Science of Synthesis

Schobert, R.; Hölzel, C.; Barnickel, B., Science of Synthesis, (2010) 47, 68.

Various two-step protocols leading to trialkyl- and tetraalkyl-substituted Z-alkenes have been reported. For example, in a total synthesis of discodermolide the Still–Gennari modification[‌480‌] of the Horner–Emmons reaction has been used to prepare a Z-configured α,β-unsaturated ester in 93% yield, which is subsequently reduced to allylic alcohol ‌146‌ with lithium aluminum hydride in 92% yield (‌Scheme 49‌).[‌22‌] Alternatively, the trisubstituted alkene ‌149‌, as a precursor to discodermolide, is built up by a Z-selective alkenation with in situ generated (1-iodoethylidene)triphenylphosphorane to give the vinyl iodide ‌147‌ (a so-called Stork–Zhao Wittig reaction[‌18‌,‌19‌]), which is then submitted to a palladium-catalyzed Negishi coupling with an alkylzinc reagent prepared efficiently in situ from just 1.1 equivalents of another iodide ‌148‌ (‌Scheme 49‌).[‌20‌] Marshall and co-workers obtained an analogous precursor to discodermolide in 74% yield by Suzuki coupling of a vinyl iodide akin to ‌147‌.[‌21‌] It was coupled in the presence of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium as a catalyst with a trialkylboronate prepared from an alkyl iodide by lithiation and subsequent addition of 9-methoxy-9-borabicyclo[3.3.1]nonane.

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References