Application of the Palladium‐Catalysed Norbornene‐Assisted Catellani Reaction Towards the Total Synthesis of (+)‐Linoxepin and Isolinoxepin. Issue 19 (14th May 2014)

• Record Type: Journal Article
• Authors: Qureshi, Zafar; Weinstabl, Harald; Suhartono, Marcel; Liu, Hongqiang; Thesmar, Pierre; Lautens, Mark
• Is Part Of: European journal of organic chemistry. Issue 19(2014)
• Page Start: 4053
• Page End: 4069
• Publication Date: 2014-05-14
• Subjects: Total synthesis -- Natural products -- Domino reactions -- C–H activation; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402218
• Languages: English
• ISSNs: 1434-193X

Abstract

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 Pd 0 /Pd II /Pd IV ‐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. Abstract : The enantioselective total synthesis of the natural product (+)‐linoxepin has been accomplished in eight steps starting from commercial materials. The key Pd‐catalysed Catellani step served to combine aryl iodide, alkyl iodide and tert ‐butyl acrylate in a domino sequence. By tuning the final Heck reaction, both the natural product and its structural isomer were synthesized.