Reactions of Atoms and Free Radicals in Solution. XII. The Addition of Bromo Esters to Olefins

Kharasch, M. S.; Skell, P. S.; Fisher, Paul

doi:10.1021/ja01183a053

Cited by 146 publications

(69 citation statements)

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“…Upon exposure of cyclopentene 29 to the optimized malonate addition protocol ( vide supra , Scheme 1), 85% of cyclized product was isolated, but this proved to be a 1:9 mixture of the anticipated reduced species 30a and bromide 30b (Figure 6). 27 Discovering these Kharasch-type byproducts 28 sparked our interest in atom transfer radical addition (ATRA) chemistry, since this offered the potential for a uniquely efficient and economical method for dual functionalization of double (and perhaps triple) bonds. Similar to the intermolecular malonate–indole coupling detailed above, these transformations are redox neutral, theoretically eliminating the need for additives and reducing the likelihood of deleterious off-target reactivity.…”

Section: Initial Methodology and Applications To Total Synthesismentioning

confidence: 99%

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

2016

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ConspectusHarnessing visible light as the driving force for chemical transformations generally offers a more environmentally friendly alternative compared with classical synthetic methodology. The transition metal-based photocatalysts commonly employed in photoredox catalysis absorb efficiently in the visible spectrum, unlike most organic substrates, allowing for orthogonal excitation. The subsequent excited states are both more reducing and more oxidizing than the ground state catalyst and are competitive with some of the more powerful single-electron oxidants or reductants available to organic chemists yet are simply accessed via irradiation. The benefits of this strategy have proven particularly useful in radical chemistry, a field that traditionally employs rather toxic and hazardous reagents to generate the desired intermediates.In this Account, we discuss our efforts to leverage visible light photoredox catalysis in radical-based bond-forming and bond-cleaving events for which few, if any, environmentally benign alternatives exist. Mechanistic investigations have driven our contributions in this field, for both facilitating desired transformations and offering new, unexpected opportunities. In fact, our total synthesis of (+)-gliocladin C was only possible upon elucidating the propensity for various trialkylamine additives to elicit a dual behavior as both a reductive quencher and a H-atom donor. Importantly, while natural product synthesis was central to our initial motivations to explore these photochemical processes, we have since demonstrated applicability within other subfields of chemistry, and our evaluation of flow technologies demonstrates the potential to translate these results from the bench to pilot scale.Our forays into photoredox catalysis began with fundamental methodology, providing a tin-free reductive dehalogenation that exchanged the gamut of hazardous reagents previously employed for such a transformation for visible light-mediated, ambient temperature conditions. Evolving from this work, a new avenue toward atom transfer radical addition (ATRA) chemistry was developed, enabling dual functionalization of both double and triple bonds. Importantly, we have also expanded our portfolio to target clinically relevant scaffolds. Photoredox catalysis proved effective in generating high value fluorinated alkyl radicals through the use of abundantly available starting materials, providing access to libraries of trifluoromethylated (hetero)arenes as well as intriguing gem-difluoro benzyl motifs via a novel photochemical radical Smiles rearrangement. Finally, we discuss a photochemical strategy toward sustainable lignin processing through selective C–O bond cleavage methodology. The collection of these efforts is meant to highlight the potential for visible light-mediated radical chemistry to impact a variety of industrial sectors.

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Section: Initial Methodology and Applications To Total Synthesismentioning

confidence: 99%

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

2016

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“…The addition of a-bromo esters to alkenes usually requires high reaction temperatures with the aid of explosive peracetic acid. 20 During the course of our study on intermolecular radical addition reaction, we found that bromine atom transfer radical addition of a-bromoacetate with 1-alkene in water could proceed at ambient temperature in the presence of a substoichiometric amount of triethylborane to yield 4-bromoalkanoate 38 (Table 4). The reaction mixture was heterogeneous yet clear.…”

Section: Triethylborane-induced Bromine Atom Transfer Radical Additiomentioning

confidence: 96%

Synthetic Radical Reactions in Aqueous Media

Yorimitsu¹,

Shinokubo²,

Oshima³

2002

Synlett

111

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This account focuses on the discovery and the rationalization of solvent effects, especially those of water, on synthetically useful radical reactions. Noteworthy advantages were observed during the course of our study on radical reactions in aqueous media. The established advantages of water as a solvent for radical reactions are (1) facile room-temperature atom transfer radical cyclization of allyl iodoacetate, (2) highly efficient construction of medium and large rings via radical cyclization of w-alkenyl iodoacetate, (3) enhancement of intermolecular radical addition, and (4) the highest deuterium incorporation in the deuterative reduction of organic halides. The favorable solvent effects of water are mainly due to its extremely high polarity, strong hydrogen bonding ability, and lack of easily transferable hydrogen via a radical process.

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“…In most of these reactions, ascorbic acid (as a reducing agent), AIBN and V-70 (free-radical initiators and reducing agents for ATRA at ambient temperatures) are used to complete the catalytic cycle by reducing the metal in the complex. [25][26][27][28][29][30][31][32][33][34][35] As a result of the factors mentioned above, metal-mediated visible lightdriven photoredox catalysis with reducing agents has been employed as a useful technique for a growing number of organic transformations.…”

Section: B26mentioning

confidence: 99%