Synthesis of Three‐, Five‐, and Six‐Membered Heterocycles Derived from New β‐Amino‐α‐(trifluoromethyl) Alcohols

Abstract

Nucleophilic trifluoromethylation of α-iminoketones 2, derived from arylglyoxal, with Ruppert-Prakash reagent (CF3SiMe3) offers a convenient access to the corresponding O-silylated β-imino-α-trifluoromethyl alcohols. In a 'one-pot' procedure, by treatment with NaBH4, these products smoothly undergo reduction and desilylation yielding the expected β-amino-α-trifluoromethyl alcohols 4. The latter were used as convenient starting materials for the synthesis of diverse trifluoromethylated heterocycles, including aziridines 5, 1,3-oxazolidines 8, 1,3-oxazolidin-2-ones 9, 1,3,2-oxazaphospholidine 2-oxides 10, 1,2,3-oxathiazolidine 2-oxides 11, and morpholine-2,3-diones 12. An optically active 5-trifluoromethyl-substituted 1,3-oxazolidin-2-one 9g was also obtained. Nucleophilic trifluoromethylation of -iminoketones 2, derived from arylglyoxal, withRuppert-Prakash reagent (CF 3 SiMe 3 ) offers a convenient access to the corresponding Osilylated -imino--trifluoromethyl alcohols. In a 'one-pot' procedure, by treatment with NaBH 4 , these products smoothly undergo reduction and desilylation yielding the expected β-amino--trifluoromethyl alcohols 4. The latter were used as convenient starting materials for the synthesis of diverse trifluoromethylated heterocycles, including aziridines 5, 1,3-oxazolidines 8, 1,3-oxazolidin-2-ones 9, 1,3,2-oxazaphospholidine 2-oxides 10, 1,2,3-oxathiazolidine 2-oxides 11, and morpholine-2,3-diones 12. An optically active 5-trifluoromethyl-substituted 1,3-oxazolidin-2-one 9g was also obtained.

Reactions of α-imino ketones derived from arylglyoxals with (trifluoromethyl)trimethylsilane; a new route to β-amino-α-trifluoromethyl alcohols

“…[10]. By analogy, the same configuration was attributed to the more polar product bearing phenyl substituent, i.e.…”

“…In extension of the results discussed in this paper, the slow-isomer of 9l was used in another work for a cyclization reaction with phosgene yielding selectively the corresponding 1,3-oxazolidin-2-one derivative [10]. The absolute configuration of both stereogenic centers in this compound was determined by Xray crystallography as (5R,1 0 S)-, evidencing thereby the same absolute configuration [(2R,1 0 S)-] in the slow-9l (minor product) Table 3 Diastereoselectivity of CF 3 SiMe 3 additions to enantiomerically pure a-imino ketones 7k-l. …”

“…Comparison of the 1 H NMR spectra of racemate and isolated enantiomers of 9k recorded after addition of 1 equiv. of (À)-(S)-(tert-butyl)(phenyl)phosponothioic acid (10).…”

“…The mixtures of diastereomers (2R,1 0 S)-9k-l and (2S,1 0 S)-9k-l were separated by column chromatography and the enantiomeric purity of the isolated fast-and slow-fractions 2 was proved by the 1 H NMR experiments with (S)-(tert-butyl)phenyltiophosphonic acid (10) [15] used as a chiral solvating agent. In each experiment only one set of signals of the corresponding salt was observed ( Fig.…”

New β-amino-α-trifluoromethyl alcohols and their exploration in the synthesis of trifluoromethylated imidazole derivatives

“…These products were applied for the preparation of aziridines as well as five-and six-membered O,N-heterocycles [6]. …”