Transforming an azaarene into the spine of fusedbicyclics via cycloaddition-induced scaffold hopping of 5-Hydroxypyrazoles

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 30, 2024

Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce because these non-strained aromatics exhibit inert reactivities, making them relatively inactive performing a dearomatization/cleavage sequence. Here, we disclose cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles to access the pyrazolopyridopyridazin-6-one skeleton through single-operation protocol. By converting five-membered aza-arene into five-unit spine 6/6 fused-bicyclic, this work unlocks ring-opening reactivity pyrazole core that involves formal C = N bond cleavage while retaining highly reactive N-N in resulting product. A [4 + 2] cycloaddition temporarily dearomatized 5-hydroxypyrrole with an situ generated aza-1,3-diene, followed by oxidative C-N cleavage, constitutes domino pathway. library pyrazolopyridopyridazin-6-ones, which are medicinally relevant nitrogen-atom-rich tricyclics, obtained efficiently from readily available materials.

Язык: Английский

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N-Benzylhydroxylamine as a “C1N1 synthon” in Imidazoles Synthesis via Activation the α–C(sp3)−H under I2-DMSO System

Authorea (Authorea), Год журнала: 2024, Номер unknown

Опубликована: Июнь 8, 2024

A novel process using N-benzylhydroxylamine hydrochloride as a “C1N1 synthon” in [2 + 2 1] cyclization for the construction of 1,2,5-trisubstituted imidazoles has been described first time. The key to realizing this lies on capturing arylamines by situ generated acyl ketonitrone intermediates. Subsequent tautomerization activates α–C(sp3)−H N-benzylhydroxylamines, thus breaks through its inherent reaction mode and achieves N, α–C site-selective cyclization. Furthermore, method enables scale-up synthesis late-stage modification complex molecules.

Язык: Английский

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From an Azaarene to the Spine of Fused Bicyclics: Cycloaddition-Induced Scaffold Hopping of 5-Hydroxypyrazoles

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 9, 2024

Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce due to these non-strained aromatics feature inert reactivities therefore relatively inactive perform a dearomatization/cleavage sequence. Herein, we disclose cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles access pyrazolopyridopyridazin-6-one skeleton in single-operation protocol. By converting five-membered azaarene into five-unit spine 6/6 fused-bicyclics, this work has unlocked new ring-opening reactivity pyrrole core that involves formal C = N bond cleavage while retaining the highly reactive N-N resulting product. A [4 + 2] cycloaddition temporary dearomatized 5-hydroxypyrrole with anin situgenerated aza-1,3-diene follow-up oxidative C-N accounted domino pathway. library pyrazolopyridopyridazin-6-one, which are medicinally relevant nitrogen-atom-rich tricyclics, was obtained efficiently from readily available materials.

Язык: Английский

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Iodine as Polarity-Reversal Catalyst: Synthesis of a Fused Heterocycle with Contiguous Stereocenters

Organic Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

We report an unconventional I

Язык: Английский

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