Electrophilic reactions lead compounds

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

A series of oxidative rearrangements of tetrahydro-j8-carbolines may be rationalized on the basis of a general reaction of 2,3-disub-stituted indoles which was recently recognized by Taylor. Attack at the 4a-position of the tetrahydrocarboline (341) by an electrophile yields the indolenine derivative 342, which is in equilibrium with the isomeric species 342a. Compounds of structure 342 and 342a can undergo a variety of reactions leading to different products. 

Finally, it should be stressed that various nucleophilic and electrophilic reactions that lead from sulfoxides and sulfinates of known absolute configuration to new chiral tri- and tetracoordinate sulfur compounds and follow a stereochemically unambiguous course can be utilized for configurational assignments. Some of these reactions... 

The Pd(0)-catalyzed electrophilic reaction of allyl acetates (301) with elec-trochemically induced carbanions leading to (302) has been performed (Scheme 115) [436], The electrolysis is carried out in a DM F-Et4NCl04-(Pt) system in the presence of the active hydrogen compound, Ph3P, and Pd(II)(PhCN)2Cl2 at a current density of 0.26 A dm and the allyl acetate (301). 

Nitric acid-acetic anhydride mixtures give poor yields for the nitration of amides with groups that hinder the amide nitrogen against electrophilic attack. The use of higher temperatures in these reactions leads to variable amounts of the A-nitroso compound as a by-product. ... 

Alkoxy-5-diazomethyl-5//-benzocyclopentenes of type 270 undergo an unusual isomerization reaction leading to tetracyclic azo compounds 271 (316,317) (Scheme 8.66). The reaction readily occurs upon chromatographic workup of the diazo compounds that are prepared by electrophilic diazoalkane substitution using benzotropylium salts. The isolated diazo compounds are thermally converted into 271. The isomerization reaction was interpreted as a formal [4 + 3] cycloaddition. Since [47I + 4ti] cycloaddition reactions are thermally disallowed processes, a... 

Only a limited number of examples are known of applications of thietanes in organic synthesis. Prominent among these examples would be electrophilic ring opening reactions leading to polyfunctional sulfur compounds (33)-(37), utilization of 3-thietanones (55) and metal complexes (87) derived therefrom as oxyallyl zwitterion equivalents in cycloaddition reactions, synthesis of dipeptide (63) with a /3-thiolactone, Raney nickel desulfurization of thietanes (e.g. 120 cf. Table 7) as a route to gem-dimethyl compounds, and desulfurization of thietanes (e.g. 17) in the synthesis of cyclopropanes (also see Table 7). 

GSH may also be coupled to electrophilic reaction intermediates nonenzymatically or by GSH transferase (GST)-catalyzed reactions. Many different types of substrates will undergo GSH conjugation, including epoxides, halogenated compounds, aromatic nitro compounds, and many others. In these reactions, GSH can interact with an electrophilic carbon or heteroatom (O, N, and S) [35]. One such substrate is a reactive metabolite of acetaminophen (APAP), N-acetyl-p-benzoquinonimine (NAPQI), which will readily form a GSH conjugate (Scheme 3.2). Other examples of Phase II bioactivation reactions that lead to toxic endpoints are shown in Table 3.1. 

Formation of the electrophilic halogen species leads to the potential for rapid reaction with compounds containing strongly activating groups, such as activated aryl compounds. Particularly, substances containing aromatic ring structures that have... 

Other problematic electrophiles are 2-(acylamino)ethyl halides and related compounds. Although numerous successful nucleophilic substitutions with such substrates have been described in the literature, occasionally a side reaction becomes dominant. If the leaving group is hard or if the reaction conditions chosen are conducive to the formation of carbocations, intramolecular O-alkylation of the electrophile will lead to the formation of oxazolines (Scheme 4.40). This cyclization can sometimes be avoided by choosing a softer leaving group. 

In the field of nucleophilic additions, Queguiner and co-workers investigated Michael-type additions onto quinoxalotropones like 376 (Schemes 100 and 101 83CJC1806) whose electrophilic sites are C-6, C-10, and C-8. The reactions lead to 1,4-monoaddition products or to bridged compounds resulting from bis-1,4-addition reactions ... 

The direct activation and transformation of a C-H bond adjacent to a carbonyl group into a C-Het bond can take place via a variety of mechanisms, depending on the organocatalyst applied. When secondary amines are used as the catalyst, the first step is the formation of an enamine intermediate, as presented in the mechanism as outlined in Scheme 2.25. The enamine is formed by reaction of the carbonyl compound with the amine, leading to an iminium intermediate, which is then converted to the enamine intermediate by cleavage of the C-H bond. This enamine has a nucleophilic carbon atom which reacts with the electrophilic heteroatom, leading to formation of the new C-Het bond. The optically active product and the chiral amine are released after hydrolysis. 

---