Nucleophiles uncharged

In this book, we follow the convention of using the symbol Nu to represent a charged nucleophile, and Nu to represent an uncharged nucleophile (uncharged nucleophiles are discussed in Section 3.2.1). 

Amines like ammonia are weak bases They are however the strongest uncharged bases found m significant quantities under physiological conditions Amines are usually the bases involved m biological acid-base reactions they are often the nucleophiles m biological nucleophilic substitutions... 

Because of the increased importance of inductive electron withdrawal, nucleophilic attack on uncharged azole rings generally occurs under milder conditions than those required for analogous reactions with pyridines or pyridones. Azolium rings are very easily attacked by nucleophilic reagents reactions similar to those of pyridinium and pyrylium compounds are known azolium rings open particularly readily. 

The reactions of nucleophilic reagents with cationic and uncharged metal carbonyl complexes have received much attention in the past, and it is not surprising that these studies have now been extended to isocyanide metal complexes. Different products in these reactions can arise by three general routes these include ligand substitution, reactions involving attack at a ligand, and reduction of the metal complex. All have been observed in reactions with metal isocyanide complexes. 

The susceptibility of a metal complex to nucleophilic attack is enhanced by a positive charge on the complex. This fact, and the fact that most metal isocyanide complexes are cationic, probably explains why no nucleophilic reactions of uncharged isocyanide complexes have yet been reported. It is... 

Because the Sn2 nucleophilic substitution of uncharged amines with uncharged aliphatic organic halides involves a transition state that is more polar than that of the starting materials, such substitution reactions... 

Epoxides, though uncharged, have a formal resemblance to cyclic bromonium ion intermediates (cf. p. 180), but unlike them are stable and may readily be isolated. They do, however, undergo nucleophilic attack under either acid- or base-catalysed conditions to yield the 1,2-diol. In either case attack by the nucleophile on a carbon atom will be on the side opposite to the oxygen bridge in (49) such attack on the epoxide will involve inversion of configuration (cf. p. 94) ... 

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

The [Rh(CO)2I2] ion is clearly an important species in systems derived from several different catalyst precursors fortuitously, it is a relatively nucleophilic rhodium species. Thus it reacts with methyl iodide at room temperature, whereas the related uncharged species, [Rh(CO)2Cl]2, is unreactive toward methyl iodide at low temperatures. This difference between neutral and charged species is also evidenced markedly in the relative reactivities of [RhL2(CO)X] and [RhL(CO)X2] toward methyl iodide, where a difference of five orders of magnitude has been observed (19). 

By contrast, in an Sn2 reaction, a charged nucleophile reacts with an uncharged substrate to form a transition state in which the negative charge of the nucleophile... 

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