Copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of environmentally benign ascorbic acid as a reducing agent

Abstract

In recent years, copper-catalyzed atom transfer radical addition (ATRA) has emerged as a viable organic procedure for the formation of carbon-carbon bonds starting from alkyl halides and alkenes. Studies have primarily focused on the use of free-radical initiators to regenerate the copper(I) complex or activator in situ. Although these initiators led to a significant decrease in the amount of metal catalyst, they were much less effective for highly active alkenes that readily undergo free-radical polymerization. In this study, the non-radical reducing agent ascorbic acid (commonly known as Vitamin C) was effectively employed resulting in TONs as high as 15,200 in the homogenous ATRA of polyhalogenated compounds to α-olefins, and enabling selective monoadduct formation for highly active alkenes such as acrylonitrile (TONs as high as 11,800). As low as 7-20 mol% of ascorbic acid relative to substrate was sufficient for all ATRA and ATRC reactions examined. Further, product isolations for all selected syntheses were quite facile and nearly quantitative, requiring only simple liquid-liquid extraction techniques. Reactions in the presence of ascorbic acid were also examined kinetically via (1)H NMR and UV/Vis spectroscopy. A half order rate dependence on reducing agent concentration was observed, but the first order kinetic plots became nonlinear as the concentration of ascorbic acid was increased. Finally, the use of ascorbic acid circumvented otherwise necessary purging techniques, successfully furthering the utility of these reactions in organic synthesis.

Trifluoroethoxy‐Coated Subphthalocyanine affects Trifluoromethylation of Alkenes and Alkynes even under Low‐Energy Red‐Light Irradiation

“…We first investigated the trifluoromethylation of hex‐5‐en‐1‐ol ( 3 a ) with CF 3 I by using various photocatalysts under red‐light irradiation (Table ). Following an earlier report by Stephenson and co‐workers, a catalytic amount of sodium l ‐ascorbate (35 mol %) was used as the initial reductant in a MeCN/MeOH system . Apparently, in the red‐light‐driven system, powerful photocatalysts such as [Ru(bpy) 3 ](PF 6 ) 2 , eosin Y, and methylene blue were completely useless (runs 1–3).…”

“…Earlier reports of CF 3 ‐I ATRA reactions have shown that the reaction is based on an effective radical chain reaction that can be initiated through visible‐light irradiation even without photocatalysts; however, our system requires both photocatalyst 2 a (run 15, Table ) and light (run 17, Table ). Thus, in the initial step, photo‐excited trifluoroethoxy subphthalocyanine 2 a receives one electron from sodium ascorbate to form an anion radical of 2 a . The anion radical [ E o ′( 2 a / 2 a ⋅− )=−0.69 V vs. SCE] should reduce CF 3 I ( E o ′=−1.22 V vs. SCE) to generate the CF 3 radical (⋅CF 3 ) (Scheme S3).…”

Atom Transfer Radical Reactions as a Tool for Olefin Functionalization – On the Way to Practical Applications

“…[21] The main disadvantage of this strategy is that AIBN or V-70 also promote the generation of free radicals, which function as efficient chain-transfer agents, in the case of the more reactive monomers such as styrene, methyl acrylate, or methyl methacrylate. Recently, they have demonstrated the efficacy and versatility of ascorbic acid as a reducing agent (Scheme 7) in copper-catalyzed ATRA reactions: [22] the addition of 7-20 mol% of ascorbic acid relative to alkene, the selective formation of the monoadduct with a catalyst loading of as as low as 5 x 10 -3 mol% was observed.…”

Towards the development of highly active copper catalysts for atom transfer radical addition (ATRA) and polymerization (ATRP)‡

“…Structural modifications of the most active TPMA and Me 6 TREN ligands , 2010Eckenhoff et al, 2008Eckenhoff et al, , 2012Eckenhoff & Pintauer, 2007, 2010a, 2010bTaylor et al, 2010) in copper catalyzed atom transfer radical addition and cyclization that employ reducing agents is perhaps the best approach towards the development of highly active complexes for activation of monohalogenated substrates. One way to decrease the reduction potential of copper(II) complexes is the systematic incorporation of electron donating groups (EDGs) to both ligands.…”