Pyridine carbon nucleophiles

In the dihapto mode the pyridine ring can be protonated intermolecularly at nitrogen, or even intramolecularly deprotonated at carbon. The first evidence for metal C—N insertion is the reaction of the metallaaziridine complex (111) with homogeneity LiHBEt3 in THF at low temperature that yields (112) (Scheme 49).251-254 Experiments with carbon nucleophiles (RMgCl, MeLi) in place of LiHBEt3 have provided valuable information to allow discrimination between... 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

Boron substituents in the [l,3,2]diazaborolo[l,5- ]pyridine derivative 109 were studied. This compound was obtained via reduction of its precursor 108 with sodium amalgam (Scheme 27). The bromide attached to the boron atom was further displaced with various halide, hydride, sulfur, and carbon nucleophiles <2001JCD378>. [l,2,5]thiadiazolo[2,3- ]pyridine derivative 110 was deprotected (R = Cbz to R=H) by classical hydrogenolysis <2002AGE3866>. 

The /V-(2,6-dimethy 1-4-oxopyridin-1 -yl)pyridinium salts (15)24 have proved to be versatile intermediates for the regiospecific synthesis of 4-substituted pyridines (17) via attack by the appropriate carbon nucleophiles, e.g. ionized ketones,90 nitroalkanes,91 esters and nitriles,92 and a-diketones, a-keto esters, a-diesters, disulfones etc. (Scheme 10).93 Aromatization of the intermediate 1,4-dihydro adduct (16) was generally achieved under free radical conditions. 

Undoubtedly the factors suggested by Gielen and Nasielski are important nucleophilic co-ordination of solvent to tin is probably the reason why compound (X) suffers restricted rotation in solvent carbon tetrachloride (when the intra-molecularly-bridged species (Xa) is present) but not in solvents such as alcohols, ethers, or pyridine/carbon tetrachloride (when the species present is now (Xb), with the tin atom five-co-ordinate through external coordination)54. ... 

The oxazole ring possesses less aromatic stabilization than a thiazole ring and is readily opened in many of its fused derivatives, especially in oxazolium salts. In the pyridazinium derivative (191) the oxazole ring is opened by oxygen, sulfur or carbon nucleophilic attack at the C-8a ring junction (77YZ422). In the mesoionic pyridine (192) an amine attacks at C-2, which is a pseudocarbonyl carbon atom (70JCS(C)1485). 

In a series of outstanding papers, Pinhey et al have shown that aryllead tricarboxylates react with soft nucleophiles to afford C-arylation products. These aryllead derivatives behave as aryl cation equivalents in reactions which involve a ligand coupling mechanism (see section 7.5).9 2 ju most cases, the reactions proceed in chloroform at 40-60 C in the presence of pyridine as a base with a ratio of substrate to organolead derivative to pyridine of 1 1 3. The substrates which easily undergo C-arylation include phenols, p-dicarbonyl compounds and their vinylogues, a-cyanoesters, a-hetero-substituted ketones, enamines and nitroalkanes. A very limited number of non-carbon nucleophiles has also been reported to react. 

Nucleophilic substitution by halide, cyanide, carbon nucleophiles, such as enamines, and acetate (by reaction with acetic anhydride), with concomitant loss of the oxide function, occur smoothly in all three systems, though the site of introduction of the nucleophile is not always that predicted by analogy with pyridine chemistry (a to the AT-oxide), as illustrated by two of the examples below. 

Functionalization of pyridine. Regioselective reaction with oxygen, sulfur, and nitrogen nucleophiles and with carbon nucleophiles at C-2 occurs via an addition-elimination pathway. 

Syntheses of substituted pyridines [73], quinolines [74], and isoquinolines [74] by SnAr reactions of haloheterocycles with sulfur, oxygen, and carbon nucleophiles under the action of focused microwave irradiation were developed by Cherng using aprotic dipolar solvents (Scheme 10.33). The reactions were complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to those conducted with conventional heating. This method is especially important for the preparation of 3-pyridyl ethers, thioethers and acetonitriles, because these compounds are not easily accessible by conventional procedures. It was next extended to the pyrimidine and pyrazine series [75]. 

Chambers, R.D. Hassan, M.A. Hoskin, RR. Kenwright, A. Richmond, P. Sandford, G. Reactions of perfluoro-isopropyl-pyridine with oxygen, nitrogen and carbon nucleophiles. 

However, Hmited work has appeared with the carbon nucleophiles. Recently, an efficient tandem process has been developed that would allow the reaction of o-QM intermediates with carbon/nitrogen nucleophiles in situ to provide xanthene, naphtho(pyrano)pyridine/amidoalkyl naphthol derivatives under solvent-free and simple reaction conditions (Scheme 7.63). Xanthenes and benzoxanthenes are... 

Carbon nucleophiles are able to react with heteroaromatic W-oxides, and these addition-elimination transformations have been found to proceed effectively in the presence of the phosphonium salt PyBroP (Scheme 36) [74]. A series of carbonyl compounds capable of enolization have been involved in the reaction with pyridine A-oxides to give 2-substituted pyridines in moderate yields, and in all these cases, it proved necessary to use threefold excess of nucleophile relative to the A-oxide in order to avoid further addition of the reaction product to the starting azine A-oxide. 

Carbon nucleophiles were added to pyridine and quinoline N-oxides in the presence of different coupling agents (Scheme 30). Primarily the nucleophile added to C-2 with strong regioselectivity, regardless of the... 

Scheme 30 Addition of carbon nucleophiles to pyridine or quinoline W-oxides.

---