Indole pyrrole

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

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. 

Tolylsulfones of indoles, pyrroles, pyrazoles, furans, thiophenes, indolines, and dibenzofurans react with tributyltin hydride under radical conditions by t/wo-substitution. The most likely mechanism appears to be addition of the RjSiv radical to the ring, followed by elimination of the sulfonyl group, but an electron-transfer mechanism cannot be excluded (Equation (61)).199... 

Bryoz.> 50/5,000 Mar. ALKAL. p-phe ylethylamine indole pyrrole Land Land ... 

Fuel contains unstable, reactive components such as quinones, indoles, pyrroles, thiophene, or naphthenic acid compounds these, as well as other components, can react to form color bodies and insoluble, higher-molecular-weight compounds... 

Review.1 Use of this reagent in organic synthesis has been reviewed. The report includes cyanation of indoles, pyrroles, and enamines. 

Selective and efficient Michael additions of heterocyclic enamines (e.g. indoles, pyrroles, and pyrazoles) to enones can be catalysed by ZrCU (2 mol%).150 Michael addition of a - cy an o k e t e n e -. V,. S - ac et al s (RS)2C=CHCN to enones R CH=CHCOR2 can be promoted by TiCl4.151 Addition of the lithium enolate, generated from (2S,5S)- (g) c -l,3-dioxolan-4-one, which in turn was prepared from (S)-mandelic acid and pival-aldehyde, to several 2-arylidene-1,3-diketones, gives the Michael adducts in good yields and diastereoselectivities.152... 

An easy and efficient method to generate indolylnitroalkane (169) and the analogous pyrrolylnitroalkane in high yields using /3-nitrostyrene derivative (168) and indole/pyrrole at room temperature in the presence of iodine (50 mol%) has been reported as an alternative to the known Lewis acid or rare earth metal catalysts.197... 

In CHEC-II(1996), several applications of dihydro-2//-l,2,3-diazaphospholes, generated in situ from a ketone hydrazone and PC13, as useful intermediates for the synthesis of indoles, pyrroles, pyrrolylacetates, and 1,2-di-hydro-2-alkenyl-37/-pyrazol-3-ones are listed <1996CHEC-II(4)771>. 

The UV photochemistry of phenol and related systems (such as indole, pyrrole, imidazole) is dominated by a hydrogen detachment reaction which is driven by repulsive 1ira states [33,35 10], For the isolated chromophores, the 1 mr -driven photodissociation has been explored in unprecedented detail by high-resolution photofragment translational spectroscopy [40], The OH (or NH) bond is broken homolytically, resulting in the formation of two radical species, the hydrogen atom and the phenoxy (or indolyl, etc.) radical. Ion pair formation (abstraction of protons) is energetically not feasible for isolated photoacids. 

Indoles, pyrroles and carbazoles themselves are suitable substrates for palladium-catalyzed amination. An initial study of this reaction using DPPF-ligated palladium as catalyst showed that these reactions occurred readily with electron-poor aryl halides. With unactivated aryl bromides, the reaction with pyrrole or indole resulted in good yield, but reaction times were long and the temperature was 120 °C. Thus, an improved catalyst system was necessary for reactions to occur in a more general fashion and with temperature- or base-sensitive substrates. 

Here again, the cycloaddition is endo-selective, with only regioisomers 79 being formed, and, when using 2- and/or 3-substituted furans, only the unsubstituted furan double-bond reacts in these inverse electron-demand Diels-Alder processes [134-136]. Indoles, pyrroles, and thiophenes can also be made to react as dienophiles with ortho-quinone monoketals... 

The reactivity of five-membered tings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (1) formylation by phosgene and A A -dimethylformamide, (2) acetylation by acetic anhydride and tin(IV) chloride, and (3) trifluoroacetylation with trifluoroacetic anhydride are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate of trifluoroacetylation, the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and the rate data for the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 18) (2-methylindole iV-methylindole > indole > pyrrole > furan > thiophene). 

Reaction of the parent heterocycle with arenesulfonyl chlorides in the presence of a suitable base constitutes the only widely applied method for the Marylsul-fonylation of indoles, pyrroles, imidazoles, etc. Three procedures using indoles illustrate the variety of conditions. Typical bases include n-BuLi [Scheme 8.268]515 or a metal hydride [Scheme 8.269]524 in THF, or phase-transfer catalysis using sodium hydroxide in aqueous dichlorome thane [Scheme 8.270].515... 

Whilst carbamate derivatives of indoles and pyrroles are easily prepared, they have limited synthetic utility because they are easily attacked by nucleophiles. For example, A -Aloc525 and A -Cbz526 derivatives of tryptophan are known, but they are destroyed by piperidine. Boc derivatives of indoles, pyrroles and imidazoles are sufficiently hindered to be synthetically useful For example, N-Boc indole is stable towards piperidine and it can be metallated in the 2-position with ferf-butyllithium.527 Nevertheless, they are still more easily cleaved by nucleophiles than Boc-derivatives of secondary amines as illustrated by the fact that Boc-derivatives of pyrrole are cleaved with sodium methoxide, ammonia or hydrazine in methanol527 In tryptophan derivatives, the Ar>w-Boc group is less susceptible to aridolysis than an Na-Boc group with trifluoroacetic acid. However, the M"-Boc group can be cleaved selectively by thermolysis as illustrated by a step in a synthesis of Asperazine [Scheme 8,271 ].52 ... 

The first reports of palladium-catalyzed arylation (equation 39) of azoles occurred with catalysts bearing DPPF as the ligand125. These reactions of indole, pyrrole and carbazole with activated aryl halides were carried out at 80-100°C. The reactions of indole and pyrrole with unactivated aryl halides such as bromobenzene, 4-bromo-r -butylbenzene and 3-bromoanisole occurred in high yields. However, the conditions of these reactions were more severe than those typically necessary to conduct palladium-catalyzed coupling of aryl halides with amines (equation 40). 

Epoxide ring-opening reactions with various nitrogen heterocycles (indoles, pyrroles, pyrazoles) have been efficiently promoted under mild conditions with high pressure or silica gel-catalysed conditions. 

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