Bases in E2 elimination

Table 6.S. Orientation in E2 Elimination as a Function of Base Strength...

Secondary and tertiary alkyl halides are not suitable, because they react with alkoxide bases by E2 elimination rather than by Sn2 substitution. Whether the alkoxide base is primary, secondary, or tertiary is much less important than the nature of the alkyl halide. Thus benzyl isopropyl ether is prepared in high yield from benzyl chloride, a primary chloride that is incapable of undergoing elimination, and sodium isopropoxide ... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

Hell-VoLhard-Zelinskii (HVZ) reaction, in which an acid is treated with Bc2 and PBr3. The a-halogenated products can then undergo base-induced E2 elimination to yield a,j6-unsaturated carbonyl compounds. 

The effect of crown ethers on the geometrical orientation in base-promoted E2 eliminations has been studied by several groups. Bartsch et al. (1973) have investigated the effect of several parameters on the potassium alkoxide-promoted eliminations of HBr from 2-bromobutane (Table 45). In the absence of crown ethers the relative amount of 1-butene formed increases, while the trans/cis ratio of the 2-butenes decreases, with decreasing solvent polarity. Furthermore, the proportion of 1-butene increases and the trans/cis ratio decreases on increasing the base concentration. These effects were explained in terms of steric interactions between the base and a- and /7-alkyl groups in the... 

It has generally been assumed that phosphorous oxychloride-pyridine dehydrations, the elimination of sulfonates, and other base catalyzed eliminations (see below) proceed by an E2 mechanism (see e.g. ref. 214, 215, 216). Concerted base catalyzed eliminations in acyclic systems follow the Saytzeff orientation rule (i.e., proceed toward the most substituted / carbon), as do Ex eliminations (see ref. 214). However, the best geometrical arrangement of the four centers involved in E2 eliminations is anti-coplanar and in the cyclohexane system only the trans-diaxial situation provides this. 

You have just seen that hydroxyl groups can be turned into good leaving groups in acid, but this is only useful for substrates that can react by El elimination. The hydroxyl group is never a leaving group in E2 eliminations, since they have to be done in base. 

Carbonyl compounds are in a rapid equilibrium with their cnols, a process called keto-enol tautomerism. Although enol tautomers arc normally present to only a small extent at equilibrium and can t usually be isolated in pure form, they nevertheless contain a highly nucleophilic double bond and react with electrophiles. P or example, aldehydes and ketones are rapidly halogenated at the a position by reaction with CI2 Br2, or I2 in acetic acid solution. Alpha bromination of carboxylic acids can be similarly accomplished by the Hell-Volhard-Zelinskii (HVZ) reaction, in which an acid is treated with Bt2 and PBrThe a--halogenated inoducts can then undergo base-induced E2 elimination to yield a,/3-un.salurated carbonyl compounds. 

But orientation in E2 elimination is not always Saytzeff, particularly when compounds other than alkyl halides are involved. To see the various factors at work here, let us take, as a simple example, elimination from the 2-hexyl halides brought about by the strong base sodium methoxide. The iodide, bromide, and... 

In E2 elimination with bases like KOH and CH30Na, most alkyl halides give Saytzeflf orientation. Certain other compounds (quaternary ammonium salts, Sec. 23.5, for example) give Hofmann orientation. Alkyl sulfonates fall in between. With each kind of compound, orientation is affected—sometimes drastically—by the choice of base and solvent, and by stereochemistry. (The percentage of 1-hexene from 2-hexyl chloride, for example, jumps from 33% in CH ONa/ CH3OH to 91% in /-BuOK//-BuOH, evidently for steric reasons.) In all this, we should remember that orientation is a matter of relative stabilities of competing transition states these stabilities are determined by electronic factors—alkene character and carbanion character—with superimposed conformational factors. 

Sx2 substitution with nonbasic nucleophiles K2 oliininalion with strong bases Mostly E2 elimination (SmI substitution and El elimination in nonbasic solvents) ... 

The nature of proton sponges does not allow them to be used directly as kinetically active bases, e.g. in E2 elimination reactions, involving the ionization of C—H bonds213. However, due to the low nucleophilicity, the proton sponges are useful reagents when it is necessary to bind an acid liberated in the course of the reaction without any effect on other base-sensitive groups. As a rule, in such cases, a proton transfer from substrate to the proton sponge requires an additional carrier, which most frequently is the solvent molecule (such as alcohol, THF, DMSO, acetone)57,214,215. Let us consider some typical examples. 

You might say that the selectivity is only 2 1 but in truth it is remarkable that the reaction is Z-selective at all. In practice 60% Z-57 can be isolated by chromatography. The obvious mechanism is the formation of a lithium derivative, SN2 coupling 60, and base-catalysed E2 elimination 62. 

In this section we focus primarily on the stereochemistry of the concerted E2 mechanism. The most familiar examples are dehydrohalogenation and dehydrosul-fonylation reactions effected by strong bases. In principle, elimination can proceed with either syn or anti stereochemistry. For acyclic systems, there is a preference for anti elimination, but this can be overridden if conformational factors favor a syn elimination. The anti TS maximizes orbital overlap and avoids the eclipsing that is present in the syn TS. 

Again, this is mainly a review of earlier material (Chapters 7 and 9). Note that, unlike the situation with base-promoted E2 eliminations, under the reaction conditions for alcohol dehydration, the usual result is formation of the most stable nlkenc (the thermodynamic product). Alcohol dehydrations are susceptible to rearrangemenl proces.ses. A cla.ssic example is encountered in attempted. syntheses of lenninal alkenes such as I -butene. Tlie only 100% reliable method is base-promoted E2 elimination of a suitable 1-buiyl compound (e.g., l-broinobutanc, l-bulyl losylale). Any other method will give mixtures ... 

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