Alkyl electrophiles, sources

The Friedel-Crafts alkylation is a classic illustration of the general class of electrophilic aromatic substitutions. Traditionally, Friedel-Crafts reactions require an alkyl halide as the electrophile source and at least a molar equivalent of aluminum chloride, a hygroscopic and caustic powder that is rather problematic to use in the introductory lab. An easy variant of this procedure utilizes the reactive substrate 1,4-dimethoxybenzene, /er butyl alcohol as the electrophile precursor, and sulfuric acid as the catalyst (72). We run this reaction on a microscale, and use commercial rubbing alcohol (70% aqueous 2-propanol) in place of methanol as the recystallization solvent. The product, l,4-di-7er/-butyl-2,5-dimethoxybenzene, exhibits simple and NMR, and... 

Similar results were reported by Reed in 2009 previously, triflic acid, methyl triflate, and trial-kylsilyl triflate have been used as electrophilic sources of H+ for protonation, of CH3+ for alkylation, and of R3Si" for silylation, respectively. Replacement of these anions by [CHBuRjXgl (R = H, Me X = Cl, Br) increases the electrophilicity of the cations and avoids the nucleophilic chemistry of the anion this allows various reactions that are not possible with commonly used reagents. 

While the metal-catalyzed fluorination of benzyl C—H bonds has generated a host of valuable compounds, extending this chenustry to saturated hydrocarbons remains a current and significant challenge. To address this issue, a successful approach for the copper-catalyzed fluorination of unfunctionaUzed hydrocarbons has been devised (Example 7.5) [23, 24]. The catalyst for this reaction was an bisimine copper complex, and Selectfluor was used as an electrophilic source of fluorine. The copper complex was essential for the reaction as no fluorination was observed in its absence. A host of cyclic and acyclic saturated hydrocarbons were successfully fluorinated using this approach, and moderate to good yields of the alkyl fluorides were obtained. For substrates such as ethylbenzene and dihydrocoumarin, fluorination of the benzylic position was preferred. 

In summary, lithium alkyl aryl sulfoxides can be efficiently used as equivalents of chiral a-hydroxy alkyl carbanion in the synthesis of 3-fiuoroalkyl 3-amino alcohols. On the other hand, fluorinated imines are versatile and readily available electrophilic sources of fluoroalkyl/fluoroaiyl amino groups. Excellent stereocontrol and reactivity can be achieved using aldimines A-protected with a PM group, which also makes fluorinated aldimines electronrich enough to be easy to handle. Furthermore, the PMP group can be cleaved readily and under mild conditions, thus representing the... 

Evidence from a variety of sources however indicates that alkenyl cations (also called vinylic cations) are much less stable than simple alkyl cations and their involve ment m these additions has been questioned Eor example although electrophilic addi tion of hydrogen halides to alkynes occurs more slowly than the corresponding additions... 

A variety of reagent combinations add fluorine and sulfur to fluonnated olefins. Typically the olefin is reacted with fluoride ion and a source of electrophilic sulfur, such as sulfur tetrafluonde[757,178,179, 7S0], alkyl or amino sulfur tnfluondes [757, 787],... 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

Stannyllithium compounds are important as sources of nucleophilic stannyl anions, and the dialkyltin lithium hydrides, R2SnLiH, have recently come to prominence as their reaction with electrophilic alkyl halides gives hydrides, R1R2SnH, with mixed alkyl groups (see Section 3.14.18.1).397... 

When the conjugate addition is carried out under kinetic conditions with stoichiometric formation of the enolate, the adduct is also an enolate until the reaction mixture is quenched with a proton source. It should therefore be possible to effect a second reaction of the enolate if an electrophile is added prior to protonation of the enolate. This can be done by adding an alkyl halide to the solution of the adduct enolate, which results in an alkylation. Two or more successive reactions conducted in this way are referred to as tandem reactions. 

Seemingly anomalous effects of substituents are known, but such effects may be due to equilibrium control. One example is the aluminum chloride-catalyzed alkylation of benzene, which leads to the formation of a 1,3,5-trialkylbenzene in preference to the expected 1,2,4-isomer (see Section 22-4E). The preferred reaction occurs particularly readily because alkylation is reversible and because alkylation is one of the least selective of the electrophilic aromatic substitutions (considerable meta isomer is formed even under conditions where kinetic control is dominant). Equilibrium control, which favors the 1,3,5-product rather than the less stable 1,2,4-product, becomes most evident when the reaction time, the reaction temperature, and aluminum chloride concentration are increased. Another source of anomalous substituent effects is discussed in the next section. 

The rates of bromine atom abstraction by tris(trimethylsilyl)silyl radicals from a range of /Jara-substitutcd benzyl bromides has indicated that the silyl radical is nucleophilic. In addition both the polar and spin-delocalization effects of the substituents play a role in the abstraction reaction with the latter effect greater than for H-atom abstractions.166 The perfluoroalkylation of aromatics and alkenes has been investigated using C4F9I as the source of C,. Measurement of rate constants indicated that perfluoroalkyl radicals were 2-3 orders of magnitude more reactive than the corresponding alkyl radicals. This was attributed primarily to the reaction enthalpy and far less to the electrophilic nature of the radicals.167... 

The alkylation of ( )-spirolactones (34a) and (34b) with higher diastereoface selectivity has been modelled by geometry-optimized ab initio 4-31G calculations which suggest that approach of the electrophile occurs at an angle of ca 80° to the plane of the enolate and with some displacement away from the oxygen linked to the metal ion.41 Asymmetric a-methylation of phenylalanine derivatives has been achieved with 82% ee and retention of configuration in the absence of any external chiral source.42... 

Two of the reactions that are used in the industrial preparation of detergents are electrophilic aromatic substitution reactions. First, a large hydrocarbon group is attached to a benzene ring by a Friedel-Crafts alkylation reaction employing tetrapropene as the source of the carbocation electrophile. The resulting alkylbenzene is then sulfonated by reaction with sulfuric acid. Deprotonation of the sulfonic acid with sodium hydroxide produces the detergent. 

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