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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Highly congested spiro-compounds via photoredox-mediated dearomative annulation cascade
Chao Zhou1, Andrey Shatskiy1, Azamat Z Temerdashev2
1Department of Chemistry, Division of Organic Chemistry, KTH Royal Institute of Technology, Teknikringen 30, 10044, Stockholm, Sweden.
Abstract:
Photo-mediated radical dearomatization involving 5-exo-trig cyclizations has proven to be an important route to accessing spirocyclic compounds, whereas 6-exo-trig spirocyclization has been much less explored. In this work, a dearomative annulation cascade is realized through photoredox-mediated C-O bond activation of aromatic carboxylic acids to produce two kinds of spirocyclic frameworks. Mechanistically, the acyl radical is formed through oxidation of triphenylphosphine and subsequent C-O bond cleavage, followed by a 6-exo-trig cyclization/SET/protonation sequence to generate the spiro-chromanone products in an intramolecular manner. Furthermore, the protocol was extended to more challenging intermolecular tandem sequences consisting of C-O bond cleavage, radical addition to an alkene substrate, and 5-exo-trig cyclization to yield complex spirocyclic lactams.
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