Synthesis of 2-hydroxy-1,4-oxazin-3-ones through ring transformation of 3-hydroxy-4-(1,2-dihydroxyethyl)-β-lactams and a study of their reactivity.
The reactivity of 3-hydroxy-4-(1,2-dihydroxyethyl)-β-lactams with regard to the oxidant sodium periodate was evaluated, unexpectedly resulting in the exclusive formation of new 2-hydroxy-1,4-oxazin-3-ones through a C3C4 bond cleavage of the intermediate 4-formyl-3-hydroxy-β-lactams followed by a ring expansion. This peculiar transformation stands in sharp contrast with the known NaIO(4)-mediated oxidation of 3-alkoxy- and 3-phenoxy-4-(1,2-dihydroxyethyl)-β-lactams, which exclusively leads to the corresponding 4-formyl-β-lactams without a subsequent ring enlargement. In addition, this new class of functionalized oxazin-3-ones was further evaluated for its potential use as building blocks in the synthesis of a variety of differently substituted oxazin-3-ones, morpholin-3-ones and pyrazinones. Furthermore, additional insights into the mechanism and the factors governing this new ring-expansion reaction were provided by means of density functional theory calculations.
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
Karen
K
Mollet
Hannelore
H
Goossens
Nicola
N
Piens
Saron
S
Catak
Michel
M
Waroquier
Karl W
KW
Törnroos
Veronique
V
Van Speybroeck
Matthias
M
D'hooghe
Norbert
N
De Kimpe
D001384:Azetidines / Q000737:chemistry*; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000737:chemistry; D013237:Stereoisomerism; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
D001384:Azetidines; D010078:Oxazines; D047090:beta-Lactams; D010504:Periodic Acid; C009288:metaperiodate