Transition metal-free reaction

A water-mediated, transition metal free reaction ... 

Provided it works (which is not always the case), this transition-metal-free reaction may be viewed as a greener alternative to traditional metal-catalyzed cyclopropanation protocols. 

Can a transition-metal-free reaction even be labeled as C—H activation Some chemists have argued that true C—H activation requires oxidative addition or other metal C—H bond insertion step therefore, some radical-mediated C—H bond activation reactions might be better classified as homoly tic aromatic substitution (HAS), the radical variant of the better known electrophilic aromatic substitution (EAS). ... 

Further complicating the development of new transition-metal-free reactions, subsequent investigations sometimes show advantageous metal contamination, even at parts per billion level, is truly responsible for the reactivity being described. The burden of proof is clearly on the corresponding authors to ensure the absence of trace transition-metal in the systan. - ... 

The iodine-catalyzed addition of carboxylic acids to styrene derivatives generated high yields of esters and related compounds (Scheme 2.17) [24], This transition metal-free reaction used TBHP as the oxidant and was carried out under very mild conditions using an assortment of alkenes and carboxylic acids as substrates. The chemistry was quite tolerant of preexisting functional groups, and even aryl bromides were retained through the oxidation process. In addition to the styrene derivatives, aliphatic alkenes such as 1-octene were also successfully converted into esters using this approach. 

The P-arylation of arynes is an interesting approach to the synthesis of arylphosphine oxides since it is typically a transition metal-free reaction that occurs at low temperatures (Scheme 4.193) [332]. In contrast to classic metal-mediated Arbuzov-type reactions between phosphinites and aryl halides that required high temperatures (150-2(X) °C), this... 

This transition metal-free reaction is typically high yielding. Bromination was promoted by the chloramine-T along with a nucleophilic hromine source [129], while chlorination used TCCA [128]... 

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

There are also useful synthetic procedures in which organotin compounds act as carbanion donors in transition metal-catalyzed reactions, as discussed in Section 8.2.33. Organotin compounds are also very important in free radical reactions, as is discussed in Chapter 10. 

A potentially interesting development is the microwave-assisted transition-metal-free Sonogashira-type coupling reaction (Eq. 4.10). The reactions were performed in water without the use of copper(I) or a transition metal-phosphine complex. A variety of different aryl and hetero-aryl halides were reactive in water.25a The amount of palladium or copper present in the reaction system was determined to be less than 1 ppm by AAS-MS technique. However, in view of the recent reassessment of a similarly claimed transition-metal-free Suzuki-type coupling reaction, the possibility of a sub-ppm level of palladium contaminants found in commercially available sodium carbonate needs to be ruled out by a more sensitive analytical method.25 ... 

The number of molecules with single electron orbitals, and therefore suitable for ESR, is limited due to the electron-sharing feature of the usual covalent bond. This tends to restrict its use to compounds containing transition metals and reactions involving free radicals. However, this does make ESR very useful for monitoring reactions involving metallo-enzymes or free radicals. 

Yonker, C. R. and Linehan, J. C., A high-pressure NMR investigation of reaction chemistries in a simple salt hydrate,. Supercrit. Fluids, 29, 257 2004. Mehnert, C. R, Supported ionic liquid catalysis, Chem. Eur. ]., 11,50,2005. Giernoth, R. and Bankmann, D., Transition-metal free synthesis of perdeuter-ated imidazolium ionic liquidsby alkylation and H/D exchange, Eur. J. Org. Chem., 2008 (in print). DOT 10.1002/ejoc.200700784. 

Transition-metal-free cross-coupling reactions. 556... 

THEMES Free Radical-Mediated Reactions Lewis Acid, Transition Metal-Mediated Reactions... 

Leadbeater, N.E. and Marco, M., Transition-metal-free Suzuki-type coupling reactions, Angew. Chem., Int. Ed. Engl, 2003,115, 1445-1447. 

As mentioned previously, the role of the metal is not specific. Even transition metal free layered double hydroxides are suitable catalysts for the olefin epoxidation with O2 and a sacrificial aldehyde (205). Leaching of the metal from the solid catalyst is a serious problem since organic acids that are potential metal ligands accumulate during the reaction. Leaching occurs, for example, with the polybenzimidazole-supported Ni2+ catalyst (199). 

The electron-releasing phosphine promotes oxidative addition of the bromo derivative to Pd(0) and, because of its bulkiness, readily generates free coordination sites by dissociation. Ethylene coordination and insertion then occur, followed by reductive elimination, triethylamine acting as a base to neutralize hydrogen bromide. As in most cases of transition metal-catalyzed reactions the fine details of the mechanism are still under investigation. Thus recent studies by Amatore s group suggest that the palladium(O) species formed by reduction of palladium acetate is an anionic acetato complex. 

The diazonium group can be replaced by a number of groups. " Some of these are nucleophilic substitutions, with S l mechanisms (p. 432), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has been shown that the Sj-jl mechanism is favored by solvents of low nucleophilicity, while those of high nucleophilicity favor free-radical mechanisms. The N2 group can be replaced by CP, Br, and CN, by a nucleophilic mechanism (see OS IV, 182), but the Sandmeyer reaction is much more useful (14-20). Transition metal catalyzed reactions are known involving aryl-diazonium salts, and diazonium variants of the Heck reaction (13-10) and Suzuki coupling (13-12) were discussed previously. As mentioned on p. 866 it must be... 

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