The enantioselective addition of organozinc reagents to some 2-alkynyl benzaldehydes and the subsequent regioselective cyclization step was performed in one pot to form chiral 1,3-dihydroisobenzofurans with good product yields and excellent regio- and enantioselectivities. In the case of 2-alkynylcycloalkene aldehydes, tetrasubstituted furans were obtained in good product yields through a 1, 5-hydride shift of the preformed cyclization product.
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http://dx.doi.org/10.1021/jo800029m | 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 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 PDFJ Org Chem
October 2024
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.
We have developed a high yielding synthesis of indolizine and directly elaborated the molecule into three optically active indolizinylalanine regioisomers. The protocols exploit metal catalyzed coupling of indolizinyl-halides with organozinc reagents derived from carbamoylated iodoalanine esters. The scalable protocols provide products in a form amenable to solid-phase peptide synthesis (SPPS).
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, 980-8578, Sendai, Japan.
A stereoselective hydroxyallylation reaction of cyclopropenes with cyclopropanols is achieved under zinc-mediated conditions, affording densely functionalized cyclopropanes with excellent diastereocontrol over three contiguous stereocenters within and outside the cyclopropane ring. A racemic variant of the reaction is synergistically promoted by catalytic N-heterocyclic carbene (NHC) and organic base, whereas chiral amino alcohol-derived bifunctional NHC enables a catalytic enantioselective variant. The reaction likely involves the generation of enolized zinc homoenolate via ring-opening of zinc cyclopropoxide and enolization of the resulting homoenolate, followed by its addition to the cyclopropene as a prochiral allylzinc nucleophile.
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