The Mechanism of Bu<sub>3</sub>SnH‐Mediated Homolytic Aromatic Substitution

Beckwith, A. L. J.; Bowry, Vincent W.; Bowman, W. Russell; Mann, Emma; Parr, Jonathan; Storey, John M. D.

doi:10.1002/ange.200352419

Cited by 28 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[5h, 25] Extrusion of radicals in ipso-substitution mechanisms [26] or in rearomatization processes, as achieved in Studers group, [27][28][29][30] have been described recently. We were able to perform homolytic substitution on a substituted aromatic carbon atom during the last step of the radical cascade.…”

Section: Introductionmentioning

confidence: 99%

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Beaume

Courillon

Derat

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

Amide-iminyl radicals are versatile and efficient intermediates in cascade radical cyclizations of N-acylcyanamides. They are easily trapped by alkenes or (hetero-)aromatic rings and cyclize into a series of new heterocyclic compounds which bear a pyrroloquinazoline moiety. As an illustration of the synthetic importance of these compounds, the total synthesis of the natural antitumor compound luotonin A was achieved through a tin-free radical cascade cyclization process. Not only do amide-iminyl radicals lead to new tetracyclic heterocycles but these nitrogen-centered radical species also react in aromatic homolytic substitutions. Indeed, the amide-iminyl radical moiety unprecedentedly displaces methyl, methoxy, and fluorine radicals from an aromatic carbon atom. This seminal reaction in the field of radical chemistry has been developed experimentally and its mechanism has additionally been investigated by a theoretical study.

show abstract

Section: Introductionmentioning

confidence: 99%

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Beaume

Courillon

Derat

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…[17][18][19][20] The net result is a "homolytic aromatic substitution". The possible mechanisms for rearomatization have been widely discussed, [21][22][23][24][25] and include disproportionation, reaction with an initiator by hydrogen transfer, and oxidation.…”

mentioning

confidence: 99%

Organocatalysis and CH Activation Meet Radical‐ and Electron‐Transfer Reactions

2011

View full text Add to dashboard Cite

aryl radicals · CÀH activation · homolytic radical substitutions · organocatalysis · radical anionsThe research groups of Shi, [1] Shirakawa/Hayashi, [2] and Kwong/Lei [3] have recently reported independently on the construction of biaryl compounds from unactivated aromatic rings by direct CÀH activation with the aid of organocatalysts.[4] Published in J. Am. Chem. Soc. and Nature Chem., the results were described as "conceptual breakthroughs" [1,3] because no metal catalyst was needed.Here we suggest that these exciting results are not best viewed in terms of C À H activation or organocatalysis, but instead in terms of homolytic radical aromatic substitution (HAS). [5][6][7][8][9] Although the results may not be conceptual breakthroughs from that viewpoint, they could well herald new opportunities for making organic molecules through organic radical and radical anion reactions.Kwong, Lei, and co-workers discovered that heating aryl iodides in benzene at 80 8C with one equivalent of potassium tert-butoxide and 20 mol % N,N'-dimethylethylenediamine (DMEDA, the organocatalyst) gave biaryls in good yields (60-85 %, Scheme 1).[3] The research groups of Shirakawa/ Hayashi [2] and Shi [1] described similar bimolecular reactions in comparable yields, although their organocatalyst was 1,10-phenanthroline (or a substituted analogue) and used at a level of 20 and 40 mol %, respectively. In addition, Shi and co-workers reported an example of a cyclization: heating 2-iodophenyl benzyl ether (1) in mesitylene with potassium tert-butoxide (3 equiv) and 1,10-phenanthroline provided benzochromene 2 in 75 % yield.In 2008, Itami and co-workers reported that potassium tert-butoxide (1.5 equiv) alone effected the addition of aryl iodides and bromides to pyridizine and other electron-poor aromatic rings. [10,11] These results are reminiscent of the Minisci reaction (addition of alkyl and other radicals to electron-poor heterocycles), [12] except that Minisci reactions are usually conducted under acidic conditions rather than basic conditions. The research groups [1,3,4] discovered these transformations through control experiments while trying to develop metal-catalyzed C À H activation reactions. They observed that with certain "ligands" and KOtBu, the metal was not needed at all to effect the conversion of the aryl halide into the biaryl. Extensive control experiments and trace analyses (Shi and co-workers, [1] Itami and co-workers [10] ) were performed to ensure that the conditions were indeed metal-free. Coming from this direction, the processes look like organocatalylic CÀH activation reactions.In all these reports there are suggestions that aryl radicals are intermediates. The scope and conditions of the reactions (large excess of acceptor needed) and the H/D isotope effects are consistent with aryl radicals being involved. The addition of 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO) and other inhibitors blocked the reactions, [1,3,10] and the successful cyclization of 1 to 2 is consistent with an aryl radical intermediate. Final...

show abstract

“…Der mögliche Mechanismus der Rearomatisierung unter reduktiven Bedingungen wurde intensiv untersucht. [21][22][23][24][25] [27] Diese Reaktionen können über einen "Innensphären"-(Atomtransfer-)Mechanismus ablaufen. [28] Im Unterschied zu den bekannten HAS-Reaktionen beruhen die neuen Prozesse auf einer sehr starken Base (Kalium-tert-butylat), meistens in Kombination mit einem zusätzlichen Katalysator.…”

unclassified

Organokatalyse und C‐H‐Aktivierung treffen auf Radikal‐ und Elektronentransferreaktionen

2011

View full text Add to dashboard Cite

Radikal(isch)e Perspektive: Kürzlich publizierte „organokatalytische C‐H‐Aktivierungen“ werden neu als Basen‐vermittelte homolytische Substitutionen interpretiert. Eine Sequenz aus Addition eines Arylradikals an ein Aren, Deprotonierung (siehe Schema) und Elektronentransfer ist ein Teil der Kettenreaktion. Die Arbeiten sind damit keine konzeptionellen Durchbrüche mehr, können aber gleichwohl neue Synthesemöglichkeiten unter Nutzung der Radikal(anionen)chemie eröffnen.

show abstract

The Mechanism of Bu₃SnH‐Mediated Homolytic Aromatic Substitution

Cited by 28 publications

References 18 publications

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Organocatalysis and CH Activation Meet Radical‐ and Electron‐Transfer Reactions

Organokatalyse und C‐H‐Aktivierung treffen auf Radikal‐ und Elektronentransferreaktionen

Contact Info

Product

Resources

About

The Mechanism of Bu3SnH‐Mediated Homolytic Aromatic Substitution

Cited by 28 publications

References 18 publications

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Unprecedented Aromatic Homolytic Substitutions and Cyclization of AmideIminyl Radicals: Experimental and Theoretical Study

Organocatalysis and CH Activation Meet Radical‐ and Electron‐Transfer Reactions

Organokatalyse und C‐H‐Aktivierung treffen auf Radikal‐ und Elektronentransferreaktionen

Contact Info

Product

Resources

About

The Mechanism of Bu₃SnH‐Mediated Homolytic Aromatic Substitution