Some synthetically important nucleophilic substitution reactions

We have recently reported ( ) several synthetic studies of weak nucleophile SnAr reactions. In the latter cases (26f-1), new synthetic methodology was reported for the direct introduction of fluoroalkoxy groups into a variety of aromatic systems. These reports represent synthetically useful procedures for obtaining some otherwise inaccessible fluoroalkoxy materials but, unfortunately, they require the use of a dipolar, aprotic solvent (usually hexamethylphosphoramide, HMPA) and, in some cases, elevated temperatures. However, because of their diverse and important applications ( ), the syntheses of these and other organofluoro compounds continue to be of interest. For example, two recent reports of useful fluoroalkoxy materials include the insecticide activity exhibited by fluoroalkoxy substituted 1,3,4-oxadiazoles... 

Only very powerful nucleophilic reagents such as HO-, NHJ, RLi, LAH, etc., react effectively at the ring carbon atoms of simple pyridines (c/. equation 22), and even then forcing conditions may be required. Oxidation of pyridine to 2-pyridone with potassium hydroxide, for example, requires a temperature of ca. 300 °C. Nevertheless, some of these reactions can be of very considerable synthetic importance, especially the classical Chichibabin reaction for the preparation of 2-amino, alkylamino and hydrazino heterocycles (equation 28). The sequence of substitution is C-2, then C-6 and finally C-4. The Chichibabin reaction also requires rather vigorous conditions and often proceeds in only moderate yield the simplicity of the approach, however, is such that it often represents the method of choice for the preparation of the requisite substituted heterocycle. 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Nucleophilic substitution at aliphatic carbon is a reaction that plays an important role in organic synthesis. The use of the reaction in construction of carbon-carbon bonds will be discussed in Part B, but the role of the reaction in interconverting certain functional groups has such a basic place in organic chemistry that it is appropriate to illustrate some examples of the synthetic utility of nucleophilic substitution. The conversion of alcohols to alkyl halides and the conversion of alcohols to ethers are among the most fundamental organic transformations. 

Nucleophilic attack to palladium is one of the important reactions that Pd 77 -allylic complexes undergo. Ligand-substitution reactions and metathesis of the auxiliary ligands lead to new TT-allyl complexes, and they are a valuable and common synthetic route for a large number of compounds. These reactions have been collected in Section 8.06.6.2.1. The fluxional behaviour of Pd 77 -allyls often involves nucleophilic attack to palladium, and some examples have been discussed in Section 8.06.6.2.3. 

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

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