The stereochemical outcome of reactions of chiral nucleophilic trisubstituted acetonide radicals with electron-deficient alkenes is dictated by a delicate balance between destabilizing non-bonding interactions and stabilizing hydrogen-bonding between substituents on the α and β carbons.
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http://dx.doi.org/10.1002/chem.201601957 | DOI Listing |
Org Lett
March 2025
Hefei National Research Center for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
Here we report a highly diastereoselective cyano group transfer radical cyclization reaction to construct 5/6-fused bicyclic ring systems that bear three contiguous and congested stereogenic elements, with 100% atom economy under catalyst-free and near-ultraviolet light irradiation conditions. Mechanistic investigations and density functional theory calculations suggest that the diastereoselectivity is governed by the conformational distribution of the triplet diradical intermediate and the rate of reverse intersystem crossing (RISC) before radical coupling.
View Article and Find Full Text PDFNat Chem
March 2025
The Institute for Advanced Studies, Wuhan University, Wuhan, China.
Despite cross-coupling strategies that enable the functionalization of aromatic heterocycles, the enantioselective C(sp)-H alkylation of readily available saturated hydrocarbons to construct C(sp)-C(sp) bonds remains a formidable challenge. Here we describe a nickel-catalysed enantioselective C(sp)-H alkylation of saturated heterocycles using olefins, providing an efficient strategy for the stereoselective construction of C(sp)-C(sp) bonds. Using readily available and stable olefins and simple saturated nitrogen and oxygen heterocycles as prochiral nucleophiles, the coupling reactions proceed under mild conditions and exhibit broad scope and high functional group tolerance.
View Article and Find Full Text PDFJ Org Chem
February 2025
CINBIO, Departamento de Química Orgánica, Universidade de Vigo, Vigo 36310, Spain.
The total synthesis of the stereoisomer of muanlactam predicted by DP4+ calculations, which differed from that reported for the natural product on the relative configuration at C19, was completed, and the structure of the polyenic macrolactam was fully confirmed. Construction of the stereocenters involved the iterative enantio- and diastereoselective Krische's allylation reaction for the formal -1,3-diol and the addition of a propargylic Grignard reagent to Ellman's chiral nonracemic -butylsulfinamide for the enantiopure amine fragment. The conjugated triene and diene units were constructed by Suzuki-Miyaura cross-coupling reactions of the corresponding alkenylboronates and alkenyl iodides.
View Article and Find Full Text PDFACS Cent Sci
January 2025
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
Multicomponent reactions (MCRs), highly sought-after methods to produce atom-, step-, and energy-economic organic syntheses, have been developed extensively. However, catalytic asymmetric MCRs, especially those involving radical species, remain largely unexplored owing to the difficulty in stereoselectively regulating the extraordinarily high reactivity of open-shell radical species. Herein, we report a conceptually novel catalytic asymmetric three-component radical cascade reaction of readily accessible glycine esters, α-bromo carbonyl compounds and 2-vinylcyclopropyl ketones via synergistic photoredox/Brønsted acid catalysis, in which three sequential C-C (σ/π/σ) bond-forming events occurred through a radical addition/ring-opening/radical-radical coupling protocol, affording an array of valuable enantioenriched unnatural α-amino acid derivatives bearing two contiguous stereogenic centers and an alkene moiety in moderate to good yield with high diastereoselectivity, excellent enantioselectivity and good -dominated geometry under mild reaction conditions.
View Article and Find Full Text PDFChemistry
January 2025
Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes)-UMR6226, F-35000, Rennes, France.
Capozzi's groundbreaking work in 1982 introduced a fascinating reaction involving highly reactive tertiary aliphatic cations and silylated alkynes. This reaction provided an innovative solution to the challenge of coupling a fully substituted tertiary aliphatic fragment with an alkyne moiety. Building upon Capozzi's pioneering efforts, we started an extensive exploration of reaction conditions to expand the initial scope of this reaction.
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