Regioselective exchange

Alkenes lacking hydrogen atoms at allylic positions are much less acidic than ordinary unsaturated hydrocarbons. Superbases regioselectively exchange allylic protons in alkenes whenever there is a choice. However, a few examples of metallation of alkenic C-H bonds with superbases are known and a compilation of them is reported in Table 1. Ethylene itself has been deprotonated by the superbasic mixture constituted by butyllithium, potassium tert-butoxide, and TMEDA.41... 

A similar regioselective exchange pattern was found later in triflic acid. Furthermore, the deuterium distribution observed in isobutane recovered after short contact times with DF-SbFs at 0°C (in contrast to -78°C) showed a fast deuterium exchange at all C-H bonds. " Three isomeric carbonium ions in equilibrium are formed (Scheme 6.5) and the relative concentration of these prevalent reaction intermediates depends only on the relative basicity of the proton-accepting bonds in accord with the Olah o-basicity concept. 

With titanated 2-alkenyl carbamates, the opposite regioselectivity can also be observed. Lithiated l-(4-methylphenylsulfonyl)-2-alkenyl diisopropylcarbamates, after metal exchange with chlorotriisopropoxytitanium, add to aldehydes y-selectivelylls. The less reactive titanat-ing reagent tetraisopropoxytitanium does not apparently react with these stabilized lithium carbanions, because in its presence a-selectivity is retained (Section 1.3.3.3.1.3.2.). 

Our own earlier work on the chlorination of toluene had been subject to similar constraints. In this case, chlorination with ferf-butyl hypochlorite had proved to be advantageous. In the presence of silica gel as catalyst the yield of chlorotoluenes was quantitative but the regioselectivity was more or less statistical (ref. 8). However, the use of proton-exchanged zeolite X allowed the production of chlorotoluenes with a para-selectivity of more than 90 % (Fig. 4) (ref. 9). No HCl is generated in this process since the by-product is tert-butanol, and there is no inhibition of the catalyst. Indeed, the catalyst can be reused if necessary. 

The direct bromination of 2-hydroxypyridine is regioselective at C-3 whereas chlorination is not. Qu6guiner has developed a halide exchange reaction. Heating 3-bromo-2-hydroxypyridine in pyridine hydrochloride at reflux gives 3-chloro-2-hydroxypyridine in good yield <96TL(37)6695>. The directed aminomethylation of 3-hydroxy-2(lH)-pyridones and 3-hydroxy-4(lfl)-pyridones has been studied <96T(52)1835>. 

The regioselectivity of the hydride addition step has been probed by searching for deuterium exchange into isomerized alkenes that have undergone partial reduction.15 The results suggest that Rh is electrophilic in the addition step and that the hydride transfer is nucleophilic. 

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