Design, Development and Mechanistic Study of Ruthenium-Based Catalysts for the Hydrogenation of Imides and Amides

  • Author / Creator
    John, Jeremy Michael
  • Prior mechanistic studies demonstrate that trans-[RuH2((R)-BINAP)((R,R)-dpen)] is a remarkably active carbonyl reducing agent at low-temperatures in THF-d8. This dissertation describes the monohydrogenation of cyclic meso-imides using this catalyst and related complexes under mild conditions. Bicyclic meso-imides were chemo-, diastereo- and enantio-selectively desymmetrized to form chiral hydroxy lactams (90-99% conversion, 88-97% ee, dr >93:7, C=O/C=C selectivity >99%) with up to five stereogenic centers in one hydrogenation under the reported reaction conditions (0.1-1 mol% Ru, 0.9-9.9 mol% KOt-Bu under 50 atm H2 at 0-22 °C in 3-57 h). Compounds of academic and commercial interest were also synthesized from these hydroxy lactams.
    A detailed low-temperature investigation into the desymmetrization-hydrogenation reaction led to the discovery of a previously unobserved active pathway for carbonyl hydrogenation. Reaction intermediates resulting from the unexpected deprotonation and di-deprotonation respectively of the parent dihydrides i.e. trans-M[RuH2((R,R)-HN–CH(Ph)CH(Ph)NH2)((R)-BINAP)], where M = K+ or Li+, and trans-M2[RuH2((R,R)-HN–CH(Ph)CH(Ph)N–H)((R)-BINAP)] where M = Li+, were synthesized and characterized. The mono-deprotonated dihydrides were found to have unprecedented activity towards the hydrogenation of imide and amide carbonyls at low temperatures in THF-d8. The origins of the enantioselection for this reaction were also proposed using simple well-defined models based on current literature and the outcomes of this investigation.
    The hydrogenation of amides using trans-[RuH2((R)-BINAP)((R,R)-dpen)] and its variants is also described herein. In contrast to the high activity of trans-[RuH2((R)-BINAP)((R,R)-dpen)] towards ketones, imides (in the presence of base), and esters, the catalyst exhibited low to moderate activity towards amides. This difference in activity was attributed to thermal instability of the catalyst at high temperatures. By tethering the phosphine and amine units together, a robust pre-catalyst, [Ru(η3-C3H5)(Ph2P(CH2)2NH2)2]BF4 was prepared, which, when combined with NaOMe (Ru:NaOMe:Amide = 1:500:10,000), catalyzes the hydrogenation of amides with a TON up to 7120. The analogous base-free system comprising [Ru(η3-C3H5)(Ph2P(CH2)2NH2)2]BF4 and NaBH4 was also shown to be an efficient catalyst system for this reaction under reported conditions (0.1 mol% Ru, 0.2 mol% NaBH4 under 50 atm H2 at 100 °C in 24 h) in contrast to trans-[RuH(η1-BH4)((R)-BINAP)((R,R)-dpen)].

  • Subjects / Keywords
  • Graduation date
    Spring 2014
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • de Klerk, Arno (Chemical and Materials Engineering)
    • Bergens, Steven (Chemistry)
    • Hall, Dennis (Chemistry)
    • Schafer, Laurel (Chemistry)
    • Buriak, Jillian (Chemistry)
    • Rivard, Eric (Chemistry)