Intramolecular Friedel-Crafts-type cyclization

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... 

Servis conditions. The resulting mesylate reacted with excess sodium cyanide in N.N -dimclhylproplcnurea (DPMU) to give the nitrile. The intramolecular Friedel-Crafts type cyclization of the hydrolysis product acid 361 provided... 

The dimethylamide function in 27 was reduced by the action of Ti(0/-Pr)4 and phenylsilane [35] to give aldehyde 29, which was then treated with p-TsOH in toluene at room temperature (Scheme 6). Under these reaction conditions, the intramolecular Friedel—Crafts-type cyclization occurred, and the subsequent dehydration of a benzylic alcohol also took place to afford phenanthrofuran skeleton (A-B-C-E ring) 30. The formation of the B-ring by way of intramolecular Friedel—Crafts acylation was first reported by Ginsburg in his synthesis of dihy-drothebainone in 1954 [36]. This transformation was also employed by White in the synthesis of (+)-morphine [37], and by Multzer in the synthesis of dihydrocodei-none [38 -0]. The Friedel—Crafts-type cyclization with an aldehyde function was used by Evans [41] in the formal synthesis of morphine and by Hudlicky in the... 

Polycyclic aromatic compounds are obtained upon irradiation of diaryl-substitnted chromium carbenes under a carbon monoxide atmosphere. The reaction probably proceeds via the formation of a biaryl-aUcoxy ketene followed by cyclization. For example, the pyrrole-substituted carbene (22) gave the tricyclic compound (23) (Scheme 34) Related intramolecular Friedel-Crafts-type reactions of carbenes having tethered electron-rich aromatic rings are feasible, usually in moderate yields (Scheme 35). A Lewis acid catalyst such as zinc dichloride is required for optimum yields. 

Titanium tetrachloride promoted a three-component cyclization involving a carbonyl compound, an allylsilane, and an acetal, as shown in Eq. (69) [188]. The reaction was initiated by allyl addition to the aldehyde this was followed by acetal exchange and intramolecular Friedel-Crafts-type alkylation of the olefinic moiety. 

Intramolecular Friedel-Crafts reaction Worthy of mention is the case of intramolecular Friedel-Crafts-type reaction affording 4(lH)-quinolone derivatives [443]. Thus, after extensive investigations, the authors prepared a solid-supported Meldrum s acid derivative by alkylation of a Merrifield resin with ethyl acetoacetate, decarboxylation, and subsequent ketalization of the resulting supported ketone with malonic acid (638). Treatment with triethyl orthoformate and various arylamines (639) afforded immobilized arylamino-methylene derivatives of Meldrum s acid (640). Upon thermal cyclization, these intermediates afforded 4(lH)-quinolone derivatives with simultaneous release from the resin (641). Highly pure final compounds were obtained in moderate to good yields. The resin was recovered in the form of the precursor of (638), i.e., the ketone (642), and thus could be potentially reused (Scheme 133). 

Functionalized alkenes containing a phenyl or carboxylic acid group at appropriate distance from the double bond undergo intramolecular cyclization during the sulfonation. On reaction of ( -4-hexenoIc add with SO3 a sulfo 5 lactone is formed (eq 8), and a Friedel-Crafts type cyclization is observed on sulfonation of ( )-5 phenyl-2-pentene (eq 9) both cyclizations proceed quantitatively and stereospedfically. 

Gold-catalysed intramolecular oxidation of terminal alkynes with an arenesulfinyl group as the tethered oxidant has been reported to involve a gold carbene generation via alkyne oxidation. DFT studies suggest that the cyclized product is formed via an intramolecular [3,3]-sigmatropic rearrangement instead of the previously proposed Friedel-Crafts-type cyclization (Scheme 12) ... 

A Cul-catalyzed synthesis of acridones via intramolecular cyclization including C(sp )-H bond activation and C(0)-CHj bond cleavage process using air as the oxidant was reported in 2013 (Scheme 8.100). Many substituents on the aromatic rings are tolerable in the reaction, and the acridin-9(10//)-ones could be obtained in moderate to excellent yields. C-labeling experiments show that only about 86% of carbon atom of carbonyl originates from the substrate. They proposed that a copper-catalyzed intramolecular Friedel-Crafts-type reaction pathway is disfavored [172]. Shortly after the previous report, Fu and coworkers developed a relevant aerobic synthesis of acridone derivatives from l-[2-(arylamino)aryl]ethanones under Cu(02CCF3)2/pyridine/02 catalytic system [173]. 

In the presence of (la) or Me3Si[B(OTf)4], the intramolecular Friedel-Crafts-type reaction of P,p-difluoro-a-enones with arenes proceeds smoothly to give 4-fluoro-1,2-dihydronaphthalenes in good yield [113]. The stabilizing effect of fluorine on a-carbenium ions enhances the reactivity to enable the rapid, efficient reaction at 0 °C (Scheme 9.44). The directing effect has also been utilized for a Nazarov-type cyclization [114]. 

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... 

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. 

Probably the two most generally useful methods for effecting intramolecular acylation are by the Friedel-Crafts type of reaction on the acid chloride and the action of anhydrous hydrogen fluoride on the free acid. In addition to these methods, cyclizations have been effected by the use of sulfuric acid and other reagents. 

Cyclization of allylic sulfones In the presence of aluminum chloride, allylic sul-fones can undergo intramolecular cyclization of the Friedel-Crafts type with displacement of the sulfone group. Examples are the cyclization of 1 and 4 to 2 and 5. respectively. 

Scheme 10.19 Synthesis of tricyclic indoles through domino Friedel-Crafts-type/intramolecular cyclization reaction.

Alkynylaziridines carrying an aryl group have been reported to give spiro [isochroman-4,2 -pyrrolines] with gold salts as catalysts and involve a Friedel-Crafts-type intramolecular reaction followed by cyclization of the aminoaUene intermediate, both initiated by the dual a and n Lewis acidities of gold. Tandem Au(in)-catalysed heterocyclization/Nazarov cyclizations leading to substituted carbocycle fused fiirans have been reported and computational studies support the function of solvent (Scheme 114). ° ... 

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). 

The examples of intramolecular acylation by the use of aluminum chloride in the Friedel-Crafts reaction occur in the literature so frequently that no attempt has been made here to enumerate all of them. Table VII includes several different types of arylpropionic and aryl-butyric acids which have been cyclized by this method. 

Cyclization of Anhydrides. Instead of the acid chloride, an intramolecular anhydride of the type LXXIX may be used for cyclization by the Friedel-Crafts reaction (Table VII, examples marked by h ). This resembles the intermolecular acylation with succinic anhydride, and a similar procedure is generally followed. The product of ring closure is a keto acid LXXX. Nitrobenzene 9i 6,1120 is a generally effective solvent for the reaction sym-tetrachloroethane also may be used.121... 

Intramolecular acylations are quite common. The normal Friedel-Crafts procedure involving an acid halide and Lewis acid is frequently used, but there are alternatives. One useful method for inducing intramolecular acylations is to dissolve the carboxylic acid in polyphosphoric acid (PPA) and heat to effect cyclization. The mechanism probably involves formation of a mixed carboxylic-phosphoric anhydride.Cyclizations of this type can also be carried out using polyphosphate ester, an esterified oligomer of phosphoric acid that is soluble iq solvents such as... 

---