Aryl halides chemoselectivity

In 2007 the scope of the trialkylborane/water system was extended to the dehalogenation of alkyl iodides and the chemoselective deoxygenation of secondary alcohols in the presence of alkyl and aryl halides [86]. The rate constants for the hydrogen-atom transfer from this reagent to secondary radicals (Scheme 37) are substantially lower than those of the Ti(III) aqua-complex [78, 87]. 

The hydroboration-coupling approach for the construction of carbon skeletons affords several advantages [139]. The high stereoselectivity of the hydroboration reaction provides a stereodefined alkyl center on boron. For instance, in the reaction shown in Scheme 2-49, the hydroboration occurs chemoselectively at the less hindered C(19)-C(20) double bond. In addition, the alkylboron group thus constructed can be readily cross-coupled with alkenyl or aryl halides under mild conditions. 

Palladium-catalyzed amination is an attractive alternative strategy to the current synthesis of fluoroquinolones because the reaction goes through an oxidative addition step in which aryl-fluoride bonds are inert. This reaction involves an efficient coupling of aryl halides and amines (eq 1) and is successful for aryl halides with a broad range of functionalities. In this paper, we report model studies of the palladium-catalyzed amination of fluorohaloarenes to produce fluoroam-lines. Indeed, the model studies demonstrate that the catalytic reaction is chemo-selective. Moreover, in this paper, we demonstrate that the palladiiun-catalyzed amination methodology can be extended toward chemoselective syntheses of fluoroquinolones. 

Ni and Pd catalysts were found to be most useful for this purpose [35]. Palladium catalysed reactions show better chemoselectivity, but are restricted to activated aryl bromides while nickel-catalysed processes are more tolerant to steric hindrance of aromatic substituents [36]. These reactions are the best alternative to Ni(0) catalysed high temperature coupling of aryl halides [37]. With stericaly hindered aryl halides generation of a Grignard reagent is recommended. Preferably the component with an ortho substituents should be converted the Grignard compound[38]. 

Generally alkenyl halides are more reactive than aryl halides. An opposite chemoselectivity was observed in the competitive reaction of chlorobenzene and... 

Moreover, since the cross-coupling reaction of hexaalkyidistannane with aryl halides strongly depends on the reactivity of the latter, a chemoselective cross-coupling of two different aryl halides has become of practical value. Thus Zhang described a simple and versatile method for synthesis of unsymmetrical biaryls from 2-bromopyridines (more reactive) and various phenyl- and 3-pyridyl bromides (less reactive) to afford the appropriate biaryls in moderate to high yields [106]. For example, 5-cyano-2-bromopyridine (167) was cross-coupled with 4-nitro-bromobenzene (168) to give the biaryl 169 in 67% yield [106], respectively, Scheme 23. 

Although the SM reactions of haloferrocenes proceed rather slow, they are clean and chemoselective, providing the production of arylferrocenes which would be hardly accessible by other strategies. Several papers regarding improved and alternative technics for performing the Suzuki-Miyaura reactions have been published. A useful procedure involves transmetallation of (half amount) simple aryl halides with only 0.5 eq. of -BuLi, followed by quenching the resulted aryllithium reagent with trimethyl borate [88], Thus obtained arylboronic ester is coupled under the standard SM conditions method A) with an excess of parent aryl halide to furnish the symmetrical biaryl in fair yields. For example, 2-bromoanisole (218) was coupled by this way to afford 2,2 -dimethoxybiphenyl (92) in 56% yield [88], Scheme 36. 

The nickel-catalyzed homocoupling of aryl halides has a long history, and the development of chemoselective heterocouplings of this type constitutes an active and evolving area of research. A key study from Semmelhack in 1971 illustrated the homocoupling of haloarenes after exposure to Ni(cod)2. Kumada then illustrated that the process could be rendered catalytic in nickel by the use of zinc dust as the stoichiometric reductantJ ... 

Nickel-catalyzed ketone and aldehyde hydrosilylations have been developed with well-defined Ni(II) hydrides using phosphine anilide ligands (Scheme 3-84). This process is tolerant of a variety of functional groups including aryl halides. In mechanistically distinct processes, nickel(O) complexes of NHCs were shown to catalyze ketone hydrosilylations using carbohydrate-derived silanes in a process that allows reductive glycosylations of ketones. Chemoselectivity of the latter method was optimal in the presence of Ti(OR)4 additives. 

The impressive chemoselectivity of the transformations shown in Scheme 4 relies on the fact that oxidative addition of aryl halides into palladium(O) complexes at ambient temperature is faster than oxidative addition of alkyl halides, as well as the demonstrated feasibility of oxidative addition of alkyl halides to palladium(ll) complexes providing palladium(lV) intermediates [7]. 

With Beller s work having demonstrated the necessity for a slow dosage of acetone cyanohydrin (145) in order to successfully cyanate aryl halides [49], it was thought that this difference in reactivity could be exploited to chemoselectively transform vinyl halides into nitriles in the presence of aryl halides. Initially, the reaction conditions were applied to bromobenzene (165), and pleasingly no reaction was observed to occur (Table 7.7, Entry 1). 

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