Chemistry, nucleophilic

Schultz and coworkers (Jackson et a ., 1988) have generated an antibody which exhibits behaviour similar to the enzyme chorismate mutase. The enzyme catalyses the conversion of chorismate [49] to prephenate [50] as part of the shikimate pathway for the biosynthesis of aromatic amino acids in plants and micro-organisms (Haslam, 1974 Dixon and Webb, 1979). It is unusual for an enzyme in that it does not seem to employ acid-base chemistry, nucleophilic or electrophilic catalysis, metal ions, or redox chemistry. Rather, it binds the substrate and forces it into the appropriate conformation for reaction and stabilizes the transition state, without using distinct catalytic groups. 

Carbon-carbon bond formation is fundamental to all of organic chemistry. Nucleophilic displacement is still the basis for most of what we do, but over the past thirty years radical addition and organometallic coupling have both been brought to a level of practical importance. 

Although rather rare in metalloenzyme chemistry, nucleophilic catalysis can be involved in reactions mediated by metalloporphyrin and metallocorrin complexes (e.g., vitamin B-12-dependent enzymes). 

Vinyl sulfones are useful building blocks for synthetic organic chemistry. Nucleophilic epoxida-tion of chiral (,S )-2-tosyl-2-cyclohexenol (1) and its 0-protected derivatives proceeds with excellent diastcrcosclcctivitics and good yields.. mt-Epoxides 2 of 98% optical purity are obtained, except for the silylated derivative which is much less selective when epoxidized with lithium tt-77-butylperoxide, and, similarly to the acetyl derivative, is incompatible with standard Weitz-Scheffer conditions68. 

The C-C and C-H bonds are also characteristically non-polar, as carbon and hydrogen have very similar electronegativities (the electronegativity difference is 0.4, C-H ). This means that alkane molecules are not susceptible to attack by the most common attacking agents in organic chemistry nucleophiles or electrophiles (electron pair donors or acceptors). 

Although surface organometallic chemistry is still in its infancy, there are already several examples of surface reactions leading to well-defined surface complexes (Table l-I). It appears that these reactions obey the same principles as those encountered in molecular chemistry nucleophilic attack at the ligands, electrophilic attack of the metal-carbon bond, oxidative addition, Lewis acid-base adduct formation, redox reactions, disproportionation, and the cooperative effect of dual acid-base sites in an insertion reaction. 

Urea derivadves are of general interest in medicinal chemistry. They may be obtained cither from urea itself (barbiturates, sec p. 306) or from amines and isocyanates. The latter are usually prepared from amines and phosgene under evolution of hydrogen chloride. Alkyl isocyanates are highly reactive in nucleophilic addidon reactions. Even amides, e.g. sulfonamides, are nucleophilic enough to produce urea derivatives. 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

Application of 7r-allylpalladium chemistry to organic synthesis has made remarkable progress[l]. As deseribed in Chapter 3, Seetion 3, Tt-allylpalladium complexes react with soft carbon nucleophiles such as maionates, /3-keto esters, and enamines in DMSO to form earbon-carbon bonds[2, 3], The characteristie feature of this reaction is that whereas organometallic reagents are eonsidered to be nucleophilic and react with electrophiles, typieally earbonyl eompounds, Tt-allylpalladium complexes are electrophilie and reaet with nucleophiles such as active methylene compounds, and Pd(0) is formed after the reaction. 

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

Alkylation of 2-methylaminothiazole (204) with ROH in 85% sulfuric acid gives 2-methylimino-3-alkyl-4-thiazoIine (54). 2-Amino-4-rnethyl-thiazoie alkylated with an excess of isopropanol, however, gives 95% of 2-isopropylamino-4-methyl-5-isopropylthiazole (56). The same result is obtained with cyclohexanol (242). These results and those reported in Sections III.l.C and IV.l.E offer interesting new synthetic possibilities in thiazole chemistry. The reactive species in these alkylations is the conjugate acid of 2-aminothiazole. and the diversity of the products obtained suggests that three nucleophilic centers may be operative in this species. 

Section 8 1 Nucleophilic substitution is an important reaction type m synthetic organic chemistry because it is one of the mam methods for functional group transformations Examples of synthetically useful nucleophilic sub stitutions were given m Table 8 1 It is a good idea to return to that table and review its entries now that the details of nucleophilic substitution have been covered... 

This kind of chemical reactivity of epoxides is rather general Nucleophiles other than Gng nard reagents react with epoxides and epoxides more elaborate than ethylene oxide may be used All these features of epoxide chemistry will be discussed m Sections 16 11-16 13... 

The structural features especially the very polar nature of the carbonyl group point clearly to the kind of chemistry we will see for aldehydes and ketones in this chapter The partially positive carbon of C=0 has carbocation character and is electrophilic The planar arrangement of its bonds make this carbon relatively uncrowded and susceptible to attack by nucleophiles Oxygen is partially negative and weakly basic... 

Carey Organic Chemistry I 17 Aldehydes and Ketones I Text Fifth Edition Nucleophilic Addition to... 

The mechanism for formation of benzaldehyde diethyl acetal which proceeds m two stages is presented m Figure 17 9 The first stage (steps 1-3) involves formation of a hemiacetal m the second stage (steps 4-7) the hemiacetal is converted to the acetal Nucleophilic addition to the carbonyl group characterizes the first stage carbocation chemistry the second The key carbocation intermediate is stabilized by electron release from oxygen... 

In the preceding chapter you learned that nucleophilic addition to the carbonyl group IS one of the fundamental reaction types of organic chemistry In addition to its own reactivity a carbonyl group can affect the chemical properties of aldehydes and ketones m other ways Aldehydes and ketones having at least one hydrogen on a carbon next to the carbonyl are m equilibrium with their enol isomers... 

The features that complicate the mechanism of nucleophilic acyl substitution are almost entirely related to acid-base chemistry We try to keep track as best we can of the form m which the various species—reactants intermediates and prod nets—exist under the reaction conditions... 

Carey Organic Chemistry I 20 Carboxylic Acid Fifth Edition Derivatives Nucleophilic... 

You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry The first was acetyhde ion m Chapter 9 followed m Chapter 14 by organometallic compounds—Grignard reagents for example—that act as sources of negatively polarized carbon In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic and that this property can be used to advantage as a method for carbon-carbon bond formation... 

The chemistry of ketenes is dominated by their high reactivity most of them are not stable under normal conditions, many exist only as transient Species. Nucleophilic attack at the j -carbon, [2 + 2] cycloadditions, and ketene iasertion iato single bonds are the most important and widely used reactions of such compounds. 

---