Air‐Stable Pd^I Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1‐Diaryl Alkanes with Unprecedented Speed

Abstract

While remote functionalization via chain walking has the potential to enable access to molecules via novel disconnections, such processes require relatively long reaction times and can be in need of elevated temperatures. This work features a remote arylation in less than 10 min reaction time at room temperature over a distance of up to 11 carbons. The unprecedented speed is enabled by the air‐stable PdI dimer [Pd(μ‐I)(PCy2tBu)]2, which in contrast to its PtBu3 counterpart does not trigger direct coupling at the initiation site, but regioconvergent and chemoselective remote functionalization to yield valuable fluorinated 1,1‐diaryl alkanes. Our combined experimental and computational studies rationalize the origins of switchability, which are primarily due to differences in dispersion interactions.

Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

“…The same group also investigated whether the air-stable C3 enabled site-selective alkylation of poly( pseudo)halogenated arenes within 10 minutes, achieving regio-and chemoselective remote coupling selectively at the OTf site at room temperature to provide an excellent branched-to-linear selectivity and up to 94% isolated yields of the branched products (Scheme 16). 59 The reaction proceeds through a rapid chain-walking mechanism, which is consistent with the earlier observation that the catalyst demonstrates efficacy in olefin migration. 58 The authors highlighted that a subtle ligand modification within the Pd(I) dimer framework can fully switch the reaction outcome toward the branched product while retaining air stability and reaction speed benefits.…”

“…58 The authors highlighted that a subtle ligand modification within the Pd(I) dimer framework can fully switch the reaction outcome toward the branched product while retaining air stability and reaction speed benefits. 59…”

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

“…Among the 23 combinations of cross-coupling partners evaluated, the yields varied between 31 and 75% and reflected directly the regioisomeric ratio rr α/β (which itself varied from 2:1 to >1:20). The lack of stereocontrol in the isomerization reaction is likely responsible for the moderate E / Z ratio measured for the overall process, except when 2-bromobenzonitrile 3x was employed ( 5ax : E / Z = 9:91). − While electron-deficient aryl bromides ( 3b – e , 3q – s , 3t – u ) and heteroaryl bromides ( 3y – z ) appeared particularly well suited for the transformation, reduced performances were obtained with electron-neutral derivatives ( 3a , 3f ). The α-regioisomer was even produced preferentially when using the electron-rich 4-bromoanisole 3i ( 5ai : rr α/β 2:1).…”

Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

“…At the beginning, several issues were considered to address in order to effectuate the hypothetical cascade processes in the desired direction. − First, a number of late transition metal systems are known to oxidize the hydroxyl group to carbonyls simply via intermolecular transfer hydrogenation, thus making the olefin chain walking unattainable . Second, olefin aziridination by the metal-nitrenoids may hamper the desired reactivity toward the migratory functionalization .…”