Heterogeneous catalysis reductive alkylation

Cobaloxime(I) generated by the electrochemical reductions of cobaloxime(III), the most simple model of vitamin Bi2, has been shown to catalyze radical cyclization of bromoacetals.307 Cobalt(I) species electrogenerated from [ConTPP] also catalyze the reductive cleavage of alkyl halides. This catalyst is much less stable than vitamin Bi2 derivatives.296 It has, however, been applied in the carboxylation of benzyl chloride and butyl halides with C02.308 Heterogeneous catalysis of organohalides reduction has also been studied at cobalt porphyrin-film modified electrodes,275,3 9-311 which have potential application in the electrochemical sensing of pollutants. 

In August 1973 it was decided to develop and establish a technical process for the production of tac-metolachlor. Two synthetic approaches were proposed and tested in the laboratotry (Figure 2) The alkylation of 2-methyl-6-ethyl-aniline (MEA) with methoxyisopropanol MOIP) and the reductive alkylation of MEA with methoxyacetone (MOA), followed by chloroacetylation. This was obviously a chance for heterogeneous catalysis. 

We have shown that heterogeneous catalysis can be applied to reductive alkylation with success in reactions such as ether synthesis or N-alkylation of amides and anilines. Concerning the mechanism, several pathways are in competition depending on the structure of the substrate and of the alkylating agent. The important point is that both the product of addition (the hemiacetal or hemiaminal) and the product of elimination (imine, enamine or enolether)... 

The mechanism of homogeneous catalysis invoives the same steps as heterogeneous catalysis. An initial tt complex is formed with the reactant. Metal-hydride bonds then react with the complexed alkene to form a C-H bond and a bond between the metal and alkyl group. There can be variation in the timing of formation of the M—H bonds. The metal carbon bond can be broken by either reductive elimination or protonolysis. Note that reductive elimination changes the metal oxidation state, whereas protonolysis does not. The catalytic cycle proceeds by addition of alkene and hydrogen. 

Polymer-bound ephedrine has interesting possibilities for heterogeneous catalysis. It has been used as a catalyst for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.) and for the enantioselective reduction of ketones to secondary alcohols16. 

Finally, actinide complexes such as [MCp 2R2] (M = Th or U, R = alkyl or H) are very active catalysts for the hydrogenation and polymerization of olefins. The complexes [U(allyl)3X] (X = Cl, Br, I) are excellent initiators for the stereospecific polymerization of butadiene, which produces rubbers that have remarkable mechanical properties. Some other complexes are active for the heterogeneous CO reduction and alkene metathesis. The field of catalysis using organoactinide complexes should considerably expand in the near future. 

Note at the outset that asymmetric catalysis in the synthesis of fine chemicals is rarely a single-step process that converts a reactant directly to the final product. It is usually one of the steps in a total synthesis but is often the key step. Hence the analysis of the overall yield will be based on the methods described in Chapter 5. There are many types of reactions where asymmetric catalysis can be applied. The most important of these are C-C bond-forming reactions such as alkylation or nucleophilic addition, oxidation, reduction, isomerization, Diels-Alder reaction, Michael addition, deracemization, and Sharpless expoxidation (of allyl alcohols). A few representative examples (homogeneous and heterogeneous) are given in Table 9.6. 

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