Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

This study describes a method for the stereoselective synthesis of highly functionalized bicyclo[2.1.0]pentanes (housanes). The approach utilizes two-step sequence, silver- or gold-catalyzed cyclopropenation alkynes followed by an intermolecular [2 + 2] photocycloaddition reaction with electron-deficient alkenes. is established aryldiazoacetates. A regioselective cycloaddition cyclopropane was developed using blue LED irradiation, commercially available photocatalyst as triplet-sensitizer, and low temperature (−40 °C). diastereoselective, when enantioenriched cyclopropenes are used, it proceeds enantioretention.

Language: Английский

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Bridge Heteroarylation of Bicyclo[1.1.1]pentane Derivatives

Organic Letters, Journal Year: 2023, Volume and Issue: 25(12), P. 2053 - 2057

Published: March 17, 2023

Herein, we report the decarboxylative Minisci heteroarylation of bicyclo[1.1.1]pentane (BCP) and 2-oxabicyclo[2.1.1]hexane (oBCH) derivatives at bridge positions. In an operationally simple, photocatalyst-free process, free carboxylic acids are directly coupled with nonprefunctionalized heteroarenes to provide rare examples polysubstituted BCP oBCH in synthetically useful yields. Additionally, impact core on physicochemical properties a representative example compared those its all-aromatic ortho- meta-substituted analogues is evaluated.

Language: Английский

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Selective P450_BM3 Hydroxylation of Cyclobutylamine and Bicyclo[1.1.1]pentylamine Derivatives: Underpinning Synthetic Chemistry for Drug Discovery

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(50), P. 27767 - 27773

Published: Dec. 5, 2023

Achieving single-step syntheses of a set related compounds divergently and selectively from common starting material affords substantial efficiency gains when compared with preparing those same by multiple individual syntheses. In order for this approach to be realized, complementary reagent systems must available; here, panel engineered P450BM3 enzymes is shown fulfill remit in the selective C–H hydroxylation cyclobutylamine derivatives at chemically unactivated sites. The oxidations can proceed high regioselectivity stereoselectivity, producing valuable bifunctional intermediates synthesis applications fragment-based drug discovery. process also applies bicyclo[1.1.1]pentyl (BCP) amine achieve first direct enantioselective functionalization bridging methylenes open short efficient route chiral BCP bioisosteres medicinal chemistry. combination substrate, enzyme, reaction engineering provides powerful general platform small-molecule elaboration diversification.

Language: Английский

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Recent Progress in Accessing Multi-functionalized Caged Hydrocarbons: En Route to Highly Functionalized Saturated (Bio)isosteres of Benzene Rings

Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract Recently, many saturated bioisosteres of the benzene ring have been developed, and their applications in drug development evaluated. Most these are caged hydrocarbons, which rigid skeletons three-dimensional spaces. Recent efforts to synthesize hydrocarbons enabled access multi-functionalized congeners that expected be (bio)isosteres benzenes. This short review summarizes recently reported methods for obtaining (typically more than disubstituted) hydrocarbons. 1 Introduction 2 Proposed Structures Caged Hydrocarbons as Saturated (Bio)isosteres Benzene Ring: A Brief Summary 3 Access Multi-functionalized Hydrocarbons: De Novo Synthetic Approaches 3.1 Bicyclo[1.1.1]pentanes (BCPs) 3.2 Bicyclo[2.1.1]hexanes (BCHs) 3.3 Bicyclo[3.1.1]heptanes (BCHeps) 3.4 Others 4 C–H Functionalization 5 Conclusion

Language: Английский

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Amine-Borane-Mediated, Nickel/Photoredox-Catalyzed Cross-Electrophile Coupling between Alkyl and Aryl Bromides

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 12658 - 12667

Published: Aug. 19, 2024

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, metallaphotoredox catalytic protocol been developed on the basis of tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety aryl heteroaryl bromides featuring different functional groups pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility Lewis base-ligated borane with nickel was well exemplified extend chemical space Ni-catalyzed cross-electrophile coupling.

Language: Английский

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