Methylcyclopentane alkylation with

Cycloalkanes possessing a tertiary carbon atom may be alkylated under conditions similar to those applied for the alkylation of isoalkanes. Methylcyclopentane and methylcyclohexane were studied most.5 Methylcyclopentane reacts with propylene and isobutylene in the presence of HF (23-25°C), and methylcyclohexane can also be reacted with isobutylene and 2-butene under the same conditions.20 Methylcyclopentane is alkylated with propylene in the presence of HBr—AlBr3 (—42°C) to produce l-ethyl-2-methylcyclohexane.21 C12H22 bicyclic compounds are also formed under alkylation conditions.21 22 Cyclohexane, in contrast, requires elevated temperature, and only strong catalysts are effective. HC1—AICI3 catalyzes the cyclohexane-ethylene reaction at 50-60°C to yield mainly dimethyl- and tetra-methylcyclohexanes (rather than mono- and diethylcyclohexanes). The relatively weak boron trifluoride, in turn, is not active in the alkylation of cyclohexane.23... 

Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at... 

None of the 3-methylpentene isomers formed more methylcyclopentane than did 3-methylpentane. With the alkene-alkyl insertion mechanism the reverse should be expected, especially for 3-methyl-l-pentene. 

One of these initiator radicals should react with methylcyclopentane to give a free-radical version of methylcyclopentane. As we have seen, a bromine or chlorine radical can abstract a hydrogen atom from an alkane to generate an alkyl radical. The bromine radical is highly selective, and the most stable alkyl radical should result. Abstraction of the tertiary hydrogen atom gives a tertiary radical. 

Cyclic 1,2-diketones, such as3-methylcyclopentane-l,2-dione, act as oxygen nucleophiles in palladium(0)-catalyzed reactions with a range of cyclic and acyclic allylic esters. The products of these reactions were subjected to a lanthanide-catalyzed Claisen rearrangement to access the C-alkylated products. 

In a study of the reaetion between alkyl halides and the electrogenerated naphthalene radical anion, Sease and Reed [297] observed that only alkyl chlorides, such as 1-chloro-hexane and 6-chloro-l-hexene, are catalytically reduced 1-chlorohexane gives only n-hex-ane, whereas 6-chloro-l-hexene affords methylcyclopentane and 1-hexene. In an earlier paper [296], the reactions of 1-bromo- and 1-chlorobutane with the electrogenerated radical anions of rmn -stilbene and anthracene in DMSO were examined. Britton and Fry [298] elucidated the kinetics of the electron-transfer reaction between 1-chlorooctane and the phenanthrene radieal anion in DMF. 

D.1. Reactions with Nucleophiles. Previously, a jr-allylic palladium complex was generated by reaction of palladium reagents with allylic hydrocarbons prior to reaction with nucleophiles. In the catalytic version of this reaction, an allylic halide or an allylic acetate is used with a palladium(O) reagent. Why use a palladium complex when enolate alkylation is a well-known process (sec. 9.3.A) A typical enolate coupling reaction is the conversion of 2-methylcyclopentane-l,3-dione (373) to the enolate anion by reaction with NaOH, allowing reaction with allyl bromide. Under these conditions only 34% of 374 was obtained. When allyl acetate was used in place of allyl bromide in this reaction and tetra w(triphenylphosphino)palladium was used as a catalyst, a 94% yield of 374 was obtained.224 in this reaction, formation of the Jt-allyl palladium complex facilitated coupling with the nucleophilic enolate derived from 373, which exhibited poor reactivity in the normal enolate alkylation sequence. 

Insertion into C-H bonds is more probable than insertion into C-C bonds. Insertion into C-C bonds does not appear to occur at all. For example, photolysis of diazomethane in cyclopentane at —75 °C produced only methylcyclopentane, with cyclohexane not being observed. Singlet carbenes are thought to add to C- H bonds by a concerted process, while triplet carbenes can produce net addition through hydrogen abstraction and then recombination of the alkyl radicals. It was found that o-(2-endo-norbornyl)phenylcarbene inserts into the 3-position in such a way as to give a trans-junction (Scheme 5.47). 

The reaction is stereospecific the alkyl group migrates with retention of configuration, as illustrated for the oxidation of c/5-l-acetyl-2-methylcyclopentane only the cis product is obtained. 

The alkyl radical should react with another starting-material molecule, in another prq>a-gation step, to generate a product and another radical. Reaction of the alkyl radical with Br2 gives 1-bromo-l-methylcyclopentane (the major product) and another bromine radical to continue the chain. 

Retrosynthetic analysis of nitrile 164 disconnects the C-CN bond because it is clear that the six carbons of the methylcyclopentene starting material are more or less intact in the remainder of the molecule. This disconnection requires a C-C bond-forming reaction involving cyanide. Because cyanide is associated with a carbon nucleophile, assign Cj to the cyanide and to the cyclopentene carbon. The synthetic equivalent for Cg is an alkyl halide, and 2-bromo-l-methylcyclopentane (168) is the disconnect product. Bromide 168 is obtained directly from the alkene starting material, but it requires the use of a radical process to generate the anti-Markovnikov product (see Chapter 10, Section 10.8.2). 

The forward scheme is shown here. Methylcyclopentane will undergo radical bromination selectively at the tertiary position, giving a tertiary alkyl bromide. This aUcyl bromide will undergo an elimination reaction upon treatment with a strong base, such as sodium ethoxide. Ozonolysis of the resulting alkene gives a dicarbonyl compound, which can then be converted into the product upon treatment with methyl amine and sodium cyanoborohydride (with acid catalysis) ... 

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