Catalytic Enantioselective Mannich Reactions

Asymmetric Synthesis of New Chiral β-Amino Acid Derivatives by Mannich-type Reactions of Chiral N-Sulfinyl Imidates with N-Tosyl Aldimines

“…The enantioselective synthesis of β-amino acid derivatives, as biologically active compounds, constituents of biologically active natural products, chiral building blocks and monomers for the preparation of β-peptides, continues to be of significant interest . The asymmetric Mannich-type reaction of enolates with activated imines is one of the most important and versatile methods for the synthesis of optically pure β-amino acid derivatives which is under continuous development . Recently, the Kobayashi group developed a DBU-catalyzed direct Mannich-type addition reaction of α-methyl-substituted sulfonylimidates with activated aldimines leading to racemic β-aryl-α-methyl-substituted β-amino acid derivatives with high anti -diastereoselectivity .…”

An Easy Stereoselective Access to β,γ-Aziridino α-Amino Ester Derivatives via Mannich Reaction of Benzophenone Imines of Glycine Esters withN-Sulfonyl α-Chloroaldimines

“…This methodology has also been applied in the synthesis of 3-amino-β-lactams via cyclization of intermediate α,β-diamino esters . Despite the numerous approaches to β-amino esters, β-trifluoromethyl-β-amino esters, α-oxy-β-amino esters, γ-alkoxy-β-amino esters, α,α-difluoro-β-amino esters, α-cyano-β-amino esters, β-amino diesters, aspartic acid derivatives, β‘-keto-β-amino esters, aziridine-2-carboxylic esters, C-glycosyl β-amino esters, and α,β-diamino acid derivatives of biological importance by Mannich condensation of ester enolates or equivalents with imines recently reported, only two isolated examples have been published in which a chloro substituent is present at the α-position of the CN double bond of the reacting imine in broad sense, that is, hydrazones and in situ formed imines included. , More specifically, it concerned here chloroacetaldehyde derivatives which are not general in view of their lability. The condensation of ester enolates with α-chloroimines would lead to β-amino-γ-chloro esters as suitable intermediates for further cyclization to 2-aziridinylacetates.…”

Asymmetric Synthesis of α-Chloro-β-amino-N-sulfinyl Imidates as Chiral Building Blocks

“…The Mannich reaction is a classic method for the preparation of β-amino carbonyl compounds and is therefore a very important carbon−carbon bond-forming reaction in organic synthesis as a key step in natural product synthesis as well as in medicinal chemistry . The unique conformational and biological properties of β-peptides incorporating β-amino acids as monomers, and the use of β-amino acid derivatives as building blocks for the preparation of pharmaceutical targets and natural products has prompted a tremendous amount of efforts in the development of asymmetric Mannich reactions to this class of amino acids. , Very recently, our group elaborated the asymmetric synthesis of new chiral β-(sulfonylamino)sulfinylimidates by highly anti -selective Mannich-type reactions of N -sulfinyl imidates across N -tosyl aldimines . These imidates proved to be excellent intermediates for the synthesis of the corresponding enantiopure β-sulfonylamino amides and esters as new chiral β-amino acid derivatives.…”