Elimination reactions anti stereospecificity

Polar Addition and Elimination Reactions non-stereospecific or syn Br Bra - anti Br+ Br- ... 

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. 

These reactions proceed by alkoxide or fluoride attack at silicon which results in C—Si bond cleavage and elimination of the leaving group from the fi carbon. These reactions are stereospecific anti eliminations. 

Recently organosilicon compounds are being used for the synthesis of olefines by elimination reactions both in acidic and basic conditions. Thus P hydroxysilanes give defines. These reactions have been shown to be highly stereospecific. The acid catalysed elimination taking place by an anti pathway and the base induced elimination taking place by a syn pathway. 

Selenosulfonylation of olefins in the presence of boron trifluoride etherate produces chiefly or exclusively M products arising from a stereospecific anti addition, from which vinyl sulfones can be obtained by stereospecific oxidation-elimination with m-chloroper-benzoic acid134. When the reaction is carried out on conjugated dienes, with the exception of isoprene, M 1,2-addition products are generally formed selectively from which, through the above-reported oxidation-elimination procedure, 2-(phenylsulfonyl)-l,3-dienes may be prepared (equation 123)135. Interestingly, the selenosulfonylation of butadiene gives quantitatively the 1,4-adduct at room temperature, but selectively 1,2-adducts at 0°C. Furthermore, while the addition to cyclic 1,3-dienes, such as cyclohexadiene and cycloheptadiene, is completely anti stereospecific, the addition to 2,4-hexadienes is nonstereospecific and affords mixtures of erythro and threo isomers. For both (E,E)- and ( ,Z)-2,4-hexadienes, the threo isomer prevails if the reaction is carried out at room temperature. 

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. 

In the last chapter, we looked at some stereospecific eliminations to give double bonds, and you know that E2 elimination reactions occur best when there is an anti-periplanar arrangement between the proton and the leaving group. 

Unfortunately, there is a grey area. There are reactions that are, in their fundamental nature, the same as those we call stereospecific, but for which it is not possible to have two stereoisomers either of the starting material or of the product. Thus the addition of bromine to an isolated double bond is stereospeci-fically anti, but the corresponding addition to an acetylene cannot be proved to be stereospecifically anti by the usual criterion, because there is no possibility of having two stereoisomers of an acetylene. The same problem arises for reactions taking place in the opposite direction—in elimination reactions producing acetylenes, one vinyl bromide may react faster than the other, but they both produce the same acetylene. 

Fumarate hydratase. The most studied enzyme of this group is probably the porcine mitochondrial fumarate hydratase (fumarase see also Chapter 9), a tetramer of 48.5-kDa subunits with a turnover number of 2 x 10 s T It accelerates the hydration reaction more than lO -fold. A similar enzyme, the 467-residue fumarase C whose three-dimensional structure is known, is foxmd in cells of E. coli when grown aerobically. The product of the fumarate hydratase reaction is L-malate (S-malate). The stereospecificity is extremely high. If the reaction is carried out in HjO an atom of H is incorporated into the pro-R position, i.e., the proton is added strictly from the re face of the trigonal carbon (Eq. 13-12). To obtain L-malate the hydroxyl must have been added from the opposite side of the double bond. Such anti (trans) addition is much more common in both nonenzymatic and enzymatic reactions than is addition of both H and OH (or -Y) from the same side (syn, cis, or adjacent addition). For concerted addition it is a natural result of stereoelectronic control. Almost all enzymatic addition and elimination reactions involving free carboxylic acids are anti with the proton entering from the re face. 

The table shows that E2 eliminations, particularly in five- and seven-membered ring systems, are not completely stereospecific, but four- and six-membered rings exhibit strong preferences. Six-membered rings in particular show distinct anti selectivity, because it is very easy for such systems to reach the rrans-diaxial conformation (12) (Scheme 11 Barton s rule). This anti selectivity can be seen very clearly in the elimination reaction with the isomers of 1,2,3,4,5,6-hexachlorocyclohexane. The isomer (13), which has no Cl trans to an H, loses HCl about 7000 times more slowly than the slowest of the other isomers. ... 

Probe orientation. Does the reaction have a preferred regiochemistry, like following Markovnikov s rule Is stereochemistry lost or retained in the reaction Is the process stereospecific Does addition or elimination occur anti or syn Is the chirality at the reacting center preserved, inverted, or lost ... 

A few more vinyl halides can be made stereospecifically by halogenation and base-catalysed elimination. One example is the vinyl bromide E-28 available by stereospecific lruns bromination of crotyl alcohol 26 followed by stereospecific elimination.4 Various regioselectivities are available in the elimination reaction so the formation of that particular alkene is in a way more surprising than the stereopecificity of the reaction. Presumably the bromine atoms increase the acidity of nearby Hs (H-2 and H-3 in anti-21) so that one or other of the vinyl bromides will be formed. One explanation is an intramolecular elimination through an anti-peri-pimsa transition state in a chair like conformation using OLi as an internal base 26. It can reach H-3 in a five-membered cyclic array. 

If planar carbonium ions were the intermediates in El reactions in the cyclohexyl series, menthyl and neomenthyl compounds should give the same product ratios. However, the olefin distribution is quite different in the two El processes and the stereospecificity is less marked than in the E2 reactions of these substrates (Table 15). Whereas the concerted eliminations always show anti stereospecificity, the unimolecular eliminations only exhibit this preference when a tertiary beta hydrogen is trans to the ionising group (e.g. neomenthyl series). Possibly in this case the tertiary hydrogen aids ionisation by forming a type of non-classical bridged intermediate, viz. 

A number of unexplained factors warrant mention. Orientation of elimination differs for secondary and tertiary structures. The peculiar predominance of cis- rather than /ra/ii-olefin may arise from the relative stabilities of the proton-olefin complexes. but a more certain conclusion would be possible if the stereochemistry of the dehydration in the acyclic series had been determined. Assumption of the anti stereospecificity known to be favoured by the cyclohexyl systems may be unsound especially in the light of the recent stereochemical findings in base-catalysed elimination reactions (Section 2..1.1(e)). The solution of the problem of the cis/trans ratios may lie in the duality of mechanism, namely the syn-clinallanti complexity. Certainly recent results on the dehydration of threo- and eo t/iro-2-methyl-4-deutero-3-pentanols on thoria show syn-clinal rather than anti stereospecificity as indicated by deuterium analysis of the cis- and /rn/iJ-4-methyl-2-pentenes, but in these cases the trans isomer was formed in a three-fold excess over the m-olefin . Of course, the dehydration reactions on the less acidic thoria may not be good models for alumina but a knowledge of stereochemistry in the acyclic series might prove an invaluable aid in the elucidation of the mechanism. There is obviously plenty of scope for future kinetic investigations which at the moment sadly lag behind preparative studies. 

Alkenes can also be obtained by elimination of p-hydroxy selenides, under the action of methanesulfonyl chloride, thionyl chloride or other acidic conditions. The reaction is stereospecific, proceeding by anti elimination, by way of the epise-lenonium ion, e.g. 29 (2.28). High yields of di-, tri- or tetrasubstituted alkenes can be obtained and the reaction provides an alternative to the Wittig reaction when the phosphonium salt cannot be readily obtained. The p-hydroxy selenides can be prepared by a number of methods, for example from a-seleno aldehydes or ketones by reduction or reaction with a Grignard reagent, or from a-lithio selenides by... 

---