemization into the corresponding α-amino aldehydes. Provided one chooses the right protecting groups (e.g., two benzyl residues on nitrogen) it is possible for the first time to carry out Grignard-like, aldol, and Me₃SiCN additions, and hetero-Diels–Alder reactions with a high degree of nonchelation control. If the reactions of classical carbanions turn out to be nonselective, transmetalation, for example into organotitanium reagents, constitutes an important tool in controlling stereoselectivity. Diastereoselectivity can be reversed by specific variation of the protecting group and reagent. “Protecting-group tuning”, “metal tuning”, and “ligand tuning” are very useful in reactions of α-amino aldimines as well. The α-amino aldehydes can also be converted by Wittig reactions into electron-poor γ-amino olefins, which in turn undergo stereoselective cuprate, Michael, and cycloadditions.     

Design of chiral tin(IV) aryloxide as a mild Lewis acid catalyst for enantioselective Diels-Alder reaction

A novel Sn(IV) aryloxide Lewis acid has been designed and prepared from SnCl₄ and (S)-3,3′-bis(3,5-bis(trifluoromethyl)phenyl)-1,1′-bi-2-naphthol. The chiral Sn(IV) Lewis acid has been successfully applied to the enantioselective Diels-Alder reaction.     

Catalytic and stereoselective glycosylation with glycosyl N-trichloroacetylcarbamate

Catalytic and stereoselective glycosylation efficiently proceeded by activating a glycosyl N-trichloroacetylcarbamate with a catalytic amount of Lewis acids in the presence of a glycosyl acceptor and molecular sieves 5 Å. Catalytic and one-pot dehydrative glycosylation of a 1-hydroxy carbohydrate was also performed stereoselectively by the reaction with trichloroacetyl isocyanate followed by activation with a catalytic amount of activators.     

NHC-copper-catalyzed asymmetric conjugate silylation of access chiral α-aminosilanes

Chiral α-aminosilane and its derivatives have found potential applications in pharmaceuticals. Yet there are rare examples have been reported for the synthesis of these molecules. Herein we report a catalytic asymmetric conjugate silylation reactions of β-amido-acrylonitriles and β-amido-acrylates for the first time in the presence of catalytic amount of chiral N-heterocyclic carbene (NHC)/Copper(I) complex. A variety of functionalized chiral α-aminosilanes were obtained at room temperature in good yields with high enantioselectivities in the presence of NHC (10 mol%), CuCl (10 mol%), NaOtBu or NaOMe (20 mol%), and MeOH (2 equivalents).