α,α-Difluoro-substituted organozinc reagents generated from conventional organozinc compounds and difluorocarbene couple with 1-bromoalkynes affording gem-difluorinated alkynes. The cross-coupling proceeds in the presence of catalytic amounts of copper iodide in dimethylformamide under ligand-free conditions.
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http://dx.doi.org/10.3762/bjoc.11.231 | DOI Listing |
J Org Chem
January 2025
Department of Chemistry, University of California, Irvine, California 92697-2025, United States.
Activating agents enable the efficient preparation of organozinc complexes from zinc metal and organohalides, but their mechanisms had been obscured by the heterogeneous nature of these systems. Fluorescence microscopy, with the sensitivity to detect surface reaction intermediates, reveals distinct activating mechanisms of widely used activation strategies: trimethylsilyl chloride, LiCl, DMSO, and Rieke zinc powder. The resulting development of mechanistic models provides a better understanding of the oxidative-addition-solubilization sequence in organozinc reagent formation and contains lessons for methods development.
View Article and Find Full Text PDFJ Org Chem
December 2024
Department of Synthetic Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
The synthesis of C1-functionalized β-carbolines from -Boc norharman is described. Substitution is realized by employing the Knochel-Hauser base (TMPMgCl·LiCl) followed by transmetalation with ZnCl and subsequent Negishi cross-coupling of the resulting organozinc species. A variety of aryl or heteroaryl bromides participated in this one-pot reaction sequence, allowing for rapid diversification of the β-carboline scaffold in moderate to excellent yields.
View Article and Find Full Text PDFBeilstein J Org Chem
November 2024
Univ Paris-Est Créteil, CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France.
The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C-Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Institute of Organic Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.
An enantioconvergent palladium-catalyzed Negishi cross-coupling with racemic secondary organozinc reagents has been developed, enabling access to enantioenriched 1,1-diarylalkane motifs in high yields and enantioselectivities. Computational data indicates that the racemization of organozinc compounds most likely occurs through a bridged bimolecular mechanism.
View Article and Find Full Text PDFChemistry
December 2024
Centre for Synthesis and Chemical Biology (CSCB), School of Chemistry, University College Dublin (UCD), Belfield, Dublin 4, Ireland.
We present an improved and convenient synthesis of [2.2]paracyclophane-imidazoline N,O-ligands with central and planar chirality in seven steps starting from [2.2]paracyclophane.
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