Intramolecular Friedel-Crafts cyclization

Benzopyrrolo[l,2]oxazepines 68 (X = O) can be obtained from the corresponding acids 67 by an intramolecular Friedel-Crafts acylation (Scheme 14, Section 2.1.1.5 (1996JMC3435, 2002JMC4276)). Similarly, pyrrolo-benzoxazepines 261 are accessible by intramolecular Friedel-Crafts cyclization of acids 260... 

Related to these intramolecular Friedel-Crafts cyclizations are the aluminum chloride and PPA catalyzed ring closures of 3-phenylpropyl iso- and thioiso-cyanates to 2H-2-benzazepin-l-ones and their -1-thiones respectively (79H(12)131i, 77JCS(Pl)2357). The method has also been applied to the cyclization of o-isocyanatodiphenylmethanes to 5,6-dihydro[6,e]azepin-6-ones (65HCA336). 

Quallich and Woodall described the first asymmetric synthesis utilizing a catalytic enantioselective reduction of the ketoester 35 with (S)-terahydro-l-methyl-3,3-diphenyl-lH,3W-pyrrolo[l,2-c][l,3.2]oxazaborole (CBS) to give the desired hydroxyester 36 (90% ee). After mesylation, Sn2 displacement with a higher-order cuprate derived from copper cyanide gave the diaryl r-butyl ester 37 with good chirality transfer. Intramolecular Friedel-Crafts cyclization gave the tetralone 31 in 90% ee (Scheme 7). ... 

Reaction between benzylmercaptans and haloacetic acids yield benzylmercaptoacetic acids (57) which, via their acid chlorides, undergo an intramolecular Friedel-Crafts cyclization to produce isothiochromanones as in Eq. (24).233-235 Attempts to cyclize 57 with sulfuric acid,... 

The intramolecular Friedel-Crafts cyclization of 3-(4-chlorophenylthio)butanoic acid to 6-chloro-2-methylthio-chroman-4-one is efficiently catalyzed by Bi and rare-earth triflates (Equation 195) <2003TL4007>. The cyclization of (3-arylthiopropanoic acids to thiochroman-4-ones by PPA is facilitated by microwave irradiation. Formation of these acids from the sodium salts of thiophenols and 3-chloropropanoic acid is similarly accelerated <2004JCM394>. 

A practical ligand-free palladium-catalyzed intramolecular reductive Heck cyclization was developed by Liu et al. <07TL2307>. The authors found that water was an essential component of the reaction mixture. Using a series of aryl halide intermediates this cyclization resulted in the desired 1,2,3,4-tetrahydroisoquinolines in high yields. Cook and co-workers found that InCU was an efficient catalyst for an intramolecular Friedel-Crafts cyclization of Ar-(4-bromobut-2-enyl)-A-(bcnzyl)-4-methylbcnzcncsulfonamidc to form the desired 3-substituted tetrahydroisoquinolines <07OL1311>. 

Friedel-Crafts intramolecular cyclization. Huisgen and Ugi7 report that aluminum bromide is superior to aluminum chloride for intramolecular Friedel-Crafts cyclization of w-phenylalkanoic acid chlorides (1) to paracyclophanes (2). In both cases high dilution was used (CS2 solvent), but in the case of aluminum bromide the acid... 

MacDowell and Wisowaty66 prepared five dibenzothiophene analogs of anthranol by intramolecular Friedel-Crafts cyclizations of various dithienyl-methane acid chlorides. The equilibrium lay in favor of the keto tautomer when any 3,4-fusion of a thiophene ring was involved (e.g., in 54) and in favor of the enol form in the two cases (55 and 56) in which only 2,3-fusion is present. 

The 1,2-benzothiazepine 1,1-dioxide (59) can be made by intramolecular Friedel-Crafts cycliz-ation of the sulfamoyl chloride (58), with aluminum chloride as the catalyst (Equation (9))... 

Nine-membered rings have been prepared using intramolecular Friedel-Crafts cyclizations. Butler and Alexander prepared the pyrazole-fused lactam (162) by the cyclization of the isocyanate (163) <82JHCU73>, and Shudo and co-workers have described the cyclization of A-amino-A-(phenyl-... 

L-tryptophan has been used as a starting point for partial ergot structures such as 1-benzoyl-4-(amino)-l,2,2a,3,4,5-hexahydrobenz[cd]indoles. An optically pure amine, a key intermediate, was prepared via a four-step sequence employing an intramolecular Friedel-Crafts cyclization and a C-5 deoxygenation procedure [50]. 

By intramolecular Friedel-Crafts cyclization of 33 with 95% sulfuric acid in CCI4 at room temperature for 0.5-4 h, 2-(9/f-fluoren-9-yl)acrylic acid derivatives 34 have been obtained in 39-92% yields (Scheme 4.11). ... 

The Pictet-Spengler (PS) reaction is an important method to construct biologically important tetrahydroisoquinoline and tetrahydro- 3-carboline skeletons. Since it represents the intramolecular Friedel-Crafts cyclization of arenes and imines, we cover the asymmetric organocatalytic PS reaction in this chapter [61]. 

The Banwell group employed an organocatalytic intramolecular Friedel-Crafts cyclization to synthesize the alkaloids (—)-rhazinal (288), (—)-rhazinilam (289), ( )-leuconolam (290), and (-i-)-ep/-leuconolam (291) (261). The spindle toxin (-)-... 

More recently, Balme and coworkers reported a new route to methylenetetrahy-drofluorene products (151) in very high yields via BF3 OEt2 induced intramolecular Friedel-Crafts cyclization of 1,3-bis-exocylic dienes (150) (Equation 90) [92]. 

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