ArticleJournal of the American Chemical Society2023
Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 102 citations in OpenAlex.
- Advancing Drug Discovery through Academia-Industry Collaborations: Lessons from Merck Discovery Chemistry Partnerships.ACS central science · 2026Review
- Photocatalytic Radical Functionalization of Alkenylammonium Salts.Precision chemistry · 2026Article
- Methyl on the Bridge: 2-Methyl Propellane as Precursor for 1,3-Substituted 2-Methylated Bicyclo[1.1.1]Pentanes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Collective synthesis of 1,2,4-trisubstituted, meta- and ortho-substituted arene bioisosteres from bicyclobutanes.Nature chemistry · 2026Article
- Substitutive Approach Toward Heteroaromatic Amino Alcohols Accessed Through Dioxolanyl Radical Linchpin.Advanced synthesis & catalysis · 2026Article
- Harnessing COJournal of the American Chemical Society · 2026Article
- Propellane-free access to bicyclo[1.1.1]pentanes.Nature communications · 2026Review
- A study towards the undirected fluorination and chlorination of cubane 1,4-diester.Beilstein journal of organic chemistry · 2026Article
- Boron-Enabled Stereoselective Synthesis of Polysubstituted Housanes.Journal of the American Chemical Society · 2025Article
- Dibromocarbene addition to bicyclo[1.1.0]butanes: A facile route to substituted bicyclo[1.1.1]pentanes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A General Metallaphotoredox Platform forJournal of the American Chemical Society · 2025Article
- Direct Synthesis of Bicyclo[1.1.1]pentanes by Sequential C═C, C-C Functionalization Reactions.Journal of the American Chemical Society · 2025Article
- DirectJournal of the American Chemical Society · 2025Article
- Article
- Mechanism-Guided Development of Directed C-H Functionalization of Bicyclo[1.1.1]pentanes.Journal of the American Chemical Society · 2025Article
- Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity.Nature chemistry · 2025Article
- Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing.Nature chemistry · 2025Article
- Facile Synthesis of Housanes by an Unexpected Strategy.Journal of the American Chemical Society · 2025Article
- Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions.Organic letters · 2025Article
- Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(spNature communications · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres for parasubstituted arene rings, appearing in a number of lead pharmaceutical candidates. However, despite the pharmaceutical value of 2-substituted BCPs as replacements for ortho- or meta-substituted arene rings, general and rapid syntheses of these scaffolds remain elusive. Current approaches to 2-substituted BCPs rely on installation of the bridge substituent prior to BCP core construction, leading to lengthy step counts and often nonmodular sequences. While challenging, direct functionalization of the strong bridge BCP C-H bonds would offer a more streamlined pathway to diverse 2-substituted BCPs. Here, we report a generalizable synthetic linchpin strategy for bridge functionalization via radical C-H abstraction of the BCP core. Through mild generation of a strong hydrogen atom abstractor, we rapidly synthesize novel 2-substituted BCP synthetic linchpins in one pot. These synthetic linchpins then serve as common precursors to complex 2-substituted BCPs, allowing one-step access to a number of previously inaccessible electrophile and nucleophile fragments at the 2-position via two new metallaphotoredox protocols. Altogether, this platform enables the expedient synthesis of four pharmaceutical analogues, all of which show similar or improved properties compared to their aryl-containing equivalents, demonstrating the potential of these 2-substituted BCPs in drug development.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.