Stereochemistry unimolecular reactions

Another important family of elimination reactions has as its common mechanistic feature cyclic TSs in which an intramolecular hydrogen transfer accompanies elimination to form a new carbon-carbon double bond. Scheme 6.20 depicts examples of these reaction types. These are thermally activated unimolecular reactions that normally do not involve acidic or basic catalysts. There is, however, a wide variation in the temperature at which elimination proceeds at a convenient rate. The cyclic TS dictates that elimination occurs with syn stereochemistry. At least in a formal sense, all the reactions can proceed by a concerted mechanism. The reactions, as a group, are often referred to as thermal syn eliminations. 

We have discussed in this chapter the thermal pyrolyses of a number of strained ring compounds. In most of the cases considered there is good evidence that the processes are unimolecular. Where possible we have tried to suggest plausible transition complexes, and reaction paths, based on a consideration of such factors as the kinetic parameters, stereochemistry of the reaction and effect of substituents. In reactions of this type, the description of the transition complex is fraught with difficulties, since the absence of such things as solvent effects (which can be so helpfrd in bimolecular reactions) limit the criteria on which such descriptions may be based. Often two types of transition complex may be equally good at accounting for the observed data. Sometimes one complex will explain some of the data while another is better able to account for the remainder. It is probable that in many cases our representation... 

This section will describe reactions in which elimination to form a double bond or a new ring occurs as a result of thermal activation. There are several such thermal elimination reactions which find use in synthesis. Some of these are concerted processes. The transition-state energy requirements and stereochemistry of concerted elimination processes can be analyzed in terms of orbital symmetry considerations. We will also consider an important group of unimolecular /1-elimination reactions in Section 6.8.3. 

With ions or dipolar substrates, radical ions undergo nucleophilic or electrophilic capture. Nucleophilic capture is a general reaction for many alkene and strained-ring radical cations and may completely suppress (unimolecular) rearrangements or dimer formation. The regio- and stereochemistry of these additions are of major interest. The experimental evidence supports several guiding principles. 

A simple example of the formation of a six-membered ring by unimolecular cyclization is provided by an alternative synthesis of the chloride of compound (93) from the pyrrolidine (95) (Equation (39)) <44JOC359>, while bimolecular reaction of piperidine (96) gives the diazoniadispiro derivative (4) (Equation (40)) <65JOC82l>. A seven-membered ring can be formed if the stereochemistry of the starting material is suitable, as in compound (97) (Equation (41)) <63JOC2843> there is no obvious reason for the difference in yield between pyrrolidine and piperidine derivatives. 

The most synthetically useful nucleophilic substitution reaction is the bimolecular Sn2 reaction, shown in the section 2.7.A. A unimolecular substitution (ionization followed by substitution) is less useful in synthesis in a general sense, but is often the best specific reaction to effect a particular functional group exchange. In Chapter 12 we will see many examples where cationic reactions are very useful. Unimolecular substitution also occurs as a side reaction in aqueous media and can influence both the yield, stereochemistry, and regiochemistry of the final product. 

There is good evidence for the existence of the 4-oxo intermediate and this means that the reversal of configuration does not arise from a bimolecular nucleophilic substitution (or Sn2 reaction), but from a unimolecular (Snl) reaction forming a carbonium ion. Hence the stereochemistry must reflect... 

In Summary We have seen further evidence supporting the SnI mechanism for the reaction of tertiary (and secondary) haloalkanes with certain nucleophiles. The stereochemistry of the process, the effects of the solvent and the leaving-group ability on the rate, and the absence of such effects when the strength of the nucleophile is varied, are consistent with the unimolecular route. 

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