Single-atom logic for heterocycle editing

Nature Synthesis, Год журнала: 2022, Номер 1(5), С. 352 - 364

Опубликована: Апрель 11, 2022

Язык: Английский

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Late-stage diversification of indole skeletons through nitrogen atom insertion

Science, Год журнала: 2022, Номер 377(6610), С. 1104 - 1109

Опубликована: Сен. 1, 2022

Compared with peripheral late-stage transformations mainly focusing on carbon-hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite recent flurry activity in this area. Herein, we report skeletal editing indoles through nitrogen atom insertion, accessing corresponding quinazoline or quinoxaline bioisosteres by trapping an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies strategic use a silyl group as labile protecting that can facilitate subsequent product release. The utility highly functional group-compatible methodology context several commercial drugs is demonstrated.

Язык: Английский

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Scaffold hopping by net photochemical carbon deletion of azaarenes

Science, Год журнала: 2022, Номер 376(6592), С. 527 - 532

Опубликована: Апрель 28, 2022

Discovery chemists routinely identify purpose-tailored molecules through an iterative structural optimization approach, but the preparation of each successive candidate in a compound series can rarely be conducted manner matching their thought process. This is because many necessary chemical transformations required to modify cores straightforward fashion are not applicable complex contexts. We report method that addresses one facet this problem by allowing hop directly between chemically distinct heteroaromatic scaffolds. Specifically, we show selective photolysis quinoline

Язык: Английский

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Dearomative ring expansion of thiophenes by bicyclobutane insertion

Science, Год журнала: 2023, Номер 381(6653), С. 75 - 81

Опубликована: Июль 6, 2023

Skeletal ring enlargement is gaining renewed interest in synthetic chemistry and has recently focused on insertion of one or two atoms. Strategies for heterocyclic expansion through small-ring remain elusive, although they would lead to the efficient formation bicyclic products. Here, we report a photoinduced dearomative thiophenes by bicyclo[1.1.0]butanes produce eight-membered rings under mild conditions. The value, broad functional-group compatibility, excellent chemo- regioselectivity were demonstrated scope evaluation product derivatization. Experimental computational studies point toward photoredox-induced radical pathway.

Язык: Английский

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Aromatic nitrogen scanning by ipso -selective nitrene internalization

Science, Год журнала: 2023, Номер 381(6665), С. 1474 - 1479

Опубликована: Сен. 28, 2023

Nitrogen scanning in aryl fragments is a valuable aspect of the drug discovery process, but current strategies require time-intensive, parallel, bottom-up synthesis each pyridyl isomer because lack direct carbon-to-nitrogen (C-to-N) replacement reactions. We report site-directable C-to-N reaction allowing unified access to various pyridine isomers through nitrene-internalization process. In two-step, one-pot procedure, azides are first photochemically converted 3

Язык: Английский

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Carbon-to-nitrogen single-atom transmutation of azaarenes

Nature, Год журнала: 2023, Номер 623(7985), С. 77 - 82

Опубликована: Ноя. 1, 2023

Язык: Английский

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Cobalt-Catalyzed Nitrogen Atom Insertion in Arylcycloalkenes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(49), С. 22433 - 22439

Опубликована: Ноя. 30, 2022

Developing strategies enabling the modification of underlying molecular frameworks facilitates access to underexplored chemical spaces. Skeletal editing is an emerging technology for late-stage diversification bioactive molecules. However, current state this knowledge remains undeveloped. This work describes a simple protocol that "inserts" nitrogen atom into arylcycloalkenes form corresponding N-heterocycles. The use inexpensive cobalt catalyst under aqueous and open-air conditions makes very practical. Examples compounds pharmaceutical interest complex fused ring further demonstrated potentially broad applicability methodology.

Язык: Английский

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Tunable molecular editing of indoles with fluoroalkyl carbenes

Nature Chemistry, Год журнала: 2024, Номер 16(6), С. 988 - 997

Опубликована: Март 5, 2024

Язык: Английский

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Ring expansion of indene by photoredox-enabled functionalized carbon-atom insertion

Nature Catalysis, Год журнала: 2024, Номер 7(3), С. 242 - 251

Опубликована: Янв. 9, 2024

Язык: Английский

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Regiodivergent Ring-Expansion of Oxindoles to Quinolinones

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(7), С. 4301 - 4308

Опубликована: Фев. 9, 2024

The development of divergent methods to expedite structure–activity relationship studies is crucial streamline discovery processes. We developed a rare example regiodivergent ring expansion access two regioisomers from common starting material. To enable this regiodivergence, we identified distinct reaction conditions for transforming oxindoles into quinolinone isomers. presented proved be compatible with variety functional groups, which enabled the late-stage diversification bioactive as well facilitated synthesis drugs and their derivatives.

Язык: Английский

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