Design and Synthesis of Two Novel Pincertype Ligands For Use in Asymmetric Catalysis

1
Design and Synthesis of Two Novel Pincer-type
Ligands For Use in Asymmetric Catalysis

• by
• Jennifer Beckman
• under the guidance of Dr. Philip Osburn
• at the University of Tennessee at Martin

2
Abstract

• In recent organometallic literature,
  palladacyclic compounds have become of great
  interest. Our research the past two years has
  been geared toward the development of two
  different types of palladacyclic catalysts an
  SCN-type palladacycle and an SCS-type
  palladacycle. There are several reasons for our
  interest in making such compounds.
• Palladium catalysts are used in many vital
  organic reactions however, the current ones in
  use are either extremely sensitive to common
  reaction conditions or they are not as efficient
  as thought possible. Thus we have tried to
  synthesize a palladium catalyst which is both
  efficient and stable the SCN-type palladacycle.

3

• Another crucial factor in current scientific
  reports deals with asymmetric catalysis. Since
  the discovery of chirality in 1874, it has proven
  to be of great importance chiral compounds play
  a major role in many industrial syntheses as well
  as the majority of human metabolic pathways.
  Depending on which enantiomeric form a compound
  has, it will exhibit extremely different effects
  and properties. As a result, it can be crucial
  for a compound to be enantiomerically pure. One
  method of obtaining enantiomerically pure
  compounds is to utilize an asymmetric catalyst.
  Our contribution to this area centered around the
  design and synthesis of a novel chiral SCS-type
  palladacycle.
• As a result of our efforts toward the synthesis
  of both types of palladacycles, we have deduced
  that their synthesis is not at all trivial. We
  have made great strides toward the completion of
  both the SCN and the SCS-type palladacyclic
  compounds however, there is still much work to
  be done in future studies before obtaining the
  desired compounds.

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Examples of chiral drugs This shows why it can
be so important to obtain enantiomerically pure
product.
Ibuprofen
Thalidomide
S enantiomer active R enantiomer inactive R
enantiomer is converted to S by the body to
become active
One enantiomer causes the relief of morning
sickness, while the other causes severe birth
defects
Not very critical to obtain an enantiomerically
pure product
Very critical to obtain in an enantiomerically
pure state
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How to get Enantiomerically Pure Compounds

• Stoichiometric
• Chiral Auxiliaries, Solvents, Reagents, etc.
• 11 correlation
• Catalytic
• Sub-stoichiometric amount of catalyst

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Current Catalysts

• Transition metals in their elemental form
• High turn over frequency
• Short catalyst lifetime
• Air, heat, and moisture sensitive
• Pd (II)/ Pd (IV) in Palladacycles
• Are heat and air STABLE
• High temperatures required for activity
• Low efficiency low TON
• RIGID
• SCS, PCP, and NCN type Palladacycles

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Questions we have attempted to answer

• Can we synthesize a palladacyclic catalyst that
  is more efficient with higher TON and better
  stability?
• Can we synthesize a palladacyclic catalyst that
  can participate in asymmetric catalysis?

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To tackle the first question, we tried to
synthesize an SCN-type Palladacycle

• S- soft ligating atom therefore, creating a
  strong Pd-S bond
• N- hard ligating atom therefore, creating a
  weak Pd-N bond

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SCS-type Palladacycle
Previous Palladacycles tested in asymmetric
catalysis have low e.e. (enantiomeric excess)
values. Their chiral centers are at least two
atoms away from the catalytically active Pd atom.
We wanted to know whether or not it would
increase the efficiency (increasing the e.e.
value) if the chiral centers were only one atom
away from the Pd atom.
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First synthesis attempt for the SCN-type
palladacycle
The last reaction resulted in nonselective
bromination.
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SCN-type Palladacycle synthesis sulfur ligand
first.
The reaction to form compound 10 remained
incomplete after several days.
12
Use of a less sterically hindered alcohol allowed
formation of the oxazoline compound. Thus,
incorporation of the Pd was attempted
Analysis of compound 13 showed formation of many
unidentifiable compounds.
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Future Work on SCN-ligand
Compound 14 has been isolated however, the next
reaction has yet to be attempted.
14
Another reaction that should be attempted for
incorporation of Pd selectively in the SCN-type
ligand
This was completed successfully by a group in
Italy who was also experiencing nonselective
incorporation of Pd into their NCN-ligand. Soro,
B., Stoccoro, S., Minghetti, G., Zucca, A.,
Cinellu, M. A., Gladiali, S., Manassero, M.,
Sansoni, M. Synthesis of the First C-2
Cyclopalladated Derivatives of 1,3-Bis(2-pyridyl)b
enzene. Crystal Structures of Hg(N-C-N)Cl,
Pd(N-C-N)Cl, and Pd2(N-C-N)2(?-Oac)2Hg2Cl6.
Catalytic Activity in the Heck Reaction.
Organometallics 2004.
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SCS-Ligand Synthesis (Part One)
Formation of compound 18 has been attempted
however, not analyzed at this point. Separation
of the diastereomers of compound 17 is not
trivial.
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The separation of the diastereomers of compound
17 proved extremely sensitive thus, a multi-step
TLC separation was attempted. After analysis by
1H NMR, separation was possible.
Diastereomer ratio
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• Indeed, separation is possible however,
  instrumental methods would be more efficient.
• HPLC will be attempted this summer

3.71
41
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Future work on the SCS-type Palladacycle Synthesi
s (Part 2)
After this step, the enantiomers of compound 18
will now be diastereomers in compound 20 and can
be separated to obtain enantiomerically pure
SCS-type Palladacycles
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Heck Reaction Future test to analyze how
efficient the SCN-type Palladacycle is.
19
Cyclopropanation Future test to analyze how
efficient the SCS-type palladacycle is in
asymmetric catalysis via measurement of the e.e.
value.
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Acknowledgements

• Dr. Philip Osburn, project mentor
• Dr. Charles Thomas, second advisor
• UTM Faculty Research Grant Program
• UTM Chemistry Department