Carbocation hydride shift

Alkene synthesis via alcohol dehydration is complicated by carbocation rearrangements A less stable carbocation can rearrange to a more sta ble one by an alkyl group migration or by a hydride shift opening the possibility for alkene formation from two different carbocations... 

In the acid catalyzed dehydration of 2 methyl 1 propanol what carbocation would be formed if a hydride shift accompanied cleavage of the carbon-oxygen bond in the alkyloxonium lon" What ion would be formed as a result of a methyl shift" Which pathway do you think will predominate a hydnde shift or a methyl shift" ... 

Addition begins m the usual way by protonation of the double bond to give m this case a secondary carbocation This carbocation can be captured by chloride to give 2 chloro 3 methylbutane (40%) or it can rearrange by way of a hydride shift to give a tertiary carbocation The tertiary carbocation reacts with chloride ion to give 2 chloro 2 methylbutane (60%)... 

A reasonable mechanism for this observation assumes rate determining ionization of the substrate as the first step followed by a hydride shift that converts the secondary carbocation to a more stable tertiary one... 

Why does the carbocation intermediate in the hydrolysis of 2 bromo 3 methylbutane rearrange by way of a hydride shift rather than a methyl shift ... 

A hydride shift produces a tertiary carbocation a methyl shift produces a secondary carbocation... 

Hydride shift (Section 5 13) Migration of a hydrogen with a pair of electrons (H ) from one atom to another Hydnde shifts are most commonly seen in carbocation rearrange ments... 

An alternative view of these addition reactions is that the rate-determining step is halide-assisted proton transfer, followed by capture of the carbocation, with or without rearrangement Bromide ion accelerates addition of HBr to 1-, 2-, and 4-octene in 20% trifluoroacetic acid in CH2CI2. In the same system, 3,3-dimethyl-1-butene shows substantial rearrangement Even 1- and 2-octene show some evidence of rearrangement, as detected by hydride shifts. These results can all be accoimted for by a halide-assisted protonation. The key intermediate in this mechanism is an ion sandwich. An estimation of the fate of the 2-octyl cation under these conditions has been made ... 

Draw a Lewis structure for the carbocation which would result from a 1,2-hydride shift in the more stable (initially-formed) cation. Is this carbocation more stable than the initially-formed ion What would be the product of bromide addition to this cation Is this the observed product ... 

Examine the transition state for the hydride shift. Calculate the barrier from the more stable initial carbocation. Is the process more facile than typical thermal rearrangements of neutral molecules (.05 to. 08 au or approximately 30-50 kcal/mol) Is the barrier so small (<.02 au or approximately 12 kcal/mol) that it would be impossible to stop the rearrangement even at very low temperature Where is the positive charge in the transition state Examine atomic charges and the electrostatic potential map to tell. Is the name hydride shift appropriate If not, propose a more appropriate name. 

The formed carbocation from the last step may abstract a hydride ion from an isohutane molecule and produce 2,2-dimethylpentane, or it may rearrange to another carbocation through a hydride shift. 

The new carbocation can rearrange again through a methide/hydride shift as shown in the following equation ... 

Evidence in support of a carbocation mechanism for electrophilic additions comes from the observation that structural rearrangements often take place during reaction. Rearrangements occur by shift of either a hydride ion, H (a hydride shift), or an alkyl anion, R-, from a carbon atom to the adjacent positively charged carbon. The result is isomerization of a less stable carbocation to a more stable one. 

Strategy A Friedel-Crafts reaction involves initial formation of a carbocation, which can rearrange by either a hydride shift or an alkyl shift to give a more stable carbocation. Draw the initial carbocation, assess its stability, and see if the shift of a hydride ion or an alkyl group from a neighboring carbon will result in increased stability. In the present instance, the initial carbocation is a secondary one that can rearrange to a more stable tertiary one by a hydride shift. 

It is likely that protonated cyclopropane transition states or intermediates are also responsible for certain non-1,2 rearrangements. For example, in superacid solution, the ions 14 and 16 are in equilibrium. It is not possible for these to interconvert solely by 1,2 alkyl or hydride shifts unless primary carbocations (which are highly unlikely) are intermediates. However, the reaction can be explained " by postulating that (in the forward reaction) it is the 1,2 bond of the intermediate or transition state 15 that opens up rather than the 2,3 bond, which is the one that would open if the reaction were a normal 1,2 shift of a methyl group. In this case, opening of the 1,2 bond produces a tertiary cation, while opening of the 2,3 bond would give a secondary cation. (In the reaction 16 14, it is of course the 1,3 bond that opens). 

Now the carbocation is ready to be attacked by chloride. However, there is something else that can happen first (before chloride has a chance to attack) A hydride shift can produce a more stable carbocation ... 

Clearly, we must be able to predict when to expect a carbocation rearrangement. There are two common ways for a carbocation to rearrange either through a hydride shift or through a methyl shift. Your textbook will have examples of each. Carbocation rearrangements are possible for any reaction that involves an intermediate carbocation (not just for addition of HX across an alkene). Later in this chapter, we will see other addition reactions that also proceed through carbocation intermediates. In those cases, you will be expected to know that there will be a possibility for carbocation rearrangements. 

An unusual cationic domino transformation has been observed by Nicolaou and coworkers during their studies on the total synthesis of the natural product azadirachtin (1-105) [30]. Thus, exposure of the substrate 1-106 to sulfuric acid in CHjClj at 0°C led to the smooth production of diketone 1-109 in 80% yield (Scheme 1.27). The reaction is initiated by proto nation of the olefinic bond in 1-106, affording the tertiary carbocation 1-107, which undergoes a 1,5-hydride shift with concomitant disconnection of the oxygen bridge between the two domains of the molecule. Subsequent hydrolysis of the formed oxenium ion 1-108 yielded the diketone 1-109. 

One very fascinating domino reaction is the fivefold anionic/pericydic sequence developed by Heathcockand coworkers for the total synthesis of alkaloids of the Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero- Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cydized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

When a terminal alkene protonates by using its tt electrons to bond a proton at the terminal carbon, a carbocation forms at the second carbon of the chain (The carbocation could also form directly from the 1° alcohol by a hydride shift from its P-carbon to the terminal carbon as the protonated hydroxyl group departs). 

Recently, we have shown that iminium ions can induce a hydride shift to form a new carbocation which then reads with a nucleophile. By this way the novel unusual bridged steroid alkaloids 25 were prepared from the secoestron derivative 19 (scheme 5) M Treatment of 20 obtained from 19 by hydrogenation with aniline or an aniline derivative 21 containing an dedron-withdrawing group in the presence of the Lewis add BF3-OEt2 leads to the iminium... 

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