Cobalt‐Catalyzed Wagner–Meerwein Rearrangements with Concomitant Nucleophilic Hydrofluorination

Hoogesteger, Reece H.; Murdoch, Nicola; Cordes, David B.; Johnston, Craig P.

doi:10.1002/anie.202308048

Cited by 6 publications

(3 citation statements)

References 71 publications

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“…Optimization of the enantioselective semipinacol rearrangement Previously we have shown that this approach is viable for conducting Wagner−Meerwein rearrangements that involve a 1,2-aryl migration. [48] These studies unveiled a phenonium ion as a probable intermediate with subsequent regioselective nucleophilic fluorination finalizing the relocation process. Thus, given this reactivity, we postulated that a hydro-semipinacol rearrangement involving a 1,2-aryl shift was viable.…”

Section: Resultsmentioning

confidence: 98%

Enantioselective Synthesis of α-Aryl Ketones by a Cobalt Catalyzed Semipinacol Rearrangement

Kalomenopoulos,

Emayavaramban,

Johnston

2024

Preprint

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A highly enantioselective cobalt-catalyzed semipinacol rearrangement of symmetric α,α-diarylallylic alcohols is disclosed. A chiral cobalt-salen catalyst generates a highly electrophilic carbocation surrogate following hydrogen atom transfer and radical–polar crossover steps. This methodology provides access to enantioenriched α-aryl ketones through invertive displacement of a cobalt(IV) complex during 1,2-aryl migration. A combination of readily available reagents, silane and N-fluoropyridinium oxidant, are used to confer this type of reactivity. An exploration into the effect of aryl substitution revealed the reaction tolerates para- and meta‑halogenated, mildly electron‑rich and electron‑poor aromatic rings with excellent enantioselectivities and yields. The yield of the rearrangement diminished with highly electron‑rich aryl rings whereas very electron‑deficient and ortho-substituted arenes led to poor enantiocontrol. A Hammett analysis demonstrated the migratory preference for electron-rich aromatic rings, which is consistent with the intermediacy of a phenonium cation.

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Section: Resultsmentioning

confidence: 98%

Enantioselective Synthesis of α-Aryl Ketones by a Cobalt Catalyzed Semipinacol Rearrangement

Kalomenopoulos,

Emayavaramban,

Johnston

2024

Preprint

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“…Furthermore, running the reaction in an NMR tube increased the yield to 60%, likely as a result of enhanced light penetration. Interestingly, for limonene (14) bearing two different types of alkenes, the catalyst was highly selective for the hydrofluorination of the terminal alkene, giving product 14−1 in 34% yield with only 2% speculative hydrofluorination of the internal alkene.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Activation methods include the use of strong acids, highly oxidizing photocatalyst, and the combination of electrochemistry and palladium catalysis . Most recently, Johnston and co-workers reported a Co(salen)-catalyzed alkene hydrofluorination reaction involving a 1,2-aryl shift using a combination of a hydrosilane and BF 4 – as reagents . These methods, while significantly expanding the toolbox for hydrofluorination reactions, are sensitive to the substitution patterns of alkenes; thus, these transformations are limited to a certain type of alkene (e.g., styrenes or 1,1-disubstituted alkenes).…”

Section: Introductionmentioning

confidence: 99%

Co-Catalyzed Hydrofluorination of Alkenes: Photocatalytic Method Development and Electroanalytical Mechanistic Investigation

Liu,

Rong,

Wood

et al. 2024

J. Am. Chem. Soc.

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The hydrofluorination of alkenes represents an attractive strategy for the synthesis of aliphatic fluorides. This approach provides a direct means to form C(sp 3 )−F bonds selectively from readily available alkenes. Nonetheless, conducting hydrofluorination using nucleophilic fluorine sources poses significant challenges due to the low acidity and high toxicity associated with HF and the poor nucleophilicity of fluoride. In this study, we present a new Co(salen)-catalyzed hydrofluorination of simple alkenes utilizing Et 3 N•3HF as the sole source of both hydrogen and fluorine. This process operates via a photoredoxmediated polar-radical-polar crossover mechanism. We also demonstrated the versatility of this method by effectively converting a diverse array of simple and activated alkenes with varying degrees of substitution into hydrofluorinated products. Furthermore, we successfully applied this methodology to 18 Fhydrofluorination reactions, enabling the introduction of 18 F into potential radiopharmaceuticals. Our mechanistic investigations, conducted using rotating disk electrode voltammetry and DFT calculations, unveiled the involvement of both carbocation and Co IV −alkyl species as viable intermediates during the fluorination step, and the contribution of each pathway depends on the structure of the starting alkene.

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Cationic [1,5]‐Aryl Migrations of Propargyl Benzyl Ethers – A Stereospecific Approach to E‐ and Z‐Tetrasubstituted Olefins

Sadhukhan,

Nair,

Baire

2024

Adv Synth Catal

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Abstract. Herein we report the discovery and development of the first example of a cationic [1,5]‐aryl migration reaction, through an unprecedented phenonium ions. This reaction does not require any acid, base, transition metal‐based catalyst or promoter, instead promoted by the water activated NXS reagents. It provides a highly diastereoselective and rapid access to the medicinally and biologically important tetra‐substituted olefins (allyl alcohols). The involvement of an ipso‐carbon, as well as the phenonium ion during this novel, cationic [1,5]‐aryl migration was strongly supported by the isolation of 2‐oxaspiro[5.5]undecane‐9‐ones. This methodology is highly tolerable for a wide range of propargyl‐benzyl ethers, resulting in a selective construction of structurally divergent library of mono‐halo‐tricarbon‐substituted alkenes. Synthetic application has also been demonstrated by converting two isomeric‐iodo‐olefins to respective E‐ and Z‐isomers of tamoxifen in a stereospecific manner.

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Cobalt‐Catalyzed Wagner–Meerwein Rearrangements with Concomitant Nucleophilic Hydrofluorination

Cited by 6 publications

References 71 publications

Enantioselective Synthesis of α-Aryl Ketones by a Cobalt Catalyzed Semipinacol Rearrangement

Enantioselective Synthesis of α-Aryl Ketones by a Cobalt Catalyzed Semipinacol Rearrangement

Co-Catalyzed Hydrofluorination of Alkenes: Photocatalytic Method Development and Electroanalytical Mechanistic Investigation

Cationic [1,5]‐Aryl Migrations of Propargyl Benzyl Ethers – A Stereospecific Approach to E‐ and Z‐Tetrasubstituted Olefins

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