Cross‐Coupling Reaction of Dimer‐Derived Persistent Tertiary‐Carbon‐Centered Radicals with Azo Compounds

Abstract

Cross-coupling reactions using tertiary carboncentered radicals are an important class of transformations for constructing C(sp 3 )À C(sp 3 ) bonds, but the use of dimers as precursors of the persistent radicals is quite rare. Herein, we describe a radical-based cross-coupling reaction between dimers (prepared from 2-oxindoles and benzofuranones) and azo compounds that proceeds simply upon heating the reaction mixture. We present a conformational analysis of the dimers and we characterize the generation of a persistent radical via cleavage of the elongated C(3)À C(3') σ-bond. The behavior of the dimers in solution was characterized by spectroscopic analysis, helping to provide a basis for expanding the substrate scope of the cross-coupling reaction.

Formal Aerobic Oxidative Cross-Coupling of Benzofuranones with Azo Compounds Using Pd-μ-hydroxo Complex

“…to 1) in toluene after replacing O 2 with Ar, according to a previously developed procedure. 8,9) As we expected, upon heating the reaction mixture to 100°C, we obtained the cross-coupling adducts 5 in reasonable yields. Benzofuranones 1a, 1b and 1c are efficiently transformed to the corresponding cross-coupling adducts (5aa: 69%, 5ba: 64%, 5ca: 52%) with the use of AIBN (3a: azobisisobutyronitrile) 32) as a precursor of the transient radical.…”

“…[12][13][14] We initiated this study with use of racemic Pd complex I as a catalyst for the proposed aerobic dimerization of 1 because the C(sp 3 )-C(sp 3 ) bond in 2 is readily cleavable even at room temperature, providing thermodynamically stable meso-2, rather than dl-2, as the major product. 8) We found that the use of CH 3 CN as the solvent is critical to obtain a high yield of meso-2a (Table 1, entry 1 vs. entry 2). When we examined the reaction of 1a in the presence of Pd complex I (5 mol%) under an oxygen atmosphere in tetrahydrofuran (THF), which is a standard solvent for acid-base catalysis with I, 21) benzofuranone 1a was recovered in 94% yield (Table 1, entry 1).…”

“…6) We recently reported the development of a radical-radical cross-coupling between the persistent (long-lived) radical 1 •7) and the transient (short-lived) radical 4 • , affording 5 with two contiguous all-carbon centers. 8,9) The persistent radical 1 • is readily generated from 2, which contains an elongated C(sp 3 )-C(sp 3 ) bond, simply by heating without the assistance of redox-active transition metals. [8][9][10][11][12][13][14][15][16] However, the requisite dimers 2 were synthesized from the corresponding monomers 1 using a stoichiometric amount of K 3 [Fe(CN) 6 ] as an oxidant under basic conditions at 80°C according to the literature procedure.…”

“…8,9) The persistent radical 1 • is readily generated from 2, which contains an elongated C(sp 3 )-C(sp 3 ) bond, simply by heating without the assistance of redox-active transition metals. [8][9][10][11][12][13][14][15][16] However, the requisite dimers 2 were synthesized from the corresponding monomers 1 using a stoichiometric amount of K 3 [Fe(CN) 6 ] as an oxidant under basic conditions at 80°C according to the literature procedure. [16][17][18][19] In this Note, we describe a mild protocol for aerobic oxidative dimerization of 1 to provide the dimers 2 by using Pd-µ-hydroxo complex I, previously employed as an acid-base catalyst 20,21) (Chart 1, i).…”

Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’‐Reductases with Photoredox Catalysts

“…These bond strengths infer radical intermediates that are dynamically stable causing them to display reactivity profiles consistent with persistent radicals . This family of radical intermediates tends to be less reactive by comparison to short‐lived transient radicals . We hypothesize that radicals formed in this reaction display low reactivity, prolonging their lifetimes thus enabling them to potentially diffuse into the enzyme active site for radical termination by flavin if they are initially formed in solution.…”