Pyrrole metallation

Inhaltsiibersicht Struktur des Pyrrol-Molekiils. — Ana-lytische Methoden. — Reaktivitat der Pyrrole. — Pyrrol-Metall-Derivate. — Pyrrole als Naturprodukte. — Pyrrol-Ringsynthesen. — Synthetische Methoden. 

Enantiomerically pure open-chain a-pyrrylalditols such as C-nucleoside analogs 1215 have been synthesized by direct coupling of sugar derivatives 1214 with pyrrole metal reagents based on magnesium-titanium" or mag-... 

Preparation of pyrrole metal complexes and their use in organic synthesis 92MI29. 

S. Kara, T. Zama, W. Takashima, and K. Kaneto, Pol) pyrrole-metal coil composite actuators as artificial muscle fibers, Synth. Met., 146 (1), 47-55 (2004). 

In the heaviest fractions such as resins and asphaltenes (see article 1.2), metal atoms such as nickel and vanadium are found. They belong in part to molecules in the porphyrine family where the basic pattern is represented by four pyrrolic rings, the metal being at the center of this complex in the form Wi - or V0+ (< 3)... 

Metal-Induced Cycloadditions. The effect of coordination on the metal-iaduced cyclo additions of maleic anhydride and the isostmctural heterocycles furan, pyrrole, and thiophene has been investigated (47). Each heterocycle is bound to an Os(II) center in the complex... 

Pyrrole is soluble in alcohol, benzene, and diethyl ether, but is only sparingly soluble in water and in aqueous alkaUes. It dissolves with decomposition in dilute acids. Pyrroles with substituents in the -position are usually less soluble in polar solvents than the corresponding a-substituted pyrroles. Pyrroles that have no substituent on nitrogen readily lose a proton to form the resonance-stabilized pyrrolyl anion, and alkaU metals react with it in hquid ammonia to form salts. However, pyrrole pK = ca 17.5) is a weaker acid than methanol (11). The acidity of the pyrrole hydrogen is gready increased by electron-withdrawing groups, eg, the pK of 2,5-dinitropyrrole [32602-96-3] is 3.6 (12,13). 

N-Alkylpyrroles may be obtained by the Knorr synthesis or by the reaction of the pyrrolyl metallates, ie, Na, K, and Tl, with alkyl haUdes such as iodomethane, eg, 1-methylpyrrole [96-54-8]. Alkylation of pyrroles at the other ring positions can be carried out under mild conditions with allyhc or hensylic hahdes or under more stringent conditions (100—150°C) with CH I. However, unless most of the other ring positions are blocked, poly alkylation and polymerisation tend to occur. N-Alkylation of pyrroles is favored by polar solvents and weakly coordinating cations (Na", K" ). More strongly coordinating cations (Li", Mg " ) lead to more C-alkylation. 

N-Acylation is readily carried out by reaction of the alkaU metal salts with the appropriate acid chloride. C-Acylation of pyrroles carrying negative substituents occurs in the presence of Friedel-Crafts catalysts. Pyrrole and alkylpyrroles can be acylated noncatalyticaHy with an acid chloride or an acid anhydride. The formation of trichloromethyl 2-pyrryl ketone [35302-72-8] (20, R = CCI3) is a particularly useful procedure because the ketonic product can be readily converted to the corresponding pyrrolecarboxyUc acid or ester by treatment with aqueous base or alcohoHc base, respectively (31). 

Pyrrole can be reduced catalyticaHy to pyrroHdine over a variety of metal catalysts, ie, Pt, Pd, Rh, and Ni. Of these, rhodium on alumina is one of the most active. Less active reducing agents have been used to produce the intermediate 3-pyrroline (36). The 2-pyrrolines are ordinarily obtained by ring-closure reactions. Nonaromatic pyrrolines can be reduced easily with to pyrroHdines. 

Vinyl Pyrroles. Relatively new synthetic routes based on a one-pot reaction between ketoximes and acetjiene ia an alkaU metal hydroxide—dimethyl sulfoxide (DMSO) system have made vinyl pyrroles accessible. It requires no pyrrole precursors and uses cheap and readily available ketones (42). 

Pyrrole and alkylpyrroles can be acylated by heating with acid anhydrides at temperatures above 100 °C. Pyrrole itself gives a mixture of 2-acetyl- and 2,5-diacetyl-pyrrole on heating with acetic anhydride at 150-200 °C. iV-Acylpyrroles are obtained by reaction of the alkali-metal salts of pyrrole with an acyl halide. AC-Acetylimidazole efficiently acetylates pyrrole on nitrogen (65CI(L)1426). Pyrrole-2-carbaldehyde is acetylated on nitrogen in 80% yield by reaction with acetic anhydride in methylene chloride and in the presence of triethylamine and 4-dimethylaminopyridine (80CB2036). 

Pyrroles do not react with alkyl halides in a simple fashion polyalkylated products are obtained from reaction with methyl iodide at elevated temperatures and also from the more reactive allyl and benzyl halides under milder conditions in the presence of weak bases. Alkylation of pyrrole Grignard reagents gives mainly 2-alkylated pyrroles whereas N-alkylated pyrroles are obtained by alkylation of pyrrole alkali-metal salts in ionizing solvents. 

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

Studies on metal-pyrazole complexes in solution are few. The enthalpy and entropy of association of Co(II), Ni(II), Cu(II) and Zn(II) with pyrazole in aqueous solution have been determined by direct calorimetry (81MI40406). The nature of the nitrogen atom, pyridinic or pyrrolic, involved in the coordination with the metal cannot be determined from the available thermodynamic data. However, other experiments in solution (Section 4.04.1.3.3(i)) prove conclusively that only the N-2 atom has coordinating capabilities. 

The synthesis of metal-eoordinated 1-azirines and the reaetions of azirines indueed by metals have opened a new area in the ehemistry of this small ring heteroeyele. Many of the reaetions eneountered bear resemblanee to previously diseussed thermally and photo-ehemieally indueed reaetions of 1-azirines. The reaetion of a series of diiron enneaearbonyls in benzene results in eoupling and insertion to give diimine eomplexes and ureadiiron eomplexes as well as pyrroles and ketones (76CC191). A meehanism for the formation of these produets whieh involves initial 1,3-bond eleavage and generation of a nitrene-iron earbonyl eomplex as an intermediate was proposed. 

Perfluoroalkylation can be accomplished via direct reaction of peifluoroalkyl halides and copper with aromatic substrates [232, 233, 234, 235, 236] Thus, perfluoroalkyl iodides or bromides react with functionalized benzenes m DMSO m the presence of copper bronze to give the corresponding perfluoroalkylated products directly in moderate to good yields [233] (equation 157) Mixtures of ortho, meta, and para isomers are obtained [232, 233], The use of acetic anhydride as solvent gives similar results [234, 235], Similarly, the direct reaction of perfluoroalkyl iodides and pyrroles with copper metal regiospecifically gives the 2-perfluoroalkylpyrroles [236] (equation 158). 

Nontransition metal cyclopentadienyl derivatives of pyrrole are quite scarce (99CRV969). The derivatives M(2,5-C4H2 Bu2N)2 (M = Sn, Pb) were studied [92AG(E)778 92JCS(CC)760]. 

Azaferrocene reacts with aromatic hydrocarbons in the presence of aluminium chloride, giving rise to the cationic complexes of the type (Ti -arene)(Ti -cyclopenta-dienyl)iron(l+) isolated as BF4 salts [87JOM(333)71]. The complex 28 is obtained by reaction of the sulfane compound [Cp(SMc2)3Fe]BF4 with pentamethyl-pyrrole [88AG(E)579 88AG(E)1468 90ICA(170)155]. The metallic site in this center reveals expressed Lewis acidity (89CB1891). 

Total syntheses of pyrrole alkaloids, furanoterpenes, macrolide antibiotics, and carbohydrates based on transformations catalyzed by transition metals 99SL1523. 

Stoichiometric closure of furan and pyrrole cycles on McMurry reaction induced by low-valent transition metals 98PAC1071. 

Reactions of metal-stabilized carbenoids with pyrroles 95M12. 

The fourth chapter of this volume comprises the second part of an ongoing series by Professor A. P. Sadimenko (Fort Hare University, South Africa) dealing with organometallic compounds of pyrrole, indole, carbazole, phospholes, siloles, and boroles. This follows the review in Volume 78 of Advances covering organometallic compounds of thiophene and furan. The enormous recent advances in this area are summarized and classified according to the nature of the heterocycle and of the metals. 

---