Limonene deprotonation

Using superbasic reagents such as BuLi t-BuOK and Me3SiCH2K, olefins with a poor kinetic acidity can be metallated relatively easily [1-4]. BuLi TMEDA is a less efficient deprotonating reagent, though good results have been reported with the metallation of limonene [5], propene, and isobutene [7]. 

The biogeneses of cyclic and polycyclic terpenes are usually assumed to involve intermediate carbenium ions, but evidence for this in vivo was given only in some specific cases. In the simple case of monocyclic monoterpenes such as limonene the allylic cation remaining after separation of the pyrophosphate anion cyclizes to a cyclohexyl cation which is deprotonated to (/ )- or (5)-limonene. 

Reagents such as n-butyllithium, methyllithium, and phenyllithium manufactured by this process are commercially available. Carbanions can also be formed by an acid-base reaction involving heterolytic dissociation of a carbon-hydrogen bond by a strong base. An example is the deprotonation of limonene (86) by -butyllithium complexed with tetramethylethylenedia-mine (TMEDA), as shown in equation 5.61. Note that there is more than one kind of allylic proton in 86, but the deprotonation preferentially produces the least-substituted carbanion. ... 

Borderline-SN2-Type Mechanism. Some enzymes, such as limonene-1,2-epoxide hydrolase, have been shown to operate via a single-step push-pull mechanism [573]. General acid catalysis by a protonated aspartic acid weakens the oxirane to facilitate a simultaneous nucleophilic attack of hydroxyl ion, which is provided by deprotonation of H2O via an aspartate anion. Due to the borderline-SN2-character of this mechanism, the nucleophile preferentially attacks the higher substituted carbon atom bearing the more stabilized 5 -charge. After liberation of the glycol, proton-transfer between both Asp-residues closes the cycle. 

Further dissociation and cyclization by electrophilic addition of the cationic carbon to the terminal double bond then gives a cyclic cation, which might either rearrange, undergo a hydride shift, be captured by a nucleophile, or be deprotonated to give any of the several hundred known monoterpenoids. As just one example, limonene, a monoterpenoid found in many citms oils, arises by the biosynthetic pathway shown in Figure 27.10. 

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