Der “Persistent Radical Effect” in der organischen Chemie

Leifert, Dirk; Studer, Armido

doi:10.1002/ange.201903726

Cited by 103 publications

(11 citation statements)

References 563 publications

(618 reference statements)

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“…Ther eaction is initiated by an EnT process from the triple state photocatalyst to the ground state oxime carbonates 1e or 1f.T he excited oxime carbonate undergoes NÀOb ond homolysis to afford the ethyloxylcarbonyloxyl radical and the iminyl radical (A or B). Addition of the ethyloxylcarbonyloxyl radical to alkenes results in the formation of carbon radical C.Under the conditions of 1e, C would be coupled to the stabilized diphenyl iminyl radical A (persistent radical effect) [17] to yield aminooxygenation products 3' ' which finally produces 3 after hydrolysis.W hen 1f is used, on the other hand, this radical coupling is difficult to occur because of the facile decomposition of the resultant iminyl radical B.Thus, C can only abstract ahydrogen atom (HAT) from the solvent [18] to give the hydrooxygenation products 2.I ti se xpected that decomposition of B would generate benzonitrile and 1-phenylethyl radical. Indeed, benzonitrile and the 1-phenylethyl radical self-coupling product were detected by GC-MS analysis of the reaction mixture,a nd the cross-coupling product of 1-phenylethyl radical with B was also detected by LC-MS (Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

et al. 2021

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A tunable photocatalytic method is reported for anti‐Markovnikov hydro‐ and aminooxygenation of unactivated alkenes using readily accessible ketoxime carbonates as the diverse functionalization reagents. Mechanistic studies reveal that this reaction is initiated through an energy‐transfer‐promoted N−O bond homolysis of ketoxime carbonates leading to alkoxylcarbonyloxyl and iminyl radicals under visible‐light photocatalysis, followed by the addition of alkoxylcarbonyloxyl radical to alkenes. By taking advantage of the different stability of the iminyl radicals, the generated carbon radical either abstracts a hydrogen atom from the media to form the anti‐Markovnikov hydrooxygenation product, or it is trapped by the persistent iminyl radical to furnish the aminooxygenation product. Notably, this is the first example of direct hydrooxygenation of unactivated olefins with anti‐Markovnikov regioselectivity involving an oxygen‐centered radical.

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Section: Methodsmentioning

confidence: 99%

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

et al. 2021

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“…58,59 High cross selectivity in such radical-radical couplings can be explained by the persistent radical effect (PRE). 60 However, involvement of a radical chain propagation by 62 directly attacking 2h to provide the 1,2oxyimination product along with the concomitant generation of 60 cannot be excluded completely. Quantum yield measurement (Φ = 0.84) could not invalidate an inefficient chain propagation (Supplementary Method 3.8).…”

Section: Mechanistic Investigationsmentioning

confidence: 99%

Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

et al. 2021

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The 1,2-aminoalcohol motif is one of the most prevalent structural components found in high-value organic molecules including pharmaceuticals and natural products. Generally, their preparation requires pre-functionalised substrates and manipulations of one functional group at a time to achieve the desired regioisomer. Herein, we describe a metal-free photosensitisation protocol for the installation of both amine and alcohol functionalities into alkene feedstocks in a single step. This approach is enabled by the identification of oxime carbonate as a suitable bifunctional source of both oxygen-and nitrogen-centred radicals for addition across alkenes with complementary regioselectivity compared to Sharpless aminohydroxylation. Use of orthogonal protection for amine and alcohol functionalities enables direct synthetic diversifications of one functional handle without influencing the other. With the use of readily available starting materials, convergent synthesis and mild reaction conditions, this process is well suited for use in various synthetic endeavors.The vicinal aminoalcohol motif is one of the most abundant structural units in natural products, pharmaceuticals, agrochemicals and privileged ligands. [1][2][3] Synthetic routes to this motif rely typically on multistep, iterative manipulations of functional groups to introduce both amine and alcohol functionalities in their desired positions. [4][5][6] Usually transition metal-catalysed directed β-C-H functionalisation of alcohols or amines offers a synthetic alternative with the necessity of a preinstalled directing group. [7][8][9][10] Nevertheless, all these approaches involve manipulation of one functional group at a time (Fig. 1a). By comparison, aminohydroxylation of alkenes is the most straightforward yet powerful approach for the synthesis of 1-amino-2-alcohols allowing simultaneous introduction of both functionalities into the molecule in a single step, as pioneered by Sharpless. 11,12 The generality of this approach however is often plagued by poor regioselectivity and the need for N-haloamides. 13 The use of a similar concept to synthesise 2-amino-1-alcohol skeleton requires a complete regioselectivity switch and remains a challenge to date (Fig. 1b). 14,15 So far, transient N-centred radical initiated aminohydroxylation strategy has been exploited in different intramolecular cyclisation context through ingenious substrate design to generate 2-amino-1-alcohol framework. [16][17][18][19] Clearly, lack of substrate generality and intramolecular nature of these transformations obviates there widespread use. In this regard, Yoon has elegantly utilized high strain of oxaziridine ring in aminal synthesis with analogous regioselectivity. [20][21][22] However, the requirement for initial radical attack by the alkene substrate to the copper-activated oxaziridine limits the use of unactivated alkenes in this aminohydroxylation approach. Alternatively, a two-step aziridination of alkene followed by nucleophilic ring opening can also deliver a similar regiosel...

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“…Notably, we reasoned that the lifetime of the aryl radical and potentially the chemoselectivity of the HATp rocess could be readily influenced by tuning the steric and electronic properties of the aryl radical to favor an intermolecular HAT process. [16] We decided to investigate the effect of introducing substituents in the ortho position of the starting aryl iodide (Supporting Information, Figure S1). This resulted in as ignificant increase in the yield of cyclooctene when amixture of alkane (5 equiv), mesityl iodide (1 equiv), diimine ligand (L 4 , 18 mol %), and Ru 3 (CO) 12 (3 mol %) were allowed to react at 150 8 8Ci nc hlorobenzene for 24 hours (see the Supporting Information:optimization of the model reaction).…”

Section: Resultsmentioning

confidence: 99%

Ruthenium‐Catalyzed Dehydrogenation Through an Intermolecular Hydrogen Atom Transfer Mechanism

et al. 2021

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The direct dehydrogenation of alkanes is among the most efficient ways to access valuable alkene products. Although several catalysts have been designed to promote this transformation, they have unfortunately found limited applications in fine chemical synthesis. Here, we report a conceptually novel strategy for the catalytic, intermolecular dehydrogenation of alkanes using a ruthenium catalyst. The combination of a redox‐active ligand and a sterically hindered aryl radical intermediate has unleashed this novel strategy. Importantly, mechanistic investigations have been performed to provide a conceptual framework for the further development of this new catalytic dehydrogenation system.

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Der “Persistent Radical Effect” in der organischen Chemie

Cited by 103 publications

References 563 publications

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

Photocatalytic Anti‐Markovnikov Radical Hydro‐ and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates

Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

Ruthenium‐Catalyzed Dehydrogenation Through an Intermolecular Hydrogen Atom Transfer Mechanism

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