Intramolecular Oxidative Dehydrogenative Coupling

Use of pivalic acid (PivOH) as a solvent with 10 mol % K2CO3 was highly effective for the acceleration of palladium-catalyzed dehydrogenative intramolecular coupling reaction [35]. For example, electron-rich diarylamines 71 underwent the cyclization smoothly to give 72 in much higher yields that those of the same reaction carried out in AcOH (Table 22.3). The examples illustrated in Table 22.3 are a synthesis of 

TABLE 22.2 Dehydrogenative Direct Coupling of Diaryl Ethers, Diarylamines, and Diaryl Ketones 

SCHEME 22.17 One-pot synthesis of carbazoles from anilines through IV-arylation/ dehydrogenative coupling cascade. 

SCHEME 22,20 Dehydrogenative-carbonylative cyclization of diaryl ethers. 

SCHEME 22.21 Intramolecular oxidative coupling of A-aryl enamines. 

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An intramolecular cross-dehydrogenative coupling of 1,2,3-triazoles with arenes was reported in the presence of Cu(OAc)2 as the oxidant and pivalic acid as the additive (eq 172). ... 

Dehydrogenation. CuClj is an efficient reagent for the preparation of pyridazinoneS from the dihydro compounds. Dehydrogenation of 1,2,3,4-tetrahydroisoquinolines to give the 3,4-dihydro derivatives is achieved under high pressure of oxygen." Substituted dibenzofurans are formed by an intramolecular oxidative coupling of o,o -dilithiodiaryl ethers with CuClj. 

Zhao and Du s group [63] developed a metal-free cross-dehydrogenative coupling (CDC) of various 2-(A -arylamino)aldehydes 79 for direct aryl-aldehyde C (sp )-C(sp ) bond formation to provide a convenient approach for the synthesis of biologically important acridone derivatives 80 (Scheme 19). PIDA was used in combination with a substoichiometric amount of benzoyl peroxide as radical initiator for this oxidative intramolecular annulation reaction which presumably proceeds via the intermediacy of acyl radicals 81. 

Recently, an efficient CuBr-catalyzed aerobic intramolecular dehydrogenative cyclization reaction of AfAf-disubstituted hydrazones to pyrazoles by a double C(sp )-H bond functionalization was developed in Ge s group (Scheme 8.67). This transformation includes C(sp )-H oxidation, cyclization, and aromatization for the formation of pyrazole products. This is the first example of an intramolecular copper-catalyzed dehydrogenative coupling reaction via an iminium ion intermediate by a C(sp )-H bond functionalization process [113]. 

Activation by rhodium complexes has been used to achieve direct exchange of ketone methyl or aryl groups with an aryl group on ArB(OH)2, selective C(CO)-C bond cleavage on reaction of ketones with water, oxidative acylation between secondary benzamides and aryl aldehydes with subsequent intramolecular cyclization to 3-hydroxyisoindolin-l-ones, " cross dehydrogenative coupling to form xanthones from 2-aryloxybenzaldehydes, and activation of the aldehydic C-H bond to achieve hydroacylation of unactivated alkenes by salicylaldehyde derivatives and of vinylsilane by benzaldehyde. ... 

The natural product, anhydrolycorinone was prepared in the palladium mediated intramolecular Heck reaction of a tetrahydroindole derivative. The coupling, which is run in air and requires the use of a stoichiometric amount of palladium, is accompanied by the dehydrogenation of the cyclohexadiene moiety and the oxidation at the benzylic position to a lactam (4.11.).12... 

If such oxidative couplings occur vithin the same molecule, cycliza-tions, usually to six-membered rings, take place. Anhydrous aluminum chloride proves useful in such intramolecular dehydrogenations. At 120 °C, it cyclizes benzil to 9,10-phenanthrenequinone [407] and bridges benzene rings in the synthesis of coronene [408], At the same time, partial aromatization takes place (equations 46 and 47). 

Other oxidants like thallium(III) oxide, vanadium(V) oxyfluoride, palladium ) acetate, and ruthenium(IV) tetrakis(trifluoracetate) have been developed as powerful tools for the intramolecular biaryl coupling reaction [7,93,113]. Nevertheless, DDQ is still one of the most versatile reagents in oxidative coupling reactions (see Scheme 14 and 29 [82,114]). The highly strained dioxa[8](2,7)pyrenophane (65), portraying an overall curvature of nearly 90° for the pyrene subunit, was finally obtained from the mefa-cyclophanediene (66) by dehydrogenation with DDQ in refluxing benzene in 67% yield [114]. 

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