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 |
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| Authors: | Hannelore Goossens Nicola Piens Dr Saron Catak Prof?Dr Michel Waroquier Prof?Dr Karl W Törnroos Prof?Dr Veronique Van?Speybroeck Prof?Dr Matthias D'hooghe Prof?Dr Norbert De?Kimpe |
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| Institution: | 1. Center for Molecular Modeling, Ghent University, Technologiepark 903, 9052 Zwijnaarde (Belgium), Member of QCMM‐Alliance, Ghent‐Brussels (Belgium), Fax: (+32)?9‐264‐66‐97;2. Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent (Belgium), Fax: (+32)?9‐264‐62‐21;3. Current address: Syngenta Crop Protection, Münchwilen AG, 4332 Stein (Switzerland);4. Department of Chemistry, University of Bergen, Allégt. 41, 5007 Bergen (Norway) |
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| Abstract: | 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 NaIO4‐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. |
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| Keywords: | β ‐lactams bond cleavage density functional calculations oxazin‐3‐ones reaction mechanisms ring expansion |
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