Catalytic Olefin Isomerization - PowerPoint PPT Presentation

1 / 16
About This Presentation
Title:

Catalytic Olefin Isomerization

Description:

While the influence of chirality on biological activity can be pronounced, the ... Horner and Knowles at Monsanto (1968) prepared an asymmetric phosphine which, ... – PowerPoint PPT presentation

Number of Views:1016
Avg rating:3.0/5.0
Slides: 17
Provided by: par55
Category:

less

Transcript and Presenter's Notes

Title: Catalytic Olefin Isomerization


1
Catalytic Olefin Isomerization
  • RuHCl(PPh3)3 will hydrogenate olefins in the
    presence of H2, but it also isomerizes a-olefins
    to internal olefins through reactions of the Ru-H
    bond.

2
Catalytic Olefin Isomerization - Product
Distribution
4-centred planar transition state
3
Enantiomers and their Properties
  • That 2-butanol and its mirror
  • image cannot be superimposed
  • shows that these are two
  • different molecules
  • these stereoisomers
  • are enantiomers
  • Chiral molecules exist as enantiomers
  • due in most cases to the presence of
  • an asymmetric carbon
  • While the influence of chirality on biological
    activity can be pronounced, the physical
    properties of enantiomers are identical except
    for optical rotation.

4
Chiral Compounds with Differing Biological Effects
5
Diastereomers and their Properties
  • Stereoisomers that are not mirror images of each
    other are called diastereomers.
  • They may chiral molecules (2,3-pentanediol,
    below) but need not be, as seen for cis- and
    trans-2-butene.
  • (2R, 3R) (2S, 3R)
  • (2R, 3S) (2S, 3S)
  • Diastereomers have different melting points,
    boiling points, refractive indices, heats of
    formation and other physical properties.
  • Reaction of a racemic mixture with a single
    enantiomer generates isolable diastereomers.

6
Production/Isolation of Chiral Compounds
  • Optical Purity
  • where a is the specific rotation of the mixture
    and ao is that of the pure enantiomer
  • Enantiomeric Excess (ee)
  • Methods of producing/isolating asymmetric
    compounds
  • Kinetic resolution and/or selective
    crystallization of racemates
  • Fermentation
  • Asymmetric transformations of prochiral compounds
  • enzyme catalyzed functionalizations
  • chemical hydrogenation, epoxidation, etc.

7
Catalytic Asymmetric Hydrogenation
  • A leading example is the synthesis of L-dopa, an
    optically active drug generated from non-chiral
    starting materials for the treatment of
    Parkinsons disease.

Phosphine ligand of rhodium catalyst precursor
8
Catalyst Precursors for Selective Hydrogenation
  • Horner and Knowles at Monsanto (1968) prepared an
    asymmetric phosphine which, when used in the
    place of PPh3 in Wilkinsons catalyst, generated
    enantioselectivity in the hydrogenation of
    prochiral olefins.
  • Refinements in ligand structure
  • (steric bulk and basicity)
  • led to steady improvements
  • in enantiomeric excess.
  • Best results were observed
  • for bidentate phosphines.

9
Catalyst Precursors for Selective Hydrogenation
10
Catalyst Precursors for Selective Hydrogenation
  • Ruthenium-base systems have a broad
  • range of utility as asymmetric catalysts.
  • a,b-unsaturated carboxylic acids are
  • hydrogenated in high yield and ee
  • (S-Naproxen, below) as well as
  • allylic alcohols.
  • Note that the BINAP ligand is an
  • example of a chiral, bidentate phosphine
  • by virtue of it having atropisomeric forms
    (isomers that can be separated only because
    rotation about a single bond is prevented).

11
Catalyst Precursors for Selective Hydrogenation
  • Organometallic compounds of the
    Schrock/Osborn-type have proven to be more
    selective hydrogenation catalysts than the
    Wilkinson derivatives
  • This catalyst precursor is readily activated by
    H2 to generate a Rh(I) complex that is
    coordinated with solvent.

12
Substrate Coordination in Asymmetric
Hydrogenations
  • Achieving high enantiomeric excesses seems to
    require a
  • substrate that is capable of
  • bidentate coordination.
  • This secondary
  • coordination generates
  • diastereomeric adducts
  • with rigid
  • phosphine/
  • substrate
  • arrangements.
  • Hydroxy, carbonyl, and
  • amino, groups in an
  • a-position to the double bond
  • are suitable.

13
Hydrogenation of Dehydroamino Acid Derivatives
14
Hydrogenation Mechanism - Achiral Phosphines
  • Mechanism of the Rh(DIPHOS) catalyzed
    hydrogenation of
  • methyl-(Z)-a-acetamidocinnamate (MAC).

15
Reaction Coordinate of an Enantioselective
Synthesis
  • To achieve high enantiomeric
  • excess, the diastereomeric
  • transition states of the rate
  • determining steps must be
  • substantially different in energy.
  • The theoretical ee is a strong
  • function of D(DG) as shown to
  • the left.

16
Enantioselective Hydrogenation Mechanism
k1 k-1
k1 k-1
Write a Comment
User Comments (0)
About PowerShow.com