Synthesis intramolecular Friedel-Crafts reaction

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... 

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. 

This method, however, is still not practical from a synthetic point of view, because a much more efficient synthesis of 29 and an equivalent oxindole 12 of the Jones synthesis had already been established in 1935 by Julian and Pikl starting from p-ethoxyacetanilide (131) and employing the intramolecular Friedel-Crafts reaction in the synthesis of physostigmine (1) 38,44) (Scheme 20). 

Substituted 2 f-l,2,4-benzothiadiazin-3(4//)-one 1,1-dioxides are available by a one-pot intramolecular Friedel-Crafts reaction involving the action of chlorosulfonyl isocyanate on a secondary aromatic amine in the presence of aluminum chloride <85IJC(B)1295>. Chlorosulfonyl isocyanate is also employed in the synthesis of oxazolo- and thiazolo[2,3-z(][l,2,4]-thiadiazin-3(2//)-ones (196 X = O and S) from 2-ethyloxazolines (195 X = O) and 2-ethylthiazolines (195 X = S) respectively (Scheme 33) <93SC121>. 

Basavaiah, D. and Reddy, R. M. 2001. One-pot inter- and intramolecular Friedel-Crafts reactions in Baylis-Hillman chemistry a novel facile synthesis of (E)-2-arylideneindan-l-ones. Tetrahedron Lett. 42 3025-3027. 

A possible synthesis of three-membered ring compound (28) is by intramolecular Friedel-Crafts reaction on acid chloride (29) and some chemists wished to investigate this possibility. They first had to synthesise... 

Searchable data bases have for some time now simplified the search for the more routine methods of 7-membered ring synthesis. For this reason it seems reasonable to omit yet further examples of cyclisation by cyclocondensation or intramolecular Friedel-Crafts reaction, as well as new examples Schmidt and Beckmann ring expansion reactions, unless specific mechanistic or stereochemical features are of interest. 

The MBH adducts, derived from methyl acrylate and aldehydes, have been employed successfully to the general synthesis of 3-arylidene(alkylidene)chro-man-4-ones 94, which involved an intramolecular Friedel-Crafts reaction as... 

In 2009, Nicolaou and co-workers reported an organocatalytic total synthesis of demethyl calamenene (168), a potent cytotoxic agent, which is a beautiful application of SOMO-activated catalysis (Scheme 17.29) [68]. The key step involved an asymmetric intramolecular Friedel-Crafts reaction of aldehyde 166 to achieve the bicyclic aldehyde 167 using imidazolidinone 122 as a SOMO-activated catalyst (56% yield, 90% ee). 

Iron salts have recently attracted considerable attention as inexpensive and environmentally friendly agents in a wide range of selective processes in organic synthesis. Over the past decade, FeCls 6H2O has shown to be an effective catalyst in the formation of carbon-carbon or carbon-nitrogen bonds, in intramolecular Friedel-Craft reactions and in the reduction of ketones or allylic alcohols. ... 

Another example is an intramolecular Friedel-Crafts reaction with the participation of compounds of type (280). Here the question arises of the stereochemistry of the linkage of the two nonaromatic rings, one already present in the molecule and the other newly formed by cyclization. In almost all cases investigated, the product of the reaction (281) had predominantly the c is-linkage of these rings (Schemes 32, 49, 51, 83, 88). The only exception is the formation in low yield of the trans-product in Johnson s process for the synthesis of estrone (Scheme 84). 

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]. 

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

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. 

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 electron-rich thiophene ring system can be annelated by intramolecular Friedel-Crafts acylation reactions to give fused thiophenes <99IJC648, 99JMC2774>. The synthesis of a thiophene isostere of ninhydrin involved an intramolecular Friedel-Crafts acylation <99SL1450>. Specifically, treatment of thiophene 86 with thionyl chloride followed by aluminum chloride gave annelated thiophene 87. The synthesis of isothianinhydrin 88 was then accomplished in six steps from 87. 

The intramolecular C-H insertion reaction of phenyldiazoacetates on cyclohexadiene, utilizing the catalyst Rh2(S-DOSP)4, leads to the asymmetric synthesis of diarylacetates (Scheme 8). Utilizing the phenyl di azoacetate 38 and cyclohexadiene, the C-H insertion product 39 was produced in 59% yield and 99% ee. Oxidative aromatization of 39 with DDQ followed by catalytic hydrogenation gave the diarylester 40 in 96% ee. Ester hydrolysis followed by intramolecular Friedel-Crafts gave the tetralone 31 (96% ee) and represents a formal synthesis of sertraline (5). Later studies utilized the catalyst on a pyridine functionalized highly cross-linked polystyrene resin. ... 

H. Heaney, The Intramolecular Aromatic Friedel-Crafts Reaction, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 753, Pergamon Press, Oxford, 1991. 

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