Research in our group is primarily aimed toward the development of catalysts, catalytic reactions and methods for organic synthesis. Ultimately, we are interested in using these methods to address problems in the synthesis of complex molecules possessing interesting structural, biological and physical properties. As such, our research program spans the areas of organic synthesis, catalysis, and organometallic chemistry. Some recent examples are listed below. Please click each subtitle to see graphical representations of our chemistry.
Gold(I)-Catalyzed C-C Bond Formation
Interest in the catalytic activity of gold complexes has undergone a dramatic upswing over the past few years. Our attention has focused on reaction development of cationic phosphine-gold(I) complexes, which are superb Lewis acids for the activation of alkynes and allenes. Early work in our group exploited this reactivity to discover gold-catalyzed versions of the Conia-ene reaction, a propargyl Claisen rearrangement, the Rautenstrauch rearrangement, and enyne cycloisomerization reactions. More recently, we have employed gold(I) catalysts toward the intramolecular hydroamination of allenes and a rearrangement of vinyl allenes to functionalized cyclopentadienes.
During the development of our methodologies, we are interested elucidating the mechanism of these reactions. For a series of nucleophilic trapping reactions, including acetylenic Schmidt, Rautenstrauch, cyclopropanation, and [4+3] annulation reactions, we have proposed the involvement of gold carbene intermediates. We have also oxidized these intermediates to aldehydes and ketones and postulated that they occur via oxygen atom transfers. Current work is underway to generate alpha-carbonyl gold-carbene intermediates from the appropriate pre-cursors.
Moreover, we are pursuing asymmetric catalysis through the use of chiral ligands on gold. Until recently, enantioselective gold catalysis seemed improbable due to the linear coordination of gold. We have, however, demonstrated the potential of chiral gold complexes in our enantioselective styrene cyclopropanation and allene hydroamination reactions.
Representative examples:
Representative examples:
Metal-Oxo Catalyzed Reactions
High oxidation state metal-oxo complexes have significant practical advantages due to their high tolerance to air and moisture. Indeed, some reactions actually require the presence of water and/or air to proceed at maximum efficiency.
In 2003, we successfully utilized rhenium(V)-oxo complexes in the hydrosilylation of aldehydes. This transformation effectively combines a reduction and a protection into one reaction. An asymmetric hydrosilylation reaction of imines was later developed. We have also employed Re(V)-oxo complexes in a wide variety of propargyl substitution reactions. Currently, we are expanding this chemistry to the development of carbon-carbon bond forming reactions and/or other asymmetric transformations. Additionally, given the metal’s history as an oxidizing reagent, we are developing transformations involving sequential reduction and oxidation reactions.
In addition to Re(V)-oxo catalysis, we have developed a vanadium-catalyzed method for the oxidative kinetic resolution of alpha-hydroxycarbonyl compounds using molecular oxygen as the terminal oxidant. The reaction allows for the enantioselective preparation of benzylic, allylic, propargylic, and aliphatic secondary alcohols.
Representative examples:
Representative examples:
Representative examples:
Representative examples:
Other Reaction Methodologies
The group’s attention also expands to the explorations of other transition metals, especially Group 8 and 10 metals, in asymmetric transformations. For example, we recently reported enantioselective Pd(II)-catalyzed enyne cyclizations and applied this methodology towards the synthesis of (-)-Laurebiphenyl. We have also collaborated with Robert Bergman to synthesize P-stereogenic phosphines with Ru(II) phosphido complexes.
in
collaboration with Robert G. Bergman
New Methods Applied to Natural Product Synthesis
Currently, we are interested in applying methodology that we have recently developed towards the total syntheses of natural products. As an example, we have already published the enantioselective synthesis of (-)-pantofuranoid E through the use of oxidative vanadium chemistry.
In addition, our gold(I) methodology is being applied to the total synthesis of molecules containing vicinal angular quaternary centers or highly substituted cyclopentenones. In one instance, a gold(I)-catalyzed 5-endo-dig Conia-ene reaction of silyl enol ether allows for the diastereoselective production of bicyclic enones. Other ways to access bicyclic enones include gold(I)-promoted ring expansion and gold(I)-catalyzed Rautenstrauch rearrangement reactions.
Representative Target Natural Products:
Representative Target Natural Products:
