Strongly Directing Substituents in the Radical Arylation of Substituted Benzenes

Abstract

Although general interest in radical arylation reactions has grown rapidly in recent years, poor regioselectivities and the need to use a large excess of the radical-accepting arene have hindered their application to substituted benzenes. We now describe experimental and computational investigations into the substituent effects that lead to regioselective addition based on the recent discovery of anilines as outstanding substrates for radical arylations.

Hydrogen Atom Transfer‐Mediated Domino Cyclisation Reaction to Access (Spiro)Quinazolinones

“…Alternatively, the preference in ortho versus para selectivity may result in polarity pairing between the iminyl radical and the aryl ring (i.e., under kinetic control). This has been found to be the case for the addition of aryl radicals to substituted benzenes, where the radical addition is believed to be the rate determining step …”

“…This has been found to be the case for the addition of aryl radicals to substituted benzenes, where the radical addition is believed to be the rate determining step. [29] In summary,w eh ave developedH AT methodology to enable the synthesis of (spiro)quinazolinone scaffolds from tractable N-cyanamide alkenes (synthesised from their acid and cyanamidec ounterparts). The reactionh as been shown to be scalablea nd has been optimised to accept challenging electron-deficient heterocycles.…”

Denitrogenative Pd/Cu‐catalyzed Suzuki‐type Cross‐coupling of Aryltrifluoroborates with Arylhydrazine Hydrochlorides in Water under Room Temperature

“…In cross‐coupling arylation. Recent advances in the coupling reactions of arylhydrazine, which is utilized as an effective arylation partner in oxidative radical arylation and Pd‐catalyzed cross‐coupling (Heck‐type, Suzuki‐type, addition, homocoupling, etc …”

“…In cross-coupling arylation. Recent advances in the coupling reactions of arylhydrazine, which is utilized as an effective arylation partner in oxidative radical arylation [43][44][45][46][47][48][49][50] and Pd-catalyzed crosscoupling (Heck-type, [51][52][53][54] Suzuki-type, [55][56][57][58] addition, [59,60] homocoupling, [61][62][63] etc. [64][65][66][67][68][69][70][71][72][73] ) via C-N bond cleavage.…”

Radical Arylation of Anilines and Pyrroles via Aryldiazotates

“…[5] Though such radical arylation reactions are formally comparable with CÀHf unctionalization, and thus relatively simple starting materials can be employed, the insufficient regioselectivity of the radical attack on most substituted benzenes represents am ajor drawback. [7] Heteroarenes,o nt he other hand, are usually more effective radicala cceptors than substituted benzenes, [8] and high selectivity for particular positions on the aromatic core is often observed. [7] Heteroarenes,o nt he other hand, are usually more effective radicala cceptors than substituted benzenes, [8] and high selectivity for particular positions on the aromatic core is often observed.…”