Tertiary alkyl groups Carbocations

FIGURE 4 13 The order of carbocation stability is methyl < primary < second ary < tertiary Alkyl groups that are directly attached to the positively charged car bon stabilize carbocations... 

The mechanism of these reactions is usually Sn2 with inversion taking place at a chiral RX, though there is strong evidence that an SET mechanism is involved in certain cases, ° especially where the nucleophile is an a-nitro carbanion and/or the substrate contains a nitro or cyano group. Tertiary alkyl groups can be introduced by an SnI mechanism if the ZCH2Z compound (not the enolate ion) is treated with a tertiary carbocation generated in situ from an alcohol or alkyl halide and BF3 or AlCla, or with a tertiary alkyl perchlorate. ... 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

Yields primary amines with tertiary alkyl groups. Satisfactory for alkenes and alcohols that give a tertiary carbocation in strong acid (see Section 24-3B). 

The most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

Esters with tertiary alkyl groups undergo hydrolysis much more rapidly than do other esters because they hydrolyze by a completely different mechanism—one that does not involve formation of a tetrahedral intermediate. The hydrolysis of an ester with a tertiary alkyl group is an SnI reaction because when the carboxylic acid leaves, it leaves behind a relatively stable tertiary carbocation. 

Ethers containing tertiary alkyl groups transform even in dilute acid to give intermediate tertiary carbocations, which are either trapped by SnI processes, when good nucleophiles are present, or deprotonated in their absence ... 

Tertiary alkyl groups cannot be attached to nitrogen by the preceding reactions, and so carbocation methods are used. In the Ritter reaction, an alcohol is converted to a carbocation that attacks the nitrogen of the cyanide ion to give, after hydration, a hydrolyzable amide (Eq. 6.61) [96]. 

Secondary carbocation Tertiary carbocation (G is a migrating group it may be either a hydrogen or an alkyl group)... 

The stability of carbocations depends on the nature of alkyl groups attached to the positive charge. The relative stability of carbenium ions is as follows [2] with tertiary ions being the most stable ... 

Figure 6.11 A comparison of inductive stabilization for methyl, primary, secondary, and tertiary carbocations. The more alkyl groups there are bonded to the positively charged carbon, the more electron density shifts toward the charge, making the charged carbon less electron-poor (blue in electrostatic potential maps).

Carbocation rearrangements can also occur by the shift of an alkyl group with its ejection pair. For example, reaction of 3,3-dimethyJ-l-butene with HCI Leads to an equal mixture of unrearranged 2-chloro-3,3-dimethyTbutane and rearranged 2-chloro-2,3-dimethyibutane. In this instance, a secondary carbocation rearranges to a more stable tertiary carbocation by the shift of a methyl group. 

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. 

We have previously mentioned (p. 219) that stable tertiary carbocations can be obtained, in solution, at very low temperatures. The NMR studies have shown that when these solutions are warmed, rapid migrations of hydride and of alkyl groups... 

The mechanism involves a simple 1,2 shift. The ion (52, where all four R groups are Me) has been trapped by the addition of tetrahydrothiophene. It may seem odd that a migration takes place when the positive charge is already at a tertiary position, but carbocations stabilized by an oxygen atom are even more stable than tertiary alkyl cations (p. 323). There is also the driving force supplied by the fact that the new carbocation can immediately stabilize itself by losing a proton. 

Recall that alkyl groups are electron donating, so the carbocation on the bottom (called a tertiary carbocation because it has three alkyl groups) will be more stable than the carbocation on the top (called a secondary carbocation because it has only two alkyl groups). 

Finally we learned that if we analyze the first factor (substrate), we will find two effects at play electroiucs and sterics. We saw that Sn2 reactions require primary or secondary substrates because of sterics—it is too crowded for the nucleophile to attack a tertiary substrate. On the other hand, SnI reactions did not have a problem with sterics, but electronics was a bigger issue. Tertiary was the best, because the alkyl groups were needed to stabilize the carbocation. 

In the step above, Br attacked the alkene at the less substituted carbon, in order to form the more substituted carbon radical (C ). Tertiary radicals are more stable than secondary radicals, for the same reason that tertiary carbocations are more stable than secondary carbocations. Just as alkyl groups donate electron density to... 

Alkyl groups are said to have a positive inductive effect. This means they are electron-donating and can push electrons onto the positively charged carbon atom, thus stabilising the carbocation. It follows that tertiary carbocatlons, with their three alkyl groups, are the most stable species and that primary carbocatlons, with just one alkyl group, are the least stable species. This suggests that tertiary haloalkanes are most likely to react with a nucleophile via an Sj. 1 mechanism. 

If we consider protonation of 2-methylbut-2-ene, then two different carbocations might be formed. One of these is tertiary, and thus favourable, because three electron-donating alkyl groups help to stabilize the cation by dispersing the charge (see Section 6.2.1). The alternative carbocation intermediate is less favourable, in that it is secondary, with just two alkyl... 

Table 1.3 provides rate constants for the decay of selected carbocations and oxocar-bocations in H2O, TFE, and HFIP. As a general comment, water, methanol, and ethanol are highly reactive solvents where many carbocations that are written as free cations in standard textbooks have very short lifetimes. The diphenylmethyl cation, with two conjugating phenyl groups, has a lifetime in water of only 1 ns. Cations such as the benzyl cation, simple tertiary alkyl cations such as tert-butyl, and oxocarbocations derived from aldehydes and simple glycosides, if they exist at all, have aqueous lifetimes in the picosecond range, and do not form and react in water as free ions. This topic is discussed in more detail in Chapter 2 in this volume. 

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