Weinstabl H, Suhartono M, Qureshi Z, Lautens M * University of Toronto, Canada
Total Synthesis of (+)-Linoxepin by Utilizing the Catellani Reaction.
Angew. Chem. Int. Ed. 2013;
52: 5305-5308
Key words
linoxepin - Catellani reaction - domino reaction - palladium catalysis - C–H functionalization
Significance
Lautens and co-workers report the synthesis of linoxepin, a lignin isolated from Linum perennne L. (Linaceae). The elegant strategy relies on the Catellani reaction, in which a strained
olefin (norbornene) is used to couple an iodoarene, an alkyl halide, and a terminal
olefin using palladium catalysis. This is the first application of the Catellani reaction
in the synthesis of a natural product and underscores the power of processes that
form multiple bonds in a single step. In this context, it is worth highlighting the
recent synthesis of linoxepin by Tietze and co-workers (Angew. Chem. Int. Ed. 2013, 52, 3191), which relies on a different palladium-catalyzed domino reaction.
Comment
Alkylation of phenol A with benzyl iodide B gave Catellani precursor C in 94% yield. The norbornene-mediated domino process involving aryl iodide C, enantiopure alkyl iodide D and acrylate E delivered key intermediate F in 89% yield. Oxidative cleavage of the olefin followed by TiCl4-promoted aldol condensation furnished G, which in the presence of catalytic amounts of a palladium catalyst underwent a Mizoroki–Heck
reaction to give (+)-linoxepin in 76% yield.
