Cross-coupling chemoselective

In terms of scope and chemoselectivity, hydrozirconation takes its place between hydroboration and hydroaiumination. However, the synthetic applications of organozirconocene complexes have been considerably expanded over these last few decades, and it can be expected that they will become more and more attractive in the future. Beside the direct substitution sequences, indirect reaction pathways involving transmetalation or activation by ligand abstraction have been successfully applied in a number of cross-coupling and C-C bond-forming reactions. 

Attainment of higher chemoselectivity (cross-coupling) and stereoselectivity in both radical reactions is expected to be one of the coming goals in this field. 

Scheme 5.13 Chemoselectivity profile in iron-catalyzed cross-coupling reactions.

The observed chemoselectivity is unique. Anodic treatment on BDD of 3,4,5-trimethoxy toluene results in the exclusive formation of the mixed biaryl 56. This method can be further performed with benzo[l,3]dioxole-containing arenes as reaction partners, giving biaryls 57 and 58 in acceptable yields. Furthermore, naphthalene moieties can be directly located onto 4-methyl guaiacol as the products 59 and 60 reveal. This novel cross-coupling can be expanded to other phenolic reaction partners as well [28]. The displayed selection of mixed biaryls 53-60 is accessible in a single step. In the workup protocol, HFIP is almost quantitatively recovered since it represents the most volatile component in the electrolyte. In addition, nonconverted starting materials can be recycled by short path distillation with approximately 80% efficiency (Scheme 23). 

The Cp2TiCl/H20 combination can also be used for the chemoselective reduction of aromatic ketones. The reaction discriminates between ketones and alkenes, between ketones and esters and, remarkably, between conjugated and non-conjugated ketones [80]. There is strong evidence that this reduction proceeds via ketyl-type radicals, which are finally reduced by H-atom transfer from 42 [81]. Under dry conditions, titanium-promoted ketyl radicals from aromatic ketones can be used for intermolecular and intramolecular cross-coupling of ketones [82], Thus, depending on whether water is added or not, complementary and versatile synthetic procedure protocols are available. 

---