Sterically Regulated α-Oxygenation of α-Bromocarbonyl Compounds Promoted Using 2-Aryl-1,3-dimethylbenzimidazolines and Air

Abstract

A debrominative oxygenation protocol has been developed for the conversion of α-bromo-α,α-dialkyl-substituted carbonyl compounds to their corresponding α-hydroxy analogues. For example, stirring a solution of α-bromoisobutyrophenone and 2-aryl-1,3-dimethylbenzimidazoline (BIH-Ar) at room temperature under an air atmosphere leads to the efficient formation of α-hydroperoxyisobutyrophenone, which can be converted to α-hydroxyisobutyrophenone using Me2S reduction. In contrast, reaction of α-bromoacetophenone under the same conditions produces the α-hydrogenated product acetophenone. α-Keto-alkyl and benzimidazolyl radicals (BI•-Ar), generated via dissociative electron transfer from BIH-Ar to α-bromoketone substrates, serve as key intermediates in the oxidation and reduction processes. The dramatic switch from hydrogenation to oxygenation is attributed to a steric effect of α-alkyl substituents, which causes hydrogen atom abstraction from sterically crowded BIH-Ar to α-keto-alkyl radicals to be slow and enable preferential reaction with molecular oxygen. Generation of the α-keto-alkyl radical and BI•-Ar intermediates in these process and their sterically governed hydrogen atom transfer reactions are supported by results arising from DFT calculations. Moreover, an electron spin resonance study showed that visible light irradiation of phenyl benzimidazoline (BIH-Ph) in the presence of molecular oxygen produces the benzimidazolyl radical (BI•-Ph). The addition of thiophenol into the reaction of α-bromoisobutyrophenone and BIH-Ph predominantly produced α-phenylthiolated isobutyrophenone even if a high concentration of molecular oxygen exists. Furthermore, the developed protocol was applied to other α-bromo-α,α-dialkylated carbonyl compounds.

Competitive Desulfonylative Reduction and Oxidation of α-Sulfonylketones Promoted by Photoinduced Electron Transfer with 2-Hydroxyaryl-1,3-dimethylbenzimidazolines under Air

“…On the other hand, 4a is not produced when the reaction is carried out under a N 2 atmosphere (entry 3). It is interesting to note that the dark reaction of α-bromoisobutyrophenone with 1g is significantly decelerated when a N 2 atmosphere is employed, but the rate of the photoreaction of 2a with 1a under N 2 is not significantly decreased (compare entry 3 to entries 1 and 2). A similar trend is seen in the reaction of α-benzylphenone 2b ( E 1/2 red = −1.48 V vs SCE, see Table S1) where oxidation product 4b is not formed when a N 2 atmosphere is used (entries 4, 5, and 6).…”

“…Reaction of 2a with 1g was first conducted under the conditions [dimethyl sulfoxide (DMSO), room temperature, air atmosphere] which would have led to complete conversion of α-bromoisobutyrophenone to the corresponding α-hydroperoxyphenone 5a (see Scheme ). However, 1 H NMR analysis of the product mixture showed that this process generates a trace of isobutyrophenone 3a and only a small quantity of α-hydroxyisobutyrophenone 4a . This observation clearly suggests that 2a and 1g do not efficiently participate in a dark SET–HAT reaction, like the one occurring between α-bromoisobutyrophenone and 1g (see Scheme ).…”

“…Recently, we found that the strong electron-accepting substrate, α-bromoisobutyrophenone [ E 1/2 red = −1.15 V vs saturated calomel electrode (SCE)], reacts with 1,3-dimethyl-2-phenylbenzimidazoline (BIH-Ph) to promote exclusive α-hydroxyketone forming reaction under the aerobic conditions without the use of heat, light, and catalysts (Scheme ). In this process, initial SET from BIH-Ph to the bromoketone induces loss of bromide ion to generate an α-ketoalkyl radical, which is subsequently trapped by molecular oxygen followed by hydrogen atom transfer (HAT) to give α-hydroperoxyisobutyrophenone and benzimidazolyl radical (BI • -Ph). Moreover, exergonic SET from the formed BI • -Ph to the bromoketone followed by bromide ion loss yields the α-ketoalkyl radical and benzimidazolium cation ( E 1/2 red = −1.61 V vs SCE).…”

Review on Asymmetric Catalysis Employing 5H‐Oxazol‐4‐Ones as α‐Hydroxy Carboxylic Acid Surrogates

“… [11–14] Owing to their significant importance in biology, they have attracted the considerable attention of synthetic organic chemists. However, direct incorporation of a hydroxy group in a stereoselective fashion at the α‐position of carbonyls is very challenging, and reports are limited [15–17] …”

A New Look into 4-(2,3-Dihydro-1,3-Dimethyl-1H-Benzimidazol-2-Yl)-N,N-Dimethylbenzenamine (DMBI-H) N-Type Dopant: Not so Stable After All, but It Does Not Necessarily Matter

“…The first one is demonstrated but the second is questionable. 26 In this paper we show the evolution over time of the NMR spectra of carefully purified samples of DMBI-H as solution in the processing solvent. We characterize and isolate the most relevant byproduct thus formed and we evaluate the impact of its presence in DMBI-H/P(NDI2OD-T2) blends.…”