Aryl halides quinoline

Polyglymes offer a viable alternative as solvents to the potentially carcinogenic HMPA.1871188 Alkyl and phenyl sulfides were prepared from the reaction of suitable aryl halide precursors and an excess of sodium thiolates in tetraglyme.188 By the same procedure 2-(alkylthio)-substituted (alkyl = Me(CH2)n n = 3, 15,17) quinolines, pyrimidines and pyrazines were prepared from the corresponding chlorides.187... 

Thienoisoquinolines can be prepared in high yields by the palladium cross-coupling reaction of o-formylarylboronic acids with aryl halides. By this method, thieno[3,2-c]- (102), thieno[3,4-c]-(103), and thieno[2,3-c]isoquinolines (104) have been prepared in yields of 90%, 52%, and 75%, respectively (Scheme 48) <86CS3il, 89JHC865). This method was unsuccessful for the preparation of thieno[3,2-c]quinoline A-oxide and thieno[3,2-c]isoquinoline A-oxide. The former compounds were readily prepared via a modification of the reaction using a palladium-catalyzed coupling reaction between 2-tributylstannyl-3-thiophenecarboxaldehyde and o-bromonitrobenzene, while the isoquinoline A-oxide was prepared by mcpba oxidation of the parent compound <90JHC1127>. 

The pyrrolyl-pyridine and -quinoline precursors 1225 have been prepared via an electroinduced SrnI reaction in liquid ammonia by reacting pyrrolyl anions 1223 and the corresponding aryl halides 1224 (pyridyl and quinolyl chlorides) (Scheme 235) <2004S0517>. 

The reactions between i-dinitrobenzene or 1,3,5-trinitrobenzene, aryl halides, and copper(I) oxide in quinoline 17-19, 21) provide a simple synthesis of nitrobiphenyls uncontaminated by symmetrical biphenyls. These couplings may be related to the Ullmann reaction, the decarboxylative coupling of benzoic acids with aryl halides, and the preparation of ethers from phenols 165). Although no intermediates... 

The classic SsAi substitution of activated aryl halides by protected cyanohydrin anions provides substituted benzophenones. Another procedure for the arylation of protected cyanohydrin anions involves the use of aromatic substrates activated as their rr-chromium tricarbonyl complexes. - Addition of the anion of (32) to the 1,3-dimethoxybenzene complex, for example, leads principally to the meta-suh-stituted isomer (33 equation 20). Preferential meta regioselectivity is also noted with other -rr-chromium tricarbonyl complexes of arenes. Other arylations of cyanohydrin anions include interesting but synthetically limited additions at the a-position of quinoline N-oxides. In a similar manner, cyanohydrin carbonates of aromatic aldehydes react with A -oxides of quinoline and isoquinoline. ... 

Aryl halides which are rather inert in usual organic reactions can undergo reactions by means of palladium catalysts. Thus, styrene and stilbene derivatives are obtained by reaction of olefins with aryl bromides at 125 °C using Pd(0Ac)2 (1 mol%) and tri-(o-tolyl)phosphine (2 mol%)83. The palladium-catalyzed vinylic substitution reaction is applicable to a variety of heterocyclic bromides including pyridine, thiophene, indole, furan, quinoline and isoquinoline84. Thus, reaction of 3-bromopyri-dine with l-(3-butenyl)phthalimide at 100 °C gives l-[4-(3 -pyridyl)-3-butenyl]-phthalimide (yield of mixed amine 57%, selectivity 68%) at 100 °C. This phthalimide is subsequently converted to nornicotine (188) (Scheme 59). The reaction of acrylic... 

Traditionally, the synthesis of symmetrical biaryls was routinely accomplished using the Ullmann reaction. Recently, Pd-catalyzed homocoupling of aryl halides has also been demonstrated to rival the utility of the Ullmann coupling. As illustrated in Scheme 21, using Pd(OAc)2 as the catalyst, K.C O. as the base in isopropanol [79], 3-bromoquinoline 58 was homocoupled to produce bis-quinoline 184 in 79% yield. Under the same reaction conditions, 2-chloroquinoline was homocoupled to give its corresponding dimer in 79% yield. 

Perfluoroarenes were also found to be highly reactive coupling partners in intermolecular direct arylation [68, 69]. A wide range of aryl halides can be employed, including heterocycles such as pyridines, thiophenes, and quinolines. A fluorinated pyridine substrate may also be cross-coupled in high yield and it was also found that the site of arylation preferentially occurs adjacent to fluorine substituents when fewer fluorine atoms are present. Interestingly, the relative rates established from competition studies reveal that the rate of the direct arylation increases with the amount of fluorine substituents on the aromatic ring. In this way, it is inversely proportional to the arene nucleophilicity and therefore cannot arise from an electrophilic aromatic substitution type process (Scheme 7). 

Treatment of the isoquinoline Reissert compound (2) with sodium hydride in dimethylformamide,96 with 50% aqueous sodium hydroxide-TEBA chloride,61 or with 50% aqueous sodium hydroxide-TBA chloride963 and an activated aryl halide, such as 2,4-dinitrofluorobenzene,96 2-bromo-3-nitropyridine,96 4-nitrochlorobenzene,61 t-butyl 2-chloro-5-nitrobenzoate,61 2-chloro-3-nitropyridine,963 4-chloro-3-nitropyridine,96a or 9-chloroacri-dine96b leads to the arylation product 43. Arylation of the quinoline Reissert compound (1) with 4-nitrofluorobenzene in the presence of sodium hydride in dimethylformamide leads to 44.96 It should be noted that alkylation of... 

Recently reported by Cottet and Schlosser regioselective synthesis of tri-fluoromethyl pyridines and -quinolines" " " is based on the trifluoromethylation of iodoheteroarynes using CF3Si(CH3)3/KF/CuI system originally applied by Urata and Fuchikami for trifiuromethylation of aryl halides." Trifluoromethyl copper in this... 

Intramolecular or intermolecular Heck-type reactions were also used in the synthesis of poly-substituted quinoline compounds. Palladium-catalyzed reaction between vinyl or aryl halides and ortAo-allyl-substituted-A -tosyl-anilides produces dihydroquinolines in an intermolecular fashion, where reaction of acrylates intramolecularly affords 4-quinolones. ° ° ... 

Formation of indole derivative by the reaction of 2-ethynylaniline, aryl halide and CO is known [53]. Cacchi extended the reaction to the synthesis of indolo[3.2-c]quinoline. Reaction of 2-(2 -aminophenylethynyl)trifluoroacetanilide 122, 4-iodoanisole and CO occurred as shown by 123 to provide 124 and then the 3-aroylindole 125. Treatment of 125 with a base gave the indoloquinoline 126 in 70% overall yield [54]. 

---