Arenes Friedel-Crafts addition

A gold(I)-catalyzed tandem heterocyclization/Friedel-Crafts addition (aryl C(sp )-H functionalization) between enynes 105 and electron-rich arenes 106... 

Gold-catalyzed direct C-H functionalizations enable the formation of polyalkylated arenes under mild conditions. In many cases, branched products are obtained. Two mechanisms are thought to operate with electron-rich arenes, an S si2-type mechanism via Au(lll) leads to the linear product. The branched product is obtained via a Friedel-Craft-type alkylation. A silver salt is often added and is believed to generate a more electrophilic Au(m) species. Often regioselectivities are poor and symmetric arenes are employed. Intramolecular variants as well as Michael additions are also known (Equations (72)-(74)).71,71a,71b... 

The addition of BF3 OEt2 to a solution containing Ph3BiF2, allyltrimethylsilane and excess arenes induces a Friedel-Crafts-type allylation at low temperatures to yield allylarenes [36]. Benzene, toluene, anisole, p-xylene, and p-dimethoxyben-zene were all allylated with ease to give the corresponding allylation products, although diallylation could not be suppressed in the reaction with electron-rich... 

The first systematic investigations of the catalytic Friedel-Crafts-type reaction with alcohols and olefines were performed by Yamamoto and colleagues. After reporting the development of a Pd-catalyzed method for the allylation of different naphthol derivatives [24], the authors used Mo(CO)g for the Friedel-Crafts-type alkylation of electron-rich arenes with allyl acetates [25], The same molybdenum catalyst was additionally used for a Friedel-Crafts-type alkylation of arenes using 1-phenylethanol and styrene as alkylating reagents [26], However, Mo(CO)g is toxic and must be handled under strictly inert conditions. Thus, more stable Lewis acids were necessary. 

In most instances these catalysts were not satisfactory in terms of yield, range of substrates and turnover numbers of the catalyst. Additionally, they were mostly efficient only in the case of activated aromatics. In order to develop also Friedel-Crafts acylations of less activated or even deactivated arenes, a new generation of catalysts had to be developed. Here, particularly bismuth(III) triflate [33] and hafnium(IV) triflate in the presence of lithium perchlorate [34] or triflic acid [35] are effective, alternative catalysts actually acylating benzene, toluene and halobenzenes. 

These catalytic reactions provide a unique pathway for addition of aromatic C-H bonds across C=C bonds. In contrast with Friedel-Crafts catalysts for olefin hydroarylation, the Ru-catalyzed hydrophenylation reactions of a-olefins selectively produce linear alkyl arenes rather than branched products. Although the selectivity is mild, the formation of anti-Markovnikov products is a unique feature of the Ru(II) and Ir(III) catalysts discussed herein. Typically, the preferred route for incorporation of long-chain linear alkyl groups into aromatic substrates is Friedel-Crafts acylation then Clemmensen reduction, and the catalysts described herein provide a more direct route to linear alkyl arenes. 

Acybaion. These anhydrides are powerful acylating agents. Thus nonactivated arenes such as benzene arc readily acylatcd without addition of Friedel Crafts catalysis ... 

Oxoalkylbismuthonium salts react with a sodium salt of dibenzoylmethane to alkylate the active methylene carbon [304]. Treatment of a mixture of Ph3BiF2 and allyltrimethylsilane with lii, -O Hl, in the presence of excess electron-rich arenes yields allylated arenes via the Friedel-Crafts reaction (Scheme 14.149) [305]. The action of tBuOK on a mixture of alkenylbismuthonium salt and styrenes gives al-kylidenecyclopropanes in high yield (Scheme 14.150) [306]. Michael addition of sodium p-toluenesulfinate to a 1-hexynylbismuthonium salt results in the formation of 3-methyl-l-tosylcyclopentene [307]. 

As with the calix[n]arene family, the oxacalixarenes may also be derivatized to yield compounds with deeper cavities or greater functionality. Unfortunately, unlike the calix[n]arenes, the 4-t-butyl group cannot be removed using retro-Friedel-Crafts methods as the etheric links are not robust under the conditions necessary. The best way to introduce functionality to the upper rim is to build it in at the start. This approach may be problematic as the precursor 2,6-bis(hydroxy) phenol derivatives are often formed in low yield or are impossible to prepare in a single step. Despite these difficulties a diverse range of such compounds exist in addition to the simple 4-t-butyl and 4-methyl derivatives bromo- and benzylox-acalix[3]arenes that bind fullerenes [1-3] have both been reported. 

Friedel-Crafts benzylation. The benzylation of arenes proceeds in good yields with benzyl chloride as reagent when ZnCh is activated by the addition of a ketone, a primary alcohol, or water. ... 

Catalytic enantioselective Friedel-Crafts type addition reactions of electron-rich arenes (indoles, pyrroles etc.) with Michael acceptors have been well developed in the past years. These reactions generally are enabled by chiral Lewis acids or organocatalysts (Scheme 6.24). Chiral Lewis acid-catalyzed processes usually require bidentate substrates (chelating a,p-unsatu-rated compounds) for strong chelation activation. Monodentate compounds (simple a,p-unsaturated compounds) prove to be less selective. With chiral... 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

Subsequently, Hennessy and Buchwald [26] disclosed an intramolecular C-H alkylation affording oxindoles from aelectron-deficient arenes, reflecting the complementary scope of this reaction with the traditional Friedel-Crafts reaction. The basic reaction conditions also allowed the use of functional groups that are incompatible with strong Lewis acids. On the basis of the kinetic isotope effects (KIEs), three different mechanisms were proposed with a common initial step of oxidative addition, which... 

Transfer of selectivity from the lower to the upper rim is the most useful method for the selective synthesis of partially functionalized calixarenes at the upper rim. Indeed, one can exploit the different reactivity of aryl ethers compared to phenols to introduce, regioselectively, additional functional groups at the upper rim of partially alkylated calixarenes. Moreover, if l,3-dialkoxy-/ -r rt-butylcalix[4]arenes are submitted to the reverse Friedel-Crafts reaction, the tert-hwiyX groups are detached only from the para position of the phenolic nuclei, obtaining compounds where only two diametral aromatic rings are available for further functionalization. 

The starting material for assembly of asar[ ]arene macrocycles is tetramethoxybenzene (12.31), which can be prepared from commercial dihydrojybenzoquinone (12.33) in abundant quantities. We subjected (Scheme 12.11) a mixture of tetramethojybenzene and paraformaldehyde to Friedel-Crafts alleviation conditions at 80 °C in chlorinated solvents, with BF3 OEt2 as the Lewis acid. Influenced by the prior work on the synthesis of pillar[n]arenes - where pillar[5]arene is formed primarily under similar reaction conditions - we were expecting this reaction mixture to form asar[5]ar-ene as the major product. To our surprise, we found, however, that the reaction mixture produced only asar[6]arene and not even a trace of asar[5]arene. It is most likely that the increased steric demand imposed on the macrocyclic framework by the two additional methojyl groups not present in pillar[ ]arenes is responsible for this striking difference in reactivity between the asar[ ]arene and pillar[ ]arene families of macrocycles. Soxhlet extraction of the crude reaction mixture with acetonitrile as the solvent was then used as a scalable method of purification to access pure asar[6]arene (12.32a) in bulk quantities. 

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