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.

Alkoxy Radical Induced Transformations from N‐Alkoxyphthalimides Under the Photoredox Catalysis

“…In 2018, Tang and co‐workers reported the alkylation of allyl/alkenyl sulfones by deoxygenation of alkoxyl radicals [45] . Mechanism was unique from previously described procedures and the high reactive oxygen radical generated from NAPI was captured by highly oxophilic triethyl phosphite, which underwent α‐fragmentation to form α ‐carbon‐centered radical via deoxygenation procedure.…”

“…Complex molecules such as sugar and amino acid derivatives were also successfully borylated, In 2018, Tang and co-workers reported the alkylation of allyl/alkenyl sulfones by deoxygenation of alkoxyl radicals. [45] Mechanism was unique from previously described procedures and the high reactive oxygen radical generated from NAPI was captured by highly oxophilic triethyl phosphite, which underwent α-fragmentation to form α-carbon-centered radical via deoxygenation procedure. The resulting α-carbon radical reacted with allyl/alkenyl sulfones to furnish varieties of CÀ C formed products.…”

“…[25][26][27][28] Due to the high bond dissociation free energy of the OÀ H bond (110 Kcal/mol) in aliphatic alcohol, it is challenging to access alkoxy radicals via direct homolysis. To overcome this challenge, numerous methods were developed for the alkoxy radical formation from aliphatic alcohol starting materials over the past decades: (1) proton-coupled electron transfer (PCET) strategy to direct access alkoxy radical from the hydroxy group, which involves the concerted movement of a proton and an electron in a single elementary step to site-separated acceptors; [29][30][31][32] (2) a photoinduced metal to ligand charge transfer (MLCT), which donates an electron from a metalcentered orbital to a ligand-centered anti-bonding orbital, resulting in formation reactive oxygen-centered radical when the hydroxy group behaved as a ligand; [33][34][35][36][37][38] (3) transition metal-oxygen bond homolysis, which is utilized to effective formation of alkoxy radical through single-electron oxidation from the hydroxy group by oxidants such as Cu(II), Fe(III) and Mn(III) species; [39][40][41][42][43][44][45][46] (4) weak oxygen-heteroatom bond especially OÀ I bond, which becomes an attractive method due to easy accessibility of the hypervalent iodine compounds. [47,48] Meanwhile, alkoxy radicals generation from NAPIs, which are triggered by a transient reductant under visible light, is provided a more elegant and alternative method, [49][50][51][52][53] among many other oxygen-heteroatom bonds precursors such as nitrites, [54] nitrates, [55] hypohalites, [56] and sulphenates, [57] etc.…”

Selective degradation of styrene-contained plastics catalyzed by iron under visible light

“…Earth abundant metals were found to transform alkanes to alcohols and ketones under oxygen atmosphere [24][25][26][27][28][29][30][31][32][33] . In addition, C-C bond scission of alcohols and ketones through alkoxyl radical intermediates applying inexpensive catalysts were reported recently [34][35][36][37][38][39][40][41][42][43] . Though with limitations, these results illustrate us the possibility of developing an economic system for oxidative C-C bond cleavage in an environmentally friendly way (Fig.…”

Radical Aryl Migration from Boron to Carbon

“…Such reactions are not restricted to the “all-carbon” case, and various elements, such as N, 27 , 28 O, 29 − 31 Si, 32 − 36 P, 37 S, 38 − 46 Sn, 47 Ge, and Se, 39 have been reported as origins in radical aryl migrations ( Scheme 1 , a). Although intensively studied and applied in synthesis, radical aryl migration generally 19 − 23 , 26 , 45 , 46 suffers from the need to preinstall the transferable aryl group onto the substrate. Considering the aryl translocation step, only one aryl migration product is accessible from the functionalized starting material.…”