Nucleophilic capture hydride shift

In addition to nucleophilic capture by alcohols, nonprotic nucleophiles also react with these intermediates. For example, the distonic dimer radical cation 96 + can be trapped by acetonitrile a hydride shift, followed by electron return, gave rise to the pyridine derivative 131. Similar acetonitrile adducts are formed in the electron-transfer photochemistry of terpenes such as ot- and (3-pinene ° or sabinene. ... 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

The rate ratio of the 6,2-hydride shift and of the ion capture by the nucleophile depends greatly on the nature of the substrate and on the reaction conditions. Thus, apoisobornyl brosylate 79 and exo-camphenyl brosylate 80 yield the same relative amount of P-phenchocamphoryl product A in a wide range of media ( 50% in CH3COOH somewhat less in more nucleophilic media)... 

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. 

The 1,2-hydride shift converts the secondary carbocation into a more stable tertiary carbocation. The tertiary carbocation reacts with chloride ion to produce the isomeric rearranged product. Some of the secondary carbocation also reacts with chloride ion without rearranging to give the expected product. The relative amounts of rearranged and unrearranged products depend on how efficiently the carbocation is captured by the nucleophile versus the rate of the rearrangement process. 

Although the homoallylic- cyclopropylcarbinyl cyclization is well-precedented in carbonium ion chemistry (101, 102) there seem to be no reports of the direct cyclization of the tertiary 4-terpinenyl carbonium ion. However, deamination of cyclohex-3-enyl amine and solvolysis cyclo-hex-3-enyl tosylate gives exo- and n /o-bicyclo[3.1.0]hex-2-yl derivatives as 6—43% of the products resulting from nucleophilic capture (101, 103, 104). The modest yield of bicyclic products in these reactions apparently is the result of competing nucleophilic capture prior to cyclization and hydride shift to the 2-cyclohexenyl cation. More efficient cyclization occurs in the acetolysis of 2-bicyclo[2.2.2]oct-5-enyl tosylate (49) owing to the rigid boat-like conformation of the precursor (105). The high efficiency of the base-catalyzed cyclization of the epoxide of 4-iso-... 

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