Pyrrole, 2-naphthyl

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

Indoles, pyrroles, and carbazoles themselves are suitable substrates for palladium-catalyzed coupling with aryl halides. Initially, these reactions occurred readily with electron-poor aryl halides in the presence of palladium and DPPF, but reactions of unactivated aryl bromides were long, even at 120 °C. Complexes of sterically hindered alkylmonophosphines have been shown to be more active catalysts (Equation (25)). 8 102 103 In the presence of these more active catalysts, reactions of electron-poor or electron-rich aryl bromides and electron-poor or electron-neutral aryl chlorides occurred at 60-120 °C. Reactions catalyzed by complexes of most of the /-butylphosphines generated a mixture of 1- and 3-substituted indoles. In addition, 2- and 7-substituted indoles reacted with unhindered aryl halides at both the N1 and C3 positions. The 2-naphthyl di-t-butylphosphinobenzene ligand in Equation (25), however, generated a catalyst that formed predominantly the product from A-arylation in these cases. 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

Under the conditions favorable for the synthesis of pyrroles from alkyl aryl ketoximes (100°C, 3 hr, 30% KOH of ketoximes mass, DMSO, acetylene under 12-16 atm pressure), the reaction with methyl naphthyl ketoximes is accompanied by considerable resinification to give low yields of pyrroles 14-17. The best results were achieved at 90°C. From methyl 1-naphthyl ketoxime at this temperature (2 hr, KOH), 2-(l-naphthyl)pyrrole (14) and 2-(l-naphthyl)-1-vinylpyrrole (15) are formed in 15 and 48% yield, respectively. 

In general, however, methyl 1-naphthyl ketoxime starts to condense with acetylene under pressure at about 60°C. At 80°C (3 hr, KOH) 2-(l-naphthyl)- 1-vinylpyrrole (15) becomes the predominant reaction product, however its yield decreases due to resinification on further elevating the temperature and increasing the reaction time. 2-(l-Naphthyl)pyrrole (14), free from the corresponding N-vinylpyrrole (15), was isolated in 22% yield when use was made of a catalytic pair LiOH/DMSO (90°C, 3 hr). The temperature effect (3 hr, 30% KOH, initial acetylenic pressure of 12 atm) on the yield of naphthylpyrroles was examined in condensation of methyl 2-naphthyl ketoxime with acetylene as an example (82KGS1351) ... 

Reaction temp. (°C) 2-(2-Naphthyl)-pyrrole (14) 2-(2-Naphthyl)-l-vinylpyrrole (15)... 

As in other cases, the nature the alkali cation has a substantial effect on the yield and ratio of pyrroles 14-17. If in the presence of KOH (70°C, 3 hr) the yield of 2-(2-naphthyl)pyrrole (14) is 33%, LiOH practically fails to catalyze the process at the same temperature. 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

Indoles can be 3-alkylated by allyl alcohols in the presence of lithium perchlorate and acetic acid 101 is an example (Scheme 42). Pyrrole -alkylation can be achieved with simple alkyl halides [1-bromopentadecane, l-(bromomethyl)-, l-(3-chloropropyl)- and l-(3-iodopropyl)benzenes, 2-(2-bromoethyl)- and 2-(3-bromopropyl)naphthalenes] and mesylates [3-phenylpropyl-, l-methyl-3-phenylpropyl-, 2-(2-naphthyl)ethyl- and 3-(2-naphthyl)propyl methanesulfonates] selectively at C(2) and C(5) positions via reaction in various ionic liquids (e.g., Scheme 43) <20050L1231>. 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

Diazirines, which on heating or irradiation are converted into carbenes either directly or via the corresponding diazo compound, have been infrequently employed for the preparation of monoarylcyclopropanes. One of the few reports involved 3-(l-naphthyl)-3/f-diazirine. When this compound was irradiated in a mixture of acetonitrile and acrylonitrile, carbene addition to the C-C double bond took place, yielding a mixture of cis- and /ranj-l-cyano-2-(l-naph-thyl)cyclopropane (1) together with the cis- and trans-isomers of 4-cyano-5-methyl-2-(l-naph-thyl)-3,4-dihydro-2//-pyrrole (2). ... 

Furusho et al. reported on a series of atropisomeric 4-methyl-3-(2 -methoxy-l -naphthyl)pyrrole-2-carboxylates. The enantiomers were obtained by crystallization of the diastereoisomers of the (R)-phenethyl ester and further hydrogenolyse. An X-ray of the isolated diastereomer allowed the determination of the absolute configuration. The (S) antipode of the free acid presented a positive CD curve at 231 nm. The acid was applied in the predetermined synthesis of a chiral atropisomeric porphyrin 213 (Figure 12) (94JCS(CC)653). 

The study was extended to the s5mthesis, resolution, and CD studies of a series of 3-naphthyl-pyrrole-2-carboxylates and 3-phenanthryl-pyirole-2-carboxylates 214-217 (96JCS(P1)183). 

This is concluded from the intensification of the naphthyl out-of-plane bands at 471, 602 and 637 cm The close position of these bands in relation to the Ni complex indicates a similar structure of the macrocycle when adsorbed on Ag, irrespective of the nature of the coordination metal. This result is also similar to that obtained for azabipiridyl macrocycle complexes. The orientation also accounts for the relative intensity decrease of the vCH band at 3, 056 cm In fact this band in the Cu complex corresponds to the vCH modes of the naphthyl moieties which are oriented parallel to the metal surface. The interaction of the macrocycle with the Ag surface is also deduced from the frequency shifts of some bands mainly those corresponding to the pyrrole moieties, which are the fragment through which the macrocycle-surface interaction takes place. The presence of the band at 224 cm corroborates this interaction. 

Frey developed a pyrrole 338 synthesis starting from vinyldibromides 336 and enamines 337 [55]. In the presence of a strong base (KOtBu) an initial dehydrobro-mination of 336 led to an alkynylbromide 339. A consecutive equilibration was found to be crucial. Involving activating aryl substituents Ar (Ph, Naphthyl), a reversible base-induced H-shift, should have formed the corresponding allene 340. 

Aryl carbene complexes with electron-donating or electron-withdrawing substituents in the ortho-, para-, or meta-positions participate in the DBR. The aryl group can also be naphthyl and heteroaryl such as furan, thiophene, pyrrole, pyrazole, and indole. Simple alkyl substituted vinyl carbene complexes have been extensively examined. The double bond can be in either a cyclic or an acyclic system. 

In many cases the silver(I)-catalyzed naphthyl ketone synthesis proceeds as well or better than the analogous gold(I)-catalyzed reaction. However, attempts at silver(I)-catalyzed rearrangement of pyrrole 72 failed to produce the desired aromatic ketone. In this case, the analogous tri-t-... 

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