Palladium phenanthridines

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

The carbon-nitrogen double bond of phenanthridine can be reduced selectively by hydrogenation over Raney nickel, and attempted reductive dechlorination of 6-chloro derivatives in the presence of this catalyst normally results in the formation of the corresponding 5,6-dihydro compounds.106 Hydrogenations over palladium catalysts are more successful.203 325 Desulfurization of phenanthridinthione... 

Various Pd-catalyzed cyclizations, which provide a convenient route to phenanthridine and related systems, e.g., <2009AGE572, 2009AGE6713, CHEC-III(7.05.2)222>. For example, palladium-catalyzed domino direct arylation/N-arylation affords phenanthridines 48 in generally high yields (Scheme 23) <2009AGE6713>. 

Reaction of 2-bromoacetophenone 45 with dimethylfomiamide dimethylacetal (DMF-DMA) to the intermediate enaminoketones followed by reaction with various arylhydrazines afforded diarylpyrazoles 46, which underwent Mizoroki-Heck palladium-catalyzed intramolecular couplings to give pyrazolo[l,5-/ phenanthridines 47 <030L1095>. 

The intramolecular Diels-Alder reaction of 5-(3-butynyl)-3//-pyran[2,3-c]isoquinoline-3,6-dione (132) in boiling benzene afforded a pyrrolophe-nanthridone, which yielded 2-methoxy-anhydrolycorin-7-one (136). Hippadine (44) was synthesized by means of l-aza-T-oxa[3.3]sigmatropic rearrangement of A-(2-methoxycarbonylvinyloxy)-8,9-methylenedioxy-phenanthridin-6-one (133) (137) or by palladium-mediated intramolecular cyclization of 7-bromo-A-[(6-bromo-3,4-methylenedioxy)benzoyl]indoline (134) (138) (Fig. 10). 

Regioselective C-H activation is often used for intramolecular biaryl preparations in Pd-mediated transformations. Thus concise syntheses of a large collection of alkaloids have been reported using variations of this approach (239-241), which differ mainly in terms of the functionalization of the precursor, palladium catalysts, and ligands. An efficient synthesis of racemic y-lycorane was recently disclosed whereby the key step is the intramolecular a-arylation of a cyclohexanone derivative (242). Some heterocycKc synthetic precursors (e.g. substituted indoles, quinolines, quinolones, phenanthridines, and phenanthridinones) have also been prepared en route to the alkaloids [hippadine, trisphaeridine (70), and crin-asiadine] via Pd- and Cu-mediated reactions (243,244). 

A series of reports from the Lautens group and others have described the synthesis of phenanthridines, an important class of compounds with a broad range of biological activities, utilizing palladium-catalyzed/norbornene-mediated... 

In 1994, a procedure for the synthesis of benzo[c]-2,7-naphthyridines from pyridine methylstannanes and ort/jo-bromoacetanilides was reported based on a palladium catalyst. " By using CuO as a promoter, good yields of the products were formed (Scheme 3.26a). In 2004, Banwell s group reported the synthesis of quinolines, 2-quinolones, phenanthridines, and 6(5H)-phe-nanthridinones via palladium-mediated Ullmann cross-coupling of... 

In 2012, a palladium-catalyzed ring opening of aminocyclopropyl Ugi adducts was presented. Dihydropyridine and benzoazepinone derivatives were produced in moderate yields (Scheme 3.35a). Catellani and co-workers reported a palladium-catalyzed synthesis of substituted phenanthridine derivatives in 2008. Selectively substituted phenanthridine derivatives were obtained by a facile reaction of o-allqrlated aiyl iodides, o-bromoar-enesulfonylanilines and activated olefins in the presence of palladium and norbornene as catalysts. The reaction takes place under mild conditions to give the products in satisfactory yields using readily available starting materials (Scheme 3.35b). 

The oxidative cleavage of C=C double bonds is found in oxidative C-C bond-forming reactions. For example, when the indolizine 87 was reacted with cinnamic acid in the presence of a palladium catalyst under oxidative reaction conditions, the acylated indolizine 88 was generated as the major product (Scheme 7.34) [49]. The acyl group derives from the p-carbon (designated by a black circle) of the cinnamic acid. When the amine 89 reacted with -butyl acrylate under analogous reaction conditions, phenanthridine was produced in... 

Candito DA, Lautens M (2009) Palladium-catalyzed domino direct arylation/N-arylation convenient synthesis of phenanthridines. Angew Chem Int Ed 48 6713-6716... 

Gerfaud T, Neuville L, Zhu J (2009) Palladium-catalyzed annulation of acyloximes with arynes (or alkynes) synthesis of phenanthridines and isoquinolines. Angew Chem Int Ed 48 572-577... 

Maesti G, Larraufie MH, Derat OUivier C, Fensterbank L, Lacote E, Malaciia M (2010) Expeditious synthesis of phenanthridines from benzylamines via dual palladium catalysis. Org Lett 12 5692-5695... 

Arynes were facilely transformable into phenanthridines 22 by palladium-catalyzed annulation with acyloximes 21 through an aminopalladation/C—H activation sequence (Scheme 28.8) [12], and a direct approach to constructing carbazole 24 from an aniline 23 and an aryne was disclosed by Shi et al. (Scheme 28.9) [13]. 

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