Complex heterocycles synthesis, pyridine

Alkyne-nitrile cyclotrimerization is a powerful synthetic methodology for the synthesis of complex heterocyclic aromatic molecules.118 Recently, Fatland et al. developed an aqueous alkyne-nitrile cyclotrimerization of one nitrile with two alkynes for the synthesis of highly functionalized pyridines by a water-soluble cobalt catalyst (Eq. 4.62). The reaction was chemospecific and several different functional groups such as unprotected alcohols, ketones, and amines were compatible with the reaction.119 In addition, photocatalyzed [2+2+2] alkyne or alkyne-nitrile cyclotrimerization in water120 and cyclotrimerization in supercritical H2O110121 have been reported in recent years. 

Methods for the construction of the thieno[2,3-c]pyridine skeleton based on the formally simultaneous formation of both the pyridine and thiophene rings were documented. Under the Pummerer rearrangement conditions, ( -s ul liny lain idc 222 underwent a cascade transformation into 223, which was oxidized to fused lactam 224 in low yield (1999JOC2038). Data on the use of cascade transformations, including the Pummerer rearrangement - cycloaddition sequence, in the synthesis of complex heterocyclic systems were summarized in a review (1997S1353). 

Hadjikakou, S.K., Xanthopoulou, M.N., Hadjiliadis, N. and Kubicki, M. (2003) Synthesis, structural characterisation and study of mercury (II) iodide complexes with the heterocyclic thioamides pyridine-2-thione (pytH) and thiazolidine-2-thione (tzdtH). Crystal structures of [Hgl2(pytH)2] and [Hgl2(tzdtH)2]. Can J Anal Sci Spec, 48 (1), 38-45. 

In 1997, a new synthetic route [30-34,43] made available a range of heterocyclic-substituted metallo-l,2-enedithiolate complexes (Scheme 1). The heterocycle (Het) and R group are readily varied using this method. Metallo-1,2-enedithiolate complexes with appended pyridines, 2-pyrazine, and 2-quinoxaline are now available. While the R group is limited only by the availability of the a-bromo- or tosyl ketone required for this synthesis, to date only complexes where R = H, Me, and CH2CH2OAC (and several derivatives of CH2CH2OH) [34] have been prepared. 

Formation of Complex Heterocycles. The C—H activation of pyridine (generally used in excess amount) has enabled the synthesis of more complex heterocycles such as imidazo and pyrazolo pyridines as well as indolizines. Copper metal salt... 

The cycloaddition of carbon-heteroatom imsaturated bonds to alkynes is a versatile method for the construction of six-membered heterocyclic molecular frameworks such as pyridine and pyran, which are widely distributed in natural products and pharmaceutical drugs. In the past few decades, transition-metal-catalyzed cycloaddition has emerged as apowerful method for the synthesis of structurally diverse heterocyclic compounds [1], Nickel complexes are the most significant transition-metal-based catalysts because as opposed to divalent nickel, which shows ir-Lewis acid behavior toward carbon-carbon unsaturated bonds, zero-valent nickel shows nucleophilic behavior toward carbon-heteroatom unsaturated bonds, thereby facilitating the formation of heteronickelacycles, which are key intermediates for heterocycle synthesis... 

In this book chapter, methods in heterocycle substitution and synthesis using catalytic C-H functionalization are presented with a focus on complex-molecule synthesis, classified by heterocycle indoles (Section 16.2.1) pyrroles (Section 16.2.2) carbazoles (Section 16.2.3) benzofurans (Section 16.2.4) imidazoles, oxazoles, andthiazoles (Section 16.2.5) quinazolines (Section 16.2.6) quinolines, isoquinolines, and phenanthridines (Section 16.2.7) pyridines (Section 16.2.8) and other heterocycles (Section 16.2.9). 

Transition metal complexes have been used in a number of reactions leading to the direct synthesis of pyridine derivatives from acyclic compounds and from other heterocycles. It is pertinent also to describe two methods that have been employed to prepare difficultly accessible 3-alkyl-, 3-formyl-, and 3-acylpyridines. By elaborating on reported194,195 procedures used in aromatic reactions, it is possible to convert 3-bromopyridines to products containing a 3-oxoalkyl function196 (Scheme 129). A minor problem in this simple catalytic process is caused by the formation in some cases of 2-substituted pyridines but this is minimized by using dimethyl-formamide as the solvent.196... 

Two independent papers have reported the synthesis of nitrogen-heterocycle complexes of the type [RhCl3(py-X)3] (py-X = 3-Etpy, 3-CNpy, 4-Etpy, or 4-CNpy) and rr(ans-[RhY2L4] (Y = Cl or Br L = several substituted pyridines, isoquinoline, pyrimidine, pyrazole, thiazole, and substituted imidazoles). All the compounds were prepared catalytically by boiling RhCl3.3H20 with ethanolic solutions of L. It is interesting that 2-substituted... 

In view of the development of the synthesis of various aromatic and heterocyclic compounds from pyrylium salts (80T679), the preparation of the unsubstituted pyrylium salt from pyridine is noteworthy (Scheme 269) (53CB1327). The pyridine-sulfur trioxide complex undergoes ring opening to the sodium salt of pent-2-ene-1,5-dial. This salt cyclizes in perchloric acid via the red oxonium salt. 

Cyclizations of alkenic amines and imines using organoiron complexes to generate bicyclic 3-lactams are discussed in Chapter 3.1 of this volume. Examples of heterocyclizations of alkenic NA/-dialkylamine and pyridine derivatives to form cyclic quaternary ammonium salts are cited in the Staninets review.Ic A cyclization of an enol thioether has been used to generate a thiazolidine intermediate used in cephalosporin synthesis (equation 131).262... 

Many publications are devoted to the synthesis of nitrile complexes, carried out by the immediate (direct) interaction of RCN and MX , mostly in the absence of a solvent [10, p. 95]. A series of N-donors, N-containing heterocyclic donors, whose complexes frequently model biologically important objects (Sec. 2.2.42), should be mentioned apart. The following compounds belong to this type azoles 188, azines 189, and their amino derivatives 572. Their interaction with metal salts takes place usually without a solvent with the use of liquid heterocyclic ligands, for example pyridine [10, ch. 4, p. 107 11], in alcohol or alcohol-aqueous mediums in cases of crystalline ligands (3.10)—(3.12). The specific conditions are presented in the literature, cited in Sec. 2.2.4.2. 

As a result of interaction of 843 and pyridine, the adduct 845 is formed [53], The structures of coordination compounds 844 and 845 were proved by x-ray diffraction. As shown above (Sec. 3.4.3.2), the direct ammonia synthesis [55,56] with participation of various ligands (especially aliphatic, aromatic, and heterocyclic amines, aminoalcohols), elemental metals (or their oxides), and NH4SCN in mostly non-aqueous media, opens definite possibilities for obtaining thiocyanate complexes. In this respect, transformation (4.9) should be mentioned [57] ... 

Tripincer template-directed cyclization of a dienic pyridine precursor leads to the formation of the 69-membered ring trimeric heterocycle 112 (Figure 2.6). Decomplexation of the tripincer from the product is realized with NaCl [72]. The synthesis of a [2]rotaxane by M-RCM using a similar pincer-pyridine complex for pre-assembly was also reported by Leigh et al. [73]. 

Copper(I) acetylides provide a useful route to the synthesis of a variety of organic acetylenic compounds and heterocycles, by reaction with aryl and other halides. A particularly important indirect use, where acetylides are probable intermediates, is the oxidative dimerization of acetylenes. A common procedure is to use the N, N,N, TV -tetramethylethylenediamine complex of CuCl in a solvent, or CuCl in pyridine-methanol, and oxygen as a reoxidant for Cu+ ... 

Review. Vollhardt has reviewed the use of cobalt-catalyzcd [2 + 2 2] cycloadditions for synthesis of annelated benzenes, pyridines, and other heterocycles, as well as of complex natural products,... 

The heterobenzene ( -C5H5P)2Cr can be directly prepared by the metal-ligand vapor cocondensation technique. This heterocycle is aromatic and prefers ( -coordination to -coordination. For pyridine, cr-coordination via a lone pair is highly preferred over bonding that utihzes the tt-electron system. Therefore the direct synthesis of jj -pyridine metal complexes requires the N-atom to be blocked by means of substitution in the 2,6-positions ... 

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