Enantiopure α-Trifluoromethylated Aziridine-2-carboxylic Acid (α-TfmAzy): Synthesis and Peptide Coupling

Asymmetric α-Fluoroalkyl-α-Amino Acids: Recent Advances in Their Synthesis and Applications

“…The so-formed amino nitriles were successfully hydrolyzed to the corresponding amino acids ( Scheme 41 ). Aziridine [ 77 ] and azetidine [ 78 ] derivatives were hydrolyzed in very high yields using basic conditions. The fully deprotected enantiopure α-CF 3 -α-carboxyazetidine was successfully obtained after cleavage of the chiral auxiliary, while the aziridine was efficiently incorporated into a dipeptide prior to N -deprotection.…”

“…The incorporation of α-amino acids with fluorinated side chains in peptides does not present any particular difficulties when the fluorine atoms are located at the γ- or ω-positions and standard peptide coupling reaction conditions can be used for solution phase or SPPS (for recent examples see [ 96 ] and references cited). The peptide coupling reactions at the C -terminal position of α-fluoroalkyl-α-amino acids can also be achieved in good yields by classical procedures [ 77 , 97 , 98 ]. However, when fluorine atoms are present at the β-position of the α-amino acids, their strong electron-withdrawing effect dramatically decreases the nucleophilicity of the nitrogen atom of the α-amino acids, and specific activation methods are generally required for their N -coupling reactions.…”

“… Towards three-, four-, five- or six-membered ring cyclic α-trifluoromethyl amino acids [ 77 , 78 , 79 ]. …”

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

“…(c)). More recently, Pytkowicz, Brigaud, [69] and co‐workers reported the enantioselective synthesis of the fluorinated amino acid, α‐trifluoromethylated aziridine‐2‐carboxylic acid. To achieve their goal, they synthesized several aziridines, 138 , 140 , 142 , and 143 in good yields from the corresponding β‐amino‐alcohols 137 and 139 or mesylated substrate 141 (Scheme 45, Eq.…”

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

“…There is a rich portfolio of fluorine-containing proline analogues that have been developed to date (Figure 1B): fluorinated [6][7][8][9][10][11][12], trifluoromethylated [13][14][15][16][17][18][19][20][21][22][23], chimeric [16,19,[24][25][26][27][28][29], conformationally restricted [30][31][32][33] having variations in the ring size [34][35][36][37][38][39], non-α [40][41][42][43][44], and other analogues [45][46][47][48]. The fluorine-containing functional groups are usually chemically inert under most biologically relevant conditions.…”