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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Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(30), С. 11337 - 11344

Опубликована: Июль 21, 2021

Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, traditional haloform-based protocol central parent Ciamician-Dennstedt rearrangement can be modified directly afford 3-(hetero)arylpyridines quinolines. Chlorodiazirines are conveniently prepared in single step oxidation of commercially available amidinium salts. Selectivity function substitution pattern was examined, predictive model based on steric effects is put forward, with DFT calculations supporting selectivity-determining cyclopropanation step. Computations surprisingly indicate stereochemistry little consequence subsequent electrocyclic ring opening forges pyridine core, due compensatory homoaromatic stabilization counterbalances orbital-controlled torquoselectivity effects. The utility this skeletal transform further demonstrated through preparation quinolinophanes editing pharmaceutically relevant pyrroles.

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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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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Dirhodium(II,II) Paddlewheel Complexes

European Journal of Inorganic Chemistry, Год журнала: 2021, Номер 2021(6), С. 501 - 528

Опубликована: Янв. 7, 2021

Abstract This minireview summarizes synthetic approaches towards homoleptic dirhodium(II,II) paddlewheel complexes with the general formula Rh 2 A 4 . These have found numerous applications in a wide range of chemical research and industry as catalysts, detectors, enzymatic inhibitors or building blocks for molecular scaffolds. In organic synthesis they are commonly used to transfer electron‐deficient species, act Lewis acids activate unsaturated bonds, serve hydrogenation catalysts participate oxidation/reduction processes. Dirhodium composed Rh‐Rh backbone four bridging anions, which surround core. According application, electrochemical potential atom can be modulated, geometry physical properties metal complex. prepared one step from basic inorganic precursors by post‐functionalization structures.

Язык: Английский

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Convergent Synthesis of 1,4-Dicarbonyl Z-Alkenes through Three-Component Coupling of Alkynes, α-Diazo Sulfonium Triflate, and Water

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(11), С. 4952 - 4965

Опубликована: Март 11, 2022

We report a general protocol for the convergent synthesis of 1,4-dicarbonyl Z-alkenes form alkynes using α-diazo sulfonium triflate and water. The C═O, C═C, C–H bonds are formed under mild conditions with wide range functional groups tolerated. reaction exhibits excellent Z-selectivity complete regioselectivity. resulting can smoothly undergo follow-up conversion to variety heteroaromatic scaffolds. Moreover, also provides facile access corresponding deuterated heteroarenes high level deuterium incorporation (90–97% D-inc.) by directly D2O, thus rendering method highly valuable. comprehensive mechanistic studies indicate that free carbyne radical intermediate is via photocatalytic single electron transfer process, KH2PO4 plays crucial role in significant improvements on yield selectivity based density-functional theory calculations, providing new direction coupling reactions diazo compounds.

Язык: Английский

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Generating Fischer-Type Rh-Carbenes with Rh-Carbynoids

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(9), С. 4975 - 4981

Опубликована: Фев. 22, 2023

We describe the first catalytic generation of Fischer-type acyloxy Rh(II)-carbenes from carboxylic acids and Rh(II)-carbynoids. This novel class transient donor/acceptor evolved through a cyclopropanation process providing access to densely functionalized cyclopropyl-fused lactones with excellent diastereoselectivity. DFT calculations allowed analysis properties Rh(II)-carbynoids as well characterization mechanism.

Язык: Английский

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Recent Progress in Synthetic Applications of Cyclic Hypervalent Iodine(III) Reagents

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(16), С. 2653 - 2675

Опубликована: Апрель 21, 2023

Abstract Hypervalent iodine compounds have found broad application in modern organic chemistry as reagents and catalysts. Cyclic hypervalent based on the benziodoxole heterocyclic system higher stability compared to their acyclic analogues, which makes possible preparation safe handling of with special ligands such azido, cyano, trifluoromethyl groups. Numerous iodine‐substituted derivatives been prepared utilized for transfer substituent substrate. Reactions these substrates can be performed under metal‐free conditions, presence transition metal catalysts, or using photocatalysts photoirradiation conditions. In this review, we focus most recent synthetic applications cyclic iodine(III) following ligands: N 3 , NHR, CN, CF SCF OR, OAc, ONO 2 C(=N )CO R. The review covers literature published mainly last 5 years.

Язык: Английский

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Enantioselective Multifunctionalization with Rh Carbynoids

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(48), С. 26403 - 26411

Опубликована: Ноя. 22, 2023

Multifunctionalization from the interception of active intermediates is an attractive synthetic strategy for efficient construction complex molecular scaffolds in atom and step economic fashion. However, design reactions involving metal carbynoids that exhibit carbene/carbocation behavior currently limited, developing catalyst-controlled highly enantioselective versions poses significant challenges. In this study, we present first asymmetric trifunctionalization with rhodium carbynoids. This reaction unveils distinctive reactivity carbynoid precursor, enabling it to react simultaneously two nucleophiles one electrophile. process involves formation distinct carbene ylides alcohol/carbamate trapping ylide imine, resulting three new bonds. Furthermore, allows divergent synthesis a wide array β-amino esters high yields exceptional enantioselectivity.

Язык: Английский

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