Postdoctoral researcher, University of Utah
Synthesis of useful, complex molecules through the combination of two simple starting materials
Alcohols are functional groups found in a wide variety of molecules, including compounds found in nature and man-made drugs. New methods that facilitate the synthesis of alcohols from simple starting materials are, therefore, important for synthetic chemists. At the University of Utah I have developed a chemical reaction that forms of alcohol derivatives through the combination of two simple and readily accessible starting materials, namely an oxygen nucleophile (e.g., peroxide) and an alkene. Both of these components are essentially feedstock chemicals, meaning they are cheap and easy to access.
The reaction is controlled by a palladium catalyst, in the absence of which no reaction occurs at all. The palladium combines the two starting materials in a selective manner such that a large excess of one specific alcohol structure is formed over all the other possibilities.
This method will allow other synthetic chemists to predictably and easily install an alcohol derivative in their molecule of choice. Ultimately, I hope the work I have been doing will be used by synthetic chemists (e.g., medicinal chemists in pharmaceutical companies) for the synthesis of new potential drug candidates.
Abstract: The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols. Use of a dilute oxygen gas source (8% O(2) in N(2)) ensures that the oxygen/organic mixture never enters the explosive regime, and efficient gas-liquid mixing in the reactor minimizes decomposition of the homogeneous catalyst into inactive Pd metal. These results provide the basis for large-scale implementation of palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical synthesis.
Pub.: 10 Aug '10, Pinned: 28 Jun '17
Abstract: The mechanism of the tert-butylhydroperoxide-mediated, Pd(Quinox)-catalyzed Wacker-type oxidation was investigated to evaluate the hypothesis that a selective catalyst-controlled oxidation could be achieved by rendering the palladium coordinatively saturated using a bidentate amine ligand. The unique role of the Quinox ligand framework was probed via systematic ligand modifications. The modified ligands were evaluated through quantitative Hammett analysis, which supports a "push-pull" relationship between the electronically asymmetric quinoline and oxazoline ligand modules.
Pub.: 11 May '11, Pinned: 28 Jun '17
Abstract: An enantioselective intermolecular coupling of oxygen nucleophiles and allylic alcohols to give β-aryloxycarbonyl compounds is disclosed using a chiral pyridine oxazoline-ligated palladium catalyst under mild conditions. As opposed to the formation of traditional Wacker-type products, enantioselective migratory insertion is followed by β-hydride elimination toward the adjacent alcohol. Deuterium labeling experiments suggest a syn-migratory insertion of the alkene into the Pd–O bond. A broad scope of phenols, various allylic alcohols, and an alkyl hydroperoxide are viable coupling partners in this process.
Pub.: 23 Nov '16, Pinned: 28 Jun '17
Join Sparrho today to stay on top of science
Discover, organise and share research that matters to you