Synthesis of (2S)-4,4-difluoroproline, (2S,4R)-4-fluoroproline and their derivatives from (S)-aspartic acid [1]

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

“…In 1994, Burger reacted ketone 91 with DAST in benzene as a solvent to obtain compound 92 in 53% yield (Scheme 18). 54 Acidic cleavage of the cyclic ketal in methanol afforded the desired pyrrolinide 93 as a hydrochloride salt in 44% yield.…”

“…During 1966–1999, many research groups independently synthesized amino acids 61 , 64 , and their protected precursors by deoxyfluorination of 4-hydroxy- l -proline derivatives with DAST (Et 2 NSF 3 ). These are contributions of Cohen and Bergmann, Smith, Kronenthal, Hudlicky, , Burger, Nishigaki and Yabe, Patino, and Hamacher (Scheme ). In most cases, the deoxyfluorination step was accompanied by formation of alkenes and epimerization at the C(4) atom.…”

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

“…13 This amino acid was converted to the diazoketone 23 in three steps, an intermediate that contains the requisite carbon skeleton for the proline derivatives. Rhodium-catalyzed cyclization produced the diketoproline derivative 24, and this was fluorinated with DAST to give 25, hydrolysis of which produced 22.…”

Hexafluoroacetone as Protecting and Activating Reagent: New Routes to Amino, Hydroxy, and Mercapto Acids and Their Application for Peptide and Glyco- and Depsipeptide Modification

“…Reduction of the 4-oxo group gives HFA-(2 S ,4 S )-hydroxyproline with 86% de because of the concave shape of the bicyclic system (Scheme , i and Scheme ). Fluorodeoxygenation with DAST provides after deprotection ( S )-4,4-difluoroproline (Scheme , ii) and fluorodehydroxylation of 4-hydroxyproline (2 S ,4 R )-4-fluoroproline (Scheme , iii) 41 …”