Metal Initiated Cation-Olefin Reactivity
One important research direction in the Gagné group focuses on new synthetic methods for complex bond construction. Consider the enzyme Squalene-Hopene Cyclase, which utilizes the cation-olefin reaction to zip up the poly-ene Squalene into the plant steroid Hopene.
Although the enzyme catalyzed reaction is proton-initiated, Pd(II) or Pt(II) can often behave similarly and activate alkenes towards nucleophilic attack. With a focus on alkene nucleophiles, this notion has led to several metal catalyzed multicyclization reactions. Below are several Pd(II)- or Pt(II)-catalyzed cation-olefin reactions. Depending on the ligands on the metal, the catalysts can turnover by beta-hydride elimination or other more-unusual mechanisms.
Enantioselective Oxidative Cyclization of Poly-enes
Chiral P2Pt-dications are capable catalysts for initiating cationic polycyclization reactions. Phenols, alcohols, and sulfonamides are all capable traps for the cation and generate multi-cyclic products with good to excellent enantioselectivities. The turnover-limiting step is beta-hydride elimination, which expels product and generates a Pt-hydride.
The key to turning over these catalysts is the addition of trityl cation to abstract the hydride and regenerate the dication. Refined conditions utilize trityl-methyl ether as the trityl source. The acid byproduct of cyclization liberates trityl cation and enables turnover. Resin-bound versions of the oxidant also work well. This new reaction is currently the subject of a mechanistic study, and additional variants for applications in synthesis are also ongoing.
Pincer and Pseudo-Pincer Catalysts for Cation-Olefin Chemistry
When pincer ligands are utilized to coordinate Pd(II) and Pt(II), extremely electrophilic catalysts can be accessed which are incapable of β-H elimination (lack of cis coordination sites); this property enables unique turnover mechanisms to operate. Triphosphine ligands strongly favor cyclopropanative cycloisomerization processes. For example the following 1,6-diene diastereoselectively generates a 4.1.0 bicycloheptane. The proposed mechanism for this process is shown below, and it is supported by D-labeling studies, and the trapping of intermediate cations. Since the intermediate alkyl-Pt catalysts cannot decompose by β-H elimination (see above P2Pt2+ chemistry), turnover is under catalyst control and 1,5-Dienes generate [3.1.0]-bicyclohexanes, which are common monoterpenes; the one step synthesis of cis-thujane is such an example.
A more recent focus has been improving catalysts using a modular combination of bi and monodentate ligands. For example, the dppm/PMe3 catalyst is the most active and tolerant catalyst yet. Rates are ∼20-times faster, and yields are uniformly improved. Highly enantioselective catalysts are also accessible in this manner.
The Gagné group is interested in synthesis, catalysis, and how molecular recognition can be used to find new approaches to solving difficult problems.
Students and postdocs come from a variety of backgrounds but primarily include organic and inorganic coworkers.
Our projects, generally speaking, straddle these areas, though some projects have a strong emphasis on synthesis and/or organometallic chemistry/catalysis.