Modified Julia Olefination Approach to Chiral α-Fluorovinyl Amino Alcohols and Amino Acids, via Fluorovinyl Oxazolidine Precursors, Conformational and Crystallographic Analyses.

Synthesis of chiral α-fluorovinyl β-aryl/heteroaryl/alkyl amino alcohols was achieved via intermediate 4-(α-fluorovinyl) 2,2-dimethyloxazolidines with stereochemically defined preexisting stereogenic centers, derived from (S)- or (R)-serine. Previously unknown 4-fluorovinyl 2,2-dimethyloxazolidines with a fluorine atom placed alpha to the oxazolidine were prepared via Julia olefination of tert-butyl (S)-4-{(S)-[benzo[d]thiazol-2-ylsulfonyl]fluoromethyl}-2,2-dimethyloxazolidine-3-carboxylate and its (R,R) enantiomer, with a series of aldehydes. By choice of conditions, olefinations could be tuned towards Z- or E-selectivity. E/Z olefin mixtures with electron-rich aryl and heteroaryl substituents were isomerized exclusively or predominantly to the Z-isomer. N-Boc protected β-aryl/alkyl substituted α-fluorovinyl amino alcohols were obtained by oxazolidine hydrolysis. To demonstrate utility for synthesis of amino acids, (R,Z)- and (S,Z)-p-methoxyphenyl- and the (S,E)-p-cyanophenyl-substituted alkenes were subjected to oxidation, which was very challenging. The use of cat. TEMPO/cat. NaOCl/NaClO