The continuing challenge of the stereo-selective formation of carbon-carbon bonds to form single enantiomers from achiral reactants is a problem with both academic and practical importance. The ultimate aim of our research is to develop catalysts that will promote stereoselective C-C bond formation reactions under mild conditions using small molecule substrates. The processes will be atom efficient, generating a minimum of byproducts that would need to be disposed or used in other processes.
We pursue the synthesis and characterization of chiral Lewis acids that will catalyze a variety of C-C bond forming reactions based on complexes containing an early transition metal (zirconium or niobium) coordinated to a facially directing penta-arylcyclo-pentadienyl ligand. The other ligands are mono- and bi-dentate alkoxide or amido ligands obtained from commercially available alcohols and amines using chloride or other ligands to complete the coordination sphere of the metal.
The complexes are tested for their efficacy in the catalysis of [4+2] cycloaddition of acrylate dienophiles, silylcyanation of aldehydes and oxo-ene reactions. Product analyses are performed by chiral column GC or HPLC. We probe the mechanism of catalysis to understand the factors underlying the selectivity in order to design more effective catalysts using NMR methods (NOSEY and VT experiments) and computational techniques (Accelerys Materials Studio Suite) to study the structure of coordination complexes formed with substrates. We have observed substrate-dependent diastereoselectivity using achiral catalysts incorporating pentaarylcyclopentadienyl ligands, so it is clear that understanding the nature of catalyst substrate interaction in key in the design of more effective catalysts.
The synthesis of niobium(V) complexes which can be converted to niobium(IV) complexes containing the C5Ph5 ligand and other ancilliary ligands such as chlorides, other halides or alkoxides. These compounds will be characterized by spectroscopic (NMR, ESR, IR or UV-Vis as appropriate) methods, elemental analysis and x-ray diffraction studies. (3) We will study the reactivity of the Nb(V) compounds as Lewis acid catalysts in [4+2] cyclization reactions and the Nb(IV) compounds in promoting two important classes of reactions; cyclization reactions and radical polymerization reactions.
Figure 1. Routes to niobium(V) complexes.
This route has been employed successfully by a number of workers (trialkyltin reagents have also been used) and Nb reduction is not as likely as in the reaction with the cyclopentadienide salts. These procedures will be optimized with appropriate choice of solvent, temperature and addition rate and order.
These compounds will then be converted to derivatives to enhance their selectivity by altering the steric demands and the Lewis acidity of the niobium atom. There are many commercially available alcohols with systematically varied steric bulk and donor properties that can be used to examine the factors leading to selectivity in the Lewis acid catalyzed [4+2] cycloaddition reaction. Non-substituted cyclopentadienyltetrachloroniobium(V) complexes undergo facile chloride exchange reactions by interaction with alcohols as shown in Figure 2. We believe that we can prepare a small library of alkoxides in a short time judging from the high yields obtained by previous workers. These compounds will be characterized by elemental analysis, NMR spectroscopy and x-ray diffraction (if suitable crystals are obtained). These complexes can then be tested for selectivity and activity in [4+2] cycloaddition.
Figure 2. Preparation of alkoxide derivatives of Cp’NbCl4.
The reduction of the Nb(V) complexes to Nb(IV) has been accomplished by use of chemical reductants1, and we will use reductants ranging from sodium naphthalide (Na(C10H8)) to lead(II)chloride or zinc dust. We expect that any of these reductants will lead to formation of the desired Nb(IV) product as shown in Figure 3.
Figure 3. Reduction of Nb(V) complexes to Nb(IV)
Figure 4. ARTP in polymerization. The atom transferred is the “X”, planned to be a halogen in the niobium systems that will be investigated. The stable radical is the metal complex to left, MLn.