Synlett
DOI: 10.1055/a-2446-3455
synpacts

Stereocontrolled Synthesis of 1,4-Dicarbonyls via [3,3]-Sulfonium Rearrangement and Application to the Synthesis of Heterocycles

Nicolas G.-Simonian
,
Philipp Spieß
,
Daniel Kaiser
,
Nuno Maulide
This research was funded in part by the Austrian Science Fund (FWF, 10.55776/P37182 to N.M.). Funding by the European Research Council (CoG 682002 VINCAT to N.M.) is acknowledged. We gratefully acknowledge generous and continued support of our research programs by the Universität Wien.


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



Publication History

Received: 13 September 2024

Accepted: 21 October 2024

Accepted Manuscript online:
21 October 2024

Article published online:
06 November 2024

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