Electrophilic reaction with Lewis acids

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

Study of the reactivity of aromatic C-H bonds in the presence of transition metal compounds began in the 1960s despite the quite early discovery of Friedel-Crafts alkylation and acylation reactions with Lewis acid catalysts. In 1967, we reported Pd(II)-mediated coupling of arenes with olefins in acetic acid under reflux [1], The reaction involves the electrophilic substitution of aromatic C-H bonds by a Pd(II) species, as shown in Scheme 2, and this is one of the earliest examples of aromatic C-H bond activation by transition metal compounds. Al-... 

Compared to monodentate Lewis acid (19), bidentate Lewis acid (17) resulted in higher electrophilic activation of carbonyl compounds. For example, in the presence of Lewis acid (17), BusSnH reduction of acetophenone smoothly proceeded at —78 °C to give phenylethanol in 91% yield. A similar reaction with Lewis acid (19) gave phenylethanol in only 9% yield (Scheme 6.43). 

Electrophilic Reactions. Perfluoroepoxides are quite resistant to electrophilic attack. However, they react readily with Lewis acids, for example SbF, to give ring-opened carbonyl compounds (20—22) (eq. 2). 

As is the case for aldol addition, chiral auxiliaries and catalysts can be used to control stereoselectivity in conjugate addition reactions. Oxazolidinone chiral auxiliaries have been used in both the nucleophilic and electrophilic components under Lewis acid-catalyzed conditions. (V-Acyloxazolidinones can be converted to nucleophilic titanium enolates with TiCl3(0-/-Pr).320... 

Specific examples include treatment of o-stannyl benzyl alcohols with TFA,55 reactions of ketones and aldehydes with Lewis acids,56 and electrophilic selenation of styrenes.57... 

The best carbonyl components for these reactions are highly electrophilic compounds such as glyocylate, pyruvate, and oxomalonate esters, as well as chlorinated and fluorinated aldehydes. Most synthetic applications of the carbonyl-ene reaction utilize Lewis acids. Although such reactions may be stepwise in character, the stereochemical outcome is often consistent with a cyclic TS. It was found, for example, that steric effects of trimethylsilyl groups provide a strong stereochemical influence.28... 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

The synthesis of 3-aryltetrahydroisoquinolines was accomplished by electrophilic aromatic substitution of polysubstituted phenols and phenyl ethers with Lewis acid-generated tosyliminium ions of 2-tosyl-3-methoxytetrahydroisoquinoline derivatives <00SL801>. In addition isoquinoline was reported to react with N-tosylated (R)- or (S)-amino acid fluorides to afford optically active dihydroimidazoisoquinolinones. The reaction proceeds via acylation followed by attack of the tosylamino group at Cl of the intermediate 2-tosylaminoacylisoquinolinium salt <00TL5479>. 

Hydroxy carboxylic acid can be used as a 1,3-diol analog in a similar reaction. Subsequent Lewis acid-mediated electrophilic attack takes place with excellent diastereoselectivity.99... 

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

Intramolecular ene reactions can also be carried out with Lewis acid catalysts. Several examples are included in Scheme 6.15. Mechanistic analysis of Lewis acid-catalyzed reactions indicates they may more closely resemble an electrophilic substitution process related to reactions which will be discussed in Section 10.1.1.210... 

If solutions of CgQ in aromatic hydrocarbons are treated with Lewis acids, such as AICI3, AlBrj, FeBrj, FeClj, GaClj or SbClj, then a fullerylation of aromatics takes place (Scheme 8.11) [66, 88, 90, 91], In this case, the Lewis acid serves as a catalyst and increases the electrophilicity of the fullerene. Mixtures of polyarylated fullerenes are obtained. Depending on the reaction conditions and the aromatic used for the fullerylation, up to 16 aryl groups are covalently bound to the fullerene core [66, 88,... 

Because of the presence of a lone pair and a vacant orbital, singlet carbenes are supposed to be able to react with both Lewis bases and acids. Transient electrophilic carbenes are known to react with Lewis bases to give normal ylides (Scheme 8.19). For example, carbene-pyridine adducts have been spectroscopically characterized and used as a proof for the formation of carbenes,and the reaction of transient dihalogenocarbenes with phosphines is even a preparative method for C-dihalogeno phosphorus ylides. Little is known about the reactivity of transient carbenes with Lewis acids. 

Neutral aminyl radicals (I), also referred to as amino radicals, can be considered to be nucleophilic species whereas aminium cation radicals (II), metal complexed aminyl radicals (III), and amidyl radicals (IV) are electrophilic in nature. Greater utility has been observed with electrophilic nitrogen radicals than with neutral aminyl radicals (71 SI). Aminyl radicals are easily protonated with Br0nsted acids to give aminium cation radicals and readily complex with Lewis acids to form radicals III therefore, control of the reaction conditions is critical to ensure that reactions of interest are occurring from only one species. 

In most of the examples of superelectrophilic reactions involving Lewis acids, they are conducted using an excess of the Lewis acid. This is in accord with electrophilic solvation by the Lewis acid, i.e. activation of the electrophile requires interaction with two or more equivalents of Lewis acid. As an example, superelectrophilic nitration can be accomplished with NO2CI and at least three equivalents of AICI3 (eq 23).46 This powerful nitrating reagent involves a superelectrophilic complexed nitronium ion (33). 

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