Aryl halides functional group tolerance

For more than a century, stoichiometric methods were presumed in the preparation of benzonitriles in laboratory and industry. These particularly include the Rosenmund-von Braun reaction of aryl halides, the diazotization of anilines and subsequent Sandmeyer reaction, and the ammoxidation. Because of (over)stoichiometric amounts of metal waste, lack of functional group tolerance, and harsh reaction conditions, these methods do not meet the criteria of modern sustainable synthesis. 

The transition metal catalyzed carbon-carbon bond formation between organomagnesium reagents and aryl (vinyl) halides has been one of the pioneering entries into cross-coupling chemistry. The reaction has been widely utilized since than in azine chemistry,22 with the limitation that the functional group tolerance of Grignard reagents is only moderate. Here only some of the more recent developments will be mentioned. 

The recent emergence of the Suzuki coupling as the method of choice for the cross-coupling of aryl halides,2 3 due to its functional group tolerance and the stability of organoboron compounds, is clearly reflected by the proportion of these transformations in the literature. 

Silyl enolates undergo Pd-catalyzed arylation with aryl halides in the presence of an additive such as Bu3SnF,327 CuF2,328 or ZnF2.329 The arylation of silyl enolates has higher functional group tolerance than that of alkali metal enolates. The ZnF2-promoted arylation is valuable for efficient, stereoselective synthesis of a-arylated esters and imides (Equation (89)). 

Early attempts to solve this problem focused on the use of weaker bases, such as Cs2C03 or K3P0460. Catalytic aminations conducted with these bases are possible in the presence of esters, aldehydes, enolizable ketones and nitro functional groups on the aryl halide. Alternatively, the functional group tolerance has been shown to be improved... 

In this variation of the Pd-catalyzed cross-coupling reaction, which is closely related to the Stephen-Castro reaction, copper acetylides are reacted with (hetero)aryl halides or triflates to produce (hetero)aryl alkynes [111]. The Sonogashira reaction is comparable to the Suzuki or Stille reactions in its scope and functional group tolerability. 

This reaction displays a diverse functional group tolerance. This reaction showed no significant differences in yields when comparing electron-donating groups and electron-withdrawing groups. The substitution pattern of the aryl halide displayed minimal effects on the isolated yields of the products. 

The reaction of pyrrolidinone with o-anisyl bromide as an electron-rich aryl halide also gave satisfactory yields of the N-arylation product Buchwald et al. [40] revealed that XantPhos (ll)/[Pd2(dba)3] and CSjCOj as base in 1,4-dioxane was a more efficient and more versatile catalyst system. The amidation of aryl bromides and sulfonates was readily achieved under mild reaction conditions (45-100°C) and displayed high functional group tolerance (Scheme 13.73). 

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