Significant Enhancement in the Efficiency and Selectivity of Iron‐Catalyzed Oxidative Cross‐Coupling of Phenols by Fluoroalcohols

Abstract

Significant enhancement of both the rate and the chemoselectivity of iron-catalyzedo xidative coupling of phenols can be achieved in fluorinated solvents,such as 1,1,1,3,3,3hexafluoropropan-2-ol (HFIP), 2,2,2-trifluoroethanol (TFE), and 1-phenyl-2,2,2-trifluoroethanol. The generality of this effect was examined for the cross-coupling of phenols with arenes and polycyclic aromatic hydrocarbons (PAHs) and of phenol with b-dicarbonyl compounds.T he new conditions were utilized in the synthesis of 2'''-dehydroxycalodenin Bi n only four synthetic steps.

Organo‐Iodine(III)‐Catalyzed Oxidative Phenol–Arene and Phenol–Phenol Cross‐Coupling Reaction

“…[7] This reaction is ac hallenge because,w hen simple phenols are employed in oxidative cross-couplings,the desired products are often concomitantly formed along with homocoupling by-products.M oreover,t he formation of higher-molecular-weight polymers or C,O-connected phenol portions,for example,quinol ethers,might also occur depending on the oxidant and the reaction conditions. [9] While recent metal-catalyzed cross-couplings of phenols have been studied, the organocatalytic cross-coupling reaction still remains particularly challenging.R ecently,w e developed the oxidative cross-coupling reaction of aromatic compounds using hypervalent iodine reagents. [8] Very recently,the iron-catalyzed oxidative crosscoupling reaction of phenols with arenes was successfully achieved.…”

Catalytic Aerobic Phenol Homo‐ and Cross‐Coupling Reactions with Copper Complexes Bearing Redox‐Active Guanidine Ligands

“…The higherc ross-coupling selectivity obtained with this solvent, which is widely applied in phenol cross-coupling reactions, is due to three effects:1 )according to the large difference in solvation of the coupling partners, the "global nucleophilicity"( N)a nd the oxidation potential are differently affected, favoring the radical-anion coupling mechanism, [22,57,58] 2) displacement of the phenol with lower oxidation potential from the metal atom, [31] 3) decrease of the reaction rate for radicalf ormation, leadingt oah igher preference for ar adicalanion coupling mechanism by inhibition of the radical-radical coupling pathway. [26,59] With 1mol %o f[ 1(CuBr) 2 ]i nd ichloromethane, complete conversiono ft he startingm aterials required less than 2h (Table 3, entry 4).…”

“…[33] Experimentsi nw hichr adical scavengersw ere added in the phenol coupling reactions are inconsistent with the involvemento ff ree radicals in the catalytic cycle. According to the pK a values, triethylamine (pK a = 10.74 in H 2 O) [62] can only deprotonate 2,6-dimethoxyphenol (pK a = 9.98 in H 2 O), [62] whereas tetramethylguanidine (pK a = 13.6 in H 2 O) [63] is also able to deprotonatet he less acidic 2,6-di-tertbutylphenol (pK a = 11.7 in H 2 O), [58] in line with the CV studies with base addition (see Supporting Information). Therefore, the phenoxyl radical formed upon phenol deprotonation and oxidation has to be bound to the copper catalyst.…”

Organo‐Iodine(III)‐Catalyzed Oxidative Phenol–Arene and Phenol–Phenol Cross‐Coupling Reaction

“…Pappo and co-workers had shown that the iron catalyst was efficient for the oxidative cross-coupling reaction of phenols, [9] but in their cases,t his procedure gave the coupling product 3aa in alow yield and the coupling product 3abwas not observed for the combination of the substrates 1a and 2b (Scheme 2).…”