Arylation of amines and alcohols

Thus, the transition metal catalyzed arylation reactions of amines and alcohols would constitute powerful tools for synthetic chemists. We have been developing practical procedures for the palladium-catalyzed arylation of amines and alcohols with aryl halides or sulfonates. During the course of our investigations [9] as well as those of John Hartwig and co-workers [10] the substrate scope of these transformations has been incrementally expanded. With each cycle of this catalyst improvement process, advances in mechanistic understanding and ligand design have also been made. 

ARYLATION OF AMINES AND ALCOHOLS CATALYZED BY NICKEL, COPPER OR PALLADIUM COMPLEXES... 

Copper-Catalyzed Arylations of Amines and Alcohols with Boron-Based Arylating Reagents... 

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

While the synthesis of fnnctionalised secondary alcohols and amines can be achieved withont catalyst by the addition of organolithium and organomagnesium reagents to C=N and C=0 gronps, these methods lack a significant functional group tolerance. In order to overcome this limitation and access to more functionalised compounds, the catalytic arylation of aldehydes and imines has been extensively studied [2]. 

Reactions of halides with 1,2-, 1,3- and 1,4-dienes generate 7i-allylpalladium intermediates, which react further with nucleophiles. The reaction of 1,3-dienes with aryl and alkenyl halides is explained by the following mechanism. The insertion of 1,3-diene to the aryl or alkenylpalladium bond generates 7r-allylpalladium complexes 54, which react further in several ways. As expected, nucleophiles such as carbon nucleophiles, amines, and alcohols attack the 7i-allylpalladium 54 to form the 1,4-... 

The arylation of aliphatic alcohols is particularly challenging because the competitive /1-hydride elimination side reaction that was problematic in the amine arylation is even more prevalent in the analogous C-O bond forming reactions. Thus, the coupling of tertiary alcohols such as ferf-butanol and aryl halides has seen considerable success, while general methods for the arylation of primary and secondary alcohols have been more elusive. 

Since the triazines obtained until 1995 have had mainly alkyl or aryl substituents, or been benzo-fused derivatives, reports concerning the reactivity of substituents have been relatively few. Gompper et al. reported that 4,5,6-trichlorotriazine (99) undergoes substitution reactions with amines and alcohols <79CB1535>. The first reaction site was the C-4 position, and successive displacement(s) occurred depending on the nature of the nucleophile (Scheme 17). 

Acyl palladium species, formed by insertion of carbon monoxide into the usual aryl palladium halides, react readily with nucleophiles such as amines and alcohols to give amides and esters respectively interception with hydride produces aldehydes. " ... 

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