No abstract

This review collates the literature to date on the development of the Nozaki-Hiyama-Kishi (NHK) reaction into an important chromium-mediated, carbon-carbon bond forming process. The initial research employed stoichiometric quantities of chromium and this was exploited in the key steps of a range of total syntheses. Thereafter, the NHK reaction was further developed with the discovery of the catalytic variant. The focus of recent investigations is on the application of this reaction in asymmetric synthesis. The asymmetric NHK typically employed a range of salen-and oxazoline-derived chiral ligands and tethered bis(8-quinolinato)-chromium complexes. To date, good to high enantioselectivities have been obtained in a variety of NHK-type processes, including allylation, crotylation, methallylation, allenylation, propargylation and vinylation of a range of aldehydes, with limited examples employing ketones as substrates. Selected examples of the asymmetric NHK in total synthesis will also be described.

No abstract

A series of symmetric and non-symmetric bis(oxazoline) ligands were applied in the Nozaki-Hiyama-Kishi methallylation of a range of aromatic and aliphatic aldehydes. A non-symmetrical ligand with tert-butyl/benzyl-substituted oxazolines provided the highest enantioselectivity of 99.5% for the methallylation of benzaldehyde.

We report the good to high-yielding three-step synthesis of non-symmetrical bis(oxazoline)-containing ligands possessing an N-thienylaniline unit. The convergent synthesis employed a palladium-catalysed aryl amination of 2-(2'-bromothiophene)nitrile as the key step, with sixteen ligands prepared in total. These ligands were subsequently applied in the chromium-catalysed enantioselective Nozaki-Hiyama-Kishi allylation of benzaldehyde with an optimal enantioselectivity of 73%.