Intramolecular coupling aromatic compounds

Anodic C, C-coupling is a very powerful tool to synthesize cyclic compounds with high regio- and stereoselectivity. It involves inter- and intramolecular coupling of arylolefins, dienes, enolethers, phenol ethers, and aromatic amines and often opens a quick entry into complex natural products in a few steps. Although the mechanism is fully established in only a few cases, it does appear to involve the coupling of two radical cations at the site of their highest radical density and is further controlled by steric constraints. This important type of reaction is reviewed in Chap. 5 and in Refs. [89, 90]. 

Photoinduced electron-transfer reactions generate the radical ion species from the electron-donating molecule to the electron-accepting molecules. The radical cations of aromatic compounds are favorably attacked by nucleophiles [Eq. (5)]. On the contrary, the radical anions of aromatic compounds react with electrophiles [Eq. (6)] or carbon radical species generated from the radical cations [Eq. (7)]. In some cases, the coupling reactions between the radical cations and the radical anions directly take place [Eq. (8)] or the proton transfer from the radical cation to the radical anion followed by the radical coupling occurs as a major pathway. In this section, we will mainly deal with the intermolecular and intramolecular photoaddition to the aromatic rings via photoinduced electron transfer. 

Reaction of electron-rich aromatic compounds with TTFA leads to intermolecular oxidative coupling to form the corresponding biaryls without aromatic thallation. The reaction proceeds through one-electron transfer from aromatic compounds to Tl(III) to give an aromatic radical cation which leads to biaryls (Schemes 9.52 and 9.53 [52]). Intramolecular aryl coupling also occurs (Schemes 9.54 [53] and 9.55 [54]) and, further, when the carboxylic acid moiety is present, intramolecular as well as intermolecular lactonization occurs (Schemes 9.56 [55] and 9.57 [56]). 

Like cerium(IV), iron(III) salts can oxidize electron-rich centers by single-electron transfer to form radicals [1]. Early applications were developed for the oxidation of aromatic compounds, which undergo C-C bond formation to dimeric products. Because of their electronic properties, methoxy substituted arenes 25 are most reactive. Iron(III) chloride supported on silica gel was the reagent of choice, since inter-and intramolecular coupling products 26 are obtained in excellent yields (Scheme 8)... 

Photoexcited acetone has been used previously to generate aromatic compounds from dihydroaromatic compounds by hydrogen abstraction. Further studies14 have revealed the limitations of this procedure, and shown that other products are often formed from ketyl and hydroaromatic radical coupling. Only the conversion of indoline into indole occurs in reasonable yield (46%). Hydrogen abstraction by excited acetone also appears to be responsible for an unusual reaction on irradiation of friedelin (13) in ether-acetone.16 The known intramolecular reaction which occurs in the cyclohexanone ring gives a keten (Scheme 2), but this is followed by addition of a ketyl radical and subsequent reduction to produce an hydroxycarbonyl compound (14). 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

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]. 

Reaction (4) implies a weak associative interaction, erroneously defined previously as of outer-sphere type (76). Encounter complexes have heen described and characterized in the nitrosylation/denitrosylation reactions of aromatic compounds and were proposed to he inner-sphere adducts containing weakly bound NO (77). They were considered as immediate precursors of transition states for intramolecular electron transfer, as in reaction (5). The equifihrium constants for reactions (6—7) should be high. The ligand interchange within the adduct-complex, reaction (6), is rate-controlled by the cleavage of the Fe —H2O bond, coupled to a fast NO -coordination. Therefore, for the kinetic analysis, processes (6—7) could be collected into a single kinetic constant fe h20-... 

The intramolecular arylative coupling of suitably linked haloaryl-arenes is also generally effective for the construction of polycyclic aromatic compounds (Scheme 10.2b, ii). 

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... 

---