Pyrrolo indoles, dihydro

Additional communications deal with the synthesis of pyrrolo[l,2-cjquinazolines by treatment of methyl 3-alkyl-l,3-dihydro-2-oxo-3-(triphenylphosphoranylidenamino)-2//-indole-l-carboxylates (275) with ketones to afford A -pyrrolin-4-ones (276). As Scheme 100 shows, 276 can... 

The stereochemistry of the cycloaddition has been studied through the reaction with methyl fumarate and maleate. The geometry is preserved and trans- and d.v-adducts are obtained. The di-adduct isomerizes rapidly into the frans-adduct on standing at room temperature. Indications of the regiochemistry were obtained from reaction with acrylonitrile which gives 2,3-dihydro-l-cyano-9-methyl-lH-pyrrolo[l,2a]indole exclusively.407,408... 

It is interesting to note that the reaction with maleic anhydride leads exclusively to a carboxylic acid, 2,3-dihydro-9-methyl-lH-pyrrolo[l,2a]indole-2-carboxylic acid, with a regiochemistry different from that observed in the case of acrylonitrile and from that... 

Treatment of pyrrole 231 and indole 233, bearing the benzotriazol-l-yl moiety (Bt) as leaving group, with isocyanates (Ar, THE, DBU, reflux, 5-7 h) gives high yields of 2,3-dihydro-l/7-pyrrolo[l,2- ]imidazoles 232 (71-95%) (Equation 56) and l/7-imidazo[l,5- ]indoles 234 (79-87%) (Equation 57), respectively <2004JOC9313>. The same conditions when... 

A tandem carbonylation-cyclization radical process in heteroaromatic systems bearing electron-attracting substituents such as l-(2-iodoethyl)indoles and pyrroles 970 result in the formation of 2,3-dihydto-l//-pyrrolo[l,2- ]indol-1-ones and 2,3-dihydro-l//-pyrrolizin-l-ones 974 (Scheme 188). The AIBN-induced radical reaction of compounds 970 with Bu3SnH under pressure of CO suggests that the acyl radical 972, derived from radical 971 and CO, would undergo intramolecular addition to C-2 of heteroaromatic system, and the benzylic radical 973 so obtained, upon in situ oxidation would produce final product 974 <1999TL7153>. 

When a benzene solution of 1 -(2-iodoethyl)indole 975 was heated at 80 °C with 1.2 equiv of Bu3SnH and 0.2 equiv of AIBN under 80 atm of carbon monoxide for 3 h, most of the starting material was recovered and low yields of cyclization and reduction products 976, 977, and 978 were isolated (Equation 230) <1996AGE1050>. Addition of tin hydride in three small portions (0.4 equiv each time) at 1 h intervals allowed minimization of the reduction product 977 and almost completely transformed starting material into 2,3-dihydro-177-pyrrolo[l,2- 7]indol-l-ones 976 <1999TL7153>. When T(2-iodoethyl)-l/7-pyrrole-2-carbaldehyde was subjected to the optimum conditions, l-oxo-2,3-dihydro-l//-pyrrolizine-5-carbaldehyde 979 was isolated in a 30% yield (Equation 231). 

Methoxy-6-nitro- IV/ld, 180 lH- 9-Formyl-7-hydroxy-6-methyl-2,3-dihydro- -5,8-chinon VII/3a, 549f. 

H5C6-CH2-0. Pt02 Athanol 2,5 20 3-Amino-2-aceloxy-6-benzyl-oxy-2,3-dihydro-1H- pyrrolo -[l,2-a]-indol) — 5... 

HMO calculations on cycl[3.2.2]azine (240)26-26 attributed substantial DE to the molecule and more recently Dewar and Trinajstic462 calculated a value for the Dewar resonance energy of 18.9 kcal mole-1. The aromaticity of 240 is reflected in the PMR spectrum101 which shows proton resonances in the region 7.20 to 7.86 ppm. Paudler and Shin463 examined an isomer of 240, viz., pyrrolo[3,2,1-/, i]indole (241), and from a comparison of the benzene-induced shifts of the proton resonances in both 241 and 7-methylindole suggested that there is no loss of aromaticity in 241 relative to the indole derivative. A further comparison of the proton chemical shifts in 241 and its dihydro derivative 242 led the authors to suggest that the former is the more aromatic. 

Another route involving intramolecular cycloaddition of nitrone and nitrile oxide functionalities of the indole derivative (166) gave a novel class of mitomycin analogues which are dihydro- and tetrahydroisooxazolo[3, 4 3,4]pyrrolo[l,2-a]indole (167) and (168) (Equation (8)) <89TL1421>. 

The susceptibility of the pyrrole ring to electrophilic attack has been used in the synthesis of pyrrolo-fused 1,4-diazepines, for example, A-(3-acetylaminopropyI)-3-methyl indole underwent a Bischler-Napierelski-type cyclodehydration on treatment with phosphorous oxychloride in benzene to give ll-methyl-4,5-dihydro-3ff-l,4-diazepine[l,2-a]indole <91IJC(B)1018>. In another example the acyl azide (143) cyclized to the furo[2,3-e]pyrrolo[l,2-a]-l,4-diazepine-9-one (144) (Scheme 25) <92JHC1507>. 

Dehydration occurred when 118 was treated with acetic acid. Reduction of the 3-carbonyl group of the product with phosphorus pentasulfide then gave 1,2-dihydro-3H-pyrrolo[l,2-a]indole derivative 119. This compound was converted into acetoxyaldehyde 120 by selenium dioxide oxidation followed by DDQ. An... 

The introduction of substituents at positions 1 and 2 of a pyrrolo[l,2-a]-indole derivative was investigated by the approach shown in Scheme 18. Compound 110 was condensed with Z-l,4-dichloro-2-butene to give a pyrroline, which afforded 131 on treatment with benzaldehyde and NaOH. Thermal isomerization produced 9,9a-dihydro-3H-pyrrolo[l,2-a]indole 132. Osmium tetroxide then converted 132 into cis-diol 133 [47]. 

Two different routes to 5,7-dimethoxy-6,9-dimethyl-l,2-dihydro-3H-pyrrolo[l,2-a]indol-3-one (137) were developed by Vice and co-workers [48, 49]. The first route (Scheme 19) was based on addition of a methylthio group at C-3 of 5,7-dimethoxy-2,3,6-trimethylindole (134) using methylsulfenyl chloride [48]. Treatment of the product (135) with lithium diethylamide and methyl iodoacetate gave ester 136. Reduction with mercaptoacetic acid followed by base-catalyzed cyclization then gave 137. 

In a 50-mL round-bottomed flask were placed 0.265 g 4-aminoindole (2.0 mmol) and 0.405 mL diethyl ethoxymethylenemalonate (2.0 mmol, d = 1.07) the mixture was heated at 130°C for 3 h. Any unreacted diethyl ethoxymethylenemalonate was removed under vacuum, leaving 0.50 g 2-[( 1//-indol-4-ylamino)methylene]malonic acid diethyl ester as a brown solid, in a yield of 83%, m.p., 122°C (ethanol). Then 0.50 g of the solid diester (1.7 mmol) was added to 50 mL boiling diphenyl ether in portions after 20 min of refluxing, the precipitate formed by cooling was collected by flltration, washed many times with diethyl ether, and recrystallized from ethanol, yielding 0.360 g ethyl 4-oxo-4,7-dihydro-lH-pyrrolo[2,3-/z]quinolin-3-carboxylate, in ayieldof83%, m.p.280°C (dec.), Rf = 0.45 (EtOAc/MeOH, 8 2). 

Chiral polycyclic indoles are ubiquitous and important ring systems found in many bioactive alkaloids and pharmaceuticals. Various methods have been developed for the efficient construction of the polycyclic indole derivatives. Recently, an unprecedented approach to a wide range of diverse, enantioenriched 2,3-dihydro-lH-pyrrolo[l,2-a]indoles 75 was demonstrated by Chen, Xiao, and co-workers. In the presence of 5 mol% Cu(OTf)2 and 5 mol% commercially available bisoxazoline 76 in toluene at 0 °C, the AFC alkylation/N-hemiacetalization cascade reaction of substituted indoles with P,y-unsaturated a-keto esters 74 occurred smoothly to afford products 75 in high yields with excellent diastereo- and enantioselectivity (Table 6.9). 

---