Assisted Tandem Pd Catalysis Enables Regiodivergent Heck Arylation of Transiently Generated Substituted Enol Ethers

Article Article scientifique Article Assisted Tandem Pd Catalysis Enables Regiodivergent Heck Arylation of Transiently Generated Substituted Enol Ethers eng 2023-01-12 2023-01-23 author Duhamel Thomas 953935 author Scaringi Simone 929834 author Leforestier Baptiste 982626 author Poblador Bahamonde Amalia Isabel 0000-0002-5266-914X 797442 author Mazet Clement 0000-0002-2385-280X 667534 261-274 10.1021/jacsau.2c00645 2691-3704 https://pubs.acs.org/doi/10.1021/jacsau.2c00645 Two complementary regiodivergent Pd-catalyzed assisted tandem [isomerization/Heck arylation] reactions are reported. They provide access to a broad array of acyclic trisubstituted vinyl ethers starting from readily available alkenyl ethers. In both cases, the isomerization is conducted with a [Pd–H] precatalyst supported by tris-tert-butyl phosphine ligands. When the catalyst is modified by the addition of a chelating bisphosphine ligand (dppp), an organic base (Cy2NMe), sodium acetate, and aryl triflates are used as electrophiles, the α-arylation pathway is promoted preferentially. The β-arylation pathway is favored for electron-deficient and electron-neutral aryl halides when the catalyst is simply modified by the addition of an excess of an organic base (Et3N) after completion of the isomerization reaction. Electron-rich aryl halides lead to reduced levels of regiocontrol. The moderate stereoselectivity obtained are proposed to reflect the absence of stereocontrol in the isomerization step. Computational analyses suggest that migratory insertion is selectivity-determining for both the arylations. For the β-selective arylation, an energy decomposition analysis underscored that electronic factors favor α-regioselectivity and steric effects favor β-regioselectivity. Preliminary investigations show that high levels of stereoselectivity can be achieved for the α-selective arylation by ligand control. Complementarily, reaction conditions for postcatalytic stereo-correction have also been identified for each catalytic system. Assisted tandem catalysis Palladium catalysis Isomerization Regiodivergent catalysis Enol ethers Heck reaction DFT calculations Stereoselectivity Dewey 540 36 Département de chimie organique 141 false 763 Groupe Mazet 1055 Groupe Poblador Bahamonde JACS Au 3 1 e41fb2e5-7404-406d-9e38-b020588a3657 Article (Published version) Public Article-scientifique-from-crossref.pdf 3730020 application/pdf Vignette Public au2c00645_0014.jpg 56762 image/jpeg openAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Assisted Tandem Pd Catalysis Enables Regiodivergent Heck Arylation of Transiently Generated Substituted Enol Ethers	JACS Au			2023	233	74

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Duhamel, Thomas