DMSO‐Enabled Selective Radical O−H Activation of 1,3(4)‐Diols

Abstract

Control of selectivity is one of the central topics in organic chemistry. Although unprecedented alkoxyl-radicalinduced transformations have drawn a lot of attention, compared to selective CÀH activation, selective radical OÀH activation remains less explored. Herein, we report a novel selective radical O À H activation strategy of diols by combining spatial effects with proton-coupled electron transfer (PCET). It was found that DMSO is an essential reagent that enables the regioselective transformation of diols. Mechanistic studies indicated the existence of the alkoxyl radical and the selective interaction between DMSO and hydroxyl groups. Moreover, the distal C À C cleavage was realized by this selective alkoxylradical-initiation protocol. The selective transformation of hydroxyl (OH) groups in diand polyols is a frequently encountered problem in organic synthesis, in contexts ranging from simple alcohol transformations to the preparation of highly functionalized natural products. [1] Despite the importance of this issue, strategies for the selective O À H activation are rare compared to the fastgrowing studies on selective CÀH activation. [2] The classic methods for selective activation of one hydroxyl in diols involve ionic transformations by steric regulation or based on special hydrocarbon structure. [3] Unlike traditional ionic alcohol transformations involving nucleophilic substitution/ addition, [4] oxidation [5] and elimination [6] of hydroxyls, the alkoxyl radical induced transformations have drawn more attention with the discovery of unprecedented strategies for the generation of alkoxy radicals from alcohol without the need for pre-activation. [7] The OÀH radical processes greatly enlarged the reaction types of alcohols either with alkoxyl radical induced b scission [8] or hydrogen abstraction. [9, 10] However, to the best of our knowledge, the general methods for the alkoxyl radical induced distal CÀC cleavage remains unexplored (Scheme 1 a). Moreover, the realized OÀH radical transformations are limited to the activation of mono-ols, so far, there is a lack of selective radical O À H activation due to the almost identical bond-dissociation energy between two hydroxyls in diols (% 105 kcal mol À1) [11] (Scheme 1 b). To address this problem, we paid our attention to the strategy of proton coupled electron transfer (PCET), which was reported that a Brønsted base and an oxidant can synergistically remove a proton and an electron from the substrate to afford a free radical (Scheme 1 c). [12] Recently, Knowles and co-workers significantly achieved the O À H bond homolysis through PCET. [13] Inspired by these reports, we hypothesized that if we could find a proper Brønsted or Lewis base that can selectively form a hydrogen bond with one hydroxyl in diols, we would have a chance to selectively activate one O À H bond and realize the selective alkoxyl radical transformation of diols (Scheme 1 d). Scheme 1. Selective hydroxyl activation of diols.

Hydrogen‐Binding‐Initiated Activation of O−H Bonds on a Nitrogen‐Doped Surface for the Catalytic Oxidation of Biomass Hydroxyl Compounds

“…Recently, some explorative studies have been performed in utilizing HBs for promoting the conversion of inert hydroxyl substrates and guiding pathways in purpose. For example, the selective activation of the primary hydroxyl group in diol could be accomplished via forming O−H⋅⋅⋅O=S HBs with DMSO as a proton acceptor, which was in favor of the selective alkoxyl radical transformation, rather than occurring β‐scission due to the unselective activation of both two hydroxyl groups [5] . Han et al [6] .…”

“…[4] Thedecreased electron cloud density near the proton nucleus might weaken OÀHbonds,thus enhancing the reactivity of hydroxyl groups.Recently,some explorative studies have been performed in utilizing HBs for promoting the conversion of inert hydroxyl substrates and guiding pathways in purpose.F or example,t he selective activation of the primary hydroxyl group in diol could be accomplished via forming OÀH•••O=SHBs with DMSO as aproton acceptor, which was in favor of the selective alkoxyl radical transformation, rather than occurring b-scission due to the unselective activation of both two hydroxyl groups. [5] Han et al [6] presented that the HBs between the alcohol hydroxyl groups and ionic liquid [EMIM]OAc could accelerate the rate-determining step of hydroxyl groups activation, thus significantly promoting the oxidative esterification of inert aliphatic alcohols.I nt he case of heterogeneous catalysis, researchers also found that the surface-grafted nitrogencontaining ligands on EPy/Pt/Al 2 O 3 catalyst could form HBs with specific hydroxyl groups. [7] However,the research of HBs on heterogeneous surface mainly concentrated on the modification of catalyst surface,p romotion of catalytic performance,a nd elimination of negative impacts via pre-converting -OH.…”

Catalytic generation of alkoxy radicals from unfunctionalized alcohols

“…Jiao and coworkers recently applied similar alcohol activation conditions to an aqueous catalyst system for the regioselective O-H homolysis of 1,3-diols in the presence of DMSO as a hydrogenbond acceptor, enabling distal C-C cleavage and 1,4-aryl migration. 63 In 2019, Pan and coworkers disclosed a protocol encompassing a copper and oxazoline catalyst system for alkoxy radical generation and C-O bond formation to access 3a,3a 0bisfuro[2,3-b]indoline scaffolds and 3-alkoxy furoindolines from tryptophol derivatives (Scheme 16). 64 Remarkably, this method does not require exogenous base, initiator, or oxidant, but the use of a dual Cu(I)/Cu(II) catalyst combination and a bisoxazoline ligand has proven to be essential to reaction efficiency.…”

“…Jiao and coworkers recently applied similar alcohol activation conditions to an aqueous catalyst system for the regioselective O–H homolysis of 1,3-diols in the presence of DMSO as a hydrogen-bond acceptor, enabling distal C–C cleavage and 1,4-aryl migration. 63 …”

Electrochemical Dimethyl Sulfide‐Mediated Esterification of Amino Acids

“…On the other hand, DMSO, serving as an important organic mediator, has attracted much attention owing to its unique properties over the past decade, and the Jiao group has made great contribution in this regard. [ 6 ] In comparison with DMSO, dimethyl sulfide (DMS) as mediator has rarely been reported in synthetic chemistry. Hence, there is great room for the development of DMS as mediator, especially in the cooperation of DMS with anodic electrochemistry in organic chemistry.…”