Diverse Reactions with Electrophiles

The enolates of fluoroacetate or fluorothioacetate esters are generated either through deprotonation with a lithium amide or by an in situ reduction of ethyl bromofluoroacetate with zinc. These enolates can undergo diverse reactions with electrophiles (Figure 2.7) ... 

Reactions with electrophilic reagents take place with substitution at C-3 or by addition at the pyridine nitrogen. All the aza-indoles are much more stable to acid than indole (cf. 20.1.1.9), no doubt due to the diversion of protonation onto the pyridine nitrogen, but the reactivity towards other electrophiles at C-3 is only slightly lower than that of indoles. Bromination and nitration occur cleanly in all four parent systems and are more controllable than in the case of indole. Maniuch and Vilsmeier reactions can be carried out in some cases, but when the latter fails, 3-aldehydes can be prepared by reaction with hexamine, possibly via the anion of the azaindole. Alkylation under neutral conditions results in quatemisation on the pyridine nitrogen and reaction with sodium salts allows A-1-alkylation. Acylation under mild conditions also occurs at N-1. The scheme below summarises these reactions for the most widely studied system - 7-azaindole. Acylation at C-3 in all four systems can be carried out at room temperature in the presence of excess aluminium chloride. ... 

Reaction with Electrophiles. Diverse thiophenols can be prepared by trapping 2-LiC6H4SLi (1) with various electrophiles, as illustrated in eq 1 and Table 1. 

A general method has been reported for the parallel solid-phase synthesis of 1,2,4-triazole derivatives based on the cyclization of polymer-bound dithiocarbazate 42 (by a two-step sequence from Fmoc-hydrazine) with electrophiles using a similar route to the formation of pyrazole 7." The linker 42 served as a nucleophile for the cyclization reactions with electrophiles such as cyanocarboimidates 46 (R diversity elements) (Scheme 10.11). 

Related Silanes. l-Trimethylsilyl-l-(ethoxyethoxy)allene (5) undergoes efficient reaction with electrophiles to produce substituted unsaturated acylsilanes (eq 5). The reaction products can be converted to diverse 2-silyloxy-1,3-butadienes. Exposure of (5) to boron trifluoride etherate leads to rearrangement in which an oxonium ion is intercepted at C-2 of the allene (eq 5). This rearrangement proceeds via an intermolecular pathway. Acylstan-nanes can also be prepared through this method. 

Lithiation of to form 184 was reported by the Harmata group to be the first example of a sulfoximine-stabilized vinyl carbanion. The resulting organolithium species 184 reacted with various electrophiles to supply structurally diverse benzothiazines <88TL5229>. However, the diastereoselectivity of the reactions with aldehydes was low (Scheme 48). 

The wide diversity of the foregoing reactions with electron-poor acceptors (which include cationic and neutral electrophiles as well as strong and weak one-electron oxidants) points to enol silyl ethers as electron donors in general. Indeed, we will show how the electron-transfer paradigm can be applied to the various reactions of enol silyl ethers listed above in which the donor/acceptor pair leads to a variety of reactive intermediates including cation radicals, anion radicals, radicals, etc. that govern the product distribution. Moreover, the modulation of ion-pair (cation radical and anion radical) dynamics by solvent and added salt allows control of the competing pathways to achieve the desired selectivity (see below). 

The cross-coupling reaction between an allene and an acetylene takes place at the terminal double bond of an allene to generate a titanacyde, which, on treatment with electrophiles, gives diverse 1,4-dienes in a highly stereoselective manner (Scheme 16.100) [105],... 

Furans also undergo cycloadditions with o-benzoquinones. Thus furan, 2-methylfuran, 2,5-diphenylfuran and benzo[ >]furan yield dihydrofurobenzodioxins of type (238) with tetrachloro-l,2-benzoquinone (Scheme 83). The reaction of furan with 1,2-benzoquinone affords only a 1% yield of adduct because most of the quinone undergoes polymerization. The reaction with 2-methylfuran produces a 25% yield of adduct, however. The reactions are thought to involve the electrophilic attack of the quinone on the furan to produce a carbonium ion. In the case of 2-methylfuran the more stable carbonium ion (239) is produced. Evidence for a two-step mechanism is the diversion of the intermediate (239) to the addition product (240) which may be isolated when the reaction is conducted in the presence of ethanol (69JCS(C)1694). 

Reactions of vinylphosphonates j2 with an equimolar amount of lithium dialkylcuprates J result in the formation of complexes 3 containing two different organic ligands. These complexes react with electrophiles in various ways. In each of them a diverse ligand plays the role of a nucleophile. Hydrolysis of 3 or alkylation with alkyl halides affords the corresponding phosphonates k and 5 comprising extended saturated carbon chains bonded to phosphorus. However, in a number of reactions with aldehydes, the complexes 3 were found to undergo almost completely selective transformation into carbinols 6... 

Reactions of acyclic phosphazenes continue to prove of value in the synthesis of new materials especially in the area of organic chemistry. Reactions in which the phosphazene unit is transformed will be considered first followed by reactions in which the phosphazene unit stays intact. The phosphazenes are usually prepared by the Staudinger reaction. The diversity of reactivity of phosphazenes such as PhN=PPh2CH=C(NH2)C H -p-Me in interactions with electrophiles is shown by reactions with protons or alkyl halides which give phosphonium salts (N-alkylation or protonation). presence of bases, alkylation of the enamlne occurs. 

Bromobenzothiazole has also been used as the electrophile in the Suzuki coupling reactions with a variety of structurally diverse boronic acids [36]. Among these examples, derivative 55, a positron emission tomography (PET) probe precursor was produced for the in vivo imaging of Alzheimer s disease. 

It is well established that sulfur and oxygen anions behave in an opposite way with electrophilic centres during nucleophilic substitutions. The comparison of the reactivity of 1-octanthiol and 1-octanol with DMC (entries 3 and 4, Table 9) outlines the difference in chemoselectivity of RS and RO anions, due to their diverse hardness. Under all of the investigated conditions, alkoxides show a Bac2 reaction mechanism, differently from thiolates, which react via a B,2 type. 

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