Hydride shifts deprotonation

Falvey examined the reactions of A-methyl-A-phenylnitrenium ion 65 (Fig. 13.37) in the presence and absence of chloride. It was found the yield of aniline (resulting from hydrolysis of the product iminium ion) was unaffected by added base. This finding ruled out a deprotonation process and led to the conclusion that a 1,2-hydride shift had occurred. Cramer et al. modeled this process using ab initio methods. 

The primary photolytic step is the homolytic scission of the C-I bond [reaction (265)]. The resulting radicals may recombine [reactions (-265) and (268)]. An ET within the solvent cage has also been suggested [reaction (269)]. Alternatively, one may consider the direct formation of the carbocation and iodide ion as a second photolytic pathway. Interestingly, there seems to be a rapid hydride shift [reaction (273)]. Deprotonation at C(l ), analogous to reaction (270), and... 

As shown in the biosynthesis of granaticin, a hydride shift occurs intramolecularly. This process is mediated by an enzyme-bond pyridine nucleotide. A concerted abstraction of H-4 as a hydride in la and a C-5 deprotonation in 2a leads to the 4,5-enol ether 3a. The reduced form of the pyridine nucleotide transfers the hydride to C-6, simultaneously releasing a hydroxide to give 4a. Final tautomerization yields the dTDP-4-keto-6-deoxy-sugar in v-xylo configuration 4a. In other enzymes of the oxidoreductase type, the active site may show a different configuration. Thus, the intermediate 3a can be protonated from above at C-5 to yield the l-arabino isomer of 4a [2]. The stereochemistry of this mechanism was demonstrated by double labelling (cf. l-4b series), and as a net result proved a suprafacial 4—>6 hydride shift. 

The mechanistic subtypes presented throughout this book include those related to the acid-base properties of organic molecules. These are protonations, deprotonations, and proton transfers. Mechanistic types based on solvation effects include solvolysis reactions, SN1, and El processes. Additional mechanisms utilizing ionic interactions include SN2, SN2, E2, 1,2-additions, 1,4-additions, and addition-elimination processes. Finally, those mechanistic types dependent upon the presence of cationic species include alkyl shifts and hydride shifts. 

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. 

Figure 5.6 Proposed mechanism for the cyclization of geranyl diphosphate to sabinene and sabinene hydrate under catalysis by monoterpene synthases the reaction begins with the hydrolysis of the diphosphate moiety to generate a resonance-stabilized carbocation (1) the carbocation then isomerizes to an intermediate capable of cyclization by return of the diphosphate (2) and rotation around a single bond (3) after a second diphosphate hydrolysis (4) the resulting carbocation undergoes a cyclization (5) a hydride shift (6) and a second cyclization (7) before the reaction terminates by deprotonation (8) or capture of the cation by water (9). Cyclizations, hydride shifts and a variety of other rearrangements of carbocationic intermediates are a characteristic of the mechanisms of terpene synthases. No known terpene synthase actually produces both sabinene and sabinene hydrate these are shown to indicate the possibilities for reaction termination. PP indicates a diphosphate moiety.

In the absence of Zn, the similar dependence of both the hydride-shift pathway and the enolisation pathway on [OD ] established that the hydrate diol anion was inert to both types of rearrangement, and that the hydride-shift mechanism probably went through the glyceraldehyde anion formed by deprotonation of 02. 

Note that the protonation of eugenol is favored for thermodynamic reasons - the protonated product can undergo a hydride shift to form a benzyl cation. Upon deprotonation / the resultant secondary alkene is more stable than eugenol due to the fact that it is more highly conjugated and substituted than before. 

Mechanism 5.3 shows how the butyloxonium ion formed on protonation of 1-butanol can give a secondary carbocation by a hydride shift from C-2 to C-1 in the step in which a molecule of water is lost. Deprotonation of this secondary carbocation leads to 1-butene, cw-2-butene, and ra/z -2-butene. 

Croteau et al., 1987). Furthermore, studies with [12,13- C 6- H]famesyl pyrophosphate as a precursor indicate that deprotonation-protonation steps to form bound ole-finic intermediates in the biosynthesis of patchoulol do not occur, providing support for a hydride shift mechanism (Croteau et al, 1987). Patchoulol synthase had a molecular weight of 80,000 and consisted of two identical subunits of 40,000. 

As depicted in Scheme 10.2, the mechanism of the reaction presumably involves protonation of 1-hexene to afford the secondary carbocation 43. Attack of bromide ion on this ion then leads to 2-bromohexane (41). The carbocation may also rearrange by way of a hydride shift (Sec. 10.3) to provide a different secondary carbocation, 44, which would provide 3-bromohexane (45) upon reaction with bromide ion. Alternatively, it may deprotonate to form 2-hexene (46), addition of H-Br to which could afford both 41 and 45. In this experiment, you will determine the regiochem-istry of the addition of H-Br to the unsymmetrical alkene 1-hexene (40) and thereby assess whether this ionic reaction proceeds according to Markovnikov s rule. 

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