Intermolecular Friedel-Crafts alkylation

First, intermolecular Friedel-Crafts alkylations take place as mono functionalizations of the aromatic ring when the primary product cannot take up any additional alkyl group for steric reasons (Figure 5.28, formation of A and B). 

In contrast to the intramolecular case just mentioned, in intermolecular Friedel-Crafts alkylations secondary carbenium ion intermediates often have sufficient time to undergo a Wagner-Meerwein rearrangement (cf. Section 14.3.1). This can lead to the formation of an unexpected alkylation product or product mixtures ... 

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. ... 

The intermolecular hydroarylation of indoles or pyrroles with alkynes in the presence of cationic gold(I) catalysts leads to 2 1-adducts With (Z)-2-en-4-yn-l-ols as an unsaturated reaction partner, indoles are converted into dihydrocyclohepta[ )] indoles in a one-pot reaction sequence that involves a gold-catalyzed intermolecular Friedel-Crafts alkylation followed by an intramolecular hydroarylation (Scheme 4-9). ... 

Similar to Rueping s procedure, Hua and coworkers developed a BiCl3-catalyzed synthesis of 1,1-diarylalkanes also starting from electron-rich arenes and styrenes [68]. They found that styrenes 37 could be transformed to the substituted cyclopentanes 39 if catalytic amounts BiCl3 were applied (Scheme 30). This reaction is believed to proceed via an intermolecular ene-reaction between styrene and the carbocationic intermediate I, followed by an intramolecular Friedel-Crafts alkylation of the resulting intermediate II. 

The synthesis of 2,4-diarylchromen-2-ols through the reaction of phenols with an excess of a chalcone in TFA involves sequential Friedel-Crafts alkylation, cyclisation to a 4/7-1-benzo-pyran, an intermolecular hydrogen transfer generates the 4-arylflavylium ion which is hydrated to give the final product (Scheme 12) <07JOC9383>. 

The indane structure is formed by an intramolecular Friedel-Crafts alkylation. To prevent intermolecular alkylation and standard vinyl polymerization, respectively, the polymerization is performed at high dilution and above the monomer s ceiling temperature. 

Intermolecular Friedel-Crafts acylation of various substituted alkyl alkoxyben-zenes 1257 with oxalyl chloride using 1,2-dichloroethane [942] or carbon disulfide [943] as solvent gives rise to benzils 1258. 

The generation of an iminium ion of a, 3-unsaturated carbonyl compounds lowers the LUMO energy. As a result, the cx-CH acidity increases as well as the ability to participate in conjugate additions. The first organocatalyzed 1,4-addition to a,j3-unsaturated aldehydes was reported by the MacMillan group [78]. For theoretical explorations of the configurative outcome of Michael additions of pyrroles and indoles to crotonaldehyde see Reference [79]. This transformation has been widely used in Friedel-Crafts alkylations of a,(5-unsaturated carbonyl compounds (see Reference [lb] and reports cited therein). Comparable examples of this transformation with ( )-crotonaldehyde in the intermolecular series were found in aryl alkylation with trifluoroborate (58 and 60) [80], indole alkylation (62) [81], Friedel-Crafts alkylation of electron-rich benzenes (64) [82], and Friedel-Crafts alkylation with phosphonates (65) [83] (Scheme 4.21). 

Two successive Friedel-Crafts alkylation reactions (the first intermolecular and the second intramolecular) will form the desired additional ring. 

Electrophilic ring closure of aryl-substituted compounds such as alkenes, halides, alcohols, and carbonyl compounds called cyclialkylation can be induced by conventional Friedel-Crafts catalysts309 and by superacids. Examples are also known in which an intermolecular alkylation step is followed by intramolecular alkylation of the intermediate to furnish a cyclic product. 

Other reactions of allyl- and vinyl-phosphine oxides include a detailed study of their intermolecular cyclization by a Friedel-Crafts-type procedure. In certain cases, the unsaturated oxides are generated in situ from /S-hydroxyalkyl(diphenyl)-phosphine oxides. Examples are given in Scheme 12 for the oxides (54)—(56). Control of double-bond position in the products of acid treatment of the oxides (57) has been achieved by using an organosilicon substituent. Thus simple alkyl... 

Generalized Friedel-Crafts Intermolecular Alkylation Reaction RiXor R-iOH or... 

Generalized Friedel-Crafts Intermolecular RX/ROH Alkylation Mechanism... 

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