Straightforward synthesis of enantiopure (R)- and (S)-trifluoroalaninol

Abstract

Two efficient routes are reported for the synthesis of both enantiomers of trifluoroalaninol in enantiopure form. The first pathway involves a Strecker-type reaction performed from a chiral trifluoromethyloxazolidine (Fox). The second route, which is more direct, involves, as a key step, the reduction of chiral oxazolidines or imines derived from ethyl trifluoropyruvate.

Incorporation of Trifluoromethylated Proline and Surrogates into Peptides: Application to the Synthesis of Fluorinated Analogues of the Neuroprotective Glycine-Proline-Glutamate (GPE) Tripeptide

“…According to our previously reported procedure, the CF 3 -oxazolidine 16 was obtained in a high yield (95%) as a 75:25 diastereomeric mixture by the condensation of the ethyl trifluoropyruvate with N -Boc-( R )-phenylglycinol in the presence of PPTS (Scheme ). We already reported that this oxazolidine proved to be a convenient building block for the synthesis of various enantiopure α-CF 3 -amino acids − , and amino alcohols . In other respect, we consider herein this kind of oxazolidines as original stable proline surrogates.…”

Enantiomeric N‐tert‐Butylsulfinyl Imines of Methyl Trifluoropyruvate: Promising Building Blocks in Asymmetric Synthesis of α‐Trifluoromethylated Amino Acids and Derivatives

“…In addition, they can be used as chiral ligands and auxiliaries. [9] We have found that the reaction of sulfinyliminopyruvates (R)-4 or (S)-4 with borane dimethylsulfide complex, independently of a reagents ratio, leads to reduction of both C=N bond and ester function with the formation of N-substituted aminoalcohols (R,R)-7 or (S,S)-7, respectively (Scheme 4). 19 F NMR monitoring of the reaction reveals that when one equivalent of BH 3 ⋅Me 2 S is used, the reaction mixture contains only signals of product 7 and unreacted starting imine 4.…”

“…[8a,9] The stereochemical assignments in Scheme 4 were made by comparing specific rotation of (S)-and (R)-8 with those of the known compounds. [9] Aza-Henry reaction with nitromethane. Reaction of imines with nitromethane is widely used for the preparation of βnitroamines and respective diamines.…”

“…Trifluoromethylated 1,2‐aminoalcohols are important building blocks in the biomedical studies. In addition, they can be used as chiral ligands and auxiliaries [9] . We have found that the reaction of sulfinyliminopyruvates ( R )‐ 4 or ( S )‐ 4 with borane dimethylsulfide complex, independently of a reagents ratio, leads to reduction of both C=N bond and ester function with the formation of N‐substituted aminoalcohols ( R,R ) ‐7 or ( S,S ) ‐7 , respectively (Scheme 4).…”

“…Enantiomeric trifluoroalaninol ( S )‐ 8 was also synthesized starting from sulfinyliminopyruvate ( S )‐ 4 . Earlier trifluoroalaninols ( R )‐ 8 and ( S )‐ 8 were prepared by more complicated scheme based on the use of ( R )‐phenylglycinol derived fluorinated oxazolidines or imines and requiring separation of diastereomers [8a,9] . The stereochemical assignments in Scheme 4 were made by comparing specific rotation of ( S )‐ and ( R )‐ 8 with those of the known compounds [9] …”