Nucleophilic substitution at saturated carbon atoms

A. R. Katritzky, B. E. Brycki, Nucleophilic Substitution at Saturated Carbon Atoms. Mechanisms and Mechanistic Borderlines Evidence from Studies with Neutral Leaving Groups, J. Rhys. Org. Chem. 1988, 1, 1-20. 

Simple nucleophilic substitutions at saturated carbon atoms are fundamental reactions found wherever organic chemistry is practised. They are used in industry on an enormous scale to make heavy chemicals and in pharmaceutical laboratories to make important drugs. They are worth studying for their importance and relevance,... 

Ring formations by nucleophilic substitution at saturated carbon atoms with primary amines as nucleophiles have rarely been carried out because the resulting secondary amines as a rule are more nucleophilic than the primary ones, and therefore competition reactions are favored. The synthesis of secondary amines often starts from toluene sulfonamides which can easily be deprotonated and alkylated. A large number of methods for detosylation exists especially the acidic cleavage with H2SO4 or with HBr/phenol have proved to be reliable. 

This contrasts markedly with most electrophihc additions to carbon—carbon double bonds and with nucleophilic substitutions at saturated carbon atoms. The latter reactions are essentially irreversible, and overall results are a function of relative reaction rates. 

Polymer-supported podands appear to be more commonly used in solid-liquid systems. A variety of chemical transformations including nucleophilic substitutions at saturated carbon atoms [214,215], esterifications [214], sodium bo-rohydride reduction [214], fluoride-catalyzed Michael addition [214], phenacyl ester synthesis, Darzen s reaction, Wittig alkenylation, and dichlorocarbene reactions can be carried out under these conditions [214],... 

If R is an alkyl group, reaction (1) leads to the familiar mechanism of nucleophilic substitution at saturated carbon whilst reaction (2) leads to an electrophilic substitution of saturated carbon. Of course for these mechanisms to be followed it is not necessary for a completely developed carbonium ion or carbanion to be formed, and both nucleophilic and electrophilic substitution at saturated carbon may proceed by mechanisms in which the carbon atom undergoing substitution has a carbonium ion character or a carbanion character respectively. 

All the mechanisms so far discussed take place at a saturated carbon atom. Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is double bonded to an oxygen, a sulfur, or a nitrogen. Nucleophilic substitution at vinylic carbons is considered in the next section at aromatic carbons in Chapter 13. 

Additional Transformation Reactions. Other reactions that can be catalyzed by mineral surfaces are substitution, elimination, and addition reactions of organic molecules. Substitution and elimination are two general types of reactions that occur at saturated carbon atoms of organic molecules. Both types are initiated by nucleophilic attack however, in elimination reactions it is the basicity of the nucleophile that determine its reactivity rather than its nucleophilicity. Since mineral surfaces are expected to have both nucleophilic and basic properties, these types of reactions should also occur at mineral-water interfaces (see Chapter 22). It remains to be shown whether or not these reactions are catalyzed under environmental conditions. 

Nucleophilic Substitution and Elimination at Saturated Carbon Atoms... 

Surprisingly, this anion is also a good soft nucleophile and attacks saturated carbon atoms through the sulfur atom. In this case attack occurs at the less substituted end of an allylic bromide to give an allylic sulfone, which we will use later on. 

C. A. Bunion, Nucleophilic Substitution at a Saturated Carbon Atom, Elsevier, New Vbrk, 1963. 

Several distinct mechanisms are possible for aliphatic nucleophilic substitution reactions, depending on the substrate, nucleophile, leaving group, and reaction conditions. In all of them, however, the attacking reagent carries the electron pair with it, so that the similarities are greater than the differences. Mechanisms that occur at a saturated carbon atom are considered first. By far the most common are the SnI and Sn2 mechanisms. 

A type of reaction that has probably received more detailed study than any other—largely due to the monumental work of Ingold and his school—is nucleophilic substitution at a saturated carbon atom the classical displacement reaction exemplified by the conversion of an alkyl halide into an alcohol by the action of aqueous base ... 

Nucleophilic substitution at a saturated carbon atom 4.3 EFFECT OF STRUCTURE... 

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