Abstract
Due to an inherent polarity mismatch of the corresponding retrosynthetic synthons, 1,4-dicarbonyl synthesis through polar pathways requires a retrosynthetic rethink. While umpolung-based approaches exist, efficient control of both the absolute and relative configuration of newly formed stereogenic centres within this motif has long proven particularly challenging. In this Synpact article, we highlight our work on the stereodivergent synthesis of 1,4-dicarbonyl compounds through an unusual transformation that relies on vinyl sulfoxides and ynamides as reactants. This method allows stereoselective access to each and every one out of the four possible stereoisomers of a generic 1,4-dicarbonyl target in a process where enantio- and diastereoselectivity are ‘dialled into’ the vinyl sulfoxide partner. Recent studies show that the thus formed 1,4-dicarbonyls serve as excellent linchpins for structural diversification into highly substituted heterocycles, including those found in natural products.
1 Introduction
2 [3,3]-Sigmatropic Rearrangement of Ynamides and Vinyl Sulfoxides under Acid Catalysis
3 Cyclisation towards γ-Lactones and γ-Lactams
4 Application in Total Synthesis
5 Conclusion
Key words
stereoselective synthesis - sigmatropic rearrangements - sulfonium rearrangements - cyclisation - lactone - lactam - natural products
