Nucleophilic attack on carbonyl groups

Nucleophilic attack on carbonyl group 86 - 90 on phosphoryl and sulfuryl groups 89,90,260-266 on saturated carbon 90,91 Nucleophilic catalysis 61, 84, 85 examples with enzymes 45, 85, 100, 101,311... 

The important part of TPP is the five-membered ring, in which a carbon is found between a nitrogen and a sulfur. This carbon forms a carbanion and is extremely reactive, making it able to perform a nucleophilic attack on carbonyl groups, leading to decarboxylation of several compounds in different pathways. 

Nucleophilic attack on carbonyl groups leaving group Kinetics and mechanism chi 2... 

We mentioned the dimer of ketene 6 itself at the start of this chapter it is a cyclic enol ether and a good acylating agent. Nucleophiles attack the carbonyl group 39 expelling the enolate 40 of the acetoacetyl derivative 41. The disconnection is shown on 41 and the ketene dimer represents synthon 42. 

Now that we have decided which are the important conformations, how do we know which gives the product We need to decide which is the most reactive. All we need to do is to remember that any nucleophile attacking the carbonyl group will do so from the Biirgi-Dunitz angle—about 107° from the C=0 bond. The attack can be from either side of C=0, and the following diagrams show the possible trajectories superimposed on the two conformations we have selected, which are in equilibrium with one another. 

In Chapter 24, we examine carbonyl condensations—that is, reactions between two carbonyl compounds—a second type of reaction that occurs at the a carbon of a carbonyl group. Much of what is presented in Chapter 24 applies principles you have already learned. Many of the reactions may look more complicated than those in previous chapters, but they are fundamentally the same. Nucleophiles attack electrophilic carbonyl groups to form the products of nucleophilic addition or substitution, depending on the structure of the carbonyl starting material. 

When a nucleophile attacks a carbonyl group (Fig. 4.41), it will approach the carbonyl group so as to achieve the best overlap of its HOMO with the carbonyl s LUMO whose largest lobe is on carbon. The attack is not vertical, but close to the tetrahedral angle. We have interacted a full orbital with an empty one to achieve stabilization. 

Lithium amides of primary / fZ-alkylamines yield N-(/ f2 -alkyl)-0-(/ f2 -butyl)hydroxylamines, whereas lithium amides of primary alkylamines yield A/-alkylbenzamides and LiOO—due to nucleophilic attack on the carbonyl group (245). 

In systems of proper geometry, nucleophiles within a side chain may be well connected for attack on ring atoms. For example, an aminomethyl group at the 5-position of a dibenzazepine-2-one was found to attack the carbonyl group (Section 5.16.3.5.2). Such reactions should be possible in rings of any size. 

Anions of heterocyclics may attack heterocumulenes to set up systems which can incorporate new atom sequences into the ring by nucleophilic attack on a ring site (such as a carbonyl group). Scheme 32 gives an example (80AG(E)466). 

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