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Synthesis of 1‑Azaspiro[4.4]nonane Derivatives Enabled by Domino Radical Bicyclization Involving Formation and Capture of Alkoxyaminyl Radicals

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journal contribution
posted on 04.12.2019, 09:30 by Alejandro Guerrero-Caicedo, Diana M. Soto-Martínez, David A. Osorio, Muskendol Novoa, Alix E. Loaiza, Luz M. Jaramillo-Gómez
The application of a domino radical bicyclization for the synthesis of compounds containing the 1-azaspiro[4.4]­nonane skeleton in 11–67% yields as a mixture of diastereomers is described (trans configuration preference). This process involved formation and capture of alkoxyaminyl radicals. For this purpose, O-benzyl oxime ethers with a brominated or iodinated aromatic ring or a terminal alkynyl group and an alkenyl moiety were employed as starting materials. The bicyclization was initiated by 2,2′-azobisisobutyronitrile or triethylborane and promoted by Bu3SnH. The best results were obtained with O-benzyl oxime ethers containing an alkenyl moiety tethered to electron withdrawing groups or aryl substituents, whereas oxime radical precursor attached to methyl-substituted olefin precluded the capture of alkoxyaminyl radical, giving rise mainly to monocyclized product.