Copper-catalyzed halide exchange reactions under very mild reaction conditions are described for the first time using a family of model aryl halide substrates. All combinations of halide exchange (I, Br, Cl, F) are observed using catalytic amounts of Cu(I). Strikingly, quantitative fluorination of aryl-X substrates is also achieved catalytically at room temperature, using common F(-) sources, via the intermediacy of aryl-Cu(III)-X species. Experimental and computational data support a redox Cu(I)/Cu(III) catalytic cycle involving aryl-X oxidative addition at the Cu(I) center, followed by halide exchange and reductive elimination steps. Additionally, defluorination of the aryl-F model system can be also achieved with Cu(I) at room temperature operating under a Cu(I)/Cu(III) redox pair.

Bulky iron complexes are described that catalyze the site-selective oxidation of alkyl C-H bonds with hydrogen peroxide under mild conditions. Steric bulk at the iron center is introduced by appending trialkylsilyl groups at the meta-position of the pyridines in tetradentate aminopyridine ligands, and this effect translates into high product yields, an enhanced preferential oxidation of secondary over tertiary C-H bonds, and the ability to perform site-selective oxidation of methylenic sites in terpenoid and steroidal substrates. Unprecedented site selective oxidation at C6 and C12 methylenic sites in steroidal substrates is shown to be governed by the chirality of the catalysts.

A well-defined macrocyclic aryl–Cu(III) complex (2) reacts readily with a variety of oxygen nucleophiles, including carboxylic acids, phenols and alcohols, under mild conditions to form the corresponding aryl esters, biaryl ethers and alkyl aryl ethers. The relationship between these reactions and catalytic C-O coupling methods is demonstrated by the reaction of the macrocyclic aryl–Br species with acetic acid and p-fluorophenol in the presence of 10 mol% Cu(I). An aryl-Cu(III)-Br species 2(Br) was observed as an intermediate in the catalytic reaction. Investigation of the stoichiometric C-O bond-forming reactions revealed nucleophile-dependent changes in the mechanism. The reaction of 2 with carboxylic acids revealed a positive correlation between the log(k(obs)) and the pK(a) of the nucleophile (less-acidic nucleophiles react more rapidly), whereas a negative correlation was observed with most phenols (more-acidic phenols react more rapidly). The latter trend resembles previous observations with nitrogen nucleophiles. With carboxylic acids and acidic phenols, UV-visible spectroscopic data support the formation of a ground-state adduct between 2 and the oxygen nucleophile. Collectively, kinetic and spectroscopic data support a unified mechanism for aryl-O coupling from the Cu(III) complex, consisting of nucleophile coordination to the Cu(III) center, deprotonation of the coordinated nucleophile, and C-O (or C-N) reductive elimination from Cu(III).

Selective oxidation of alkyl C-H groups constitutes one of the highest challenges in organic synthesis. In this work, we show that mononuclear iron coordination complexes Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H(2)O(2) as terminal oxidant. These complexes are based on tetradentate N-based ligands and contain iron centers embedded in highly structured coordination sites defined by two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand backbone, and chirality at the metal (Λ or Δ). X-ray diffraction analysis shows that in Λ-1P and Λ-2P the pinene rings create cavity-like structures that isolate the iron site. The efficiency and regioselectivity in catalytic C-H oxidation reactions of these structurally rich complexes has been compared with those of Λ-[Fe(CF(3)SO(3))(2)((S,S)-MCP)] (Λ-1), Λ-[Fe(CF(3)SO(3))(2)((S,S)-BPBP)] (Λ-2), Δ-[Fe(CF(3)SO(3))(2)((R,R)-BPBP)] (Δ-2), Λ-[Fe(CH(3)CN)(2)((S,S)-BPBP)](SbF(6))(2) (Λ-2SbF(6)), and Δ-[Fe(CH(3)CN)(2)((R,R)-BPBP)](SbF(6))(2) (Δ-2SbF(6)), which lack the steric bulk introduced by the pinene rings. Cavity-containing complexes Λ-1P and Λ-2P exhibit enhanced activity in comparison with Δ-1P, Δ-2P, Λ-1, Λ-2, and Λ-2SbF(6). The regioselectivity exhibited by catalysts Λ-1P, Λ-2P, Δ-1P, and Δ-2P in the C-H oxidation of simple organic molecules can be predicted on the basis of the innate properties of the distinct C-H groups of the substrate. However, in specific complex organic molecules where oxidation of multiple C-H sites is competitive, the highly elaborate structure of the catalysts allows modulation of C-H regioselectivity between the oxidation of tertiary and secondary C-H groups and also among multiple methylene sites, providing oxidation products in synthetically valuable yields. These selectivities complement those accomplished with structurally simpler oxidants, including non-heme iron catalysts Λ-2 and Λ-2SbF(6).

The efficient and selective oxidation of secondary C À H sites of alkanes is achieved by using low catalyst loadings of a non-expensive, readily available iron catalyst [Fe(II)-trans-1,2-diamine]}, and hydrogen peroxide (H 2 O 2 ) as oxidant, via a simple reaction protocol. Natural products are selectively oxidized and isolated in synthetically amenable yields. The easy access to large quantities of the catalyst and the simplicity of the C À H oxidation procedure make this system a particularly convenient tool to carry out alkane C À H oxidation reactions on the preparative scale, and in short reaction times.