Current Organic Chemistry - Volume 4, Issue 8, 2000

The number of asymmetric transformations catalyzed by chiral transition metal complexes is growing exponentially. With this growth, application to kinetic resolution processes is also blossoming. These include metal salen complexes for epoxide opening, reductions, and recent examples of Sharpless oxidation methods. Great strides have been made in Zr-catalyzed carbon-carbon bond formations and Mo-catalyzed olefin metathesis. New Fe-based nucleophilic catalysts allow for the resolution of a wide range of secondary alcohols. Palladium-catalyzed asymmetric allylic substitution has most recently appeared on the scene with outstanding levels of efficiency for kinetic and dynamic kinetic resolution. This review presents an overview of new developments in transition metal-mediated kinetic resolution from the last two years.

Under the conditions originally developed by Taber and Nugent, a 1,6- or a 1,7-diene will smoothly condense with zirconocene to give the intermediate metallacycle. While these zirconacycles can be isolated and characterized, they usually are carried on directly, by reaction with a suitable electrophile (e.g. O2, or CO), to give the organic product. As zirconium is inexpensive, the procedure is operationally simple, and the byproduct zirconium sulfate is nontoxic, intramolecular diene cyclozirconation has become a useful tool for carbocyclic and heterocyclic ring construction. From the inception of this reaction, it was anticipated that the central Zr could serve as a scaffold to direct the formation of two, three or even four new stereogenic carbon centers. Subsequent work has shown that the cyclometallations are reversible, and that the reaction can be carried out under either kinetic or thermodynamic control. It is particularly exciting that the semiempirical computational package ZINDO can serve effectively to predict the relative stability of the intermediate diastereomeric zirconacycles. This has allowed ZINDO to be used in a predictive sense, to guide the design of dienes that cyclize with high diastereoslectivity. The use of this approach in conjunction with total syntheses of the natural products elemol, dendrobine, haliclonadiamine and androstenedione is described in this article.

One of the current approaches to prepare enantiomerically pure materials is to use catalytic quantities of chiral transition metal complexes in a homogeneous medium. The catalytic activity originates from the metal and the asymmetry of the metal - catalysed process is induced by the chiral organic ligands attached to that metal. Commonly used donor atoms, which include phosphorus, nitrogen, oxygen and sulfur, help to electronically tune the metal. A vast number of mono-, bi- and polydentate ligands have been successfully applied in asymmetric catalysis. In this review, an attempt is made to systemise the role which bidentate, axially chiral phosphinamine ligands play in asymmetric catalysis. The ligands are classified, not by the reaction to which their metal complexes have been applied, but by the biaryl and other groups present which induce chirality. These biaryl groupings include 3,5-dihydro-4H-dinaphthazepines, 1-naphthyl-2-naphthylamines, 1,1-biarylphosphiteoxazolines, 1,1-binaphthyloxazolines, isoquinolines, quinazolinones and our work on pyrazine- and quinazoline-containing axially chiral ligands. Within this sub-classification the ligands are described, where feasible, in the chronological order in which they were reported so that the development of ligand architectural design can be more easily monitored. The asymmetric transformations to which metal complexes of these ligands have been applied include palladium catalysed allylic substitutions, copper catalysed 1,4-additions to enones and rhodium catalysed hydroboration of vinylarenes. Excellent enantioselectivities, regioselectivities and reactivities have been achieved in each of these processes.

The application of acyclic (diene)iron complexes and (pentadienyl)iron cations in organic synthesis has steadily increased over the past 20 years. This is due to their ease of preparation, their stability toward a wide variety of reaction conditions, the manifold method for removal of the Fe(CO)3 group, and the low cost of iron carbonyls. The (tricarbonyl)iron adjunct may serve in three capacities: i) as a protecting group for conjugated dienes, ii) to direct the formation of chiral centers adjacent to the complexed dient, and iii) to stabilize the formation of positive charge adjacent ot the complexed diene (i.e. pentadienyl cations). Specific examples of these attributes will be presented in this review. One of the advantages of stoichiometric organometallic reagents is the ability to repeatedly utilize the same metal center to control a number of different bond forming reactions. Six examples will be presented which demonstrate this potential for acyclic (diene)iron complexes and (pentadienyl) iron cations.