Stereoselective Nozaki‐Hiyama‐Kishi Reaction

Abstract

This chapter reviews the literature on the development of the Nozaki‐Hiyama‐Kishi (NHK) reaction into an important chromium‐mediated, stereoselective, 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 has been 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, homoallenylation, and vinylation of a range of aldehydes, with limited examples employing ketones as substrates. Selected examples of the asymmetric NHK in total synthesis will be described, in addition to selected experimental procedures.