Carbonyl group nucleophilicity

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. ... 

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... 

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

Nitriles can also be used as starting materials for the synthesis of ketones. Discussed in Chapter 21, nitriles are compounds containing the cyano (—C=N) functional group. Since nitrogen is more electronegative than carbon, the —C=N triple bond is polarized like the C=O bond of the carbonyl group. Nucleophiles can add to the — C = N triple bond by attacking the electrophilic carbon atom. 

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. 

Although somewhat less reactive than acid chlorides, anhydrides nonetheless readily react with most nucleophiles to form substitution products. Nucleophilic substitution reactions of anhydrides are no different than the reactions of other carboxylic acid derivatives, even though anhydrides contain two carbonyl groups. Nucleophilic attack occurs at one carbonyl group, while the second carbonyl becomes part of the leaving group. 

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. 

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. 

Much of the chemical reactivity of ketenes can be understood on the basis of the preference for nucleophilic attack at the carbonyl carbon in the ketene plane and electrophUic attack at C2, perpendicular to the ketene plane. As shown in Scheme 4.1, C2 is electron rich due to resonance donation from the carbonyl group. Nucleophilic attack at Ci in the plane preferentially occurs from the side of the less stericaUy demanding substituent, while electrophilic attack at C2 is less influenced by the steric effects of the substituents. 

Design of Enamine-Enamine Cascades Three possible active sites (e.g., carbonyl group, nucleophilic a- and Y-positions) of enamine catalysis product 4 or 6 (Figure 1.1) can be further functionalized via a second enamine process in a cascade manner. Taking advantage of the electrophilic carbonyl in 4 and 6, intermolecular enamine-enamine (Scheme 1.3a) and enamine-enamine cyclization (Scheme 1.3b) cascades could be possible. In addition, the a-position of the same (Scheme 1.3c) or different (Scheme 1.3d, e.g., Robinson annulation) carbonyl group can be subjected to a second enamine process. 

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