Atom Transfer Radical Cyclization of Trichloroacetamides to Electron-Rich Acceptors Using Grubbs’ Catalysts: Synthesis of the Tricyclic Framework of FR901483

Abstract

Intramolecular Kharasch-type additions of trichloroacetamides on anisole and enol acetates catalyzed by Grubbs' ruthenium carbenes are described. This protocol provides access to highly functionalized 2-azaspiro[4.5]decanes, morphan compounds, and the azatricyclic core of FR901483.

Recent Advances in the Synthesis of Hydrogenated Azocine-Containing­ Molecules

“…Diaba, Bonjoch, and co-worker obtained morphan compounds 249 via the first intramolecular atom transfer radical process between trichloroacetamide and enol acetate used as a radical acceptor. 79 The reaction was promoted by Grubbs II catalyst, thus expending the scope of these catalysts beyond the metathesis reaction (Scheme 71 ).…”

“…The reaction of compound 253 with zinc led to dechlorinated derivative 256 , possessing the tricyclic skeleton of immunosuppressant FR901483, in 58% yield (Scheme 72 ). 79…”

Radical Cyclization of Trichloroacetamides: Synthesis of Lactams

“…Following their work on copper-mediated ATRC (Schemes 27 and 29), Bonjoch's group obtained access to the morphan compound 57 and 2-azaspiro[4.5]decane 67 using ATRC-mediated by the Grubbs II catalyst (Scheme 38). 49 In these reactions a possible SET leading to an oxonium intermediate, instead of an atom-transfer process, may be involved.…”

Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes

“…In an innovatory undertaking, graphene oxide was used to support ruthenium catalysts in order to activate self-healing in multifunctional materials that are able to simultaneously integrate the healing process with the advantageous properties of graphene-based materials [159]. Part of a large body of work concerns fundamental reactions studied anew with Ru complexes including hydrogenation and transfer hydrogenation; oxidation and hydroxylation; C–C, C–X and N–X bond formation; olefin metathesis and related C–C couplings; alkylation; arylation; isomerization; epimerization; condensation; cyclization; atom transfer radical reactions; oligomerization and polymerization [160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193]. Among non-metathetical reactions, the versatile and easy to handle transfer hydrogenation is often chosen as standard method for appraising and comparing the catalytic activity of ruthenium promoters [167,168,169,170,171,172,173].…”