Highly Functionalized Tricyclic Oxazinanones via Pairwise Oxidative Dearomatization and <i>N</i>-Hydroxycarbamate Dehydrogenation: Molecular Diversity Inspired by Tetrodotoxin

Good, Steffen; Sharpe, Robert J.; Johnson, Jeffrey S.

doi:10.1021/jacs.7b07745

Cited by 36 publications

(28 citation statements)

References 46 publications

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“…Overall, the current method provides am echanistically distinct pathway towards previously described chemistry involving N-hydroxycarbamates under oxidative conditions. [11,12,18] It also offers anovel umpolung strategy,through sequential photocatalytic SET oxidations, [19] to invert the indole derivatives from nucleophiles to electrophilic species, which would react in turn with external nucleophiles.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

et al. 2019

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Dearomatization of indoles provides efficient synthetic routes for substituted indolines.I nm ost cases,i ndoles serve as nucleophiles.R eported here is an asymmetric dearomatization reaction of indole derivatives that function as electrophiles.T he combination of ap hotocatalyst and chiral phosphoric acid open to air unlocksthe umpolung reactivity of indoles,enabling their dearomatization with N-hydroxycarbamates as nucleophiles.Avariety of fused indolines bearing intriguing oxy-amines were constructed in excellent yields with moderate to high enantioselectivities.Mechanistic studies show that the realization of two sequential single-electron transfer oxidations of the indole derivatives is key,g enerating the configurationally biased carbocation species while providing the source of stereochemical induction. These results not only providea ne fficient synthesis of enantioenriched indoline derivatives,but also offer anovel strategy for further designing asymmetric dearomatization reactions. Scheme 1. Catalytic asymmetric dearomatization of indole derivatives. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 2. Mechanistic studies. a) Stern-Volmer luminescence quenchinge xperiments. b) Cyclic voltammetry experiments (1a and 2a). c) Cyclic voltammetry experimentso f1a with varying amounts of PA (diphenylphosphoric acid). Boc = tert-butylcarbonyl. Scheme 3. Proposed mechanism.

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Section: Resultsmentioning

confidence: 99%

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

et al. 2019

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“…Other modifications to the Adler–Becker reaction have been reported such as one-pot oxidative dearomatization/acylnitroso cycloaddition 11 and in situ elimination under basic conditions of salicylic alcohol as dichloroacetate to quinone methide followed by epoxidation with H 2 O 2 . 12 …”

Section: Introductionmentioning

confidence: 99%

One-Pot Transformation of Salicylaldehydes to Spiroepoxydienones via the Adler–Becker Reaction in a Continuous Flow

Rosatella

Afonso

2022

ACS Omega

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The Adler–Becker reaction is a useful approach for the oxidative dearomatization of salicylic alcohols to spiroepoxydienones and has been applied in the total synthesis of several natural products. Despite the advantages, the substrate and product instability under the reaction conditions can decrease the reaction efficiency, leading to lower yields. Herein, we report the Adler–Becker reaction in a continuous flow for the transformation of reduced salicylaldehydes into spiroepoxydienones in a one-pot approach. For that, a heterogeneous oxidant based on periodate is developed, leading to an efficient continuous flow process, with higher productivity and shorter reaction times, when compared with batch conditions.

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“…21 Other approaches toward the molecule have been outlined. 19,[22][23][24][25][26][27][28][29][30][31][32]…”

Section: Introductionmentioning

confidence: 99%

An Efficient Synthesis of Tetrodotoxin

Konrad

Ruehmann

Ando

et al. 2021

Preprint

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Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.

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Highly Functionalized Tricyclic Oxazinanones via Pairwise Oxidative Dearomatization and N-Hydroxycarbamate Dehydrogenation: Molecular Diversity Inspired by Tetrodotoxin

Cited by 36 publications

References 46 publications

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

One-Pot Transformation of Salicylaldehydes to Spiroepoxydienones via the Adler–Becker Reaction in a Continuous Flow

An Efficient Synthesis of Tetrodotoxin

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