Pd(0)/Blue Light Promoted Carboiodination Reaction – Evidence for Reversible C–I Bond Formation via a Radical Pathway

Abstract

A Pd(0)/blue light catalyzed carboiodination reaction is reported. A simple, air-stable catalytic system, utilizing [Pd(allyl)Cl] 2 and DPEPhos, generated a variety of iodinated hetero-and carbocycles including oxindoles, dihydrobenzofurans, indolines, a chromane, and a tetrahydronaphthalene. This protocol was tolerant of sensitive functional groups including free carboxylic acids, phenols, and anilines, as well as pyridines, while delivering products in up to 94% yield. Support for a reversible C−I bond formation via a single electron mechanism was obtained using a deuterium labeled substrate and a stoichiometric neopentylpalladium species.T ransition-metal catalyzed halogenation protocols have often hinged on gaining a deeper understanding of the reversibility of carbon−halogen bond forming events. One powerful synthetic strategy that implements reversible C−X bond formation is the palladium-catalyzed carboiodination reaction, wherein halogenated heterocycles can be built from the intramolecular transfer of a C(sp 2 )−X group across a tethered π-system. 1−4 Traditionally, palladium catalyzed carboiodination reactions involve a 2-electron mechanistic cycle and are initiated by a ground-state Pd(0) catalyst undergoing an oxidative addition with an aryl halide. 1,2,4 Recently, the use of blue light in conjunction with palladium catalysis has offered a convenient route to access excited-state palladium species. 5−10 Unlike their thermal counterparts, photochemical reactions involving excited-state Pd(0) are typically thought to involve tandem palladium/radical intermediates. These reactions can mimic the reactivity of ground state palladium species, via a single electron mechanism in domino reactions. 6,8,10−13 Though the presence of radical intermediates has been well established, 5,6,14 a mechanism involving both discrete Pd(II) intermediates and alkyl radical/Pd(I) species has not been broadly explored.Thermally initiated carboiodination reactions typically employ a palladium catalyst bearing bulky electron-rich phosphines, or a nickel catalyst and a PPh 3 , P(OR) 3 or an N,N-ligand. 1,15−20 These reaction mechanism initiate via an oxidative addition to the C−I bond, followed by a migratory insertion across the π-system, and terminate with a ligandmediated 3-center 2-electron, 18 or an H-bonding initiated S N 2type reductive elimination. 21 The most successful conditions for the palladium carboiodination reactions utilize high temperatures and QPhos or t-Bu 3 P, costly and air-sensitive bulky phosphines (Scheme 1a). Often times, bulky 3°-amine

Flipping the Switch on Palladium-Catalyzed Carboiodination: Accessing Kinetic and Thermodynamic Products

“…The conditions we previously employed for Pd/blue light carboiodination worked, however in lower yield. 24 When the reaction was run with no light at 100 °C, we observed slight epimerization, in line with the thermal Pd-catalyzed carboiodination reactions reported by Tong in 2011. 27 Moreover, when subjecting the syn carboiodination product bearing an iodide on the exo face to UV light, which is wellestablished to induce C−I bond homolysis, we observed complete decomposition.…”

“…17−23 Recently, we disclosed a Pd/blue-light-catalyzed carboiodination reaction to form 1°alkyl iodide bonds (Scheme 1B). 24 Notably, under photoirradiation, we found the C−I bond formation step to be reversible through a one-electron process.…”

“…Upon addition of 12.5 mol % of the complex to the starting material, the desired product was formed in 40% yield after 24 h. To date, photoinduced C(sp 3 )−X reductive elimination from alkyl−Pd(II) complexes has been limited to C(sp 3 )−I bonds. To build on our previous work 24 as well as related studies from the Arndtsen group, 30,31 we explored the potential for a photoinduced reductive elimination of other C−X bonds, namely, C(sp 3 )−Br. Complex III was prepared by a modified procedure and subjected to the reaction conditions (See Supporting Information for details).…”

Pd-Catalyzed Photochemical Alkylative Functionalization of C═C and C═N Bonds

“…Based on the control experiments mentioned in Table , results from Figure , and literature reports, ,,, we propose a plausible mechanism outlined in Figure . The excited-state palladium catalyst interacts with the alkyl halide to generate the Pd­(I)/alkyl radical hybrid species which intercepts the π-bond of precursor 1a to result in the radical intermediate ii .…”

gem-Bromonitrocyclobutane induced radical cyclization of acrylanilides to construct 2-oxindolesviaphotoredox catalysis

“…Since 1988, 1 several strategies have been devised to construct 2-oxindoles from acrylanilide derivatives, which could be deemed as difunctionalizations of an activated CC double bond. Starting from 2-halo acrylanilide, an aryl radical 1,2 or a Pd 3 or Ni 4 complex was involved in the synthesis of 2-oxindoles (Scheme 1a). Starting from acrylanilide without a 2-functional group, Pd(OAc) 2 catalysed cyclizations were realized by Liu (Scheme 1b).…”