Lewis acid activation of chiral 2-trifluoromethyl-1,3-oxazolidines. Application to the stereoselective synthesis of trifluoromethylated amines, α- and β-amino acids

New synthesis of polyfluoroalkyl racemic α-amino acids

“…The products were characterised by 1 H 19 F and 13 C NMR spectroscopy, all at room temperature and recorded in CDCl 3 and [(CD 3 ) 2 SO)] on a Brucker AVANCE 300 spectrometer. All chemical shifts are reported in parts per million (ppm) downfield of the standard (TMS and CCl 3 F).…”

“…1 H NMR (CDCl 3 ) d (ppm): 1.31 (t, 6H, J = 7.1 Hz); 4.32 (q, 4H, J = 7.2 Hz); 5.49 (s, 1H); 7.76-7.89 (m, 4H). 13 Triethylborane (1.0 M hexane solution, 4.35 mL, 4.35 Â 10 À3 mol) was added to a solution of 3 (10 g, 3.0 Â 10 À2 mol) and R F I (3.0 Â 10 À2 mol, 7.1 g R F = C 2 F 5 , 12.9 g R F = C 6 F 13 , 15.8 g R F = C 8 F 17 ) in 1,2-dichloroethane (10 mL) at 25 8C. The resultant mixture was stirred at 25 8C during 0.5 h. Bu 3 SnH (8.4 g, 7.8 mL, 3.0 Â 10 À2 mol) was added via a syringe and the mixture was stirred at 25 8C during 2 h. Solvent was distilled under reduce pressure, the crude product was dissolved in Et 2 O (60 mL) and KF (6.9 g, 0.12 mol) was added to the solution.…”

“…For example, a-trifluoroalanine is an important compound of this class of fluorinated amino acids [11][12][13] and it is known to act as a suicide inhibitor for a number of pyridoxal enzymes [14][15][16]. Whereas the literature is rich in methodologies for the preparation of mono-or di-fluorinated a-amino acids [17][18][19], few examples of synthetic routes leading to a-amino acids containing highly fluorinated n-alkyl chains have been reported [20][21][22][23][24][25].…”

Organocatalytic Enantioselective Strecker Synthesis of α‐Quaternary α‐Trifluoromethyl Amino Acids

“…[7] The asymmetric synthesis of a-trifluoromethyl a-amino acids remains a synthetic challenge and in most of the methods developed so far chiral auxiliaries have been employed. [8] Either alkyl substituents [9] or cyanide [10] are added to imines and the chirality information is introduced via the imine protecting group or the nucleophile. Other synthetic strategies involve asymmetric hydrogenation, enantiopure starting materials or enzymatic resolution.…”

“…and Lu et al [10] Diastereomerically pure a-amino nitriles have also been synthesized by stereoselective addition of trimethylsilyl cyanide (TMSCN) to trifluoromethyl imines bearing chiral protecting groups.…”