Iron catalysis nucleophilic

Magens S, Plietker B (2010) Nucleophilic iron catalysis in transesterifications scope and limitations. J Org Cbem 75 3715-3721... 

Nitrogen-directed C—H activation to form C—C bonds like aryl-aryl is a relatively recent class of reactions. In 2008, Nakamura and coworkers presented the first report of an iron-catalyzed C—H arylation reaction—a homogeneous iron catalysis featuring C—C bond formation via C—H activation. As an overall synthetic transformation, it was a formal nucleophilic displacement of the ort/ o-hydrogen atom by... 

Cationic cyclopentadienyliron dicarbonyl (Fp) alkene complexes are generally reactive towards a wide variety of nucleophiles, including nitrogen nucleophiles, but they too generate stable chemical step (usually oxidation). This makes catalysis impossible and severely limits application of this methodology to organic synthesis (equation 21 ).36 However, in contrast to palladium, iron is relatively inexpensive and stoichiometric procedures... 

Recently, Taillefer et al. reported an Fe/Cu cooperative catalysis in the assembly of N-aryl heterocycles by C—N bond formation [90]. Similarly, Wakharkar and coworkers described the N-arylation of various amines with aryl halides in the presence of Cu—Fe hydrotalcite [91]. Interestingly, Correa and Bolm developed a novel and promising ligand-assisted iron-catalyzed N-arylation of nitrogen nucleophiles without any Cu co-catalysts (Scheme 6.19) [92]. Differently substituted aryl iodides and bromides react with various amides and N-heterocycles. The new catalyst system consists of a mixture of inexpensive FeCl3 and N,N -dimethylethylenediamine (dmeda). Clearly, this research established a useful starting point for numerous future applications of iron-catalyzed arylation reactions. 

Bauld and coworkers studied the [2+2] cycloaddition of A-vinyl carbazoles 86a and electron-rich styrenes 86b catalyzed by iron(III) catalysts A or B in the presence of 2,2 -bipyridine as a ligand, which was reported originally by Ledwith and coworkers (Fig. 21) [142, 143]. Deuterium-labeling studies provided support for the stepwise nature of the process, consisting of reversible SET oxidation of the electron-rich olefin to a radical cation 86 A. Nucleophilic addition of excess 86 leads to distonic radical cation 86B, which cyclizes to cyclobutane radical cation 86C. Back electron transfer affords cyclobutanes 87 and regenerates the catalyst. Photoelectron transfer catalysis gave essentially the same result, thus supporting the pathway. 

Two systems have been developed to the level of useful organic synthesis methodology spontaneous coordination of the alkene to Pd and the preparation of discrete Cp(CO)2Fe-alkene cationic complexes. With the Pd system, efficient catalytic processes have been developed for the addition of heteroatom nucleophiles, while the coupling with carbon nucleophiles is mainly relegated to stoichiometric reactions these two topics will be presented separately. In the iron series, the reactions involve stable intermediates and are invariably not amenable to catalysis. 

The catalytic mechanism for IDO and TDO is believed to proceed via the formation of a hydroperoxide at C-3 of the indole ring, followed either by dioxetane formation or Criegee rearrangement, as shown in Figure 26. Formation of the hydroperoxide could either take place via nucleophilic attack upon heme-bound dioxygen, or via the formation of an indole radical, followed by recombination with iron(III)-superoxide. The structure of human IDO was published in 2006. Site-directed mutagenesis of active site residues has established that Phe-226, Phe-227, and Arg-231 contribute toward catalysis. ... 

The use of a mixed-valent, dinuclear iron site, similar to those in hemerythrin and ribonucleotide reductase,to catalyze a nonredox reaction such as phosphate ester hydrolysis is novel and unexpected for a variant of the familiar oxo(hydroxo)-bridged diiron center. In contrast to the general agreement that exists regarding the spectroscopic and physical properties of the PAPs, their kinetics properties and especially their mechanism of action remain controversial. Much of the disagreement stems from the different pH dependences of the catalytic activity of BSPAP and Uf, which is due to the fact that the former is isolated in a proteolytically activated form while the latter is not. Proteolysis results in a substantial increase in optimal pH in addition to an increase in catalytic activity at the optimal pH. "" Current data suggest that many of the spectroscopic studies described in the literature were performed on a catalytically inactive form of the enzyme. As a result, the roles of the trivalent and divalent metal ions in catalysis and in particular the identity of the nucleophilic hydroxide that directly attacks the phosphate ester remain unresolved. 

The 1,3-dicarbonyl unit has been shown to be an excellent leaving group in 5 1 reactions catalysed by FeCl3. °" The catalysis is thought to occur when the iron coordinates with the two carbonyl oxygens before the ionization step. These reactions proceed via either a free carbenium ion or a carbenium ion-pair intermediate, which is consumed in a second reaction with a nucleophile such as C(3) of 5-bromoindole. Yields of these alkylation reaetions range from 73 to 99%. 

---