Chromium in organic synthesis. From methodology to natural products total synthesis

Since their discovery in 1957, organochromium reagents have been the area of constant developments and innovations. Initially prepared in aqueous phase, the synthesis of these unrivaled synthetic tools has been optimized in organic solvents for the construction of carbon-carbon bonds. Due to their unique combination of chemical features, these reagents have become indispensable tools for advanced organic synthesis, as witnessed, by a rapidly growing number of impressive applications in total synthesis of natural products such as palitoxine, brevetoxine and brefeldine. Of particular interest the Nozaki-Hiyama-Kishi (NHK) and the Takai reactions are part of the most popular tools in organic synthesis. In this regard a great number of milestones and achievements have been made, such as the development of reactions using a catalytic amount of chromium and the discovery of asymmetric ligands for the preparation of chiral molecules. The last ten years have witnessed an enormous growth in terms of new reagents and reaction development. Most importantly, several chromium intermediates have emerged: chromium vinyliden carbenoids, carbenes and carbynes have been successfully generated and used for the stereoselective synthesis of halogenated olefins. Recently, the synthetic utility of these reactions have been elegantly demonstrated for the synthesis of halogenated olefins and for the total synthesis of the natural hateramulide. Accordingly, the use of chromium vinylidene carbenoids in organic synthesis has been recognized, by the chemical community, as the Falck-Mioskowski reaction. The rapid and exciting expansion of the area of organochromium reagents will no doubt spawn novel transformations and methodologies to complement the synthetic chemist's arsenal of selective reactions.