Hydrogen Atom Transfer from Alkanols and Alkanediols to the Cumyloxyl Radical: Kinetic Evaluation of the Contribution of α-C–H Activation and β-C–H Deactivation

Abstract

A kinetic study on the reactions of the cumyloxyl radical (CumO) with a series of alkanols and alkanediols has been carried out. Predominant hydrogen atom transfer (HAT) from the α-C-H bonds of these substrates, activated by the presence of the OH group, is observed. The comparable k values measured for ethanol and 1-propanol and the increase in k measured upon going from 1,2-diols to structurally related 1,3- and 1,4-diols is indicative of β-C-H deactivation toward HAT to the electrophilic CumO, determined by the electron-withdrawing character of the OH group. No analogous deactivation is observed for the corresponding diamines, in agreement with the weaker electron-withdrawing character of the NH group. The significantly lower k values measured for reaction of CumO with densely oxygenated methyl pyranosides as compared to cyclohexanol derivatives highlights the role of β-C-H deactivation. The contribution of torsional effects on reactivity is evidenced by the ∼2-fold increase in k observed upon going from the trans isomers of 4- tert-butylcyclohexanol and 1,2- and 1,4-cyclohexanediol to the corresponding cis isomers. These results provide an evaluation of the role of electronic and torsional effects on HAT reactions from alcohols and diols to CumO, uncovering moreover β-C-H deactivation as a relevant contributor in defining site selectivity.

Activation and Deactivation Strategies Promoted by Medium Effects for Selective Aliphatic C−H Bond Functionalization

“…Representative substrates,s uch as THF, [41] cyclohexanol (CyOH), [45] 2,2-dimethylpropanal (DMPA), [43] N,N-dimethylacetamide (DMA), [44] and triethylamine (TEA), [42,45] all undergo predominant or almost exclusive HATt oC umOC from the a-C À Hb onds (the formyl C À Hb ond with DMPA and the CÀHbonds a to the nitrogen center with DMA). The highest k H values were measured in isooctane and the lowest ones in TFE (Scheme 14), which leads to the following k H (isooctane)/k H (TFE) ratios:4.5, 7.9, 11, > 540, and > 2900, for THF,CyOH, DMPA, DMA, and TEA, respectively.…”

“…[30] Opposite behavior was observed in the reactions of CumO C with ether, alcohol, aldehyde,a mide,a nd amine substrates,w here the value of k H was observed to decrease with an increasing HBD ability of the solvent. [41][42][43][44][45] This behavior was explained in terms of hydrogen bonding of the solvent to the HBAs ite of the substrate,w hich outcompetes hydrogen bonding to the radical with these basic substrates. Very interestingly,a nu pt o1 26-fold increase in the k H value was measured for the reactions of COH with alcohols and ethers on going from MeCN to H 2 O, which indicates in this case that kinetic solvent effects are mainly governed by hydrogen bonding of the solvent to the radical.…”

“…Opposite behavior was observed in the reactions of CumO . with ether, alcohol, aldehyde, amide, and amine substrates, where the value of k H was observed to decrease with an increasing HBD ability of the solvent . This behavior was explained in terms of hydrogen bonding of the solvent to the HBA site of the substrate, which outcompetes hydrogen bonding to the radical with these basic substrates.…”

Anwendung von Mediumeffekten in Aktivierungs‐ und Deaktivierungsstrategien zur selektiven Funktionalisierung aliphatischer C‐H‐Bindungen

“…Ein gegensätzliches Verhalten wurde in den Reaktionen von CumO . mit Ether‐, Alkohol‐, Aldehyd‐, Amid‐ und Aminsubstraten beobachtet, in denen k H mit zunehmendem HBD‐Charakter des Lösungsmittels abnahm . Diese Beobachtung wurde der Wasserstoffbrücke des Lösungsmittels zur HBA‐Stelle des Substrats zugeschrieben, die der Wasserstoffbrücke zum Radikal bei diesen basischen Substraten überlegen ist.…”

“…Mit repräsentativen Substraten wie THF, Cyclohexanol (CyOH), 2,2‐Dimethylpropanal (DMPA), N , N ‐Dimethylacetamid (DMA) und Triethylamin (TEA), bei denen der HAT auf CumO . überwiegend oder nahezu ausschließlich aus den α‐C‐H‐Bindungen (der C‐H‐Formylbindung in DMPA und den C‐H‐Bindungen in α‐Position zum Stickstoff in DMA) erfolgt, wurden die höchsten k H ‐Werte in Isooctan und die niedrigsten in TFE (Schema ) mit den folgenden k H (Isooctan)/ k H (TFE)‐Verhältnissen gemessen: 4.5, 7.9, 11, >540 und >2900 für THF, CyOH, DMPA, DMA bzw.…”