Friedel-Crafts intramolecular

Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

Laurino examined a similar method in which methanesulfonanilides were alkylated with bromoacetaldehyde diethyl acetal and then cyclized with TiCU[4J. 1 hese methods presumably involve generation of an electrophilic intermediate from the acetal functionality, followed by an intramolecular Friedel-Crafts reaction. As a consequence, the cyclization is favoured by ER substituents and retarded by EW groups on the benzene ring. 

Intramolecular Friedel-Crafts substitution has also figured prominently in the synthesis of oxindoles from cx-haloacelanilides. Typical reaction conditions for cyclizalion involve heating with A1CI,[13-17]. 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Quinolin-2-one, 3-cyano-4-hydroxy-synthesis, 2, 428 Quinolin-2-one, 3,4-dialkyl-Knorr synthesis, 2, 425 Quinolin-2-one, dihydro-Camps synthesis, 2, 418 synthesis, 2, 402 from benzazepinones, 2, 506 from indanone oxime, 2, 487 from indanones, 2, 488 by intramolecular Friedel-Crafts reactions, 2, 421... 

Each of the compounds indicated undergoes an intramolecular Friedel-Crafts acylation reaction to yield a cyclic ketone. Write the structure of the expected product in each case. 

Dibenzo[7>,/]thiepins, e.g. 2, are obtained from 2-(arylsulfanyl)benzenepyruvic or -acetic acids by intramolecular Friedel-Crafts acylation, followed by elimination of water or hydrochloric acid.3 60... 

Polyphosphoric acid is a commonly used catalyst for this reaction however, in some cases a mixture of hydrogen bromide/acetic acid gives better results. Acylation of the S-phenyl-, V-(4-tolyl)- or S-(l-naphthyl)-substituted thiobenzenepyruvic acids 3a-c affords the corresponding dibenzo[A,/]thiepins in satisfactory yields, while reaction of the S-(4-methoxyphenyl) or S-(2-naphthyl) derivatives fails to provide any thiepin.60 The intramolecular Friedel-Crafts acylation of 2-(arylsulfanyl)benzeneacetic acids also yields the corrresponding dibenzothiepins in this case the use of hydrogen fluoride sometimes results in purer products.38 The applicability of this method is restricted to the synthesis of stable bisannulated thiepins. 

Of Acid Chlorides by Intramolecular Friedel-Crafts Reaction... 

Intramolecular Friedel-Crafts acylation has been observed with bonellin dimethyl ester (20).53 The reaction proceeds in contrast to corresponding porphyrins, very smoothly with concentrated sulfuric acid because the propanoic acid side chain at the sp3 center is located above the macrocyclic ring system and therefore can better fulfill the stereoelectronic requirements for the ring-closure reaction. The ring closure is accompanied by racemization in the product 21. 

By Arenes Intramolecular Friedel-Crafts Arene Acylation.189... 

Chromium carbene complexes having electron-rich arenes tethered to the car-bene oxygen or carbon underwent photodriven intramolecular Friedel-Crafts acylation in the presence of zinc chloride (Eqs. 32 and 33) [118]. The process was highly regioselective, undergoing acylation exclusively para to the activating group. 

Intramolecular Friedel-Crafts acylation of diaryl ketones Oxidation of phenols or aromatic amines Oxidation of aromatic hydrocarbons... 

In 2007, Womack et al. published the conversion of 2-aUcylcinnamyldehydes to 2-aLkylindanones via a catalytic intramolecular Friedel-Crafts reaction. In the presence of 5-10 mol% FeCls different in situ generated ( )-2-alkylcinnamaldehydes-derived dimethyl acetals cyclized to l-methoxy-2-aIkyl-7//-indenes in good to high yields (Scheme 6) [22]. The transformation corresponds to a formal intramolecular Friedel-Crafts acylation which is achieved with catalytic quantities of Lewis acid. This result is in strong contrast to traditional Friedel-Crafts acylations which require stoichiometric amounts of Lewis acid. 

Scheme 6 Iron(III)-catalyzed conversion of 2-alkylcinnamaldehydes to 2-alkylindanones via a catalytic intramolecular Friedel-Craft reaction...

Friedel-Crafts reaction remains unexplored, possibly due to the difficulty of the cycloalkyne formation. A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3-6H20-catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols (Scheme 8) [24, 25]. FeCls, InCls, and Yb(OTf)3 also exhibit good catalytic activity for the reaction. 

Scheme 8 One-step synthesis of substituted dihydro- and tetrahydroisoquinolines by FeCl3-6H20-catalyzed intramolecular Friedel-Crafts...

An interesting intramolecular Friedel-Crafts-type cyclization was developed by Pericas et al. Thus, aryl glycidyl ethers reacted to 3-chromanols as the only reaction product when treated with a catalytic amount of FeBr3 in the presence of AgOTf in CH2CI2 at room temperature (Scheme 9) [26]. The addition of a silver salt proved to... 

Ferrocene Bisimidazoline Platinacycle-Catalyzed Intramolecular Friedel-Crafts Alkylations... 

Highly reactive mixed anhydrides can also promote acylation. Phenylacetic acid reacts with alkenes to give 2-tetralones in TFAA-H3P04.55 This reaction involves an intramolecular Friedel-Crafts alkylation subsequent to the acylation. 

Friedel-Crafts alkylation can occur intramolecularly to form a fused ring. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. It is somewhat easier to form six-membered than five-membered rings in such reactions. Thus, whereas 4-phenyl-1-butanol gives a 50% yield of a cyclized product in phosphoric acid, 3-phenyl-1-propanol is mainly dehydrated to alkenes.43... 

Cyclizations can also be carried out with an esterified oligomer of phosphoric acid called polyphosphate ester, which is chloroform soluble.55 Another reagent of this type is trimethylsilyl polyphosphate (Scheme 11.4, Entry 13).56 Neat methanesul-fonic acid is also an effective reagent for intramolecular Friedel-Crafts acylation (Scheme 11.4, Entry 14).57... 

Furthermore, if the 2,4,6-triphenyl ester (187a) is dissolved in cone. H2S04 the brilliant colour of 1,3-diphenylfluorenone is at once observed—obtained via ring-closure (intramolecular Friedel-Crafts acylation) of the acyl cation (188a) ... 

A bottle of the dichloride exploded violently while on a bench. No cause was established, but diffusive ingress of moisture, or an intramolecular Friedel-Crafts reaction, both of which would form free hydrogen chloride, seem possible contributory factors. 

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. 

Derivatives 30 (R OH, R2 = iV-acetyl-indol-3-yl-(CH2)2 and (R = OEt, R2 = Ph-(CH2) (n — 2, 3)) were transformed into intramolecular Friedel-Crafts type reactions involving A-acyliminium cation intermediates into the cis-and trans-isomeric mixtures of the corresponding fused derivatives on treatment with strong acid <2000TL2745, 2001JOC5731>. 

Intramolecular Friedel-Crafts acylation of the furan ring of 403, which reacted at the 2-position, led to efficient formation of the linear 5 6 5 tricyclic system 404 in good yield (Equation 109) <1998JHC1371>. 

The 977-pyrido[3,4- ]pyrrolizin-9-one 145 has been prepared for its photochemical properties. The preparation involves an intramolecular Friedel-Crafts acylation of the acid chloride formed from 3-(l-pyrrolyl)pyridine-4-carboxy-late (Scheme 40). The product is a photosensitizer, which absorbs visible light its absorption spectra are pH, solvent, and concentration dependent <1994SAA57>. 

Titanium-mediated intramolecular Friedel-Crafts acylation and alkylation are important methods for construction of fused-ring systems (Scheme 29).107 As well as aromatics, olefin units also react in the same way.108 Alkylation of electron-rich olefins such as enol ethers or silyl enol ethers proceeds effectively in the presence of TiCl4.109... 

Typically in ring-opening reactions of aziridines, the amine functional group is retained in the product molecule. An example of such a reaction where the amine group has been lost has recently been reported <06TL977>. An intramolecular Friedel-Craft reaction of aziridine 91 leads to the expected product as an intermediate. Under the rather drastic reaction conditions, the sulfonamide is lost leading to formation of the naphthalene ring. 

A synthesis of 2-acyl and 2-alkoxycarbonyl-indoles was carried out by Tamariz and coworkers via an intramolecular Friedel-Crafts heteroannulation of enaminone precursors <06SL749>. A lac type palladium-catalyzed intramolecular indolization of alkyne-tethered 2-chloroanilines has been reported by Lu and co-workers <06OL3573>. 

Intramolecular Friedel-Crafts reactions can sometimes compete with organosil-icon hydride reductions of benzylic-type alcohols to cause formation of undesired products. An example is the attempted reduction of alcohol 26 to the corresponding hydrocarbon. When 26 is treated with triethylsilane in trifluoroacetic acid at room temperature for 15 hours, a mixture of the two fluorene isomers 27 and 28 is obtained in a combined yield of 45%. None of the hydrocarbon structurally related to the substrate alcohol 26 is obtained.171 Whether this problem could be circumvented by running the reduction at a lower temperature or with a different acid remains subject to experimentation. 

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