Concise synthesis of enantiopure (S)- and (R)-α-trifluoromethyl aspartic acid and α-trifluoromethyl serine from chiral trifluoromethyl oxazolidines (Fox) via a Strecker-type reaction

A concise synthesis of enantiopure (S)- and (R)-α-Tfm-aspartic acid and α-Tfm-serine is reported. The key step involves a Strecker-type reaction on chiral CF3-oxazolidines (Fox) derived from ethyl 4,4,4-trifluoroacetoacetate (ETFAA) or ethyl trifluoropyruvate.

Figure optionsDownload as PowerPoint slide

(3S,5R)-3-Carboethoxymethyl-3-trifluoromethyl-5-phenylmorpholin-2-oneC15H16F3NO4[α]D21=+55.3 (c 1.3, CH2Cl2)Source of chirality: (R)-phenylglycinolAbsolute configuration: (3S,5R)

(3R,5R)-3-Carboethoxymethyl-3-trifluoromethyl-5-phenylmorpholin-2-oneC15H16F3NO4[α]D21=-24 (c 0.5, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (3R,5R)

(S)-α-Trifluoromethylaspartic acid hydrochlorideC5H7ClF3NO4[α]D21=+25 (c 0.25, H2O)Source of chirality: (R)-phenylglycinol and asymmetric synthesisAbsolute configuration: (S)

(S)-2-Trifluoro-3-hydroxy-2-[(1R)-2-hydroxy-1-phenyl-amino]propanenitrileC12H13F3N2O2[α]D21=-77.4 (c 1.0, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (S,R)

(R)-2-Trifluoro-3-hydroxy-2-[(1R)-2-hydroxy-1-phenyl-amino]propanenitrileC12H13F3N2O2[α]D21=-83.3 (c 1.0, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (R,R)

(R)-α-TrifluoromethylserineC4H6F3NO3[α]D23=+10.6 (c 1, H2O)Source of chirality: (R)-phenylglycinol and asymmetric synthesisAbsolute configuration: (R)