Carbonyl Transfer Reactions

Steps 2 and 4 are proton transfer reactions and are very fast Nucleophilic addi tion to the carbonyl group has a higher activation energy than dissociation of the tetra hedral intermediate step 1 is rate determining... 

Naphthaleneacetic acid has also been prepared by the carbonyl-insertion reaction of 1-chloromethylnaphthalene cataly2ed by carbonyl cobalt cation (90,91). Carboxylation of 1-chloromethylnaphthalene in the presence of the catalyst Pd[P(CgH )2]2Cl2 under phase-transfer conditions gave 1-naphthaleneacetic acid in 78% yield (92). 

L = P(CH3)3 or CO, oxidatively add arene and alkane carbon—hydrogen bonds (181,182). Catalytic dehydrogenation of alkanes (183) and carbonylation of bensene (184) has also been observed. Iridium compounds have also been shown to catalyse hydrogenation (185) and isomerisation of unsaturated alkanes (186), hydrogen-transfer reactions, and enantioselective hydrogenation of ketones (187) and imines (188). 

Three-dimensional potential energy diagrams of the type discussed in connection with the variable E2 transition state theory for elimination reactions can be used to consider structural effects on the reactivity of carbonyl compounds and the tetrahedral intermediates involved in carbonyl-group reactions. Many of these reactions involve the formation or breaking of two separate bonds. This is the case in the first stage of acetal hydrolysis, which involves both a proton transfer and breaking of a C—O bond. The overall reaction might take place in several ways. There are two mechanistic extremes ... 

Ester hydrolysis can also be promoted by nucleophilic catalysis. If a component of the reaction system is a more effective nucleophile toward the carbonyl group than hydroxide ion or water under a given set of conditions, an acyl-transfer reaction can take place to form an intermediate ... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

The Clemmensen reduction can be formulated to proceed by a sequence of one-electron and proton transfer reactions. It is a heterogenous reaction, taking place at the zinc surface. Initially an electron is transferred from zinc to the carbonyl group of ketone 1, leading to a radical species 3, which is presumed to react further to a zinc-carbenoid species 4 ... 

The mechanism of the C02 transfer reaction with acetyl CoA to give mal-onyl CoA is thought to involve C02 as the reactive species. One proposal is that loss of C02 is favored by hydrogen-bond formation between the A -carboxy-biotin carbonyl group and a nearby acidic site in the enzyme. Simultaneous deprotonation of acetyl CoA by a basic site in the enzyme gives a thioester eno-late ion that can react with C02 as it is formed (Figure 29.6). 

Lewis acid catalyzed carbonyl addition reactions of nonracemic chiral allylsilanes34 were shown to proceed with anti-S E attack, thus also enabling 1,3-chirality transfer in an opposite direction (Section D.l. 3.3.3.5.2.3.). 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

This proton transfer reaction is not fast, and it is suggested that this may be a more complicated reaction than was anticipated, perhaps occurring by initial addition of OH or OR to the metal followed by H2O or ROH expulsion. In support of this is the isolation of a complex Os(CO)-(CNC6H4CH3)(PPh3)2(H)OR from an analogous reaction sequence. (This is the only reference yet to any osmium carbonyl-isocyanide chemistry.)... 

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Another common hydrogen transfer reaction of carbonyl triplet is the photoenolization of the c-methylbenzoyl chromophore, illustrated in reaction 3 for the syn conformer of c-methylaceto-phenone (j+). Reaction 3 can act as a very efficient energy sink, and a number of properties of this group led us to believe that this process could be used to reduce photodegradation i.e. the excellent absorption characteristics of the chromophore, the short triplet lifetime and the fact that the disappearance of the carbonyl triplet does not take place at the expense of the formation of another excited state. 

In reaction (11) the metal-hydride addition suggests a protonation reaction whereas, in reaction (12) the addition appears to be a hydride transfer reaction. If the reaction is indeed a hydride transfer reaction then the introduction of p-electron donating substituents, which place more electron density at the carbonyl carbon, (the site of hydride attack) will inhibit hydride addition. The data in Table 2 show that the introduction of p-electron donating substituents reduces the turnover frequency. This is consistent with hydride attack at the benzaldehyde carbonyl carbon, (12). 

In carbonyl addition reactions, a commonly occurring and important mechanistic step is the transfer of a proton from one site to another in a reactive intermediate (proton switch). If the proton switch occurs sufficiently rapidly compared with the rate of collapse of the intermediate to reactants, the overall reaction may be facilitated by trapping of the unstable intermediate by the proton switch (Jencks, 1976). For example, in the formation of oximes from the reaction of benzaldehyde with O-methylhydroxylamine shown in (87H89) (Sayer and Jencks, 1973 Rosenberg et al., 1974), the first unstable intermediate (It) on the reaction pathway is converted by a proton switch (88) to the intermediate (I2) which has less tendency than It to... 

The asymmetric alkylation of a carbonyl group is one of the most commonly used chirality transfer reactions. The chirality of a substrate can be transferred to the newly formed asymmetric carbon atom through this process. In surveying chiral enolate systems as a class of nucleophile, three general subdivisions can be made in such asymmetric nucleophilic addition reactions intra-annular, extra-annular, and chelation enforced intra-annular. 

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