The development of the asymmetric Nozaki-Hiyama-Knishi reaction

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. 1 Introduction 2 Development of a Catalytic Nozaki-Hiyama-Kishi Reaction 3 Diastereoselectivity in Reactions with Monosubstituted Allylic Halides 4 Catalytic Enantioselective Nozaki-Hiyama-Kishi Reaction 5 Application of Salen-Derived Ligands in the Enantioselective Nozaki-Hiyama-Kishi Reaction 6 Application of Oxazoline-Containing Ligands in the Catalytic Enantioselective Nozaki-HiyamaKishi Reaction 7 Application of Tethered Bis(8-quinolinato)Chromium Complexes in the Catalytic Enantioselective Nozaki-Hiyama-Kishi Reaction 8 Applications of Catalytic Nozaki-Hiyama-Kishi Reaction in Total Synthesis 9 Conclusion