Dichotomous mechanistic behavior in Narasaka-Heck cyclizations: electron rich Pd-catalysts generate iminyl radicals

• Published in: Chemical science (Cambridge) Vol. 7; no. 2; pp. 158 - 1513
• Main Authors: Race, Nicholas J, Faulkner, Adele, Shaw, Megan H, Bower, John F
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2016; Royal Society of Chemistry
• Subjects: Alkenes; Bonding; Chemistry; Chemistry, Multidisciplinary; Esters; Ligands; Palladium; Pathways; Phosphines; Physical Sciences; Radicals; Science & Technology; PALLADIUM; AMINATION; NITRILES; ALKENES SYNTHESIS; ALLYLATION; C-C; DIHYDROPYRROLES; OXIME ESTERS; DERIVATIVES; ACCESS
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c5sc04037j

Pd-catalyzed cyclizations of oxime esters with pendant alkenes are subject to an unusual ligand controlled mechanistic divergence. Pd-systems modified with electron deficient phosphines ( e.g. P(3,5-(CF 3 ) 2 C 6 H 3 ) 3 ) promote efficient aza-Heck cyclization, wherein C-N bond formation occurs via alkene imino-palladation. Conversely, electron rich ligands, such as P( t -Bu) 3 , cause deviation to a SET pathway and, in these cases, C-N bond formation occurs via cyclization of an iminyl radical. A series of mechanistic experiments differentiate the two pathways and the scope of the hybrid organometallic radical cyclization is outlined. This study represents a rare example in Pd-catalysis where selection between dichotomous mechanistic manifolds is facilitated solely by choice of phosphine ligand. Pd-catalyzed cyclizations of oxime esters with pendant alkenes undergo ligand controlled mechanistic divergence. Electron deficient phosphines promote aza-Heck cyclization; electron rich systems favour a SET pathway. Mechanistic experiments differentiate the two manifolds.