Cross-coupling reactions cyanation

There are many other examples in the literature where sealed-vessel microwave conditions have been employed to heat water as a reaction solvent well above its boiling point. Examples include transition metal catalyzed transformations such as Suzuki [43], Heck [44], Sonogashira [45], and Stille [46] cross-coupling reactions, in addition to cyanation reactions [47], phenylations [48], heterocycle formation [49], and even solid-phase organic syntheses [50] (see Chapters 6 and 7 for details). In many of these studies, reaction temperatures lower than those normally considered near-critical (Table 4.2) have been employed (100-150 °C). This is due in part to the fact that with single-mode microwave reactors (see Section 3.5) 200-220 °C is the current limit to which water can be safely heated under pressure since these instruments generally have a 20 bar pressure limit. For generating truly near-critical conditions around 280 °C, special microwave reactors able to withstand pressures of up to 80 bar have to be utilized (see Section 3.4.4). 

Inspection of Table 1 indicates that acylation, cyanation and enolate substitution represent the other classes of Pd- or Ni-catalyzed cross-coupling. The vast topic of Pd-catalyzed enolate -substitution including the Tsuji-Trost reaction and other -substitution reactions22 is not discussed in this chapter, and the readers are referred to pertinent reviews including that cited above. The other topics are very briefly discussed below. 

Palladium catalyzed cyanation [71] has recently received a lot of attention in the literature as a cross-coupling which employs cheap, commercially available metal cyanides and incorporates the versatile and synthetically useful cyano group. The development of a domino ort/ o-functionalization/cyanation reaction represents an advance in palladium catalysis as there are very few, if any palladium-catalyzed domino cyanation reactions. The development of the domino ortfto-functionalization/ cyanation [72, 73] by Lautens has led to some of the most significant discoveries of highly functionalized alkyl halides as coupling partners, as well as further development in the selectivity and scope of o/t/to-arylation chemistry. 

Recently, studies in urea synthesis have focused on transition-metal-catalyzed reactions. Buchwald et al. reported a Pd-catalyzed cross-coupling of aryl chlorides with sodium cyanate, which represented a practical way to synthesize unsymmet-rical ureas [50]. The protocol allows for the synthesis of unsymmetrical N,N -di-and A. A. A -trisubstituted ureas in one pot and is tolerant of a wide range of functional groups (Scheme 5.19). Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive... 

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