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Polycyclic Ring Formation Using Bis-diazolactams for Cascade Stitching

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journal contribution
posted on 15.12.2016, 00:00 authored by Sara A. Bonderoff, Albert Padwa
The chemoselective reaction of donor/acceptor (D/A) and acceptor/acceptor (A/A) diazo moieties in the same molecule was examined using 3-diazo-1-(ethyl 2-diazomalonyl)­indolin-2-one under rhodium­(II) catalysis. The metallo carbenoid derived from the D/A diazo group is preferentially formed and undergoes selective CH, NH, and OH insertion reactions, cyclopropanation, cyclopropenation, sulfur ylide formation/2,3-sigmatropic rearrangement, as well as nitrogen ylide formation followed by azetidine ring expansion. The initial reaction can be paired with a subsequent tandem cascade sequence involving dipole formation/cycloaddition in either an intra- or intermolecular sense to generate polycyclic N-heterocycles in one pot, with the formation up to three new rings in a single operation. Excellent diastereoselectivity was observed in the intramolecular cycloaddition reaction producing 5 to 7-membered rings.