Primary alcohols are important molecules in both the commodity and pharmaceutical chemical industries. Currently, their large-scale production involves the use of either high pressures of toxic and hazardous carbon monoxide and hydrogen gasses, or stoichiometric metal and peroxide reagents. A new method for their direct, catalytic synthesis by anti-Markovnikov hydration from readily available olefin precursors would be beneficial for the synthesis of bioactive small molecules, as well as polymers and commodity chemicals that benefit human health and quality of life. Current solutions to this problem either require multistep procedures, stoichiometric amounts of oxidant and/or reductant, or are limited in scope. A general approach to anti- Markovnikov hydration is proposed to proceed through radical addition to olefins, which provide the more highly substituted radical intermediate. A new catalytic cycle is developed where hydrogen atom transfer from a metal-hydroxo species generates the new carbon-hydrogen bond and propagates the radical reaction be regenerating the metal-oxo catalyst. This cycle involves two organometallic species of interchanging oxidation states, allowing reaction to proceed without the need for exogenous oxidants or reductants. This dual-mode catalysis will be facilitated by the design of dinuclear organometallic frameworks where the metal-oxo and the metal-hydroxo components are present in close proximity. This approach allows for hydrogen atom transfer to be accelerated by nature of it being an intramolecular process, and creates formal symmetry in the dinuclear redox transfer. Manganese oxo complexes have been identified as the ideal starting point for this investigation due to their known radical-type reactivity in both oxygen atom transfer and hydrogen atom transfer reactions. Olefin hydration catalysts developed from this proposal are anticipated to have general scope due to the typically high functional-group tolerance of radical reactions, allowing a wide range of alcohols to be synthesized from readily available olefin feedstocks.

Public Health Relevance

Over one million tons of primary alcohols are produced by the commodity and pharmaceutical chemical industries every year. These products are important intermediates in the synthesis of many bioactive compounds, but their synthesis from common olefin precursors requires either high pressures of toxic and hazardous gasses, or the use of processes with heavy waste streams. This proposal seeks to address the health issues of hazardous reaction conditions and waste production by developing a new method for the conversion of terminal olefins to primary alcohols utilizing substrate, catalyst and water as the only reagents.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Barski, Oleg
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California Institute of Technology
Biomed Engr/Col Engr/Engr Sta
United States
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Cannon, Jeffrey S; Zou, Lufeng; Liu, Peng et al. (2014) Carboxylate-assisted C(spĀ³)-H activation in olefin metathesis-relevant ruthenium complexes. J Am Chem Soc 136:6733-43
Cannon, Jeffrey S; Grubbs, Robert H (2013) Alkene chemoselectivity in ruthenium-catalyzed Z-selective olefin metathesis. Angew Chem Int Ed Engl 52:9001-4