Desulfonylative Radical Ring Closure onto Aromatics. A Modular Route to Benzazepin-2-ones and 5-Arylpiperidin-2-ones

Abstract

Adducts from the intermolecular radical addition of N-xanthylacetyl-N-methanesulfanilides to Boc-protected allylamine undergo ring closure with loss of a methanesulfonyl radical to give benzazepin-2-ones. Upon deprotection and exposure to triethylamine, these compounds rearrange into 5-aryl-2-piperidones. This approach also represents a useful route to benzazepin-2-ones unsubstituted on the nitrogen atom of the azepinone ring.

Some aspects of radical cascade and relay reactions

“…A conceptually similar approach to N-unsubstituted benzazepinones relies on the fragmentation of a nitrogen-sulfur bond in sulfonanilides. This is illustrated by the synthesis of benzazepinones 103 and 106 from xanthates 100 and 104 pictured in scheme 17 [44]. The cyclization of the respective intermediate adducts 101 and 105 requires higher temperature and Scheme 17.…”

“…The cyclization of the respective intermediate adducts 101 and 105 requires higher temperature and Scheme 17. Further examples of benzazepinones [44].…”

“…This is illustrated by the synthesis of benzazepinones 103 and 106 from xanthates 100 and 104 pictured in scheme 17 [44]. …”

The xanthate route to lactams

“…A simpler and more appealing solution is to start with methanesulfonylanilide 270 (Scheme 58). 90 Addition to the alkene affords the usual adduct 271 and heating with di-t-butyl peroxide at the higher temperature of refluxing chlorobenzene regenerates intermediate radical 272, which undergoes cyclization and concomitant expulsion of a methanesulfonyl radical. Prototropic isomerization the resulting acylimine 273 finally gives the desired N-unsubstituted benzazepinone 275.…”

“…This strategy is illustrated by examples 274a-j displayed in Scheme 58. 90 Here again, the yields of intermediates 271a-j are given without the structures. Note the presence of halides on the aromatic ring, especially iodine and fluorinated groups, and a boronate on the side of benzazepinone 24j.…”