Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(22), С. 12313 - 12370

Опубликована: Ноя. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Язык: Английский

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‘Almost magical’: chemists can now move single atoms in and out of a molecule’s core

Nature, Год журнала: 2023, Номер 618(7963), С. 21 - 24

Опубликована: Май 31, 2023

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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Dearomatization of Pyridines: Photochemical Skeletal Enlargement for the Synthesis of 1,2-Diazepines

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2845 - 2854

Опубликована: Янв. 18, 2024

In this report, we developed a unified and standardized one-pot sequence that converts pyridine derivatives into 1,2-diazepines by inserting nitrogen atom. This skeletal transformation capitalizes on the in situ generation of 1-aminopyridinium ylides, which rearrange under UV light irradiation. A thorough evaluation key parameters (wavelength, reaction conditions, activating agent) allowed us to elaborate simple, mild, user-friendly protocol. The model was extrapolated more than 40 examples, including drug derivatives, affording unique 7-membered structures. Mechanistic evidence supports transient presence diazanorcaradiene species. Finally, pertinent transformations products, ring contraction reactions form pyrazoles, were conducted paved way broad application

Язык: Английский

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A deconstruction-reconstruction strategy for pyrimidine diversification

Nature, Год журнала: 2024, Номер 631(8019), С. 87 - 93

Опубликована: Май 2, 2024

Язык: Английский

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Interrogation of Enantioselectivity in the Photomediated Ring Contractions of Saturated Heterocycles

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding single heteroatom from ring, this transformation builds desirable C(sp3)–C(sp3) bonds in the contracted products; however, origins enantioselectivity remain poorly understood. In work, has been explored across an expanded structurally diverse substrate scope, revealing wide range enantioselectivities (0–99%) using two distinct CPA catalysts. Mechanistic investigations support rate-determining excitation that generates short-lived achiral intermediates are intercepted by enantiodetermining closure. The effects competitive uncatalyzed reactivity light-driven reversibility closure on have elucidated. Statistical models were built regressing scope against key structural features products for both resultant suggested factors influence response each catalyst enabled rational modification pharmaceutically relevant target molecule to improve enantioselectivity. Finally, density functional theory (DFT)-based transition state analysis identified noncovalent interactions with correlated unique selectivity-relevant uncovered through statistical modeling. Our findings not only offer comprehensive insight into system but should also aid future development related CPA-catalyzed reactions.

Язык: Английский

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Spiro-C(sp ³ )-atom transfer: Creating rigid three-dimensional structures with Ph ₂ SCN ₂

Science, Год журнала: 2025, Номер 387(6736), С. 885 - 892

Опубликована: Фев. 20, 2025

The introduction of a single C-atom into organic substrates typically results in the formation flat molecules containing unsaturated C(sp)-centers. Adding C(sp3)-atom surrounded by four σ-C-C bonds, which opens up three-dimensional space, is an unresolved problem synthetic chemistry. We report synthesis and application diazosulfur ylide Ph2S=C=N2 reagent that combines reactivity both sulfur ylides diazo compounds to create carbon spiro-centers general fashion sequential or single-step installation C(sp3)-atom. New C-C C-X (where X O N) bonds can be created around C(sp3)-atom, ultimately extended σ-bonds one step without resorting transition metal catalysis. Ph2SCN2 also used access highly strained frameworks (oxa)spiro[2.2]pentanes as well tricyclic spiro-compounds.

Язык: Английский

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One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(40), С. 16383 - 16387

Опубликована: Сен. 27, 2021

Complanadine A and lycodine are representative members of the Lycopodium alkaloids with a characteristic pyridine-containing tetracyclic skeleton. has demonstrated promising neurotrophic activity potential for persistent pain management. Herein we report pyrrole strategy enabled by one-carbon insertion polarity inversion concise total syntheses complanadine lycodine. The use as pyridine precursor allowed rapid construction their skeleton via one-pot Staudinger reduction, amine-ketone condensation, Mannich-type cyclization. group was then converted to desired Ciamician–Dennstedt rearrangement process, which also simultaneously introduced chloride at C3 next C–H arylation. Other key steps include direct anti-Markovnikov hydroazidation, Mukaiyama–Michael addition, Paal–Knorr synthesis. Lycodine were prepared in 8 11 steps, respectively, from readily available known compound.

Язык: Английский

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Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(11), С. 4739 - 4745

Опубликована: Март 8, 2022

We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity engineered "carbene transferase" enzymes. A laboratory-evolved variant cytochrome P450BM3, P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over [1,2]-Stevens rearrangement but also overrides the inherent reactivity aziridinium ylides, cheletropic extrusion olefins, perform rearrangement. By controlling fate highly reactive ylide intermediates, these evolvable biocatalysts promote transformation which cannot currently be performed using other catalyst classes.

Язык: Английский

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