Superacid-Catalyzed Reactions of Olefinic Pyrazines:  an Example of Anti-Markovnikov Addition Involving Superelectrophiles

Abstract

[reaction: see text] Olefinic pyrazines are found to react with benzene in CF3SO3H and give anti-Markovnikov-type addition products. We propose that this is caused by two effects: destabilization of the carbocationic intermediates that would lead to Markovnikov-type products and the generation of a considerable amount of positive charge at the terminal carbon of the olefinic groups. This suggests that acid-catalyzed addition reactions can give anti-Markovnikov-type products when a multiply charged (i.e., superelectrophilic) group is adjacent to the olefinic site.

Activation of Electrophilic Sites by Adjacent Cationic Groups

“…It is known that acetophenone is completely protonated in CF 3 S0 3 H, however in the presence of benzene there is no hydroxyalkylation (condensation) reaction. 12 On the other hand, acetyl-substituted W-heterocyclic aromatic compounds (19)(20)(21)(22) and Nacetonylpyridine (23) condense with benzene in good yields (Table l). 13 The dicationic intermediates (24-28) are proposed as intermediates in the reactions.…”

“…We have also found several interesting examples suggesting that positive charge centers can influence the regiochemistry of nucleophilic attack. There are two reported examples of superelectrophilic species undergoing nucleophilic attack at the less-substituted positions of olefins (eqs [21][22]. 20 In these reactions, diprotonated species 51 and 52 are likely involved, both of which have a considerable amount of positive charge located on the terminal carbon.…”

“…Our studies have found a remarkable difference between vinylpyridine (53) and vinylpyrazine (54). 21 The vinylpyridine gives the expected Markovnikov-type addition product (eq 23), while the vinylpyrazine gives an apparent anti-Markovnikov addition product (61, Table 2). Remarkably, the 2-propenyl and ct-styryl substituted pyrazines (55-56) also give the anti-Markovnikov-type of products (62-63).…”

“…Several experiments have been done to probe the mechanisms of these unusual addition reactions, 21 although certain aspects of the mechanisms are still not fully understood. Based on isotopic labeling experiments, a mechanism has been proposed involving formation of a triprotonated species (Scheme 2).…”

Superacid-Promoted Additions Involving Vinyl-Substituted Pyrimidines, Quinoxalines, and Quinazolines: Mechanisms Correlated to Charge Distributions

“…6 This is contrasted with the product ( 2 ) from 2-vinylpyridine under similar reaction conditions. 7 These results suggest two types of addition mechanisms operating: a conjugate addition in the case of vinylpyrazine and a Markovnikov-type addition with 2-vinylpyridine (involving dication 3 ).…”