Asymmetric Hydrogenation of Esters and Efforts Towards Photohydrogenation

  • Author / Creator
    Endean, Riley Thomas
  • A thorough overview of esters and their reductions is presented. A large focus was placed on reductions via homogeneous catalytic hydrogenation. Although several ester hydrogenation systems have been developed, the production of highly enantioenriched alcohols has generally relied upon the usage of enantioenriched esters.
    A system for homogeneous asymmetric hydrogenation of esters to enantioenriched alcohols was discovered and optimized via an in-house screening method. The optimal system uses an in situ formed Ru-based catalyst made from [Ru(1-3:5,6-η5-C8H11)(η6-anthracene)]BF4, the chiral ligand (1R,2R)-N,N′-bis{2-[bis(3,5-dimethylphenyl)phosphino]benzyl}cyclohexane-1,2-diamine, and H2. This catalyst is highly active and enantioselective towards hydrogenating α phenoxy esters to β-chiral primary alcohols under mild conditions. The system operates via dynamic kinetic resolution (DKR), where the esters undergo base-assisted racemization and the catalyst preferentially reacts with one enantiomer. Specifically, NaOiPr in THF and NaOEt in DME were optimal base and solvent combinations for the DKR. The alkoxide bases participate in transesterification and catalyst activation. Under 4 atm H2 and at room temperature, the catalyst provides quantitative conversion (50 turnovers) over 1 h for α-phenoxy propionate and butyrate esters (2 mol% catalyst, 50 mol% base). The enantiomeric excesses of the resulting β chiral alcohols ranged from 79 to 93%. The hydrogenation of (±)-ethyl 2-phenoxypropionate at 0 C resulted in a 95% enantiomeric excess (ee). Under 15 atm H2 and at room temperature, the catalyst performed 950 turnovers of (±)-ethyl 2-phenoxypropionate over 9 h and resulted in a 91% ee towards (R)-2-phenoxypropan-1-ol (0.1 mol% catalyst, 20 mol% NaOEt, DME). Hydrogenation of the potential intermediate aldehyde (±) 2 phenoxypropionaldehyde and deuteration of (±)-ethyl 2-phenoxypropionate were performed to experimentally investigate the mechanism.
    Three Ru(II)–polypyridyl complexes were prepared for the underexplored area of photohydrogenation. [Ru(bipy)2(1,10-phenanthroline-5,6-diamine)](OTf)2 (bipy = 2,2′ bipyridine) was synthesized in 56% yield from [Ru(MeCN)2(bipy)2](OTf)2 and the bis bidentate ligand 1,10-phenanthroline-5,6-diamine in MeOH at 70 C. The dinuclear complex was not the major product. The imidazolium ligand 1-benzyl-3-(propan-2-yl)-1H-imidazol[4,5-f][1,10]phenanthroline-3-ium (bpip) was prepared in 55% yield over three steps from 1,10 phenanthroline-5,6-diamine. The complexation of bpip to the Ru–dichloride precursors cis [Ru(Cl)2(bipy)2] and cis-[Ru(Cl)2(dmbipy)2] (dmbipy = 4,4′-dimethyl-2,2′-bipyridine) proceeded smoothly in MeOH at 70 C. [Ru(bpip)(bipy)2](OTf)3 and [Ru(bpip)(dmbipy)2](OTf)3 were prepared from their respective dichloride precursors, over two steps, in 87 and 73% yields, respectively. Crystals suitable for X ray diffraction were obtained for [Ru(bpip)(bipy)2](BF4)3.
    The [Ru(bipy)2(1,10-phenanthroline-5,6-diamine)](OTf)2 and [Ru(bpip)(dmbipy)2](OTf)3 were incorporated into two separate known hydrogenation systems. The photohydrogenation of acetophenone was attempted with in situ catalyst formation from [Ru(bipy)2(1,10 phenanthroline-5,6-diamine)](OTf)2 and fac-[Ru((R)-BINAP)(H)(iPrOH)3]BF4 (BINAP = 2,2′ bis(diphenylphosphino)-1,1′-binaphthyl). Only ~2% of the acetophenone was converted (~10 turnovers) over 45 min (0.2 mol% catalyst, 10 mol% KOtBu, iPrOH, ~1 atm H2, rt, 15 min 400–700 nm hv). The photohydrogenation of styrene was attempted with in situ catalyst formation from [Ru(bpip)(dmbipy)2](OTf)3 and [Co(TMEDA)(CH2SiMe3)] (TMEDA = N,N,N′,N′ tetramethylethylenediamine). No detectable reaction occurred under the conditions examined (0.2 mol% catalyst, 0.2 mol% KOtBu, MeOH, ~1 atm H2, 450 nm hv, 10.5 h).

  • Subjects / Keywords
  • Graduation date
    Spring 2021
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
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