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The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an -benzoyl oxime is reported. In this transformation, -benzoyl oxime acted as a radical precursor and XAT mediator. In addition to common alkyl iodides, other alkyl iodides such as iodomethane, iodomethane-, trifluoroiodomethane, ethyl difluoroiodoacetate, and iodoalkanes containing unprotected hydroxyl and amide groups can also serve as C-radical precursors in the 1,2-iminylalkylation with electrophilic diazenes as radical acceptors.
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http://dx.doi.org/10.1021/acs.orglett.3c02584 | DOI Listing |
J Am Chem Soc
September 2025
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
The direct cross-coupling of unactivated alkyl halides with aryl or heteroaryl partners remains a fundamental challenge in synthetic chemistry due to their inertness and propensity for side reactions. Herein, we report a transition-metal-free electrochemical halogen-atom transfer strategy that enables efficient alkyl radical cross-coupling via convergent paired electrolysis. In this system, anodically generated α-aminoalkyl radicals mediate the activation of alkyl iodides, while aryl/heteroaryl aldehydes or nitriles undergo cathodic reduction to afford persistent ketyl radical anions or aryl radical anions.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Shenzhen Key Laboratory of Cross Coupling Reactions & Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.
Currently, most sulfoximine clinical candidates feature both -aryl and -alkyl substituents. The asymmetric synthesis of these compounds typically relies on oxidizing corresponding enantioenriched sulfilimines. Herein, we describe an effective catalytic system comprising CuI and an azabicyclo[2.
View Article and Find Full Text PDFAdv Synth Catal
April 2025
Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd., Queens, New York 11367, USA.
Over the past two decades, iodine-mediated free radical reactions have been extensively explored and employed in chemical transformations that complement traditional ionic reactions. In this review, we have updated the progress of the iodine-mediated radical reactions in organic synthesis reported between 2015 and mid-2024, and organized the reactions according to their mechanistic pathways. In general, the proposed mechanisms can be divided into four categories based on the radical initiation or its preceding steps, namely, (1) formation of a covalent X-I (X=C, N, S, Se) bond, which subsequently participates in a radical reaction; (2) formation of a noncovalent N···I bond, which assists the homolysis of the I-I bond; (3) formation of the key iodine radicals by visible-light or heat induced homolysis of I or by electrochemical oxidation of iodide; (4) iodine induced peroxide decomposition single electron transfer (SET) mechanism to generate alkoxy or alkyl peroxy radicals.
View Article and Find Full Text PDFACS Cent Sci
August 2025
Department of Chemistry, Scripps Research, La Jolla, California 92037, United States.
We report a bidirectional diversification and optimization campaign of the newly identified - and -opioid receptor antagonist GB18, a naturally occurring alkaloid. First, we find that replacement of the GB18 piperidine with pyridine alters the pharmacology from antagonism to partial agonism, with reduced potency but markedly higher receptor selectivity for over . Second, we optimize this hit via development of a mutually chemoselective cross-coupling of an alkyl iodide/vinyl triflate pair that leads to a series of low- and sub-nanomolar KOR-selective full agonists, some of which demonstrate bias for G protein activation over β-arrestin2 recruitment.
View Article and Find Full Text PDFSmall
August 2025
National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
Perovskite solar cells (PSCs) utilizing poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA) as hole-transport materials (HTMs) in n-i-p structures are promising owing to their thermal stability. However, they suffer from the absence of perovskite passivation techniques suitably combined with PTAA HTMs. Herein, phenylalkylammonium bis(trifluoromethylsulfonyl)imides (PRA-TFSIs) are presented as spontaneous perovskite passivators specifically tailored for PTAA HTMs.
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