Intra/intermolecular nucleophilic

The second synthetically useful general transformation of any of the chloro esters 1,2 consists of an intra- or intermolecular nucleophilic substitution of the chlorine atom in any of the Michael adducts. Several examples of such reactions have been mentioned above (Table 1 and Scheme 26), and substitutions of any specific importance (for example, with hydride or azide anion [9,10,62]) as well as subsequent transformations of such substitution products will be discussed in the corresponding Sections [66]. 

In a recent report, Shi et al. developed a valuable tool for the synthesis of 2,6-trans substituted morpholines by addition of water and alcohol to epoxy alkynes [109]. The procedure involved a domino three-membered ring opening, 6-exo-cycloisomerization, and subsequent intra-or intermolecular nucleophilic addition or a double-bond sequence. 

Four different probes gave short reactivity orders toward vinyl cations (1) common ion rate depression in solvolysis (2) competitive capture of solvolytically generated ions (3) direct reaction of a vinyl cation with nucleophiles and (4) competition between intra- and intermolecular nucleophilic capture. A short reactivity order is obtained in each case, but because of the different solvents and conditions the orders cannot be combined to a single series. However, a selectivity rule that governs the relative reactivities toward different vinyl cations in terms of a constant selectivity or a reactivity-selectivity relationship can be determined. 

The product of the palladation reaction exists as an active intermediate and cannot be isolated in general. However, the product of palladation was isolated as a stable compound in the reaction of cyclooctadiene palladium complex with carbanions such as malonate or alcoholate. Further reaction of the complex with base to give bicyclo (6,1,0) nonene and bicyclo (3,3,0) octane systems was reported by Takahashi and Tsuji 108>. The reactions are understood as intra-and intermolecular nucleophilic addition reactions. 

These initial steps involve the Jt-coordination of the unsaturated substrate which activates the substrate for the attack of an intra- or intermolecular nucleophile. At the other end of the catalytic cycle, typically the last step is a proto-deauration, setting free the LAu" " fragment for the next turnover of the catalytic cycle. 

S.9.4 Intramolecular General-Acid-Assisted Intra- and Intermolecular Nucleophilic Reactions... 

Amination of aromatic nitro compounds is a very important process in both industry and laboratory. A simple synthesis of 4-aminodiphenyl amine (4-ADPA) has been achieved by utilizing a nucleophilic aromatic substitution. 4-ADPA is a key intermediate in the rubber chemical family of antioxidants. By means of a nucleophibc attack of the anilide anion on a nitrobenzene, a o-complex is formed first, which is then converted into 4-nitrosodiphenylamine and 4-nitrodiphenylamine by intra- and intermolecular oxidation. Catalytic hydrogenation finally affords 4-ADPA. Azobenzene, which is formed as a by-product, can be hydrogenated to aniline and thus recycled into the process. Switching this new atom-economy route allows for a dramatic reduction of chemical waste (Scheme 9.9).73 The United States Environmental Protection Agency gave the Green Chemistry Award for this process in 1998.74... 

Since the decarboxylation of 161 to 162 proceeds in a poor yield, it was suggested that formation of 162 in benzene occurs directly from 2-benzopyrylium salts 62 through primary nucleophilic attack by amine in position 3. In this case, an enamine fragment of pyruvic acid appears in the ring-opened intermediate 163, which undergoes easy decarboxylation (82TL459). The vinylic carbanion 164, formed by the loss of carbon dioxide, captures a proton by intra- or intermolecular process, then hetero-cyclization takes place. 

The design of polydentate ligands containing imines has exercised many minds over many years, and imine formation is probably one of the commonest reactions in the synthetic co-ordination chemist s arsenal. Once again, the chelate effect plays an important role in stabilising the co-ordinated products and the majority of imine ligands contain other donor atoms that are also co-ordinated to the metal centre. The above brief discussion of imine formation will have shown that the formation of the imine from amine and carbonyl may be an intra- or intermolecular process. In many cases, the detailed mechanism of the imine formation reaction is not fully understood. In particular, it is not always clear whether the nucleophile is metal-co-ordinated amine or amide. Some intramolecular imine formation reactions at cobalt(m) are known to proceed through amido intermediates. A particularly useful intermediate (5.24) in metal-directed amino acid chemistry is... 

Alcohols are not only source of ketyl radicals generated by hydrogen abstraction from the a-C-H position (Eq. (7), Table 1). Oxidation of alcohols with Pb(OAc)4, PhI(OAc)2, and S2082 with Ag(I) as catalyst produces alkoxy radicals (RO-) which may further undergo /3-scission (Eq. 13), intramolecular hydrogen abstraction, or intra- and intermolecular addition to alkenes, generating a nucleophilic carbon-centered radical useful for heteroaromatic substitution (Scheme 6) [2]. 

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