Diastereoseletive Transannular Oxa-Conjugate Addition Generates the 2,6-cis-Disubstituted Tetrahydropyran of Neopeltolide
| Autor: | Burkardt I. Wilke, Taylor P. A. Hari, James A. Davey, Christopher N. Boddy |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
chemistry.chemical_classification
Natural product Ketone Bicyclic molecule 010405 organic chemistry Stereochemistry Organic Chemistry Diastereomer Tetrahydropyran 010402 general chemistry Ring (chemistry) 01 natural sciences Combinatorial chemistry 0104 chemical sciences chemistry.chemical_compound chemistry Functional group Michael reaction |
| Zdroj: | The Journal of organic chemistry. 81(2) |
| ISSN: | 1520-6904 |
| Popis: | Transannular 2,6-disubstituted pyrans, like the one found in the cytotoxic marine natural product neopeltolide, are a key functional group in many polyketides. While oxa-conjugate additions have been shown to provide direct and rapid access to tetrahydropyrans in acyclic neopeltolide intermediates, a transannular strategy for construction of this ring system in a macrocyclic core has not been investigated. In this study, we demonstrate that a transannular oxa-conjugate addition strategy is a viable approach to the construction of the bicyclic core of neopeltolide. We show that transannular addition occurs readily with an α,β-unsaturated ketone as the Michael acceptor and does not occur when an α,β-unsaturated ester is the Michael acceptor. Our data indicates that oxa-conjugate addition is reversible and that the stereochemical outcome can be under thermodynamic control. Using computational chemistry, we show that the lowest energy diastereomer is the desired cis-pyran found in neopeltolide, and we experimentally demonstrate that the trans and cis diastereomers are interconvertible under reaction conditions with the cis-pyran product predominating. This oxa-conjugate addition strategy should provide a viable route to accessing the fully elaborated macrocyclic core of neopeltolide. |
| Databáze: | OpenAIRE |
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