Aryl compounds intramolecular coupling reactions

For the domino transition metal-catalyzed synthesis of macrocycles, conditions must be found for two distinct cross-coupling reactions, of which one is inter- and the other intramolecular. For this purpose, Zhu s group [115] has developed a process of a Miyura arylboronic ester formation followed by an intramolecular Suzuki reaction to give model compounds of the biphenomycin structure 6/1-232 containing an endo-aryl-aryl bond. 

Intramolecularly coordinated A1 and In compounds (e.g., (75), (76)) transfer the Me group in cross-coupling reactions with various aryl halides, including chlorides, catalyzed by Pd and Ni complexes.16 262 265 Monoorganobismuth compounds are reactive in cross-coupling reactions only if they contain an intramolecularly coordinating residue (77),266 267... 

Reaction of aryl Grignard compounds, obtained in situ by iodine-magnesium exchange, with C0CI2, presumably generates aryl radicals. In the presence of a double bond or aromatic ring an intramolecular radical cyclization may take place. This reaction was used for the synthesis of spiro-indolines.244 Oshima has applied cobalt-mediated tandem radical cyclization-cross-coupling reaction for the synthesis of benzyl-substituted heterocycles (Scheme 80).245... 

Fused pyrazole compounds have been prepared from A -alkyl-substituted pyrazoles. For example, a palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp C-H functionalization as the key step has been described, in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one pot. A variety of highly substituted six-membered annulated pyrazoles 433 were synthesized in a one-step process in moderate yields from iV-bromoalkyl pyrazoles 431 and aryl iodides 432 (Equation 87) <20060L2043>. An intramolecular cyclization version has also been reported. Exposure of 2equiv of -butyllithium to l//-pyrazole-l-alkanoic acids 434 afforded the cyclic ketones 435 via a Parham-type cyclization process (Equation 88) <1997SL1013>. 

The intramolecular version has become a useful method of constructing heterocyclic compounds, especially as the mild Jeffery conditions which suffice to achieve such coupling reactions of some aryl and vinyl bromides or iodides (eq. (13) L = P(Q,H5)3) [16 c],... 

Recently it was shown that intramolecular coordination at tin in tetraorganotin compounds promotes the transfer of an organic group from tin to an organic halide in the Stille coupling reaction. In the presence of a Pd catalyst, the exocyclic alkyl group of l-aza-5-alkyl-5-stannabicyclo [3.3.3]undecane selectively couples with aryl or alkenyl halides (111) ... 

Recently, Buchwald and Hartwig have developed the palladium-catalyzed coupling reaction of aryl halides with amines (Scheme 165), and they have extended this reaction to the intramolecular version to give a variety of the aza-heterocyclic compounds 547 (Scheme 166).231 This methodology has provided a wide variety of alkaloids, such as indoles,232 inda-zoles,233 benzimidazoles,234 benazepines,235 phena-zines,236 carbapenems,237 the mitomycin ring system,238 a-carbolines,239 and polyheterocycles.240 Pharmacologically active natural products, such as (—)-asperlicin (550) (Scheme 167),241 dehydrobufotenine (553) (Scheme 168),242 and makaluvamine C... 

The Heck reaction can be used to couple alkenyl, aryl, allyl (the intramolecular Heck reaction on aUyUc substrates is called a palladaene reaction),f ° t f benzyl, methyl, alkoxycarbonyhnethyl, alkynyl, certain alkyl, and silyl fragments to a variety of alkenes. The nature of the leaving group greatly affects the reaction rate aryl iodides react faster than bromides, and aryl chlorides are notoriously unreactive unless special catalysts or ligands and elevated temperatures are used to enhance the reaction rate. This has been taken to indicate that the oxidative addition of the haloarene (haloalkene) to pal-ladium(O) is the rate-determining step. " It has been shown that the Heck reaction can be performed with aryldiazonium salts, A -nitroso-Af-arylacetamides, and hy-pervalent iodo compounds " at room temperature. 

Ames et al. reported the cyclization of bromocinnolines as one of the early important examples of the intramolecular aryl-aryl coupling (Equation 10.29) [48-50]. Today, this type of intramolecular coupling is a standard method for the synthesis of polycyclic compounds [1-9], with the possible cyclization mechanisms perhaps being similar to those for the intermolecular reactions (Scheme 10.4). Among the most recent significant examples is the double cyclization of diiodo compounds by the combination of intramolecular aromatic arylation and N-arylation (Equation 10.30) [51]. Interestingly, the reaction of N-(2-bromobenzyl)-l-naphthylamines... 

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