854029-97-3Relevant academic research and scientific papers
Stereoselective synthesis of multiply substituted [1,2]oxazinan-3-ones via ring-closing metathesis
Shustov, Gennady V.,Chandler, Melanie K.,Wolfe, Saul
, p. 93 - 103 (2005)
The title compounds are α-amino acids whose nitrogen atoms are enclosed within 4,5-disubstituted, six-membered cyclic hydroxamates and they are of interest as potential β-lactam surrogates. The compounds have been synthesized in the present work by functionalization of the double bonds of N-substituted 6H-[1,2]oxazin-3-ones, which are obtained upon successive reaction of the inflates of 5-α-hydroxy esters with O-allylhydroxylamine and acryloyl chloride, followed by cyclization of the resulting A-α-TV- acryloyl-N-allyloxyamino esters in the presence of the ring-closing metathesis (RCM) catalyst bis(tricyclohexylphosphine)benzylideneruthenium dichloride. The olefins are also accessible, but less efficiently so, by a Wittig sequence that employs bromoacetyl bromide in place of acryloyl chloride, followed successively by triphenylphosphine, silver triflate, ozonolysis, and cyclization. Asymmetric dihydroxylation of these chiral olefins affords a single diastereomer in high yield having either the αR,4S,5S- or the αR,4R,5R configuration, depending on the auxiliary. The configuration of the αR,4R,5R isomer has been confirmed by its conversion to (αR,4S,5R)-2-(α-carboxyethyl)-4- phenylacetylamino-5-hydroxy-1,2-oxazinan-3-one, whose αR,4K,5S diastereomer was previously prepared from L-ascorbic acid. With N-bromosuccinimide in aqueous dimethylformamide, a 6H-[1,2]oxazin-3-one afforded a separable 1:1 mixture of bromohydrins, which could be cyclized to epoxides or hydrogenolyzed to 5-hydroxy-1,2-oxazinan-3-ones.
