title: Solution-, solid-phase, and fluorous synthesis of beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives: a comparative study.
abstract: The diastereoselective synthesis of cyclic beta,beta-difluorinated alpha-amino acid derivatives bearing a quaternary stereocenter is described. The process relies on the chemo- and diastereoselective addition of allylic organometallic reagents to fluorinated alpha-imino esters and a subsequent ring-closing metathesis reaction (RCM). Complete selectivity in the nucleophilic addition was achieved with (R)-phenylglycinol methyl ether as a chiral auxiliary. The resulting amino acids were introduced into peptide chains, which could facilitate the preparation of potentially bioactive dipeptide derivatives. In addition, the solution synthesis of these cyclic fluorinated alpha-amino acids was successfully adapted to solid-phase and fluorous-phase techniques. The reaction times and final deprotection were clearly more favorable in the latter, in which a fluorous trimethylsilylethanol (TMSE) tag was used. The tag was then easily removed upon treatment with TBAF in a high-yield transesterification process.
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain. santos.fustero@uv.es
authors.forename: Santos
authors.initials: S
authors.lastname: Fustero
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Roselló
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rodrigo
authors.forename: Juan F
authors.initials: JF
authors.lastname: Sanz-Cervera
authors.forename: Julio
authors.initials: J
authors.lastname: Piera
authors.forename: Antonio
authors.initials: A
authors.lastname: Simón-Fuentes
authors.forename: Carlos
authors.initials: C
authors.lastname: del Pozo
mesh_terms: D000586:Amination; D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D015394:Molecular Structure; D011522:Protons; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D000598:Amino Acids, Cyclic; D004952:Esters; D017611:Fluorine Compounds; D007097:Imines; D011522:Protons; D012996:Solutions