Photocatalyzed [2σ + 2σ] and [2σ + 2π] Cycloadditions for the Synthesis of Bicyclo[3.1.1]heptanes and 5- or 6-Membered Carbocycles

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(46), С. 25411 - 25421

Опубликована: Ноя. 7, 2023

We report the use of photocatalysis for homolytic ring-opening carbonyl cyclopropanes. In contrast to previous studies, our approach does not require a metal cocatalyst or strong reductant. The cyclopropanes can be employed both [2σ + 2σ] and 2π] annulation with either alkenes/alkynes bicyclo[1.1.0]butanes, yielding cyclopent-anes/-enes bicyclo[3.1.1]heptanes (BCHs), respectively. BCHs are promising bioisosteres 1,2,4,5 tetra-substituted aromatic rings. Mechanistic including density functional theory computation trapping experiment DMPO, support 1,3-biradical generated from cyclopropane as key intermediate these transformations.

Язык: Английский

---

Light‐Driven Synthesis and Functionalization of Bicycloalkanes, Cubanes and Related Bioisosteres

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Янв. 5, 2024

Bicycloalkanes, cubanes and their structural analogues have emerged as bioisosteres of (hetero)arenes. To meet increasing demand, the chemical community has developed a plethora novel synthetic methods. In this review, we assess progress made in field light-driven construction functionalization such relevant molecules. We focused on diverse targets, well reaction processes giving access to: (i) [1.1.1]-bicyclopentanes (BCPs); (ii) [2.2.1]-bicyclohexanes (BCHs); (iii) [3.1.1]-bicycloheptanes (BCHeps); (iv) cubanes; other structurally related scaffolds. Finally, future perspectives dealing with identification manifolds to new functionalized bioisosteric units are discussed.

Язык: Английский

---

Visible-Light-Induced Energy-Transfer-Mediated Hydrofunctionalization and Difunctionalization of Unsaturated Compounds via Sigma-Bond Homolysis of Energy-Transfer Acceptors

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 1854 - 1941

Опубликована: Янв. 17, 2025

Over the past decade, visible-light-mediated energy-transfer (EnT) catalysis, particularly triplet–triplet (TTEnT) has emerged as a mild and environmentally friendly approach for diverse organic synthetic transformations. In contrast to photoredox which typically requires sacrificial electron donors or acceptors complete catalytic cycle, EnT photocatalysis generally proceeds with high atom economy while minimizing generation of wasteful byproducts. Furthermore, successful catalysis is contingent upon precise control redox potentials both photocatalysts substrates, strategies are primarily influenced by triplet energy compatibility between these entities. Considering growing importance photocatalysis, well hydrofunctionalization difunctionalization reactions in synthesis, this review systematically summarizes significant advancements EnT-enabled unsaturated compounds via sigma-bond homolysis over decade. Special emphasis placed on elucidating substrate scopes mechanistic scenarios. Additionally, discusses versatile applications methodologies addresses current challenges opportunities within evolving research field. This structured into six main categories based different types sigma-bonds undergoing homolysis. These include transformations mediated 1) N–O bond oxime esters other N,O-radical precursors; 2) N–S N-sulfonyl imines N,S-radical 3) chalcogen–chalcogen disulfides oxy/thio/selenosulfonates; 4) C–S tri/difluoromethylated sulfinates, acetylenic triflones, arylsulfonium salts; 5) C–X (X = halogen) halides; 6) acceptors. Through providing theoretical backgrounds along comprehensive overview currently employed acceptors, photosensitizers, contemporary EnT-induced compounds, aims serve an invaluable resource future innovations rapidly

Язык: Английский

---

Rejuvenation of dearomative cycloaddition reactions via visible light energy transfer catalysis

Chemical Science, Год журнала: 2023, Номер 14(43), С. 12004 - 12025

Опубликована: Янв. 1, 2023

Dearomative cycloaddition is a powerful technique to access sp

Язык: Английский

---

Photosensitized [4+2]‐ and [2+2]‐Cycloaddition Reactions of N‐Sulfonylimines

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(32)

Опубликована: Июль 3, 2023

Abstract The synthesis of polycyclic compounds is high interest due to the prevalence these motifs in drugs and natural products. Herein, we report on stereoselective construction 3D bicyclic scaffolds azetidine derivatives by modulation N ‐sulfonylimines achieve either [4+2]‐ or [2+2]‐cycloaddition reactions. utility method was established further product. Mechanistic studies are also included, which support reaction via Dexter energy transfer.

Язык: Английский

---

Asymmetric Transfer Hydrogenation of Cyclobutenediones

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(7), С. 4942 - 4957

Опубликована: Фев. 7, 2024

Four-membered carbocycles are fundamental substructures in bioactive molecules and approved drugs serve as irreplaceable building blocks organic synthesis. However, developing efficient protocols furnishing diversified four-membered ring compounds a highly regio-, diastereo-, enantioselective fashion remains challenging but very desirable. Here, we report the unprecedented asymmetric transfer hydrogenation of cyclobutenediones. The reaction can selectively afford three types products high yields with stereoselectivities, functionalized enable series further transformations to form more compounds. Asymmetric synthesis di-, tri-, tetrasubstituted has also been achieved. Systematic mechanistic studies theoretical calculations have revealed origin regioselectivity, key transition state models, sequence double triple processes. work provides new choice for catalytic cyclobutanes related structures demonstrates robustness accurate selectivity control substrates.

Язык: Английский

---

Photochemistry in Medicinal Chemistry and Chemical Biology

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(6), С. 4322 - 4345

Опубликована: Март 8, 2024

Photochemistry has emerged as a transformative force in organic chemistry, significantly expanding the chemical space accessible for medicinal chemistry. Light-induced reactions enable efficient synthesis of intricate structures and have found applications throughout different stages drug discovery development processes. Moreover, photochemical techniques provide innovative solutions biology, allowing precise spatiotemporal activation targeted delivery. In this Perspective, we highlight already numerous remarkable even more promising future photochemistry chemistry biology.

Язык: Английский

---

Visible photons as ideal reagents for the activation of coloured organic compounds

Chemical Society Reviews, Год журнала: 2024, Номер 53(10), С. 4926 - 4975

Опубликована: Янв. 1, 2024

In search for the perfect wave(length). This review is dedicated to recent efforts in development of visible light driven photochemical strategies occurring coloured organic compounds.

Язык: Английский

---

Radical strain-release photocatalysis for the synthesis of azetidines

Nature Catalysis, Год журнала: 2024, Номер 7(11), С. 1223 - 1231

Опубликована: Авг. 14, 2024

The increasing popularity of four-member rings in drug discovery has prompted the synthetic chemistry community to advance and reinvent old strategies craft these structures. Recently, strain-release concept been used build complex architectures. However, although there are many for accessing small carbocyclic derivatives, synthesis azetidines remains underdeveloped. Here we report a photocatalytic radical strategy densely functionalized from azabicyclo[1.1.0]butanes. protocol operates with an organic photosensitizer, which finely controls key energy-transfer process distinct types sulfonyl imines. intermediates intercepted by azabicyclo[1.1.0]butanes via process, providing access difunctionalized single step. This is revealed combination spectroscopic optical techniques density functional theory calculations. power generality this method illustrated various azetidine targets, including derivatives celecoxib naproxen. Four-membered have become popular motifs discovery, prompting develop more expedite approaches scaffolds. Here, authors

Язык: Английский

---

Accessing ladder-shape azetidine-fused indoline pentacycles through intermolecular regiodivergent aza-Paternò–Büchi reactions

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 16, 2024

Abstract Small molecules with conformationally rigid, three-dimensional geometry are highly desirable in drug development, toward which a direct, simple-to-complexity synthetic logic is still of considerable challenges. Here, we report intermolecular aza-[2 + 2] photocycloaddition (the aza-Paternò–Büchi reaction) indole that facilely assembles planar building blocks into ladder-shape azetidine-fused indoline pentacycles contiguous quaternary carbons, divergent head-to-head/head-to-tail regioselectivity, and absolute exo stereoselectivity. These products exhibit marked three-dimensionality, many possess 3D score values distributed the highest 0.5% region reference to structures from DrugBank database. Mechanistic studies elucidated origin observed regio- stereoselectivities, arise distortion-controlled C-N coupling scenarios. This study expands repertoire energy transfer catalysis for accessing structurally intriguing architectures high molecular complexity underexplored topological chemical space.

Язык: Английский

---