Skeletal editing of pyridines through atom-pair swap from CN to CC

Nature Chemistry, Год журнала: 2024, Номер 16(5), С. 741 - 748

Опубликована: Янв. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Язык: Английский

---

‘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

---

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

---

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

---

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

---

The impact of UV light on synthetic photochemistry and photocatalysis

Nature Chemistry, Год журнала: 2024, Номер 16(5), С. 684 - 692

Опубликована: Март 1, 2024

Язык: Английский

---

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

---

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

---

A deconstruction-reconstruction strategy for pyrimidine diversification

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

Опубликована: Май 2, 2024

Язык: Английский

---

Rhodium-Catalyzed Intramolecular Nitrogen Atom Insertion into Arene Rings

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(32), С. 17570 - 17576

Опубликована: Авг. 3, 2023

In this study, we describe the direct insertion of an intramolecular nitrogen atom into aromatic C–C bond. transformation, carbamoyl azides are activated by a Rh catalyst and subsequently directly inserted bond arene ring to access fused azepine products. This transformation is challenging, owing existence competitive C–H amination pathway. The use paddlewheel dirhodium complex Rh2(esp)2 effectively inhibited undesired insertion. Density functional theory calculations were performed reveal reaction mechanism origin chemoselectivity Rh-catalyzed reactions. novel products highly robust allow for downstream diversification.

Язык: Английский

---