Stability functional groups* reactivity

The fundamental aspects of the structure and stability of carbanions were discussed in Chapter 6 of Part A. In the present chapter we relate the properties and reactivity of carbanions stabilized by carbonyl and other EWG substituents to their application as nucleophiles in synthesis. As discussed in Section 6.3 of Part A, there is a fundamental relationship between the stabilizing functional group and the acidity of the C-H groups, as illustrated by the pK data summarized in Table 6.7 in Part A. These pK data provide a basis for assessing the stability and reactivity of carbanions. The acidity of the reactant determines which bases can be used for generation of the anion. Another crucial factor is the distinction between kinetic or thermodynamic control of enolate formation by deprotonation (Part A, Section 6.3), which determines the enolate composition. Fundamental mechanisms of Sw2 alkylation reactions of carbanions are discussed in Section 6.5 of Part A. A review of this material may prove helpful. 

It is possible to achieve some selectivity using this method. As illustrated above, tertiary C—H sites are much more reactive than primary C—H sites. Radical-stabilizing functional groups also impart selectivity, as illustrated by the regioselective functionalization of (9 equation 4). ... 

Azo compounds having functional groups that stabilize the radical products are especially reactive. The stabilizing effect of the cyano substituent is responsible for the easy decomposition of azobis(isobutyronitrile) (AIBN), which is frequently used as a radical initiator. 

A collection of databases of chemicals and of functional groups which rank chemicals and groups relative to their reactivity, stability, toxicity, and flammability categories. This would assist in the evaluation of the potential benefits of substituting one, somewhat safer, chemical for another. 

Intramolecular chalcogen interactions may also stabilize reactive functional groups enabling the isolation of otherwise unstable species or their use as transient intermediates, especially in the case of selenium and tellurium. For example, tellurium(II) compounds of the type ArTeCl are unstable with respect to disproportionation in the absence of such interactions. The diazene derivative 15.23 is stabilized by a Te N interaction. Presumably, intramolecular coordination hinders the disproportionation process. Other derivatives of the type RTeX that are stabilized by a Te N interaction include 8-(dimethylamino)-l-(naphthyl)tellurium bromide, 2-(bromotelluro)-A-(p-tolyl)benzylamine, and 2-[(dimethylammo)methyl]phenyltellunum iodide. Intramolecular donation from a nitrogen donor can also be used to stabilize the Se-I functionality in related compounds." ... 

There can be significant differences in the detailed structure and mechanism of these catalysts. For example, the geometry of the phosphine ligands may affect the reactivity at the metal ion, but the basic elements of the mechanism of enantioselection are similar. The phosphine ligands establish a chiral environment and provide an appropriate balance of reactivity and stability for the metal center. The reactants bind to the metal through the double bond and at least one other functional group, and mutual interaction with the chiral environment is the basis for enantioselectivity. The new stereocenters are established under the influence of the chiral environment. 

Several functional groups containing carbon-nitrogen double bonds can participate in radical cyclizations. Among these are oxime ethers, imines, and hydrazones.337 Hydrazones and oximes are somewhat more reactive than imines, evidently because the adjacent substituents can stabilize the radical center at nitrogen.338 Cyclization at these functional groups leads to amino- substituted products. 

Figure 2.2 A number of small thiol-containing molecules have proven useful for modification of gold or metallic surfaces. The dithiol derivatives provide better dative bond stability and can t be displaced easily by competing thiols or oxidation. Most thiol-containing compounds used for surface modification also contain terminal functional groups or reactive groups for coupling affinity ligands.

Both THP and THPP are stable in aqueous solution, as the only potential product of hydrolysis is the reformation of the hydroxymethyl groups. It is unusual for an amine-reactive functional group to have long-term stability in water or buffer, which makes these reagents uniquely suitable for creating reactive surfaces or reactive molecules for subsequent... 

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