Diastereoselective Mannich Reactions Using Fluorinated Ketones: Synthesis of Stereogenic Carbon-Fluorine Units.

A diastereoselective Mannich reaction of simple α-fluoro ketones with N-tert-butylsulfinylimines was developed. This method provides a concise route to a variety of structurally diverse α-fluoro-β-amino ketones containing fluorinated stereogenic carbon centers; good yields and high diastereoselectivities were achieved. This method uses readily accessible starting materials and has a broad substrate scope: cyclic and linear α-fluoro ketones and fluoromethyl ketones are all suitable substrates.

A diastereoselective Mannich-type reaction of α-fluorinated carboxylate esters: synthesis of β-amino acids containing α-quaternary fluorinated carbon centers.

We report a diastereoselective Mannich-type reaction of α-alkyl, α-aryl, and α-vinyl fluoroacetates with N-tert-butylsulfinyl imines. This method provides a powerful means to access a broad range of highly functionalized β-amino acids containing α-fluorinated quaternary stereogenic carbon centers. We also show that the stereochemical outcome of the present reaction is highly dependent on the steric and electronic properties of the fluorocarbon nucleophiles.

Diastereoselective Addition of Metal α-Fluoroenolates of Carboxylate Esters to N-tert-Butylsulfinyl Imines: Synthesis of α-Fluoro-β-amino Acids.

We report a diastereoselective addition reaction of fluoroacetate and α-alkylated fluoroacetate to N-tert-butylsulfinyl imines. This method provides a concise route to α-fluoro-β-amino acids containing fluorinated quaternary stereogenic carbon centers with very good yields and high diastereoselectivities. This protocol has the benefit of using abundant and readily accessible starting materials and is operationally simple.