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International audience; Apratoxin A is a potent anticancer natural product whose key polyketide fragment constitutes a considerable challenge for organic synthesis, with five prior syntheses requiring 12 to 20 steps for its preparation. By combining di erent redoxeconomical catalytic stereoselective transformations, the key polyketide fragment could be rapidly prepared. Followed by a siteselective protection of the diol, this strategy enables the preparation of the apratoxin A fragment in only six steps, representing the shortest route to this polyketide.

International audience; Stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3-ones can be prepared efficiently by a three-component reaction involving a 1,3-dipolar cycloaddition of azomethine imines obtained from hydrazones with alpha-oxo-ketene dipolarophiles generated in situ. The reaction allows the creation of four covalent bonds and two contiguous chiral quaternary centers with excellent diastereoselectivity in a single catalyst/additive-free, highly atom-economical transformation. From a fundamental point of view, the reaction introduces alpha-oxo-ketenes as effective dipolarophiles in 1,3-dipolar cycloadditions.

[reaction: see text]. A unique domino reaction of alpha-nitrocycloalkanones with alpha-alkyl alpha,beta-unsaturated aldehydes in aqueous base was discovered, leading to the one-pot synthesis of hitherto unknown functionalized, bridged, bicyclic lactones containing 10-, 11-, 13-, and 15-membered rings. The structures of these heterocyclic compounds, containing also an unusual 6-hydroxy-1,2-oxazine ring, were determined by spectral and single-crystal X-ray diffraction studies.

[reaction: see text] A new versatile methodology, resulting in a formal three-carbon ring expansion of cyclopentanones, for the efficient assembly of functionalized cyclooctanoids is described. The approach is based on the chemo-, regio-, and stereoselective alpha,gamma-difunctionalization of beta-ketoesters followed by ring-closing metathesis to form functionalized bicyclo[4.2.1]nonanes, precursors of the corresponding cyclooctanes, by selective ring cleavage of the one-carbon-atom bridge.

International audience; The reactions between electron-rich 2-aza- dienes and α-oxo-ketenes derived from the Wolff rearrange- ment of 2-diazocycloalkane-1,3-diones chemo- and regiose- lectively produced spiro hydropyrid-4-ones with good to excellent diastereoselectivities. These reactions are likely to proceed via a domino Wolff/Friedel−Crafts/intramolecular Mannich process. Prolonged domino sequences also allowed the expeditious preparation of a series of pyrazolopyridine and pyridopyrimidine heterocycles.

[reaction: see text] The first multicomponent domino transformation between 1,3-dicarbonyls 1, alpha,beta-unsaturated compounds 2, and functionalized amines 3 is described, providing a one-pot access to fused polyheterocyclic or spiropolyheterocyclic compounds 5 or 6 bearing an aminal function by formation of up to three new cycles, five novel bonds, and up to six stereogenic centers.