Nucleophilic addition carbonyl groups

Various structural factors have been considered in interpreting this result The most generally satisfactory approach is based on a transition>state model, advanced by Felkin and co-woricers, in which the largest group is oriented perpendiculariy to the carbonyl group. Nucleophilic addition to the carbonyl groi occurs from the opposite side. ... 

Carbonyl group, nucleophilic addition cychzation, 230, 233, 245-52, 253 Carbonyl hydrate, hydroperoxide hydrogenolysis, 156 Carbonyl oxides... 

Problem 3.14 a. This is another example of the reaction of an amine with a carbonyl compound in the presence of an acid catalyst. The first steps are protonation of the carbonyl group, nucleophilic addition of the amine, and deprotonation of the nitrogen to give intermediate 3-49. 

In proton-catalyzed hydrolysis (specific acid catalyzed hydrolysis), protonation of the carbonyl O-atom leads to polarization of the carbonyl group, facilitating addition of the nucleophile, i. e., a H20 molecule (Fig. 3.1, Pathway a). The acid-catalyzed hydrolysis of esters is reversible because the neutral alcohol or phenol released is nucleophilic, whereas hydrolysis of amides is irreversible because the amine released is protonated in the acidic medium and, hence, has considerably reduced nucleophilicity. 

Mesylation of the alcohol 65 followed by deprotonation afforded the sul-fone-stabilized carbanion 66 that underwent a macrocyclization to afford the artificial dolabellane 67 in moderate yield (Scheme 9). Hydrolytic cleavage of the ketal (67) followed by a base-mediated double bond isomerization (into conjugation) afforded an enone containing an exocyclic carbonyl group. Nucleophilic 1,2-addition of methyl lithium introduced the missing... 

Nitrogen nucleophiles add to the carbonyl group. Often, addition is followed by elimination of water to give a product with a R2C=NR group in place of the R2C=0 group. 

When we come to reactions of amides we are at the bottom of the scale of reactivity. Because of the efficient delocalization of the nitrogen lone pair into the carbonyl group, nucleophilic attack on the carbonyl group is very difficult. In addition the leaving group (NH2, pkTaH about 35) is very bad indeed. 

We commented earlier in this chapter that carboxylic acids are similar in some respects to both alcohols and ketones. Like alcohols, carboxylic acids can be deprotonated to give anions, which are good nucleophiles in Sn2 reao tions. Like ketones, carboxylic acids undergo attack by nucleophiles on the carbonyl group. In addition, carboxylic acids undergo other reactions characteristic neither of alcohols nor ketones. Figure 20.4 shows some of the general reactions of carboxylic acids. 

Fu and co-workers recently reported a new approach to restricting the rotational degree of freedom (see complex F), which focuses on the development of Lewis acids that bear an empty rr-symmetry and an empty 7t-symmetry orbital as illustrated in Fig. 1-8 [27]. These vacant orbitals can simultaneously accept electron from an oxygen lone pair and from the 7r-system of a carbonyl group. The distinguishing feature of this approach is the r-symmetry interaction, which at once organizes the Lewis acid-base complex and activates the carbonyl toward nucleophilic addition. 

Aspects of stereochemistry are explored through consideration of addition reactions to alkenes and carbonyl groups, nucleophilic substitution, and reactions (and interactions) involved in the resolution of racemic mixtures. 

Likewise, when an electrophile attacks a carbonyl group, it will approach the carbonyl group so as to achieve the best overlap of its LUMO with the carbonyl s HOMO, the lone pair on oxygen (Fig. 4.42). The molecular orbitals are telling us what we already knew from the minor resonance form of the carbonyl group. Nucleophiles attack the 6+ end, and electrophiles attack the 6- end of the carbonyl group. The orientations of the orbitals tell us additional information on the position of attack. 

In a solution that contains both an aldehyde and its enolate ion, the enolate undergoes nucleophilic addition to the carbonyl group. This addition is analogous to the addition reactions of other nucleophilic reagents to aldehydes and ketones described in Chapter 17. 

The position of the equilibrium depends on the structure of the carbonyl compound. Nucleophilic addition is favoured by small alkyl groups attached to the carbonyl group and also by electron-withdrawing groups (e.g. CC13), which increase the 8+ character of the carbonyl carbon atom (see Section 8.3.1). 

III. FROM CARBONYL COMPOUNDS NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP... 

Up to now, we have studied two of the main types of carbonyl reactions nucleophilic addition and nucleophilic acyl substitution. In these reactions, the carbonyl group serves as an electrophile by accepting electrons from an attacking nucleophile. In this chapter, we consider two more types of reactions substitution at the carbon atom next to the carbonyl group (called alpha substitution) and carbonyl condensations. 

The partially positive charge on the carbonyl carbon (Section 12.3) is the cause of the most common reaction theme of the carbonyl group, the addition of a nucleophile to form a tetrahedral carbonyl addition intermediate. In the following general reaction, the nucleophilic reagent is written as Nu to emphasize the presence of its unshared pair of electrons ... 

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