ORGN 737 |
| Studies on the hetero-Diels-Alder cycloaddition of various 3-siloxy-1-aza-1,3-butadienes with electron-deficient acetylenes have been carried out. Microwave irradiation has been employed to decrease the extended reaction times and increase the poor yields often associated with this reaction. This methodology has successfully been employed in the synthesis of a range of tri- and tetra-substituted pyridines (Scheme 1). Using this methodology, we have embarked on a total synthesis of streptonigrin (1). Retrosynthetically, a change in oxidation levels and functional group transformations leads to the advanced intermediate 2 (Scheme 2). Compound 2 will arise from cyclic ether 3 via oxidation to the lactone, hydrolysis and modified Curtius rearrangement. Disconnection of the pyridine ring of 3 reveals the intramolecular hetero-Diels-Alder substrate 4. In the forward sense, compound 4 was rapidly constructed through Sonogashira coupling between iodoquinoline 5 and acetylene 6, followed by elaboration into the required 1-azadiene unit. Pleasingly, the intramolecular hetero-Diels-Alder reaction proceeded smoothly to afford the desired penta-substituted pyridines 3 (R = Me, CH2OMe, CH2OPMB). The final few stages towards the total synthesis of streptonigrin (1) are currently under investigation.
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Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Organic Chemistry |
