Elimination reactions orientation

Enby 6 is an example of a stereospecific elimination reaction of an alkyl halide in which the transition state requires die proton and bromide ion that are lost to be in an anti orientation with respect to each odier. The diastereomeric threo- and e/ytAra-l-bromo-1,2-diphenyl-propanes undergo )3-elimination to produce stereoisomeric products. Enby 7 is an example of a pyrolytic elimination requiring a syn orientation of die proton that is removed and the nitrogen atom of the amine oxide group. The elimination proceeds through a cyclic transition state in which the proton is transferred to die oxygen of die amine oxide group. 

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

Compounds with axial and equatorial orientation of substitutents not only differ in physical properties but in reactivity as well, because the rates of formation of equatorial and axial isomers and rates of substituion and elimination reactions are different. 

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

Another type of elimination reaction favoured under plasma conditions is the decarboxylation. Carbocyclic acids easily lose carbon dioxide to form the parent hydrocarbons. In acid anhydrides decarboxylation is followed by a decar-bonylation. Cyclic or bicyclic anhydrides fragment forming unsaturated compounds, a reaction which has been studied with phthalie anhydride 24>. This anhydride decomposes to dehydrobenzene which, in the absence of other compounds, dimerizes, trimerizes or polymerizes. Orientation experiments indicated similar results for aliphatic acid anhydrides. 

Dimethyl sulphoxide has recently been used for tosylate elimination reactions [131 ], It is not clear whether this is a simple Ei process. The nucleophilic reactivity of dimethyl sulphoxide (p. 46) suggests the possibility of an indirect mechanism, with preliminary Sn2 substitution of the tosylate group by the oxygen atom of the reagent. This would permit elimination of an equatorial tosylate via the more favourably oriented axial oxysulphonium ion (c/. p. 47). 

In another type of elimination reaction, called Ei or intramolecular, the base, which removes the proton, is another part of the same molecule. Such eliminations from amine oxides or sulfoxides have five-membered-ring transition states. These transition states are more stable with syn than with anti orientations of proton and leaving group, producing very high syn stereoselectivity. 

The reaction is especially suited to the generation of optically active diazonium ions with specifically oriented counter-ions. In this respect it has possibilities which are absent for the reaction of diazoalkanes with acids and the deamination of aliphatic amines. However, in carrying out stereochemical studies, great care must be exercised to avoid spurious results, since the transient formation of a diazoalkane, either by loss of a proton from the diazonium ion or by what is probably a concerted elimination reaction of the diazoester, can lead to racemisation of the alkyl function and loss of asymmetry in the anion. Moreover, the diazoester is liable to nucleophilic displacement, for example by an acid molecule formed from already rearranged nitrosoamide, and this can lead to inverted product. 

If a substrate molecule has more than one P-H atom, the elimination reaction may lead to more than one alkene. The orientation is called Zaitsev orientation if the resulting double bond has the iargest numbers of substituents possible this means that the proton is abstracted from the most highiy substituted carbon. If the elimination reaction runs the other way, the orientation is called Hofmann orientation. In general, the Zaitsev product is thermodynamically more stable than the Hofmann product, due to hyperconjugation (Scheme 16). 

Sunderwirth, S. G., Wood, J. K. Stereochemistry and orientation in bimolecular elimination reactions. Trans. Kans. Acad. Sci. 1967, 70, 17-32. 

Hofmann rule The principal alkene formed in the decomposition of quaternary ammonium hydroxides that contain different primary alkyl groups is always ethylene, if an ethyl group is present. Originally given in this limited form by A.W. Hofmann, the rule has since been extended and modified as follows When two or more alkenes can be produced in a P-elimination reaction, the alkene having the smallest number of alkyl groups attached to the double bond carbon atoms will be the predominant product. This orientation described by the Hofmann rule is observed in elimination reactions of quaternary ammonium salts and tertiary sulfonium salts, and in certain other cases. 

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