Reactions with Sterically Crowded Halides

6 Reactions with Sterically Crowded Halides 1SI78 

The discovery, at the end of the 1970s [24], of a remarkably unreactive solution of a tertiary organolithium compound was the start of an interesting expansion of Li-Barbier chemistry. 

Organobromide Nitrile Product Yield (%) Yield from reaction with RMgX (%) RLi (%)  

1-Lithioadamantane, formed by reaction of 1-bromo- or 1-chloroadaman-tane (1-AdBr or 1-AdCl) with lithium in diethyl ether at — 20 °C, yielded 75% 1-Ad-D on deuterolysis. Addition of hexamethylacetone (HMA) to the reaction mixture yielded virtually no carbonyl addition reaction product. 

In contrast, when this reaction was performed as a one-step process, on deuterolysis, products were obtained which suggested that an intermediate organolithium compound had been formed  

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The effect of steric crowding on the rates of reaction of the Ni1 tetraaza macrocycle complex [Ni(dmc)]+ with organic halides and hydroperoxides has also been examined. Reaction with this complex was found to be about 104 times slower than with the corresponding [Ni(tmc)]+ complex.2329... 

In steric terms there is a relief of crowding on going from the initial halide, with a tetrahedral disposition of four substituents about the sp3 hybridised carbon atom, to the carbocation, with a planar disposition of only three substituents (cf. five for the SN2 T.S.) about the now sp2 hybridised carbon atom. The three substituents are as far apart from each other as they can get in the planar carbocation, and the relative relief of crowding (halide - carbocation) will increase as the substituents increase in size (H- Me- Me3C). The SN1 reaction rate would thus be expected to increase markedly (on both electronic and steric grounds) as the series of halides is traversed. It has not, however, proved possible to confirm this experimentally by setting up conditions such that the four halides of Fig. 4.1 (p. 82) all react via the SN1 pathway. 

Although the SRNl reaction is shown to be prone to steric limitations, most of the C-alkylated products obtained in these studies are sterically congested molecules, whose preparation would be difficult by other methods. Indeed, the reaction of sterically hindered /7-nitrobenzyl halides with nucleophiles by an S l mechanism affords a synthetic route to extremely sterically crowded molecules72. 

Although the alkylation of ammonia with simple alkyl halides does not generally afford high yields of 1° amines (Section 25.7A), this reaction using a-halo carboxylic acids does form the desired amino acids in good yields. In this case, the amino group in the product is both less basic and more sterically crowded than other 1° amines, so that a single alkylation occurs and the desired amino acid is obtained. 

Clearly, the steric crowding that influences reaction rates in Sn2 processes plays no role in SnI reactions. The order of alkyl hahde reactivity in SnI reactions is the same as the order of carbocation stability the more stable the carbocation, the more reactive the alkyl halide. We have seen this situation before in the reaction of alcohols with hydrogen halides (Section 4.12), in the acid-catalyzed dehydration of alcohols (Section 5.9), and in the conversion of alkyl hahdes to alkenes by the El mechanism (Section 5.17). As in these other reactions, an electronic effect, specifically, the stabilization of the carbocation intermediate by alkyl substiments, is the decisive factor. 

Relief of steric strain also influences the rate of SnI reactions, although the effect is usually relatively small. When R is large there is more steric hindrance in the tetrahedral precursor than in the planar carbocation, accelerating the ionization process. A comparison of the chlorides in Table 2.15 3ig illustrates that as the steric crowding increases, the rate of ionization is accelerated. 31g Such crowding was called back strain by Brownl3ld and it contributes to the increased rate of ionization observed with hindered halides. 32d... 

The synthesis of Cp 3U Cp = p -CsMes carved a new path for the researchers to go one step ahead in the electrochemical studies of organoac-tinide complexes. The reduction reaction involving more than two electrons are not common for metal complexes containing just one metal. However, the synthesis of complexes of the type Cp 3M led to the development of sterically induced reduction (SIR) chemistry in which sterically crowded complexes of redox inactive metals act as reductants [87,88]. Evans et al. showed that the sterically induced reduction couple, U(III)/U(IV), can act as a multielectron reductant [89]. As an example, Cp 3U reacts as a three-electron reductant with 1,3,5,7-C8H8, (Eq. 12) in which one electron arises from U(III) (Eq. 13) and two result from two CsMes /CsMes half reactions (Eq. 14) presumably via SIR. This phenomenon was further corroborated by the stepwise reduction of phenyl halide with Cp 3lJ (Eq. 15) ... 

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