Pyrroles transition metal-catalyzed

The last method for the preparation of 2-quinolones described in this chapter relies on a intramolecular Heck cyclization starting from heteroaryl-amides (Table 2) [57]. These are synthesized either from commercially available pyrrole- and thiophene-2-carboxylic acids (a, Table 2) or thiophene-and furan-3-carboxylic acids (b, Table 2) in three steps. The Heck cyclization is conventionally performed with W,Ar-dimethylacetamide (DMA) as solvent, KOAc as base and Pd(PPh3)4 as catalyst for 24 h at 120 °C resulting in the coupled products in 56-89% yields. As discussed in Sect. 3.4, transition metal-catalyzed reactions often benefit from microwave irradiation [58-61], and so is the case also for this intramolecular reaction. In fact, derivatives with an aryl iodide were successfully coupled by conventional methods, whereas the heteroarylbromides 18 and 19, shown in Table 2, could only be coupled in satisfying yields by using MAOS (Table 2). 

Noteworthy as more frequent than previously are applications of transition metal catalyzed cross-couplings in their numerous modifications to functionalize the pyrrole ring, which often can be formally classified as aromatic nucleophilic substitutions <2006EJ03043>. 

Transition metal-catalyzed annulations (cycloisomerizations of alkynylimines to pyrroles, alkynylketones to furans, and syntheses of multisubstituted heterocycles, particularly, alkaloids) 03SL2265. 

Transition metal-catalyzed addition of heteroatom-hydrogen bonds to alkynes in syntheses of cyclic amines and pyrroles by hydroamination reactions, in syntheses of O-heterocycles by hydroalkoxylation of alkynes, and in syntheses of S- and Se-heterocycles 04CRV3079. 

Abstract An overview of recent transition metal-catalyzed syntheses of pyrroles and carbazoles is presented. The focus is on methods which have been applied to the preparation of biologically active namrally occurring pyrrole and carbazole alkaloids. For pyrroles, special attention is paid to silver(I)-catalyzed cyclization reactions. For carbazoles, iron(0)-mediated and palladium(0/ll)-catalyzed cychza-tion reactions are highlighted and their broad range of applications is discussed. 

After that, the same group also reported catalytie, enantioselective hydroacylations of AT-allylindole-2-carboxaldehyes and N-allylpyrrole-2-car-boxaldehydes (Scheme 8.12)/ These hydroacylations occur smoothly to form dihydropyridoindolones and dihydroindolizinones in moderate to high yields and excellent enantioselectivity from a variety of indole and pyrrole substrates and represent the first example of highly enantioselective, transition metal-catalyzed hydroacylation reactions to form six-membered-rings in the absence of chelation assistance. 

Sonmez, G., P. Schottland, and K.K. Zong. 2001. Highly transmissive and conductive poly[(3,4-alkylenedioxy) pyrrole-2,5-diyl] (PXDOP) films prepared by air or transition metal catalyzed chemical oxidation. / Mater Chem 11 289. 

Synthesis of pyrroles, indoles, and carbazoles through transition-metal-catalyzed C—H functionalization 13AJ0466. 

Analogously to the precedent transition metal-catalyzed cycloisomerization of (Z)-pent-2-en-4-yn-l-ols like 113 into furan compounds (Scheme 8.45), Gabriele disclosed a general and a very convenient route leading to pyrroles 218 from nitrogen analogs of these reactive precursors (Scheme 8.81) [269]. Thus, di-, tri-, and tetra-substituted pyrroles 218 with different substitution patterns could be readily synthesized via the Cu(I)- or Cu(II)-catalyzed [270] cycloisomerization of (Z)-(2-en-4-ynyl)amines 217. The mechanism of this transformation is similar to that proposed for the transition metal-catalyzed synthesis of furans (Scheme 8.46). 

Schulte [285, 286] and later Chalk [287] described the Cu(I)-catalyzed synthesis of symmetrical 2,5-diarylpyrroles 261 from conjugated diynes 257 and primary amines 258. The reaction is believed to proceed via the transition metal-catalyzed hydroamination [33, 288-291] leading to tautomeric aminoenyne 259 or homopro-pargylic imine 260 intermediates, which further undergo 5-endo-dig cyclization to furnish pyrrole product 261 (Scheme 8.95). 

In their recent work, Liang s group disclosed a convenient protocol for accessing complex pyrrole structures based on a transition metal-catalyzed SnI or SN2 -like substitution reaction of allylpropargylic alcohols with primary amine derivatives (Scheme 8.99) [294]. Thus, easily accessible l-en-4-yn-3-ols 272, upon Au(III)-... 

The reaction of isocyanide 42 and phenylacetylene (43) afforded pyrrole 44 under silver-catalyzed conditions. The pyrroles are formed regioselec-tively, in high yields, and with broad functional group tolerance. This represents the first example of the transition metal-catalyzed cycloaddition of isocyanides with unactivated terminal alkynes (13AG(I)6953). A similar system for the synthesis of substituted pyrroles was reported by Lei (13AG(1)6958). 

Some drawbacks of the precursor routes mentioned above have been overcome by the use of polycondensation- and C-C-bond-coupling reactions. To produce soluble PPV-, poly(thiophene)-, or poly(pyrrol) derivatives for spin coating preparation, various types of transition metal catalyzed reactions, such as the Heck-, Suzuki-, and Sonogashira-reaction, Wittig- and Wittig-Horner-type coupling reactions, or the McMurry- and Knoevenagel-condensation have been utilized. 

In both cases, 2,3-disubstituted pyrroles were efficiently synthesized, and for the first time the transition-metal-catalyzed cycloaddition of isocyanides with unactivated terminal alkynes was realized. Bi and coworkers also used the same conditions with electron-deficient alkynes to form 2,3,4-trisubstituted pyrroles (Scheme 9.35b). 

Another approach to pyrrole synthesis is based on transition metal catalyzed rearrangement of azirines [57]. 

Transition-metal-mediated C—X bond formation by intramolecular reactions with alkynes is a powerful strategy for the construction of heteroarene rings such as pyridines, pyrroles, and furans. Because of the wide availability of Sonogashira coupling of various haloarenes with terminal alkynes, these transformations provide efficient routes to synthesize fused heteroarenes, including isoquinolines, indoles, and benzofurans. In this chapter the construction of aromatic rings by transition-metal-catalyzed or transition-metal-mediated intramolecular C—X bond formation between C—X or X—H and alkynes is described. As shown in Scheme 19.1, Section... 

The discussed variants of novel ethynylation of the pyrrole nucleus look even more attractive taking into account that the standard transition metal-catalyzed reactions, including the Sonogashira cross-coupling, do not allow the ethynylpyrroles with electron-withdrawing functions in acetylene substituent to be synthesized [525]. 

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

Pyrroles, H.M.L. Davies. Synthesis of Porphyrins with Exocy-clic Rings from Cycloalkenopyrroles, T.D. Lash. Palladium-Catalyzed Coupling Reactions of Indoles, A.R. Martin and Q. Zheng. Cycloaddition Reactions of Indole Derivatives, U. Pindur. Transition-Metal Mediated Synthesis of Carbazole Derivatives, H. J. Knoiker. Synthesis of [b]-Annelated Indoles by Thermal Electrocyclic Reactions, S. Hibino and E. Sugi-no. Total Synthesis of (-) and ent (-) Duocarmycin SA, D.L. Boger. Index. I... 

The synthesis of bicyclo[3.2.1]octadienes 86 has been accomplished by refluxing divinyl-cyclopropanes 85 in xylene. Subsequent research led to the development of conditions employing a rhodium-catalyzed step for the synthesis of bridged systems via the cyclopropanation of cyclopentadienes, furans and pyrroles (see section on transition-metal-mediated rearrangements). 

The following section looks at how palladium-catalyzed C-H functionalization has been successfully applied in synthetic strategies enabling rapid and elegant routes to complex natural products containing the indole and pyrrole nucleus. There are a number of metal-mediated examples where stoichiometric quantities of transition metals are employed to affect the desired transformation however, there are very few cases of catalytic functionalization with in the context of complex molecule synthesis. 

A titanium-catalyzed hydroamination of 1,4-diynes and 1,5-diynes produces 1,2,5-trisubstituted pyrrroles in one synthetic step <04OL2957>. Treatment of 1,4-diyne 33 with titanium complex 34 led to the formation of pyrrole 35 via a hydroamination to an imino alkyne followed by an intramolecular 5-endo dig cyclization. Another transition metal-mediated pyrrole... 

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