Indenylidene complexes of ruthenium: Optimized synthesis, structure elucidation, and performance as catalysts for olefin metathesis - Application to the synthesis of the ADE-ring system of nakadomarin A

An optimized and large scale adaptable synthesis of the ruthenium phenylind enylidene complex 3 is described which employs commercially available diphe nyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual structure of the complex have been ruled out by a full analysis of its NMR spectra. A series of applications to ring clo sing metathesis (RCM) reactions shows that complex 3 is as good as or even superior to the classical Grubbs carbene 1 in terms of yield, reaction rate , and tolerance towards polar functional groups. Complex 3 turns out to be the catalyst of choice for the synthesis of the enantiopure core segment 77 of the marine alkaloid nakadomarin A 60 comprising the ADE rings of this t arget. Together with a series of other examples, this particular applicatio n illustrates that catalyst 3 is particularly well suited for the cyclizati on of medium-sized rings by RCM. Other key steps en route to nakadomarinA a re a highly selective intramolecular Michael addition setting the quaternar y center at the juncture of the A and D rings and a Takai - Nozaki olefinat ion of aldehyde 73 with CH2I2, Ti(OiPr)(4) and activated zinc dust.