Digital Discovery, Journal Year: 2023, Volume and Issue: 2(6), P. 1900 - 1910
Published: Jan. 1, 2023
Bond dissociation energetics underpin the thermodynamics of chemical transformations where bonds are broken or formed and can also be used to predict reaction rates selectivities.
Language: Английский
Chemical Science, Journal Year: 2022, Volume and Issue: 13(40), P. 11721 - 11737
Published: Jan. 1, 2022
A flurry of reports for preparing, functionalizing, and using bicyclo[1.1.0]butanes (BCBs) have positioned them to be powerful synthons with numerous applications. This review discusses the recent developments regarding this strained carbocycle.
Language: Английский
Citations
157
Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(5), P. 3092 - 3100
Published: Jan. 25, 2023
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 parasubstituted arene rings, appearing a number lead pharmaceutical candidates. However, despite value 2-substituted BCPs replacements ortho- or meta-substituted general and rapid syntheses these scaffolds remain elusive. Current approaches rely on installation bridge substituent prior BCP core construction, leading lengthy step counts often nonmodular sequences. While challenging, direct functionalization strong C-H bonds would offer more streamlined pathway diverse BCPs. Here, we report generalizable synthetic linchpin strategy via radical abstraction core. Through mild generation hydrogen atom abstractor, rapidly synthesize novel linchpins one pot. These then serve common precursors complex BCPs, allowing one-step access previously inaccessible electrophile nucleophile fragments at 2-position two new metallaphotoredox protocols. Altogether, this platform enables expedient synthesis four analogues, all which show similar compared their aryl-containing equivalents, demonstrating development.
Language: Английский
Citations
64
Chemical Science, Journal Year: 2024, Volume and Issue: 15(28), P. 10823 - 10829
Published: Jan. 1, 2024
Bicyclo[4.1.1]octanes (BCOs) were synthesized in up to quantitative yields through the formal [4+2] cycloaddition of aryl and alkyl bicyclobutane (BCB) ketones with dienol silyl ethers using Al(OTf) 3 as a Lewis acid catalyst.
Language: Английский
Citations
25
Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)
Published: June 11, 2022
Abstract Sulfonyl fluorides have attracted considerable and growing research interests from various disciplines, which raises a high demand for novel effective methods to access this class of compounds. Radical flurosulfonylation is recently emerging as promising approach the synthesis sulfonyl fluorides. However, scope applicable substrate reaction types are severely restricted by limited known radical reagents. Here, we introduce solid state, redox-active type fluorosulfonyl reagents, 1-fluorosulfonyl 2-aryl benzoimidazolium triflate (FABI) salts, enable fluorosulfonylation olefins under photoredox conditions. In comparison with precursor, gaseous FSO 2 Cl, FABI salts bench-stable, easy handle, affording yields in before challenging substrates. The advantage FABIs further demonstrated development an alkoxyl-fluorosulfonyl difunctionalization olefins, forges facile useful β-alkoxyl related compounds, would thus benefit study context chemical biology drug discovery future.
Language: Английский
Citations
67
Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(19)
Published: Feb. 11, 2022
Physico-chemical properties important to drug discovery (pKa , LogP, and aqueous solubility), as well metabolic stability, were studied for a series of functionalized gem-difluorinated cycloalkanes compared those non-fluorinated acyclic counterparts evaluate the impact fluorination. It was found that influence CF2 moiety on acidity/basicity corresponding carboxylic acids amines defined by inductive effect fluorine atoms nearly same cyclic aliphatic compounds. Lipophilicity solubility followed more complex trends affected position atoms, ring size, even nature functional group present; also, significant differences series. Also, gem-difluorination either did not affect or slightly improved stability model derivatives. The presented results can be used guide rational design employing establish first chapter in catalog key vitro fluorinated cycloalkanes.
Language: Английский
Citations
59
ChemMedChem, Journal Year: 2022, Volume and Issue: 17(21)
Published: Aug. 29, 2022
The review covers various aspects of fluorinated cycloalkyl (C3 -C7 ) building blocks for drug discovery, including their synthesis, key physicochemical properties, and biological medicinal applications derivatives. discussed synthetic methods include classical nucleophilic fluorinations substrates, the addition fluorine another heteroatom to double bonds, cycloadditions other transformations fluorine-containing as well some newer reactions like fluorination non-activated remotely activated C-H decarboxylative deborylative fluorinations, etc. known data on effect introducing groups compound's in vitro parameters (such acidity/basicity, lipophilicity, conformational behavior, short contact capabilities) are surveyed. Finally, block derivatives design biologically active compounds (including marketed drugs Maraviroc, Ivosidenib, Sitafloxacin) covered, with a focus impact.
Language: Английский
Citations
59
ChemCatChem, Journal Year: 2022, Volume and Issue: 14(24)
Published: Aug. 11, 2022
Abstract gem ‐Difluorocyclopropanes (F 2 CPs) have aroused considerable attention not only from the structural perspective but also due to their ability participate in various valuable transformations. This Review summarizes advances catalytic ring‐opening reactions of ‐F CPs, especially emphasizing reactivities and applications those non‐activated ones under transition‐metal catalysis. Their achievements, synthetic limitations are discussed with aim stimulate enthusiasm for further development.
Language: Английский
Citations
48
RSC Advances, Journal Year: 2023, Volume and Issue: 13(24), P. 16619 - 16629
Published: Jan. 1, 2023
Tetronic acid, a versatile synthon, has been extensively investigated by numerous researchers in synthetic chemistry due to its crucial role synthesizing heterocycles which makes this compound particularly advantageous both pharmaceutical and biological fields.
Language: Английский
Citations
42
Chemical Science, Journal Year: 2023, Volume and Issue: 14(30), P. 8070 - 8075
Published: Jan. 1, 2023
Identification of rigid counterparts for common flexible scaffolds is crucial to the advancement medicinal chemistry. Here we showcase a new class building blocks, 2,5-disubstituted bicyclo[2.1.1]hexanes that can act as rigidified
Language: Английский
Citations
33
Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)
Published: March 24, 2023
Herein we reported a transition metal-free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The of geminal-bis(boronates) bearing leaving group was highly diastereoselective, tolerating few functional groups applicable to heterocycles. When optically active epoxides were used as the starting materials, cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that at γ-position played crucial role significantly promoted activation gem-diboron moiety.
Language: Английский
Citations
27