Electrophilic displacement, pathway

The C-H activation step could, in principle, occur either by oxidative addition of the C-H bond - pathway (a) - or by electrophilic displacement - pathway (b). The oxidative addition pathway would proceed via the formation of a palla-dium(IV) species. Although such intermediates have been postulated in some coupling reactions catalyzed by palladacycles, as yet no conclusive experimental evidence has been presented [14], It is perhaps more likely that C-H activation results from electrophilic displacement of the ortho proton [15]. 

A variety of halide sources have been shown to be capable of displacing the nitro group of the 1,2,4-triazolo[5,l-c][l, 2,4] triazines (180). Unexpectedly, chlorine and bromine in acetic acid gave the same products, presumably via electrophilic pathways (82CHE992). 

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

Electrophilic halogenation processes can involve conventional mechanisms with a carbocation intermediate, or pathways that are of the addition-elimination type. Sometimes the process does not go beyond the addition stage there are also examples of halodehalogenation in which the displaced halogen attaches elsewhere in the ring, as in the chlorination of 3-bromobenzo[fe]thiophene to give 2-bromo-3-chlorobenzo[6]thiophene as one of the products (73IJS233). 

Sulfonates such as mesylates or tosylates are readily prepared from alcohols under mild conditions, and are therefore attractive alternatives to halides as electrophiles. Although sulfonates often undergo clean displacement by nucleophiles, alternative reaction pathways are accessible to these intermediates, which can lead to unexpected results. If the nucleophile used is strongly basic, metalation instead of displacement of the sulfonate can occur. Some potential reactions of such metalated sulfonates include fragmentation into sulfenes and alcoholates, or into sulfmates and carbonyl compounds, or self-alkylation (Scheme4.15). 

Coordinated alkenes may be displaced by other ligands (equation 23.73). Unlike free alkenes, which undergo electrophilic additions, coordinated alkenes are more susceptible to nucleophilic attack and many reactions of catalytic importance involve this pathway (see Chapter 26). Reaction 23.77 shows that addition of a nucleophile, R , leads to a a-bonded complex the mechanism may involve direct attack at... 

Electrophilic Attack by Phosphorus. A detailed discussion has appeared of the displacement reactions of l-chloro-2,2,3,4,4-pentamethylphosphetan (8) and its oxide and sulphide. The chloride (8) always undergoes inversion as a result of substitution at phosphorus, and this is rationalized on the basis of a transition state (9) in which the entering nucleophile (Nu) and the chloride leaving-group occupy apical sites. Although a pathway via (9)... 

Various pathways for the electrophilic addition to a glycal followed by nucleophilic opening of the resulting halonium ion can account for the different product distributions obtained from these reactions [74]. Irreversible formation of the halonium ion and subsequent nucleophilic displacement leads to the (B-g/wco compound, while reversible formation of the halonium ion followed by slow nucleophilic trans diaxial opening leads to the a-manno compound. Common T sources used to synthesise a-manno species include V-iodosuccinimide (NIS), and iodonium di-iym-collidine perchlorate (IDCP). An iodonium source is particularly favoured over a bromonium source, as this more readily allows further subsequent functionalisation of the product often via radical chemistry. The yields of... 

Allylic acetates or related compounds can also be displaced by organo-cuprates. A synthetic approach to prostaglandins (PC s) via cross-coupling of a vinylic copper reagent with an allylic electrophile has been elaborated (Corey and Mann, 1973). Notably the reaction of LXI and LXII proceeds exclusively by an Sn2 pathway. 

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