Catalysis in carbonyl substitution reactions

King, J. A., Jr. Nucleophilic versus general base catalysis in carbonyl substitution reactions the influence of acylpyridinium/acylammonium salt formation on the observed reaction rate. Trends in Organic Chemistry QQ7, 6, 67-89. 

In Chapter 12 pyridine was often used as a catalyst in carbonyl substitution reactions. It can act in two ways. In making esters from acid chlorides or anhydrides pyridine can act as a nucleophile as well as a convenient solvent. It is a better nucleophile than the alcohol and this nucleophilic catalysis is discussed in Chapter 12 (p. 282). But nonnucleophilic bases also catalyse these reactions. For example, acetate ion catalyses ester formation from acetic anhydride and alcohols. 

In Chapter 10 we used pyridine as a catalyst in carbonyl substitution reactions, even though it is only a weak base. Catalysis by pyridine involves two mechanisms, and is discussed on p. 200.Acetate ion is another weak base which can catalyse the formation of esters from anhydrides ... 

The general chemistry of acylpyridinium salts (181) and their role in the nucleophilic catalysis by pyridine of carbonyl substitution reactions have been reviewed and compared with the role of acylammonium salts (182). ... 

We now move to the key 2e ligand types, CO, phosphines, and N-heterocyclic carbenes. We see how one ligand replaces another in a substitution reaction, Eq. 4.1, specifically for the classic case of the substitution of CO groups in metal carbonyls by phosphines, PRj. Hie principles involved will appear again later, for example, in catalysis. 

Carbonyl reactions are extremely important in chemistry and biochemistry, yet they are often given short shrift in textbooks on physical organic chemistry, partly because the subject was historically developed by the study of nucleophilic substitution at saturated carbon, and partly because carbonyl reactions are often more difhcult to study. They are generally reversible under usual conditions and involve complicated multistep mechanisms and general acid/base catalysis. In thinking about carbonyl reactions, 1 find it helpful to consider the carbonyl group as a (very) stabilized carbenium ion, with an O substituent. Then one can immediately draw on everything one has learned about carbenium ion reactivity and see that the reactivity order for carbonyl compounds ... 

Base catalysis of ligand substitutional processes of metal carbonyl complexes in the presence of oxygen donor bases may be apportioned into two distinct classifications. The first category of reactions involves nucleophilic addition of oxygen bases at the carbon center in metal carbonyls with subsequent oxidation of CO to C02, eqns. 1 and 2 (l, 2). Secondly, there are... 

In the mid-1960s, Dessy and coworkers [12, 13] provided an extensive survey of the anodic and cathodic reactions of transition metal organometallic species, including binary (homoleptic) carbonyls, and this provided a stimulus for many later detailed studies. Whereas the electrochemistry of heteroleptic transition metal carbonyls is covered elsewhere in this volume, that of the binary carbonyls, which is covered here, provides paradigms for the electrochemistry of their substituted counterparts. A key aspect is the generation of reactive 17-electron or 19-electron intermediates that can play key roles in the electrocatalytic processes and electron-transfer catalysis of CO substitution by other ligands. 

In a number of classes of systems, the catalytic and other chemical effects of metal ions on reactions of organic and inorganic molecules are generally recognized the catalysis of nucleophilic reactions such as ester hydrolysis the reactions of alkenes and alkynes in the presence of metal carbonyls (8, 9, 69) stereospecific polymerization in the presence of Ziegler catalysts (20, 55, 56) the activation of such small molecules as H2 (37), 02 (13), H202 (13), and possibly N2 (58) and aromatic substitution reactions of metal-cyclopentadienyl compounds (59, 63). 

Another innovation in this text is the use of three-dimensional reaction coordinate diagrams, pioneered by Thornton, More O Ferrall, and Jencks, in the discussions of nucleophilic substitutions, eliminations, and acid catalysis of carbonyl additions. We hope that the examples may lead to more widespread use of these highly informative diagrams. 

There are a series of communications about the formation of dihydroazines by direct reaction of urea-like compounds with synthetic precursors of unsaturated carbonyls—ketones, containing an activated methyl or methylene group. The reaction products formed in this case are usually identical to the heterocycles obtained in reactions of the same binuclephiles with a,(3-unsatu-rated ketones. For example, interaction of 2 equiv of acetophenone 103 with urea under acidic catalysis yielded 6-methyl-4,6-diphenyl-2-oxi- 1,6-dihydro-pyrimidine 106 and two products of the self-condensation of acetophenone— dipnone 104 and 1,3,5-triphenylbenzene 105 [100] (Scheme 3.32). When urea was absent from the reaction mixture or substituted with 1,3-dimethylurea, the only isolated product was dipnon 104. In addition, ketone 104 and urea in a multicomponent reaction form the same pyrimidine derivative 106. All these facts suggest mechanism for the heterocyclization shown in Scheme 3.32. 

A variety of methods are available for the stereochemical construction of these optically active a-heteroatom-substituted carbonyl compounds, and in recent years a large number of new procedures have been developed applying asymmetric catalysis to carbonyl compounds, or their equivalents, as substrates [1]. The trick to these reactions is the direct C-H to C-Het transformation, as outlined in... 

The compound Rh4(CO)12 has a large number of applications. It is used in catalysis directly or as a catalyst precursor, and it is the starting material both for substitution reactions and for the synthesis of other rhodium carbonyl... 

Co2(CO)g has been used in numerous reactions in addition to the plethora of substitution reactions that it undergoes with phosphines, nitrosyls, alkynes, and so forth. Many of these substituted carbonyl complexes and their reactions have been discussed elsewhere in this report. One area in which Co2(CO)g has received much attention is catalysis two classes of catalytic reactions of which Co2(CO)g plays a major role are hydroformylation (see Hydroformylation) and Pauson Khand cycloaddition (see Pauson-Khand Reaction). 

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