Mechanism of Aryl Halide Amination and Etheration

The previous sections described synthetic methods involving palladium- and nickel-catalyzed additions of alcohols and amines to aryl halides and triflates. The development of procedures and catalysts used in these processes has occurred hand-in-hand with mechanistic analysis of the amination chemistry. The following sections describe the current understanding of why these procedures and catalysts are effective, and how this understanding led to some of the breakthroughs described above. 

1 Oxidative Addition of Aryl Halides to LjPd complexes (L = P(o-tolyl)3, BINAP, DPPF) and its Mechanism 

The mechanism of the oxidative addition of aryl bromides to the bis-P(o-tolyl)3 Pd(0) complex 3 was surprising [196]. It has been well established that aryl halides undergo oxidative addition to L2Pd fragments [197 -200] thus, one would expect oxidative addition of the aryl halide to occur directly to 3 and ligand dissociation and dimerization to occur subsequently. Instead, the addition of aryl halide to [Pd[P(o-tolyl)3]2] occurs after phosphine dissociation, as shown by an inverse first-order dependence of the reaction rate on phosphine concentration and the absence of any tris-phosphine complex in solution [196]. 

Oxidative addition to a monophosphine palladium complex is unusual, but is a reasonable pathway if one bears in mind that reductive eliminations often occur from monophosphine palladium complexes [202,203]. These reductive eliminations from monophosphine Pdn species would form a monophosphine Pd° complex as the initial metal product, and these Pd° products are similar to the intermediate in the oxidative addition of aryl halide deduced from kinetic studies. 

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Scheme 2 shows a similar mechanistic pathway for a Heck reaction taking place on a Pd octahedral comer. This mechanism is based on that established for soluble Pd catalysts (ref. 5). Adsorption of the aryl halide (or aryl acid chloride after decarbonylation) gives the aryl Pd halide, 15, by way of the adsorbed intermediate, 14. Vinyl ether adsorption, as in 16, takes place as described in Scheme 1. Aryl insertion gives the halometalalkyl, 17, which on f) elimination to the available 4dxy orbital gives the aryl enol ether, 2 (or 1 depending on which hydrogen is eliminated in 17). The resulting halo palladium hydride, 18, then reacts with the tertiary amine to give the amine hydrochloride and regenerates the octahedral comer for further reaction.

No studies on the mechanism of the complete catalytic cycle for formation of aryl ethers from aryl halides have been conducted, but the elementary reactions in the cycle are likely to be similar to those in the catalytic cycle for formation of aryl amines. Oxidative addition, formation of an alkoxo complex, and reductive elimination of ether are likely to occur. It is the slow reductive elimination of ether that allows for amide complexes to form and undergo reductive elimination in the presence of t-BuO" instead of undergoing reductive elimination of ether. 

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