Carbon=oxygen double bonds, addition reactions

Although the high reactivity of metal-chalcogen double bonds of isolated heavy ketones is somewhat suppressed by the steric protecting groups, Tbt-substituted heavy ketones allow the examination of their intermolecular reactions with relatively small substrates. The most important feature in the reactivity of a carbonyl functionality is reversibility in reactions across its carbon-oxygen double bond (addition-elimination mechanism via a tetracoordinate intermediate) as is observed, for example, in reactions with water and alcohols. The energetic basis... 

By now, you may be getting the impression that almost any nucleophile will add to carbonyl compounds. If so, you are quite right. So far, we have seen water, cyanide, bisulfite, and alcohols act as nucleophiles toward the Lewis acidic carbon of the carbon-oxygen double bond. Addition can take place under neutral, acidic, or basic conditions. All of the addition reactions are similar, with only the details being different. Those details are important though, as well as highly effective at camouflaging the essential similarity of the reactions. We ll now see some examples of acetal chemistry. 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the carbon-oxygen double bond of aldehydes and ketones Strongly basic nucleophiles such as Gngnard reagents however do react with nitriles in a reaction that IS of synthetic value... 

The most common reaction of aldehydes and ketones is the nucleophilic addition reaction, in which a nucleophile, Nu , adds to the electrophilic carbon of the carbonyl group. Since the nucleophile uses an electron pair to form a new bond to carbon, two electrons from the carbon-oxygen double bond must move toward the electronegative oxygen atom to give an alkoxide anion. The carbonyl carbon rehybridizes from sp2 to sp3 during the reaction, and the alkoxide ion product therefore has tetrahedral geometry. 

No rate enhancement of the enantioselective hydrogenation pathway is expected, in the manner adduced for the Pt-catalysed reaction, because the process is not one of simple H-atom addition across a carbon-oxygen double bond. 

Certain electrophilic carbon-carbon and carbon-oxygen double bonds can undergo an addition reaction with alkenes in which an allylic hydrogen is transferred to the... 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

The relationship between the molecular formula of acrolein (C3H40) and the product (C3H5N30) corresponds to the addition of HN3 to acrolein. Because propanal (CH3CH2CH=0) does not react under these conditions, the carbon-carbon, not the carbon-oxygen, double bond of acrolein is the reactive site. Conjugate addition is the reaction that occurs. 

The main reactions of the carbonyl group are nucleophilic additions to the carbon-oxygen double bond. As shown below, this addition consists of adding a nucleophile and a hydrogen across the carbon-oxygen double bond. 

The ene reaction,3 6360-365 the addition of a carbon-carbon or carbon-oxygen double bond with concomitant transfer of an allylic hydrogen, can allow for chirality transfer.366-369 The reaction has similarities to the Diels-Alder reaction in that a o-bond is formed at the expense of a 7t-bond. In addition, the use of a Lewis acid as a catalyst allows for control of the relative stereochemistry (Scheme 26.14).370-372 Large-scale reactions will be complicated by the need to use either high temperatures or Lewis acids. In addition, thermal and Friedel-Crafts-type degradation products may be problematic with the use of these conditions.361373... 

A reaction of an achiral molecule may introduce a chirality center, producing a chiral product. For example, reaction of the following ketone with hydrogen in the presence of a catalyst results in addition of the hydrogen to the carbon-oxygen double bond, producing 2-butanol ... 

When the catalytic hydrogenation reaction is run under relatively mild conditions (room temperature and a pressure of hydrogen gas of several atmospheres or less), the reaction is very selective. Carbon-carbon double bonds of alkenes and carbon-carbon triple bonds of alkynes react readily, whereas carbon-carbon double bonds of aromatic rings and carbon-oxygen double bonds are usually inert under these reaction conditions. Some examples are provided in the following equations. Note that the stereochemistry of the addition reaction makes no difference in the first two examples. In the last example the major product results from syn addition. 

In Chapter 6, elimination reactions were presented. In the context of elimination reactions, the formation of double bonds was noted regardless of the elimination mechanism discussed. Continuing from the concept of using elimination reactions to form sites of unsaturation, one may reason that addition reactions can be used to remove sites of unsaturation. Thus, elaborating upon addition reactions, this chapter provides an introduction to relevant mechanisms applied to both carbon-carbon double bonds (olefins) and carbon-oxygen double bonds (carbonyls). 

Active Substrate. If a new chiral center is created in a molecule that is already optically active, the two diastereomers are not (except fortuitously) formed in equal amounts. The reason is that the direction of attack by the reagent is determined by the groups already there. For certain additions to the carbon-oxygen double bond of ketones containing an asymmetric a carbon. Cram s rule predicts which of two diastereomers will predominate (diastereoselectivity). The reaction of 46, which has a stereogenic center at the ot-carbon, and HCN can generate two possible diastereomers. 

The emphasis of this chapter will be on the mechanistic aspects of the ( normal ) addition reaction of Grignard reagents to the carbon-oxygen double bond, as is found for ketones. However, it will become clear that for reactions with other substrates, the general mechanistic aspects of these carbonyl addition reactions are also applicable. 

The formal addition of an oxygen atom across the carbonyl group gives rise to dioxiranes (equation 33). In practice, this reaction is effected with Oxone, and dimethyldioxirane (30) and other dioxiranes have been generated in solutions of their parent ketones.Dioxirane (30) has been implicated in oxidations of alkenes, sulfides and iinines. The formal addition of nitrogen across a carbon-oxygen double bond to afford oxaziridines has been reviewed (equation 34).There are also many methods available for the indirect conversion of carbonyl compounds to aziridines > and thiiranes using multi-step conversions. 

As we saw in Part III of A Preview of Carbonyl Compounds, the most gejb eral reaction of aldehydes and ketones is the nucleophilic addition reaction. A nucleophile, Nu , attacks the electrophilic C=0 carbon atom from a direction approximately 45 to the plane of the carbonyl group. At the same time, rehybridization of the carbonyl carbon from sp to sp occurs, an electron pair from the carbon-oxygen double bond moves toward the electronegative oxygen atom, and a tetrahedral alkoxide ion intermediate is produced (Figure 19.1). 

The two types of sulfur ylides also differ in their reactions with a,p-unsaturated carbonyl compounds. The highly reactive sulfonium ylides react rapidly by 1,2-addition across the carbon-oxygen double bond to yield the epoxides. On the other hand, the less reactive sulfoxonium ylides react by slower conjugate addition (1,4-addition) to give substituted ketocyclopropanes. Thus, dimethylsulfonium methylide (21) reacts rapidly with benzylideneacetophenone (chalcone) (37)... 

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