Benzene derivatives intramolecular arylation

In contrast to facile reactions of aryl halides with alkenes and alkynes, reactions of aromatic compounds with aryl halides have received less attention. Only intramolecular arylation of benzene derivatives, except phenols, is known [1]. On the other hand, electron-rich heterocycles such as ffirans, thiophenes, pyrroles, oxa-zoles, imidazoles, and thiazoles undergo facile inter- and intramolecular arylation with aryl halides. These are called heteroaryl Heck reactions [2]. 

The Pd-catalyzed intramolecular coupling of aryl halides or triflates with aromatic rings to give biaryl compounds offers useful synthetic methods. Intramolecular aryla-tion of benzene derivatives was reported first by Ames. Cyclization of 102, catalyzed by Pd(OAc)2 in the presence of DBU, is an example [23]. Pyrimido[4,5-fe]indole was prepared by intramolecular arylation of 4-anilino-5-iodopyrimidine 103 in 86 % yield in the presence of Pd(OAc>2, PPh3 and AcONa in DMF [24]. Cyclization of the monobrominated diarylpyrazole 104 afforded pyrazolo[l,5-/]phenanthridine in 65 % yield in the presence of phosphine-free Pd(OAc>2, Bu NBr, LiCl and K2CO3 in DMF at 110°C [25]. 

The intramolecular Pd-catalysed Heck arylation of the nitroalkene (18) which affords the isochroman (19) is unusual in that Ag2CC>3 is the essential base and that benzene is the preferred solvent. The nitroalkane derivative (20) is a significant by-product, but its conversion to the nitroalkene can be accomplished in three steps in 70% yield (95JOC1013). 

When the methyl substituted derivatives of u-bis(phenylsulfonyl)benzene (99) are reduced in DMSO, good yields of the intramolecularly coupled products are obtained. These are methyl-substituted dibenzothiophene dioxides (100a), formed after initial cleavage of PhSOo from the radical anion followed by intramolecular attack of the aryl radical on the phenyl group [290] (Scheme 26). 

Photolysis of benzene solutions of l-methoxycarbonyl-2-naphthylmethyl 2,6-di-methyl substituted phenyl ethers induces C-O cleavage with formation of 2,4-cyclohexadienone intermediates which are subsequently photo-rearranged into meta substituted phenols. In methanol, 9-anthrylmethoxy-pyrid-2-one or l-pyrenylmethoxypyrid-2-one undergo photoheterolysis to give the C-O heterolysis products l-hydroxypyrid-2-one and the arylmethyl methyl ether, together with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from homolysis of the N-O bond. Evidence shows that an intramolecular exciplex plays a crucial role in C-O bond heterolysis. 

Heterocycles were synthesized by arylation of vinylogous amides, followed by Heck reaction. Monoarylation of the vinylogous amide 54 with 1, 2-dibromo-benzene afforded 55. The indole derivative 56 was obtained by intramolecular... 

Haseltine has described an enantioselective formal synthesis of pancratistatin in which the stereocontrol is driven by the aeetonide of conduritol A. The enantioselective hydrolysis (desymmetrization) of this compound was achieved with a lipase, and the aryl-cyclohexane ring bond was formed through an intramolecular cyclization of the activated benzene ring with an allylic triflate (278). Plumet reported a total synthesis of (-l-)-7-deoxypaneratistatin based on the conjugate addition of an aryl-lithium species to a bicyclic conjugated sulfone derived from furan, which enabled the efficient installation of the six stereogenic centers of the cyclohexane ring (279) (Scheme 13). 

The reaction of 2-bromo-A(Ai-diisopropylbenzamide derivatives 78 (X=Br) affords the 2,3-dihydro-1/f-inden-l-one derivatives 79 and 80 by Ni-mediated intramolecular aiylation (Scheme 9.10) [53], A plausible mechanism could involve intramolecular H-atom abstraction fiom aryl radical 81 providing the stabilized tertiary aUcyl radical 82, which by attack to the benzene ring affords the radicals 83 and 84 to furnish ultimately the products observed. The same synthesis was... 

Side Reactions. The most common side reaction is the formation of a sulfone, Ar2S02. This reaction is favored by an excess of the hydrocarbon or aryl halide and by an active sulfonating agent, such as sulfur trioxide, oleum, or chlorosulfonic acid. The reaction between benzene and sulfur trioxide in the vapor phase has been patented as a method of preparing phenyl sulfone. The formation of 2,2 -cyclic sulfones is characteristic of biphenyl and its derivatives, where the structure is favorable for intramolecular sulfone formation. Sulfone formation. 

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