Detailed Mechanistic Studies on Palladium-Catalyzed Selective C–H Olefination with Aliphatic Alkenes: A Significant Influence of Proton Shuttling

Abstract

Directing group-assisted regioselective C-H olefination with electronically biased olefins is well studied. However, the incorporation of unactivated olefins has remained largely unsuccessful. A proper mechanistic understanding of olefination involving unactivated alkenes is therefore essential for enhancing their usage in future. In this Article, detailed experimental and computational mechanistic studies on palladium catalyzed C-H olefination with unactivated, aliphatic alkenes are described. The isolation of Pd(II) intermediates is shown to be effective for elucidating the elementary steps involved in catalytic olefination. Reaction rate and order determination, control experiments, isotopic labeling studies, and Hammett analysis have been used to understand the reaction mechanism. The results from these experimental studies implicate β-hydride elimination as the rate-determining step and that a mechanistic switch occurs between cationic and neutral pathway. Computational studies support this interpretation of the experimental evidence and are used to uncover the origins of selectivity.

Tridentate Directing Groups Stabilize 6-Membered Palladacycles in Catalytic Alkene Hydrofunctionalization

“…Notably, the corresponding processes involving bidentate directing groups are much less exergonic. [2,14] In our previous results with AQ, the corresponding π-alkene complex is formed under analogous conditions. [4] Tridentate π-alkene complex 16 , in contrast, was not observed experimentally (see SI), presumably since its formation by dissociation of acetate from 15 is endergonic by 5.8 kcal/mol.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…It is worth to mention that a mechanistic study regarding the Pd-catalysed regioselective C–H olefination reaction with aliphatic alkenes was reported by Peng, Paton and Maiti. 422 …”

Full Selectivity Control in Cobalt(III)‐Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism

“…[3a,d] Therein, the key to success was the use of noble iridium catalysts derived from bulky bisphosphines, leading to branched-selective hydroarylations through repulsive steric interactions (Figure 1b). Indeed, earth-abundant cobalt [9] catalysis sets the stage for predictable C À Ha lkylations with electronically unbiased alkenes.N otable features of our approach include reaction conditions that obviate the need for stoichiometric amounts of reactive Grignard reagents,a nd an excellent functional group tolerance.T hus,h eteroarenes of relevance to drug discovery [10] were accessed in as tep-economical fashion through ap rogrammable switch from al inear-selective ligand-toligand hydrogen transfer (LLHT) [11] to ab ase-assisted internal electrophilic-type substitution (BIES) [12] C À Hmetalation (Figure 1c), as elaborated by detailed experimental and computational [13] mechanistic studies. Indeed, earth-abundant cobalt [9] catalysis sets the stage for predictable C À Ha lkylations with electronically unbiased alkenes.N otable features of our approach include reaction conditions that obviate the need for stoichiometric amounts of reactive Grignard reagents,a nd an excellent functional group tolerance.T hus,h eteroarenes of relevance to drug discovery [10] were accessed in as tep-economical fashion through ap rogrammable switch from al inear-selective ligand-toligand hydrogen transfer (LLHT) [11] to ab ase-assisted internal electrophilic-type substitution (BIES) [12] C À Hmetalation (Figure 1c), as elaborated by detailed experimental and computational [13] mechanistic studies.…”

“…[3a,d, 8] Contrarily,w eh ave now elucidated ac onceptually distinct strategy that orchestrates as witchable regiocontrol in CÀHa lkylations through the judicious choice of the C À Ha ctivation method. Indeed, earth-abundant cobalt [9] catalysis sets the stage for predictable C À Ha lkylations with electronically unbiased alkenes.N otable features of our approach include reaction conditions that obviate the need for stoichiometric amounts of reactive Grignard reagents,a nd an excellent functional group tolerance.T hus,h eteroarenes of relevance to drug discovery [10] were accessed in as tep-economical fashion through ap rogrammable switch from al inear-selective ligand-toligand hydrogen transfer (LLHT) [11] to ab ase-assisted internal electrophilic-type substitution (BIES) [12] C À Hmetalation (Figure 1c), as elaborated by detailed experimental and computational [13] mechanistic studies.…”