Adamantyl derivatives mechanism

Scheme 10.11 Possible mechanisms of the Negishi reaction catalyzed by the adamantyl-derived, phosphine-based palladium pincer complex [C- QH- 3-l,3-(CH2P(Cy2)2)Pd(CI)] (22), of which only path C (bold arrows) explains all the experimental observations. The relative energies are given for aryl Ar = Ar = phenyl.

Adamantylation of benzotriazole represents a special case because direct substitution in adamantanyl halides by an Sn2 mechanism is impossible, and an SnI mechanism is improbable. In this case, reactive cation 91 is generated by oxidative cleavage of the C-I bond in 1-iodoadamantane 90. Benzotriazole added to the reaction mixture binds cations 91 to afford a mixture of benzotriazol-l-yl 92 and -2-yl 93 derivatives in a ratio of 26 74 and the total yield of 67% (Scheme 5) <2001RJ01762>. 

More recently, and based on the same concept, O Neill and coworkers have prepared a series of related systems (80a-c) based on Vennerstrom s adamantyl trioxolane unit". These derivatives, which are synthesized in only three steps from adamantan-2-one, have activity in the low nanomolar region (<3 nM versus K1 P. falciparum). Like the prototypes synthesized by the groups of Meunier" and Singh", these compounds can be formulated as water-soluble salts and it is anticipated that these agents may have the capacity to hit the parasite by two distinctive mechanisms. Indeed, any chemical or metabolic degradation of the endoperoxide bridge in these compounds will result in metabolites that may still have the ability to function as inhibitors of heme polymerization provided that they do not become covalently attached to proteins in the bioactivation process. 

A final example of the utility of adamantyl substrates as model systems in mechanistic investigations is provided by 1-adamantylcarbinyl derivatives. Detailed product and rate constant determinations of 1-adamantylcarbinyl solvolyses have been interpreted relative to the mechanism of the solvolysis reactions of neopentyl systems in general. 

Substituted adamantanes have been employed in the study of several reaction mechanisms. The Kolbe electrolyses of 1- and 2-adamantane carboxylic acids and 1- and 2-adamantyl acetic acids have been compared in detail. Car-bonium ion-derived products are observed from the electrolyses of both 1-adamantyl carboxylic acid and 1-adamantyl acetic acid. A mixture of radical and carbonium ion-derived products are obtained from 2-adamantyl carboxylic acid and mainly radical-derived products are obtained from 2-adamantyl acetic acid. These results parallel the known or expected stabilities of the intermediate carbonium ions 366 ... 

Acetylenes. hvdromagncsiation 82 -4 Acid derivatives IS Aetiv.itect ethers 53 Acyl chlorides 70 Adamantyl bromide 220-30 Addition-diminution mechanism 58-9 Addition process lb Advocin 176 Aldehydes... 

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