KOtBu : a privileged reagent for electron transfer reactions?

Many recent studies have used KOtBu in organic reactions that involve single electron transfer; in the literature, the electron transfer is proposed to occur either directly from the metal alkoxide or indirectly, following reaction of the alkoxide with a solvent or additive. These reaction classes include coupling reactions of halobenzenes and arenes, reductive cleavages of dithianes and SRN1 reactions. Direct electron transfer would imply that alkali metal alkoxides are willing partners in these electron transfer reactions, but the literature reports provide little or no experimental evidence for this. This paper examines each of these classes of reaction in turn, and contests the roles proposed for KOtBu; instead, it provides new mechanistic information that in each case supports the in situ formation of organic electron donors. We go on to show that direct electron transfer from KOtBu can however occur in appropriate cases, where the electron acceptor has a reduction potential near the oxidation potential of KOtBu, and the example that we use is CBr4. In this case, computational results support electrochemical data in backing a direct electron transfer reaction

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

Novel applications of a 4-DMAP-derived organic electron donor under photoactivation

Strathclyde theses - ask staff. Thesis no. : T134614-DMAP-derived neutral organic super-electron-donor 1 has previously been successfully applied to a number of electron transfer reactions under thermal activation in the Murphy group. The research programme focuses on the photoactivation of the donor 1 and its novel applications in achieving more demanding electron-transfer reactions. Chapter Two highlights the enhanced reducing power of the donor 1 under photoactivation. The reduction of the most challenging unactivated arenesulfonamides, where the nitrogen leaving group will be an unstabilised dialkylamide anion, e.g. 2 and 3, had not been achieved under thermal activation of 1. In contrast, photoactivated donor 1 has now provided the reduction of 2 and 3 in good yields, while activated sulfonamides e.g. 4 were reduced in excellent yields with lower loadings of 1 at room temperature compared with the thermal activation. Chapter Three investigates metal-free reductive C-O bond fragmentations of benzylic esters and ethers with photoactivated donor 1. Benzylic esters e.g. 8 were reduced to acids e.g. 10 via SET process and the complete absence of isolated toluenes e.g. 9 was attributed to trapping of benzyl radical intermediates with the radical-cation of 1. Interestingly, benzylic ethers e.g. 11 provided reduced products 9 and 12 from either side of the ether moiety, and the generation of 9 indicated the presence of benzyl anion intermediates that were arising via a DET process. [IMAGES UNAVAILABLE - SEE FULLTEXT].;To test whether the benzylic radicals were mandatory intermediates in these cleavages, cyclopropyl substrates 13 and 14 were prepared and tested. Cyclopropyl ester 13 afforded acid product 10 only and this supported the trapping of radical intermediates formed via a SET process. On the other hand, cyclopropyl ether 14 afforded intact cyclopropane 15 that could not have arisen from a benzylic radical intermediate; rather the benzylic anion must be its precursor, supporting a DET process in reaction of 14. To probe further for benzylic anion intermediates, substrates 16 and 17, containing not only a benzylic leaving group but also a potential leaving group (pivalate) in the adjacent β- position, have been designed and synthesised. Upon photoactivation, substrate 17 provided a considerably better yield of α-methylstyrene 18 compared with substrate 16 and supported a DET process in the ether cleavage seen in the challenging substrate 17. Chapter Four describes briefly the discovery of benzylic C-N bond cleavages e.g. 20 and provides a detailed account of challenging benzylic C-C σ-bond fragmentations under photoactivation of 1. This chemistry is perfectly general as seen when it was extended to substrates including e.g. electron-rich 22, electron-poor 24, dicinnamyl 26 (for an example of homologous cleavage) and cyanoester 28. [IMAGES UNAVAILABLE - SEE FULLTEXT].;All these reactions proceeded through a SET process as evident from the complete absence of toluene products. However, B-ketoester 30 provided fragmentation of the acyl group and this was further supported by Spartan calculations. Chapter Five discusses the decyanation of malononitriles e.g. 32 and cyanoacetates e.g. 34 under photoactivation of the donor 1 and provided an alternative to the traditional methods involving metal reagents such as SmI2 and carcinogenic solvents e.g. HMPA. Decyanation of malononitriles was faster than that of cyanoacetates and required lower loadings of 1. Chapter Six provides an insight into regioselective ArO-C bond cleavages of orthodialkoxybenzenes, under Birch conditions. The site of fragmentation, generally, depends upon the combined stability of the fragmented species. It was also found that the greater the stability of the charge on the alkyl group, the greater was its ease of formation. Chapter Seven provides the detailed experimental procedures and data for the compounds discussed in the Chapters two to six. [IMAGES UNAVAILABLE - SEE FULLTEXT].4-DMAP-derived neutral organic super-electron-donor 1 has previously been successfully applied to a number of electron transfer reactions under thermal activation in the Murphy group. The research programme focuses on the photoactivation of the donor 1 and its novel applications in achieving more demanding electron-transfer reactions. Chapter Two highlights the enhanced reducing power of the donor 1 under photoactivation. The reduction of the most challenging unactivated arenesulfonamides, where the nitrogen leaving group will be an unstabilised dialkylamide anion, e.g. 2 and 3, had not been achieved under thermal activation of 1. In contrast, photoactivated donor 1 has now provided the reduction of 2 and 3 in good yields, while activated sulfonamides e.g. 4 were reduced in excellent yields with lower loadings of 1 at room temperature compared with the thermal activation. Chapter Three investigates metal-free reductive C-O bond fragmentations of benzylic esters and ethers with photoactivated donor 1. Benzylic esters e.g. 8 were reduced to acids e.g. 10 via SET process and the complete absence of isolated toluenes e.g. 9 was attributed to trapping of benzyl radical intermediates with the radical-cation of 1. Interestingly, benzylic ethers e.g. 11 provided reduced products 9 and 12 from either side of the ether moiety, and the generation of 9 indicated the presence of benzyl anion intermediates that were arising via a DET process. [IMAGES UNAVAILABLE - SEE FULLTEXT].;To test whether the benzylic radicals were mandatory intermediates in these cleavages, cyclopropyl substrates 13 and 14 were prepared and tested. Cyclopropyl ester 13 afforded acid product 10 only and this supported the trapping of radical intermediates formed via a SET process. On the other hand, cyclopropyl ether 14 afforded intact cyclopropane 15 that could not have arisen from a benzylic radical intermediate; rather the benzylic anion must be its precursor, supporting a DET process in reaction of 14. To probe further for benzylic anion intermediates, substrates 16 and 17, containing not only a benzylic leaving group but also a potential leaving group (pivalate) in the adjacent β- position, have been designed and synthesised. Upon photoactivation, substrate 17 provided a considerably better yield of α-methylstyrene 18 compared with substrate 16 and supported a DET process in the ether cleavage seen in the challenging substrate 17. Chapter Four describes briefly the discovery of benzylic C-N bond cleavages e.g. 20 and provides a detailed account of challenging benzylic C-C σ-bond fragmentations under photoactivation of 1. This chemistry is perfectly general as seen when it was extended to substrates including e.g. electron-rich 22, electron-poor 24, dicinnamyl 26 (for an example of homologous cleavage) and cyanoester 28. [IMAGES UNAVAILABLE - SEE FULLTEXT].;All these reactions proceeded through a SET process as evident from the complete absence of toluene products. However, B-ketoester 30 provided fragmentation of the acyl group and this was further supported by Spartan calculations. Chapter Five discusses the decyanation of malononitriles e.g. 32 and cyanoacetates e.g. 34 under photoactivation of the donor 1 and provided an alternative to the traditional methods involving metal reagents such as SmI2 and carcinogenic solvents e.g. HMPA. Decyanation of malononitriles was faster than that of cyanoacetates and required lower loadings of 1. Chapter Six provides an insight into regioselective ArO-C bond cleavages of orthodialkoxybenzenes, under Birch conditions. The site of fragmentation, generally, depends upon the combined stability of the fragmented species. It was also found that the greater the stability of the charge on the alkyl group, the greater was its ease of formation. Chapter Seven provides the detailed experimental procedures and data for the compounds discussed in the Chapters two to six. [IMAGES UNAVAILABLE - SEE FULLTEXT]

Electron transfer-induced coupling of haloarenes to styrenes and 1,1-diphenylethenes triggered by diketopiperazines and potassium tert-butoxide

The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead to either 1,1,2-triarylethenes or 1,1,2-triarylethanes, depending on the conditions used

Reactions of triflate esters and triflamides with an organic neutral super-electron-donor

The bis-pyridinylidene 13 converts aliphatic and aryl triflate esters to the corresponding alcohols and phenols respectively using DMF as solvent, generally in excellent yields. While the deprotection of aryl tiflates has been seen with other reagents and by more than one mechanism, the deprotection of alkyl triflates is a new reaction. Studies with 18-O labelled DMF studies indicate that the C-O bond of the triflate ester stays intact and hence it is the S-O bond that cleaves, underlining that the cleavage results from the extraordinary electron donor capability of 13. Trifluoromethanesulfonamides are converted to the parent amines in like manner, representing the first cleavage of such substrates by a ground-state organic reducing reagent

Overturning Established Chemoselectivities: Selective Reduction of Arenes over Malonates and Cyanoacetates by Photoactivated Organic Electron Donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate–metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor <b>5</b> selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

KO<i>t</i>Bu: A Privileged Reagent for Electron Transfer Reactions?

Many recent studies have used KO<i>t</i>Bu in organic reactions that involve single electron transfer; in the literature, the electron transfer is proposed to occur either directly from the metal alkoxide or indirectly, following reaction of the alkoxide with a solvent or additive. These reaction classes include coupling reactions of halobenzenes and arenes, reductive cleavages of dithianes, and S_RN1 reactions. Direct electron transfer would imply that alkali metal alkoxides are willing partners in these electron transfer reactions, but the literature reports provide little or no experimental evidence for this. This paper examines each of these classes of reaction in turn, and contests the roles proposed for KO<i>t</i>Bu; instead, it provides new mechanistic information that in each case supports the <i>in situ</i> formation of organic electron donors. We go on to show that direct electron transfer from KO<i>t</i>Bu can however occur in appropriate cases, where the electron acceptor has a reduction potential near the oxidation potential of KO<i>t</i>Bu, and the example that we use is CBr₄. In this case, computational results support electrochemical data in backing a direct electron transfer reaction

Identifying the roles of amino acids, alcohols and 1,2-diamines as mediators in coupling of haloarenes to arenes

Coupling of haloarenes to arenes has been facilitated by a diverse range of organic additives in the presence of KO(t)Bu or NaO(t)Bu since the first report in 2008. Very recently, we showed that the reactivity of some of these additives (e.g., compounds 6 and 7) could be explained by the formation of organic electron donors in situ, but the role of other additives was not addressed. The simplest of these, alcohols, including 1,2-diols, 1,2-diamines, and amino acids are the most intriguing, and we now report experiments that support their roles as precursors of organic electron donors, underlining the importance of this mode of initiation in these coupling reactions