Alkyl shifts mechanism

Coordination to the metal is not shown. The enediolate in the intermediate is intended to be below the plane of the paper, (b) Dinuclear complex of Mo and o-arabinose. Single bonds to molybdenum are drawn as broken. On the alkyl shift mechanism the C3 shifts with its bonding pair of electrons from C2 to Cl. 

Reaction catalysed by 2-C-methyl-D-erythritol-4-phosphate synthetase. The reaction is drawn with a metal-templated reverse aldol-aldol mechanism, rather than the alkyl shift mechanism. The prop-2-en-2,3-diolate is below the plane of the glycolaldehyde phosphate. 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

Double cyclization was observed with siloxy enynes when a new cycloisomerization mechanism was used that involved a cascade of 1,2- alkyl shifts [154]. 

Mild Ni(0)-catalysed rearrangements of l-acyl-2-vinylcyclopropanes to substituted dihydrofurans have been developed.86 The room temperature isomerizations afford dihydrofuran products in high yield. A highly substituted, stereochemically defined cyclopropane has been employed in the rearrangement to evaluate the reaction mechanism. The Cu(II)-catalysed cycloisomerization of tertiary 5-en-l-yn-3-ols with a 1,2-alkyl shift affords stereoselectively tri- and tetra-cyclic compounds of high molecular complexity (Scheme 29).87 A proposed mechanism has been outlined in which... 

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. 

This mechanism consists of the same steps as are seen in Problem 17.37. Two different alkyl shifts result in two different cycloalkenes. 

In the case of the tricyclic epoxides la-c the outcome of the reaction depends on the ring size. The formation of 2 and 3 was explained by the following mechanism. Cleavage of the epoxide ring with boron trifluoride diethyl ether complex gives the zwitterionic intermediate 4. Subsequent transfer of fluoride anion to the cationic center C2 leads to fluoroborate 5 (path a), which is hydrolyzed to yield 2. Spiro ketone 3 is obtained by a 1,2-alkyl shift in 4 (path b). 

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. 

Finally, 4-9 undergoes another alkyl shift, followed by loss of a proton, to give the product. Looking at the resonance structures that can be drawn for all the cations involved in the mechanism suggests that their energy should be comparable to that of the initial cation, 4-8-2. The driving force for the reaction comes from the formation of the aromatic ring. 

The first leads to formation of a primary carbocation. The instability of the primary carbocation is not so great that it is grounds for eliminating this step from consideration however, the intermediate ion also contains a four-membered ring, a structural feature not found in the product. The second alkyl shift leads to the carbocation encountered in the mechanism shown previously. 

Intermediate 4-49 of mechanism 2 undergoes a hydride shift, instead of an alkyl shift, to give the following ... 

The major mechanisms for carbocationic rearrangements are 1,2-hydride shifts and 1,2-alkyl shifts. Both of these occur in the rearrangement of the cyclo-hexylium ion (a 2° carbocation) to the 1-methylcyclopentylium ion (a 3° carbocation). A 1,2-alkyl shift of the C3-C2 bond of cyclohexylium from C2 to Cl gives a cyclopentylmethylium ion (a 1° carbocation). This reaction is uphill in energy. However, a 1,2-hydride shift of the Cl-H bond from Cl to C2 gives a much more stable product. 

It is sometimes difficult to discern that a mechanism involves a 1,2-alkyl shift. Look at your list of bonds broken and bonds made. If a group migrates from one atom to its next-door neighbor, you may have a 1,2-shift. 

All these results are readily interpreted by assuming the existence of two bond shift mechanisms. The first one, which accounts for methyl shift, may be ascribed to the metallocyclobutane mechanism responsible for the group III reactions of n-pentane and isopentane. The second one, which accounts for chain lengthening (and chain shortening) is the same as the mechanism of higher activation energy (group II) responsible for the interconversion between n-pentane and isopentane. The first is very sensitive to alkyl substitution, while the latter seems relatively insensitive to structural effects. 

For isospecific polymerization by the Cossee-Arlman mechanism, migration of the vacant site back to its original position is necessary, as otherwise an alternating position is offered to the incoming monomer and a syndiotactic polymer would result. This implies that the tacticity of the polymer formed depends essentially on the rates of both the alkyl shift and the migration. Since both these processes slow down at lower temperatures, syndiotactic polymer would be formed when the temperature is decreased. In fact, syndiotactic polypropylene can be obtained at —IQPC. 

The enzyme 2-C-methyl-D-erythritol-4-phosphate synthetase appears to catalyse a Bilik reaction (Figure 6.10) the substrate l-deoxyxylulose-5-phosphate is converted to the title compound via an intermediate aldehyde, whose carbonyl derives from C3 of the substrate. The first step is thus a Bilik reaction and the aldehyde is subsequently reduced by the enzyme using NADPH as reductant, The X-ray crystal structure of the Escherichia coli enzyme in complex with the promising antimalarial Fosmidomycin (a hydroxamic acid) reveals a bound Mn " coordinated to oxygens equivalent to the substrate carbonyl and 03. The stereochemistry and regiochemistry follow the normal Bilik course, although the crystallographers favour an alkyl shift rather than a reverse aldol-aldol mechanism. The intermediate aldehyde has been shown to be a catalytically competent intermediate. 

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