Reductive Elimination and Coupling Reactions

Early coupling processes, such as the Ullmann reaction (1901) for the conversion of ArHal to Ar—Ar with Cu powder, were very inefficient. In the 1990s, the discovery of a broad series of coupling reactions, often catalyzed by Pd complexes (Section 9.6), has transformed the situation, and these reactions now find very widespread use in organic synthesis. C—C, C—N, and C—O bonds can all be formed. Bromo- and iodoarenes are the most reactive, but the use of bulky, basic phosphines such as P(r-Bu) can even allow use of the much more available, but less reactive, cbloroarenes. Examples are shown in Eq. 14.55, where Pd2(dba)s is a common precursor of Pd(0), lightly stabilized by the labile dba ligand. 

The same strategy makes the Heck reaction efficient for chloroarenes (Eq. 14.56). A feature of all these reactions is that the R groups to be coupled must in general resist elimination so that they survive unchanged during the catalytic reaction while attached to Pd this means that aryls, vinyls, and benzyls are useful, and this type of reaction has become a standard method in the synthesis of conqplex organic molecules  

Many vanants or tnese paiiaoium coupling reactions nave neen aeveiopea. ror example, in a synthesis of Pumilitoxin, Kibayashi et al., have used the sequence 

Nicolaou et al. developed the vinylphosphate route shown in Eq. 14.58 for the synthesis of Brevetoxin. Equation 14.59 shows how the I Br Cl reactivity order can be used to differentiate positions on an arene ring this was a key step of the synthesis of a napyradiomycin antibiotic.  

We saw in Section 6.7 that the oxidative coupling of two acetylenes is a common process for a variety of low-valent metal complexes. The metalacyclic product can go on to an arene with excess alkyne, leading to a catalytic cyclotrimerization of the alkyne (Eq. 14.60).  

---