Cross couplings nucleophilic partner

Coupling of aromatic heterocycles goes well. The 2-position of a pyridine is very electrophilic and not at all nucleophilic (Chapter 43) but couplings at this position are fine with either the halide or the boronic acid in that position. Clearly, it is a mistake to see either of these substituents as contributing a nucleophilic carbon . It is better to see the reaction as a coupling of two equal partners and the two substituents (halide and boronic acid) as a control element to ensure cross-coupling and prevent dimerization. In the second example potassium te t-butoxide was crucial as weaker and less hindered bases gave poor yields. 

Perfluoroarenes were also found to be highly reactive coupling partners in intermolecular direct arylation [68, 69]. A wide range of aryl halides can be employed, including heterocycles such as pyridines, thiophenes, and quinolines. A fluorinated pyridine substrate may also be cross-coupled in high yield and it was also found that the site of arylation preferentially occurs adjacent to fluorine substituents when fewer fluorine atoms are present. Interestingly, the relative rates established from competition studies reveal that the rate of the direct arylation increases with the amount of fluorine substituents on the aromatic ring. In this way, it is inversely proportional to the arene nucleophilicity and therefore cannot arise from an electrophilic aromatic substitution type process (Scheme 7). 

As is evident from Scheme 55, the nucleophilic partner in cross-coupling need not be a phosphine. This section surveys recent results with other P-nucleophiles. 

In studies concerned with optimization of the Suzuki cross-coupling of 2-pyridyl nucleophiles, lithium triisopropyl 2-pyridylborates are shown to be the most suitable boron coupling partners (eq 60). The borates are isolated and subjected to coupling with various aryl and hetaryl halides (X = Cl, Br) to give the corresponding azabiaryls. ... 

These silyl enol ethers are probably the best way of carrying out crossed aldol reactions with an aldehyde as the nucleophilic (enol or enolate) partner. An example is the reaction of the enol of the not very enolizable isobutyraldehyde with the very enolizable 3-phenylpropanal. Mixing the two aldehydes and adding base would of course lead to an orgy of self-condensation and cross-couplings. 

Adjusting the Nucleophilicity of Oi anoboron Cross-Coupling Partners... 

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