Synthetic Strategies for 5- and 6-Membered Ring Azaheterocycles Facilitated by Iminyl Radicals

Abstract

Abstract:The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes figure prominently. This review focuses on the search for fast, efficient and environmentally friendly preparative methods for these rings with specific emphasis on iminyl radical-mediated procedures. Oxime derivatives, particularly oxime esters and oxime ethers, are attractive precursors for these radicals. Their use is described in conventional thermolytic, microwave-assisted and UV-vis based preparative procedures. Photoredox-catalyzed protocols involving designer oxime ethers are also covered. Choice can be made amongst these synthetic strategies for a wide variety of 5-and 6-membered ring heterocycles including phenanthridine and related aza-arenes. Applications to selected natural products and bioactive molecules, including trispheridine, vasconine, luotonin A and rutaecarpine, are included.

Cathode Material Determines Product Selectivity for Electrochemical C−H Functionalization of Biaryl Ketoximes

“…Recently, radical‐mediated C−N bond construction has gained traction because the relatively high reactivity of the open‐shell species provides opportunities for the development of transformations that are difficult using the two‐electron manifold . In this context, many research groups have employed the easily available oximes and their derivatives as radical precursors in radical C−N coupling reactions . The cleavage of the O−H bond in oxime produces a σ‐type iminoxyl radical with both a reactive oxygen and nitrogen atom .…”

“…[2] In this context, many research groups have employed the easily available oximes and their derivatives as radical precursors in radical CÀN coupling reactions. [3] Thecleavage of the OÀHbond in oxime produces a s-type iminoxyl radical with both ar eactive oxygen and nitrogen atom. [4] Han and co-workers have demonstrated that iminoxyl radicals can cyclize with alkenes or alkynes to form 5-membered N-heterocyclic compounds (Scheme 1a).…”

“…[5] However,t ot he best of our knowledge, similar cyclization reactions with the less reactive arenes have only been mentioned in mechanistic proposals. [6] On the other hand, the thermal or photochemical cleavage of the relatively weak N À Ob ond in oxime ethers and oxime esters generates an iminyl radical [3,7] that is reactive toward various p-systems, including arenes,t oa fford phenanthridines and some other N-heteroaromatics (Scheme 1b). [8] Although these oxime derivatives are easily prepared, their usage reduces the step and atom economy of the synthetic method.…”

Copper-catalyzed oxidative benzylic C-H cyclization via iminyl radical from intermolecular anion-radical redox relay

“…On the other hand, iminyl radical has been well-established as intermediates for the construction of N -containing 5- and 6-membered heterocycles including indoles and pyridines 16–21 . Iminyl radical is normally generated from N-O bond cleavage using either light or initiators (Fig.…”

Vanadium(V) Complex-Catalyzed One-Pot Synthesis of Phenanthridines via a Pictet-Spengler-Dehydrogenative Aromatization Sequence

“…Phenanthridine and its structurally related compounds play essential roles in a variety of chemical fields due to their existence in a broad range of natural products, bioactive compounds, and functional materials ( Figure 1) [1][2][3][4][5]. Phenanthridine was first synthesized from the reaction between benzaldehyde and aniline in 1889 [6], and a number of preparative methods have been reported to date [1,[7][8][9]. However, since most protocols necessitate harsh reaction conditions and/or multi-step reaction sequences from commercially available starting materials [10,11], concise and mild preparation procedures for this important class of compounds are still in high demand [12][13][14][15].…”