Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 721 - 726

Published: Sept. 15, 2022

Language: Английский

---

Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible-Light-Induced Energy Transfer

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(44), P. 20207 - 20213

Published: Oct. 27, 2022

Synthesis of bicyclic scaffolds has attracted growing interest because they are high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy transfer catalysis. The process is proposed involve formal [2π + 2σ] photocycloaddition/backbone C-H abstraction/aryl group migration sequence. A diverse range (hetero)aryl groups successfully underwent the backbone (C2) position provide previously inaccessible molecules, ester product can serve as handle for downstream manipulation, thus offering opportunities rapidly build up molecular complexity new sp3-rich chemical space.

Language: Английский

---

Asymmetric intermolecular allylic C–H amination of alkenes with aliphatic amines

Science, Journal Year: 2022, Volume and Issue: 378(6625), P. 1207 - 1213

Published: Dec. 15, 2022

Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct C-H amination alkenes serves as the most straightforward method toward these motifs. However, use widely available internal with aliphatic this transformation remains synthetic challenge. In particular, palladium catalysis faces twin challenges inefficient coordination Pd(II) to but excessively tight therefore inhibitory by basic amines. We report general solution problems. developed protocol, contrast classical Pd(II/0) scenario, operates through blue light-induced Pd(0/I/II) manifold mild aryl bromide oxidant. This open-shell approach also enables enantio- diastereoselective amination.

Language: Английский

---

Catalytic Formal [2π+2σ] Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2‐Oxabicyclo[2.1.1]hexanes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: June 12, 2023

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres benzenoids in modern drug discovery. Here, we report a BF3 -catalyzed [2π+2σ] cycloaddition aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2-oxabicyclo[2.1.1]hexanes. A new kind BCB containing acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides be utilized substrates undergo BCBs after situ rearrangement aldehydes. We anticipate that our results will promote challenging sp3 -rich frameworks exploration BCB-based chemistry.

Language: Английский

---

Exploiting the sp2 character of bicyclo[1.1.1]pentyl radicals in the transition-metal-free multi-component difunctionalization of [1.1.1]propellane

Nature Chemistry, Journal Year: 2022, Volume and Issue: 14(9), P. 1068 - 1077

Published: July 21, 2022

Language: Английский

---

2-Oxabicyclo[2.1.1]hexanes as saturated bioisosteres of the ortho-substituted phenyl ring

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(8), P. 1155 - 1163

Published: June 5, 2023

Abstract The ortho -substituted phenyl ring is a basic structural element in chemistry. It found more than three hundred drugs and agrochemicals. During the past decade, scientists have tried to replace bioactive compounds with saturated bioisosteres obtain novel patentable structures. However, most of research this area has been devoted replacement para ring. Here we developed improved physicochemical properties: 2-oxabicyclo[2.1.1]hexanes. Crystallographic analysis revealed that these structures indeed similar geometric properties. Replacement marketed agrochemicals fluxapyroxad (BASF) boscalid 2-oxabicyclo[2.1.1]hexanes dramatically their water solubility, reduced lipophilicity importantly retained bioactivity. This work suggests an opportunity for chemists medicinal chemistry agrochemistry.

Language: Английский

---

A Practical and Scalable Approach to Fluoro‐Substituted Bicyclo[1.1.1]pentanes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(29)

Published: May 31, 2022

After more than 20 years of trials, a practical scalable approach to fluoro-substituted bicyclo[1.1.1]pentanes (F-BCPs) has been developed. The physicochemical properties the F-BCPs have studied, and core was incorporated into structure anti-inflammatory drug Flurbiprofen in place fluorophenyl ring.

Language: Английский

---

Conquering the Synthesis and Functionalization of Bicyclo[1.1.1]pentanes

JACS Au, Journal Year: 2023, Volume and Issue: 3(6), P. 1539 - 1553

Published: May 16, 2023

Bicyclo[1.1.1]pentanes (BCPs) have become established as attractive bioisosteres for para-substituted benzene rings in drug design. Conferring various beneficial properties compared with their aromatic "parents," BCPs featuring a wide array of bridgehead substituents can now be accessed by an equivalent variety methods. In this perspective, we discuss the evolution field and focus on most enabling general methods synthesis, considering both scope limitation. Recent breakthroughs synthesis bridge-substituted are described, well methodologies postsynthesis functionalization. We further explore new challenges directions field, such emergence other rigid small ring hydrocarbons heterocycles possessing unique substituent exit vectors.

Language: Английский

---

Silver‐Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 12, 2023

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles bicyclobutane precursors is described. The strain-release operates under mild conditions, tolerating wide range functional groups. It capable forming with up four contiguous quaternary carbon centers, achieving yields 99 %. In addition, scale-up experiment synthetic transformations cycloadducts further highlighted utility.

Language: Английский

---

Visible-light-induced direct perfluoroalkylation/heteroarylation of [1.1.1]propellane to diverse bicyclo[1.1.1]pentanes (BCPs) under metal and photocatalyst-free conditions

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(3), P. 986 - 992

Published: Jan. 1, 2023

This study describes a green and novel multi-component reaction for direct perfluoroalkylation/heteroarylation of [1.1.1]propellane with heteroarenes perfluoroalkyl iodines to diverse bicyclo[1.1.1]pentanes (BCPs).

Language: Английский

---