ABSTRACT
New gem-difluoroalkenes were synthesized by the dehydrofluorination of the corresponding 4-CF3-ß-lactams. An unexpected rearrangement mechanism of the ester moiety dependent on a stabilizing negative charge was observed. Hydrogenation to 4-CHF2-ß-lactams was successful from gem-difluoro-ß-lactams.
Subject(s)
Anti-Bacterial Agents , beta-Lactams , beta-Lactams/pharmacology , Anti-Bacterial Agents/pharmacology , Hydrogenation , EstersABSTRACT
The synthesis of the stable surrogates of an important amino acid (R)-4-amino-3-hydroxybutyric acid (GABOB) such as substituted hydroxy aminophosphonic acids bearing a quaternary stereogenic center is presented. Highly diastereoselective formations of fluorinated spiroepoxy alkylphosphonate or related tertiary carbon-containing oxiranes from ß-keto phosphonates possessing methyl, phenyl, or cyclohexenyl substituents, are reported. Stereoselective acid-promoted epoxide opening by bromide or azide followed by reduction/protection afforded tertiary bromides or N-Boc derivatives of ß-amino-γ-hydroxy alkylphosphonates in most cases, while the reactions of oxiranes with different amines yielded their ß-hydroxy-γ-amino regioisomers. Surprisingly, during the synthesis of amino phosphonic acids, we observe that the acid-induced rearrangement proceeded in a high diastereospecific manner, leading finally to substituted ß-hydroxy-γ-aminoalkylphosphonic acids.
ABSTRACT
Mono- and disubstituted 4-CF3 ß-lactams at the C-3 position have been obtained stereoselectively under basic conditions. A wide range of function such as alcohols, alkyls, aryls, esters, and double and triple bonds have been introduced.
ABSTRACT
Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b-37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b-21a,b in the presence of K2CO3, via the retro-Abramov reaction of the appropriate aldehydes, 1-5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b-37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.