Friedel-Crafts alkylation with alcohols

SCHEME 10.21 Calcium-catalyzed intramolecular Friedel-Crafts alkylation with alcohols. 

On the basis of these initial results, various rare earth metal triflates, including Sc(OTf)3, Hf(OTf)4 and Yb(OTf)3 were applied as catalysts [27-29]. Recently Beller and coworkers developed efficient Friedel-Crafts alkylations with catalytic amounts of Rh, W, Pd, Pt and Ir complexes [30] or FeCl3 [31-34] as Lewis acid catalysts. However, in the latter cases high catalyst loadings had to be applied. To overcome these major drawbacks, we decided to develop a Bi(III)-catalyzed Friedel-Crafts alkylation of arenes with benzyl alcohols. Although bismuth-catalyzed Friedel-Crafts acylations were well known at this time, Friedel-Crafts alkylations using benzyl alcohols had not been reported. 

Fujiwara et al.227 tested a nanocomposite material having Nafion immobilized in MCM-41 mesoporous silica in Friedel-Crafts alkylations with benzyl alcohol. Whereas Nafion-MCM-41 showed lower activity in the alkylation of toluene than 13% Nafion SAC-13 under identical conditions, it exhibited increased activity when used in the alkylation of para-xylene. 

Reductive Friedel-Crafts alkylation Benzylic alcohols obtained from the InClj-catalyzed alkylation with aldehydes can be reduced in situ by a hydrosilane (e.g., chlorodimethylsilane). The latter process is also catalyzed by Lewis acid. 

Phenols undergo Friedel-Crafts alkylations with allylic chlorides or allylic alcohols over solid acid catalysts such as acidic KIO clay. For example, 2-buten-l-ol gives 3-aryl-1-butene and 1-ary 1-2-butene, albeit in low yields (12%) (equation 11). Allyl carbocations are involved as the reaction intermediates in these reactions. ... 

The intermolecular Friedel-Crafts alkylation with benzyUc and aUyUc halides occurs at room temperature in CH2CI2. Diarylmethanes are also obtained in moderate yields from arenes and benzyl alcohols on heating the mixtures with InCls 4H2O and acetylacetone at 120°. l-VinyltetraUn and 4-vinyltetrahydrDisoquinoline derivatives are readily formed by an intramolecular aUylation. ... 

Other reactions include enamination, " acetalization, dithioacetalization, Friedel-Crafts alkylation with allylic alcohols and tertiary alcohols."... 

C. Friedel-Crafts Alkylation with Alkenes and Alcohols... 

SCHEME 10.20 Calcium-catalyzed intennolecular Friedel-Crafts alkylation with Jt-activated alcohols. 

Benzyl and allyl alcohols which can generate stabilized caibocations give Friedel-Crafts alkylation products with mild Lewis acid catalysts such as scandium triflate. ... 

Friedel-Crafts alkylation Alcohols in combination with acids serve as sources of carbocations. Attack of a carbocation on the electron-rich ring of a phenol brings about its alkylation. 

The synthesis of an alkylated aromatic compound 3 by reaction of an aromatic substrate 1 with an alkyl halide 2, catalyzed by a Lewis acid, is called the Friedel-Crafts alkylation This method is closely related to the Friedel-Crafts acylation. Instead of the alkyl halide, an alcohol or alkene can be used as reactant for the aromatic substrate under Friedel-Crafts conditions. The general principle is the intermediate formation of a carbenium ion species, which is capable of reacting as the electrophile in an electrophilic aromatic substitution reaction. 

As catalysts Lewis acids such as AICI3, TiCU, SbFs, BF3, ZnCh or FeCl3 are used. Protic acids such as FI2SO4 or FIF are also used, especially for reaction with alkenes or alcohols. Recent developments include the use of acidic polymer resins, e.g. Nafion-Fl, as catalysts for Friedel-Crafts alkylations and the use of asymmetric catalysts. ... 

Scheme 4 FeCb catalyzed Friedel-Crafts alkylations of indoles with alcohols...

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

In addition to 1-phenylethanol and benzyl alcohol, cinnamyl alcohol has also been utilized as alkylating reagent. In contrast to the Bi(OTf)3-catalyzed Friedel-Crafts alkylation of benzyl alcohols, in which the corresponding acetate was shown to be more reactive than the free benzyl alcohol (Scheme 8), in this case the alkylation with cinnamyl alcohol or the corresponding acetate provided almost similar results. With 5 mol% BifOTfh. the desired allylated 2,4-pentanediones were isolated in good yields (Scheme 15). 

The Friedel-Crafts alkylation reaction usually involves the interaction of an alkylation agent such as an alkyl halide, alcohol, or alkene with an aromatic compound, to form an alkylated aromatic compound (Scheme 5.1-44). 

Besides aluminum chloride, the most often used and studied Friedel-Crafts catalyst, many other acid catalysts are effective in alkylation. Although Friedel-Crafts alkylation was discovered and explored mainly with alkyl halides, from a practical point of view, alkenes are the most important alkylating agents. Others include alcohols, ethers, and esters. 

Acidic clay catalysts can also be used in alkylation with alcohols 98 The main advantages of these catalysts are the reduced amount necessary to carry out alkylation compared with conventional Friedel-Crafts halides, possible regeneration, and good yields. Natural montmorillonite (K10 clay) doped with transition metal cations was shown to be an effective catalyst 200... 

A novel mesoporous intercalate belonging to the class of mesostructured solid acids known as porous clay heterostructures (PCH) has been synthesized through the surfactant - directed assembly of silica in the two - dimensional galleries of saponite. The new saponite PCH, denoted SAP-PCH, exhibits a basal spacing of 32.9 A, a BET surface area of 850 m2/g and pore volume of 0.46 cm3/g. SAP-PCH is an effective catalyst for the condensed phase Friedel-Crafts alkylation of bulky 2,4-di-tert-butylphenol (DBP) with cinnamyl alcohol to produce a large flavan, namely, 6,8-di-tert-butyl-2,3-dihydro[4H]benzopyran. 

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