Generation and Intermolecular Reactions of 2-Indolylacyl Radicals

Abstract

The generation of 2-indolylacyl radicals from the corresponding phenyl selenoesters, aldehydes, and alpha-keto carboxylic acids and the scope of their participation in intermolecular addition reactions to carbon-carbon double bonds have been studied. Whereas the phenyl selenoester method has provided easy access to a variety of 1,4-dicarbonyl compounds bearing the 2-acylindole moiety, the glyoxylic acid route has been employed for the preparation of 2-indolyl pyridyl ketones.

Intramolecular Reactions of 2-Indolylacyl Radicals: Access to 1,2-Fused Ring Indole Derivatives

“…Our interest in the chemistry of functionalized indoles as common substructures of many natural and medicinal compounds 5 led us to explore the reactivity and synthetic possibilities of indolylacyl radicals. Thus, with Boger's work on benzoyl radicals in mind, 2- and 3-indolylacyl radicals were generated from the corresponding phenyl selenoesters under reductive conditions and allowed to intermolecularly react with alkene acceptors, providing easy access to 2- and 3-acylindoles (Scheme ). Our efforts were then focused on the intramolecular version of the above radical reactions, as a general approach to a great variety of polycyclic indolyl ketones .…”

Cyclization of Aryl Acyl Radicals Generated fromS-(4-Cyano)phenyl Thiolesters by a Nickel Complex Catalyzed Electroreduction

“…6-Exo cyclizations are slower than the related 5-exo cyclizations, and the intramolecular allylic hydrogen transfer to give hydrogenated products of the initial radicals usually becomes a serious concern . However, the results of entries 9 and 10 suggest that 6-exo cyclization of the aryl acyl radicals can compete with the intramolecular allylic hydrogen transfer even with a thiolester 1f bearing unactivated alkene under the present reaction conditions. 1b, Definite explanations for the observations in entries 9 and 10 seem to be unobtainable until mechanistic behaviors of alk-6-enoyl radicals are fully investigated like the related alk-5-enoyl radicals. 11a, Under the present reaction conditions, the rate of competitive decarbonylation of aryl acyl radicals 1 ‘ could be presumed to be significantly smaller than those for 5-exo and 6-exo cyclizations of the corresponding acyl radicals 1 ‘ onto alkene acceptors judging from the observation that the products derived from the decarbonylation of acyl radical 1 ‘ were not detected …”

“…The generation of acyl radicals and their intra- and intermolecular carbon−carbon bond-forming reactions has long been recognized as a useful tool for homolytic synthesis. The majority of the above reactions have been achieved by employing acyl selenides, aryl acyl tellurides, and S -acylxanthates as the acyl radical precursors by means of organostannane-mediated chain reactions. In the tin hydride method, the use of S -phenyl thiolesters which are more stable under oxidizing conditions and attractive as acyl radical precursors is known not to be practical, since the reactions of stannyl radical with simple S -phenyl thiolesters are too sluggish to set the chain propagation viable .…”

Radical-mediated dehydrative preparation of cyclic imides using (NH4)2S2O8–DMSO: application to the synthesis of vernakalant

“…Optimization of the protocol using various permutations and combinations provided the ideal reaction conditions for imide synthesis ( Table 1 , entry 9). To the best of our knowledge, although, APS is being used in several commercial applications [ 55 ] and in organic [ 56 – 60 ] as well as polymer [ 55 ] chemistry as an oxidizing agent, it has been never reported to work as a dehydrating reagent via a radical pathway.…”