Annulation palladium-mediated

A palladium-mediated annulation of Y-( o-bromoary l)pyrroles across strained alkenes led to the formation of pyrrolo[l,2-a]quinolines <07OL1761>. An intramolecular Heck reaction involving tethered iodoarenes produced an entry to pyrrolo[2,3-t/][2]benzazepin-7-ones, analogues of the pyrrole natural product latonduines <07T867>. A Heck reaction of a 3-iodopyrrole with a 2,3-dihydrofuran provided pyrrole deoxyribonucleosides <07T12747>. 

Metal-mediated C-H activation processes are useful for the annulation of the indole ring. Palladium-mediated intramolecular annulation reactions were utilized in the preparation of... 

An efficient synthetic methodology was developed in which the palladium-mediated intramolecular carbonylative annulation of o-alkynylphenols was employed to construct benzo[l>]furo[3,4-d]furan-l-ones by a tandem reaction. Several densely functionalized alkynyl- phenols were cyclized into their respective substituted benzo[fc]furo[3,4-d]furan-l-ones in good yields under conditions of a combination of PdCljfPPh,), dppp and CsOAc in acetonitrile at 55°C under a balloon pressure of CO. An example is depicted below <01OL1387>. 

Fused pyrazole compounds have been prepared from A-alkyl substituted pyrazoles. For example, a palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp2 C-H functionalization as the key step has been described, in which an alkyl-aryl bond and an aryl-heteroaryl bond were formed in one pot <060L2043>. A variety of highly substituted six-membered annulated pyrazoles 59 were synthesized in a one-step process in moderate yields from IV-bromoalkyl pyrazoles 57 and aryl iodides 58. 

A variety of substituted seven-membered annulated pyrroles can be synthesized in a one-step process in good yields from readily accessible N-bromoalkyl pyrroles 75 and aryl iodides. The synthesis is based on a palladium-catalyzed/ norbornene-mediated sequential coupling reaction involving an aromatic sp C-H functionalization as the key step. The proposed mechanism suggests that orffzo-alkylation with the formation of intermediate 76 most likely precedes aryl-heteroaryl coupling (Scheme 15 (20060L2043)). 

Ill. N. Naz, T. H. Al-Tel, Y. Al-Abed, and W. Voelter, Palladium-cobalt-mediated double annulation process a new strategy to chiral and poly substituted bis-cyclopentanoids on carbohydrate precursors, J. Org. Chem., 61 (1996) 3250-3255. 

An example illustrating an approach to a set of substituted aminoindoles employed the starting material 209, which could be annulated to the protected indole 210 in a palladium-catalyzed reaction involving allylamine (Equation 67). The application of cyclic secondary amines as well as aniline derivatives also gave excellent results <2003AGE4257>. An indium-mediated synthesis of ( )-3-alkylideneoxindoles by annulation of related A -(2-iodo-phenyl)-ynamides has also been described <2004OL2825>. 

As depicted below, a procedure for the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisole and subsequent direct palladium-catalyzed earbonylatiori/lactonization was reported as an efficient entry to naturally occurring eoumestan and coumestrol <05IOC9985>. A novel Pd(II)-mediated cascade carbonylative annulation of substituted o-hydroxyphenylacetylenes to give benzo[fo]furan-3-carboxylie adds was achieved in a one-pot reaction <050L2707>. 

A pyrrole ring may be formed from azines and either anhydrous nickel chloride or paUadium(II) chloride. Palladium-assisted C—C bond formation connecting one benzene ring to another is also a useful method. A review of transition metal-mediated heterocyclizations was published in 1980 [B-S6]. Bis(methyl-thio)methylenemalonic acid derivatives annulate two methylene groups [2881]. 

Diunsubstituted coumarins are available from the palladium(II)-catalyzed intermolecular annulation reaction of phenols with methyl acrylate (13AGE12669) and from an organocatalytic cascade reaction of salicylalde-hydes with malonic acid half-thioesters mediated by a combination of ben-zylamine and triethylamine (Scheme 60) (13EJ04499). 

Disubstituted isocoumarins arise from the copper(II)-catalyzed addition of o-halobenzoic acids to active internal alkynes (13JOC1660), rhodium(III)-mediated oxidative coupling ofbenzoic acids with disubsti-tuted alkynes (13T4454), palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone (13T8626), and nickel(II)-promoted t-butyl isocyanide insertion in 2-(o-bromophenyl)-1-ethanones followed by hydrolysis (Scheme 69) (13SC3262). 

A norbornene-mediated, palladium-catalyzed sequence was described to form annulated indoles (eq 155). Furans or thiophenes can undergo a similar cycUzation to provide annulated... 

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