Acyl anion synthons: benzotriazole stabilized compared to classical

Katritzky, Alan R.; Kirichenko, Kostyantyn

doi:10.3998/ark.5550190.0007.409

Cited by 16 publications

(4 citation statements)

References 50 publications

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“…Nevertheless, in reconsidering the balance between umpolung anion stability and reactivity, we were inspired by the work of Katritzky and co-workers, who first reported the use of lithiated aldehyde-derived benzotriazole O -alkyl hemiaminals as acyl anion equivalents for addition to carbonyl compounds, albeit at cryogenic temperatures . Accordingly, we prepared O- methyl hemiaminal 17 by treating 2-fluorobenzaldehyde ( 2 ) with benzotriazole, trimethyl orthoformate, and 4 mol % p -toluenesulfonic acid monohydrate in 2-MeTHF (Scheme a).…”

Section: Resultsmentioning

confidence: 99%

Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3H-spiro[benzofuran-2,4′-piperidine] Building Block

Pompeo,

Kelly,

St-Jean

et al. 2024

J. Org. Chem.

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An efficient and scalable route to tert-butyl 3-oxo-3H-spiro[benzofuran-2,4′-piperidine]-1′-carboxylate, a central prochiral intermediate in the synthesis of SHP2 inhibitor GDC-1971 (migoprotafib), was achieved. Preparation of the title compound from readily available 2-fluorobenzaldehyde included formation of a modified Katritzky benzotriazole hemiaminal, which, upon deprotonation by n-butyllithium, participated in umpolung reactivity via 1,2-addition to tert-butyl 4-oxopiperidine-1-carboxylate (N-Boc-4-piperidone). Most notably, this reaction was developed as a robust plug-flow process that could be executed on multiple kilograms without the need for pilot-scale reaction vessels operating at low cryogenic temperatures. Treatment of the resulting tetrahedral intermediate with oxalic acid resulted in collapse to the corresponding 4-(2-fluorobenzoyl)-4-hydroxypiperidine, which was isolated as a solid via crystallization. The synthesis concluded with an optimized intramolecular S N Ar reaction and final crystallization to generate tert-butyl 3-oxo-3H-spiro[benzofuran-2,4′-piperidine]-1′-carboxylate as a stable, high-quality intermediate suitable for further functionalization toward GDC-1971.

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Section: Resultsmentioning

confidence: 99%

Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3H-spiro[benzofuran-2,4′-piperidine] Building Block

Pompeo,

Kelly,

St-Jean

et al. 2024

J. Org. Chem.

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“…During the reaction with asymmetric alkynes, a mixture of reg was obtained with the major product bearing the bulkier group at C-2 of the in The plausible mechanism for the reaction involved oxidative Pd (0) insertion to bond of diazonium species present in the 2-imino benzenediazonium (315), rel and affording the intermediates (316) or (317). The (315) was generated therm benzotriazole (311) [241][242][243][244] [240]. The yields of the corresponding indoles were good.…”

Section: Indole Synthesis Via C-h Activationmentioning

confidence: 99%

“…The plausible mechanism for the reaction involved oxidative Pd (0) insertion to the C-N bond of diazonium species present in the 2-imino benzenediazonium (315), releasing N 2 and affording the intermediates (316) or (317). The (315) was generated thermally from benzotriazole (311) [241][242][243][244]. The Palladacycle species (318) was obtained after internal alkyne (312) insertion into the C-Pd formed bond present on the intermediates (316) or (317).…”

Section: Indole Synthesis Via C-h Activationmentioning

confidence: 99%

Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

et al. 2021

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As part of natural products or biologically active compounds, the synthesis of nitrogen-containing heterocycles is becoming incredibly valuable. Palladium is a transition metal that is widely utilized as a catalyst to facilitate carbon-carbon and carbon-heteroatom coupling; it is used in the synthesis of various heterocycles. This review includes the twelve years of successful indole synthesis using various palladium catalysts to establish carbon-carbon or carbon-nitrogen coupling, as well as the conditions that have been optimized.

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“…Benzotriazole is a useful synthetic auxiliary: it is easily introduced, activates molecules toward numerous transformations, and can be removed readily at the end of the reaction sequence . However, in some reactions cleavage of the triazole ring occurs.…”

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confidence: 99%

Synthesis of o-Sulfamidotriazobenzenes from 1,1‘-Sulfonylbis(benzotriazole)

Katritzky

Khelashvili

et al. 2007

J. Org. Chem.

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Easily accessible 1,1'-sulfonylbis(benzotriazole) (Bt2SO2, 1) reacts with secondary amines at room temperature to afford (i) the corresponding o-sulfamidotriazobenzenes 2a-d (53-75%) via concurrent substitution of the first and ring opening of the second benzotriazolyl group and (ii) N-sulfonylbenzotriazoles 3b,c,e,f (7-73%). 1-(Morpholine-4-sulfonyl)-1H-benzotriazole 3c reacts with piperidine, pyrolidine, and N-methylpiperazine under microwave irradiation (120 W) at 120 degrees C for 10 min to give the unsymmetrical sulfamides 4a-c (80-90%).

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Acyl anion synthons: benzotriazole stabilized compared to classical

Cited by 16 publications

References 50 publications

Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3H-spiro[benzofuran-2,4′-piperidine] Building Block

Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3H-spiro[benzofuran-2,4′-piperidine] Building Block

Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

Synthesis of o-Sulfamidotriazobenzenes from 1,1‘-Sulfonylbis(benzotriazole)

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