Practical and General Alcohol Deoxygenation Protocol

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(18)

Опубликована: Фев. 25, 2023

Herein, we describe a practical protocol for the removal of alcohol functional groups through reductive cleavage their benzoate ester analogs. This transformation requires strong single electron transfer (SET) reductant and means to accelerate slow fragmentation following substrate reduction. To accomplish this, developed photocatalytic system that generates potent from formate salts alongside Brønsted or Lewis acids promote reduced intermediate. deoxygenation procedure is effective across structurally electronically diverse alcohols enables variety difficult net transformations. no precautions exclude air moisture remains efficient on multigram scale. Finally, can be adapted one-pot benzoylation-deoxygenation sequence enable direct deletion. Mechanistic studies validate role acidic additives key C(sp

Язык: Английский

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Direct Deaminative Functionalization

Journal of the American Chemical Society, Год журнала: 2022, Номер 145(1), С. 17 - 24

Опубликована: Дек. 22, 2022

Selective functional group interconversions in complex molecular settings underpin many of the challenges facing modern organic synthesis. Currently, a privileged subset groups dominates this landscape, while others, despite their abundance, are sorely underdeveloped. Amines epitomize dichotomy; they abundant but otherwise intransigent toward direct interconversion. Here, we report an approach that enables conversion amines to bromides, chlorides, iodides, phosphates, thioethers, and alcohols, heart which is deaminative carbon-centered radical formation process using anomeric amide reagent. Experimental computational mechanistic studies demonstrate successful functionalization relies not only on outcompeting H-atom transfer incipient also generation polarity-matched, productive chain-carrying radicals continue react efficiently. The overall implications technology for interconverting amine libraries were evaluated via high-throughput parallel synthesis applied development one-pot diversification protocols.

Язык: Английский

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C(sp3)–C(sp3) bond formation through nitrogen deletion of secondary amines using O-diphenylphosphinylhydroxylamine

Nature Synthesis, Год журнала: 2024, Номер 3(7), С. 913 - 921

Опубликована: Июнь 7, 2024

Язык: Английский

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Photocatalytic furan-to-pyrrole conversion

Science, Год журнала: 2024, Номер 386(6717), С. 99 - 105

Опубликована: Окт. 3, 2024

The identity of a heteroatom within an aromatic ring influences the chemical properties that heterocyclic compound. Systematically evaluating effect single atom, however, poses synthetic challenges, primarily as result thermodynamic mismatches in atomic exchange processes. We present photocatalytic strategy swaps oxygen atom furan with nitrogen group, directly converting into pyrrole analog intermolecular reaction. High compatibility was observed various derivatives and nucleophiles commonly used drug discovery, late-stage functionalization furnished otherwise difficult-to-access pyrroles from naturally occurring furans high molecular complexity. Mechanistic analysis suggested polarity inversion through electron transfer initiates redox-neutral processes at room temperature.

Язык: Английский

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Site‐Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines**

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(8)

Опубликована: Янв. 5, 2024

Abstract The introduction of trifluoromethyl groups into organic molecules is paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp 2 )−CF 3 bonds have been well established, the advancement practical comprehensive approaches forming remains considerably restricted. In this work, we describe an efficient site‐specific deaminative trifluoromethylation reaction aliphatic primary amines to afford corresponding alkyl compounds. proceeds at room temperature with readily accessible N ‐anomeric amide (Levin's reagent) bench‐stable bpyCu(CF ) (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. protocol features mild conditions, good functional group tolerance, moderate yields. Remarkably, method can be applied direct, late‐stage natural products bioactive molecules. Experimental mechanistic studies were conducted, a radical mechanism proposed, wherein dual roles Grushin's reagent elucidated.

Язык: Английский

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Precision single-atom editing: new frontiers in nitrogen insertion and substitution for the generation of N-heterocycles

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(14), С. 4041 - 4053

Опубликована: Янв. 1, 2024

This paper primarily focuses on the editing of nitrogen atoms, encompassing insertion N, substitution C with and utilization 15 N in place 14 for construction N-heterocycles.

Язык: Английский

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Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(25)

Опубликована: Апрель 15, 2024

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through common isonitrile intermediate. To cleave the relatively inert C-NC bond, leveraged dual hydrogen atom transfer (HAT) photoredox catalysis to generate nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from isonitrile. Rapid β-scission then accomplishes defunctionalization. This method has been applied both amine alcohol-containing pharmaceuticals, natural products, biomolecules. We extended this approach reduction carbonyls olefins their saturated counterparts, as well hydrodecyanation alkyl nitriles. Both experimental computational studies demonstrate facile reconcile differences in reactivity between nitriles isonitriles within our protocol.

Язык: Английский

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Evidence for Dearomatizing Spirocyclization and Dynamic Effects in the Quasi-stereospecific Nitrogen Deletion of Tetrahydroisoquinolines

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(26), С. 17719 - 17727

Опубликована: Июнь 20, 2024

Selectivity in organic chemistry is generally presumed to arise from energy differences between competing selectivity-determining transition states. However, cases where static density functional theory (DFT) fails reproduce experimental product distributions, dynamic effects can be examined understand the behavior of more complex reaction systems. Previously, we reported a method for nitrogen deletion secondary amines which relies on formation isodiazene intermediates that subsequently extrude dinitrogen with concomitant C-C bond via caged diradical. Herein, detailed mechanistic analysis 1-aryl-tetrahydroisoquinolines presented, suggesting this system previously determined diradical mechanism undergoes dynamically controlled partitioning both normal 1,5-coupling and an unexpected spirocyclic dearomatized intermediate, converges expected indane by unusually facile 1,3-sigmatropic rearrangement. This not reproduced DFT but supported quasi-classical molecular dynamics calculations unifies several unusual observations system, including partial chirality transfer, nonstatistical isotopic scrambling at ethylene bridge, isolation species related heterocyclic series, observation introduction 8-substituent dramatically improves enantiospecificity.

Язык: Английский

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Molecular Editing of Pyrroles via a Skeletal Recasting Strategy

ACS Central Science, Год журнала: 2023, Номер 9(9), С. 1758 - 1767

Опубликована: Авг. 15, 2023

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization allow for peripheral modifications of heterocyclic motifs, often being specific taking place at multiple sites. The past few years seen the quick emergence exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion structural diversification, as well scaffold hopping. construction heterocycles via deconstruction simple is unknown. Herein, we disclose a new method which name recasting strategy. Specifically, by tapping on 1,3-dipolar property azoalkenes, recast pyrroles to fully substituted pyrroles, phosphoric acid-promoted one-pot reaction consisting dearomative rearomative reconstruction steps. allows easy access synthetically challenging tetra-substituted otherwise difficult synthesize. Furthermore, construct N-N axial chirality our pyrrole products, accomplish facile synthesis anticancer drug, Sutent. potential application this other has also demonstrated.

Язык: Английский

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Isonitriles as Alkyl Radical Precursors in Visible Light Mediated Hydro‐ and Deuterodeamination Reactions**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(7)

Опубликована: Дек. 27, 2023

Herein, we report the use of isonitriles as alkyl radical precursors in light-mediated hydro- and deuterodeamination reactions. The reaction is scalable, shows broad functional group compatibility potential to be used late-stage functionalization. Importantly, method general for C

Язык: Английский

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