Application of the Palladium‐Catalysed Norbornene‐Assisted Catellani Reaction Towards the Total Synthesis of (+)‐Linoxepin and Isolinoxepin

Abstract

Our ongoing effort towards the development of highly selective transition‐metal‐catalysed C–H activation processes has led to the expansion of the Catellani reaction. In a Pd0/PdII/PdIV‐catalysed domino reaction, an aryl iodide, alkyl iodide and tert‐butyl acrylate were combined to synthesize the carbon framework of the novel lignan (+)‐linoxepin. The enantioselective synthesis highlights the work accomplished in our group and provides an excellent procedure for the reliable and scalable synthesis of architecturally complex scaffolds. This report outlines the synthetic approaches towards this interesting class of biologically active molecules. After the key Catellani/Heck reaction, our synthesis features a Leimeux–Johnson oxidation and a titanium tetrachloride mediated aldol condensation. Finally, a tuneable Mizoroki–Heck reaction was performed to furnish not only the natural product (+)‐linoxepin but also its isoform, which we have named isolinoxepin.

Application of the Palladium‐Catalysed Norbornene‐Assisted Catellani Reaction Towards the Total Synthesis of (+)‐Linoxepin and Isolinoxepin

“…Scheme 18 on page 4061 of the original article 1 was inadvertently replaced by a copy of Scheme 17. The correct Scheme is given below.…”

Kinetic resolution of (E)-4-(2′,5′-dimethylphenyl)-but-3-en-2-ol and (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol through lipase-catalyzed transesterification

“…26 Moreover, the 1,3-benzodioxole system is present in various natural and synthetic biologically active compounds, which show antiproliferative, antiinflammatory or anticonvulsant properties. [27][28][29][30] …”

Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones

“…As a proof of concept and using ethylene glycol as starting material, monosilylation, Swern oxidation and Baylis-Hillman reaction provided 19, which uneventfully and in high yield provided bromolactone 20 upon treatment with 48% HBr. While numerous syntheses of 20 exist, [50][51] this approach demonstrates that TBS is a suitable protecting group during the preparation of substrates in which the alcohol is involved in the lactonisation process during the HBrmediated reaction, thereby paving the way to the successful design and synthesis of further bromolactones. The acid-labile TES group may however also be used: and indeed, Baylis-Hillman reaction on aldehyde 21, readily available from lactic acid, 52 followed by treatment with 48% HBr provided bromolactone 23.…”