Nucleophilic tetrahedral carbon

In contrast to such systems, substrates of the type RCOX are usually much more reactive than the corresponding RCH2X. Of course, the mechanism here is almost always the tetrahedral one. Three reasons can be given for the enhanced reactivity of RCOX (1) The carbonyl carbon has a sizable partial positive charge that makes it very attractive to nucleophiles. (2) In an Sn2 reaction a cr bond must break in the rate-determining step, which requires more energy than the shift of a pair of n electrons, which is what happens in a tetrahedral mechanism. (3) A trigonal carbon offers less steric hindrance to a nucleophile than a tetrahedral carbon. 

This is reminiscent of the nucleophilic tetrahedral mechanism at a vinylic carbon (p. 429). 

Concerted bond-forming/bond-breaking processes at tetrahedral carbon (the familiar SN2 reaction) are not easily studied by the crystal structure correlation method. The preferred approach of a nucleophile is sterically more encumbered than the approach to a singly or doubly bonded centre, and the transition states involved are generally of high energy. Intramolecular displacements, such as those described on pages 117-118, are a possible way round this problem, but no systematic study is available. 

As we have seen (Section 4, p. 191) the range of effective molarities associated with ring-closure reactions is very much greater than that characteristic of intramolecular general acid-base catalysis the main classification is therefore in terms of mechanism. By far the largest section (I, Tables A-D) gives EM s for intramolecular nucleophilic reactions. These can be concerted displacements (mostly at tetrahedral carbon), stepwise displacements (mostly addition-elimination reactions at trigonal carbon), or additions, and they have been classified in terms of the nucleophilic and electrophilic centres. 

Incidentally, I should say that the thermodynamic data on cobalt(III) indicates that it is a hard acid, but just barely so, and one might say borderline. It is a little harder than tetrahedral carbon and alkyl halides. So hydroxide ion in that sense would be expected perhaps to be a good nucleophilic reagent, as hard acids would like hydroxide ion. 

The absence of nitro groups in these substrates is noteworthy. The observed adducts are exclusively stabilized by the electron-withdrawing capacity of the aza groups present in the fused ring system of purine. Accordingly, all ring protons in the adducts are more shielded than the corresponding protons in the substrates. Adducts 19 and 20 can be taken as models for intermediates in nucleophilic aromatic substitution at the C-6 position of purine. Moreover, their formation support the view that a tetrahedral carbon at C-6 is involved in the mechanism of the adenosine deaminase-catalyzed hydrolysis of 6-substituted purine ribonucleosides.43... 

Both reactions involve nucleophilic attack of tricoordinated phosphorus on tetrahedral carbon and show all the characteristics of non-polar reactants combining through polar transition states although the solvent effects are sometimes quite modest.— Subsequent studies have demonstrated nucleophilic attack on activated alkenes,Z activated alkynes,Z the carbonyl groupZ-Z and halogen , whilst in the Perkow reaction (eqn. 1) all four possible sites in... 

Thus, when identifying sites where SN2 reactions can occur, the following criteria must be met. First, Sn2 reactions occur at tetrahedral carbon atoms. Second, SN2 reactions occur at molecular sites bearing the greatest degree of positive charge. Lastly, SN2 reactions occur at sites that are sterically accessible to the incoming nucleophile. 

For nucleophilic substitution at tetrahedral carbon, the relationships between stereochemistry and mechanism are well understood. Direct displacement on a carbon turns the molecule inside out (inversion of configuration) if the site of reaction is an asymmetric carbon, a molecule in the D series will be converted to one in the L series (or vice versa). Substitution by the dissociation mechanism at an asymmetric carbon... 

Steric hindrance decreases nucleophilicity but not basicity. Because bases pull off. small, easily accessible protons, they are unaffected by steric hindrance. Nucleophiles, on the other hand, must attack a crowded tetrahedral carbon, so bulky groups decrease reactivity. 

The concept of a halonium ion solves both of the problems associated with an open carbonium ion a halogen bridge prevents rotation about the carbon-carbon bond, and at the same time restricts bromide ion attack exclusively to the opposite face of the cation. This opposite-side approach, we shall find (Sec. 14.10), is typical of attack by bases (nucleophiles) on tetrahedral carbon. 

A number of equations have been developed to model the nucleophilic substitution reaction at tetrahedral carbon. These equations use reference reactions ranging from other 8 2 displacement reactions to physical processes such as electron transfer. 

An important substrate for nucleophilic reactivity is methyl iodide. This serves as a model for substitution reactions at tetrahedral carbon in general, the Sn2 reaction... 

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