Single-atom logic for heterocycle editing

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(5), P. 352 - 364

Published: April 11, 2022

Language: Английский

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Late-stage diversification of indole skeletons through nitrogen atom insertion

Science, Journal Year: 2022, Volume and Issue: 377(6610), P. 1104 - 1109

Published: Sept. 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.

Language: Английский

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Scaffold hopping by net photochemical carbon deletion of azaarenes

Science, Journal Year: 2022, Volume and Issue: 376(6592), P. 527 - 532

Published: April 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

Language: Английский

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Dearomative ring expansion of thiophenes by bicyclobutane insertion

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 75 - 81

Published: July 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.

Language: Английский

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Aromatic nitrogen scanning by ipso -selective nitrene internalization

Science, Journal Year: 2023, Volume and Issue: 381(6665), P. 1474 - 1479

Published: Sept. 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

Language: Английский

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Carbon-to-nitrogen single-atom transmutation of azaarenes

Nature, Journal Year: 2023, Volume and Issue: 623(7985), P. 77 - 82

Published: Nov. 1, 2023

Language: Английский

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Cobalt-Catalyzed Nitrogen Atom Insertion in Arylcycloalkenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(49), P. 22433 - 22439

Published: Nov. 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.

Language: Английский

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Tunable molecular editing of indoles with fluoroalkyl carbenes

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(6), P. 988 - 997

Published: March 5, 2024

Language: Английский

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

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(3), P. 242 - 251

Published: Jan. 9, 2024

Language: Английский

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Regiodivergent Ring-Expansion of Oxindoles to Quinolinones

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4301 - 4308

Published: Feb. 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.

Language: Английский

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