Imperial College

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Imperial College London
4I-11 Case studies in Inorganic Chemistry
Lecture 8 Biorenewable Polymers 2 The
Stereoselective Polymerisation of Lactide Dr. Ed
Marshall Rm M220, Mezzanine Floor, RCS
1 e.marshall_at_imperial.ac.uk www.ch.ic.ac.uk/mars
hall/4I11.html
4I-11 - Lecture 8 - Slide 1
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Recap of Lecture 7 Mechanism of propagation

Every step is reversible.
Coordinative-insertion Mechanism
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Last lecture
(salen)Al(OR) and derivatives convert rac-lactide
into isotactic poly(lactide)
Product is believed to be a stereoblock
copolymer, with short sequences of all R
alternating with short sequences of all S (as
opposed to a stereocomplex, formed from complete
all R chains and all S chains)
correct structure
incorrect structure
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Remaining learning outcomes

• Over these two lectures you should acquire the
  knowledge to allow you to
• 1. Describe why the polymerisation of lactide is
  so intensely researched.
• 2. Explain how chiral and achiral
  (salen)-supported Al complexes may be used to
  prepare isotactic and syndiotactic polylactide.
• 3. Explain how b-diketiminate supported complexes
  of Zn and Mg may be used to prepare heterotactic
  polylactide.
• 4. Understand how computational chemistry may be
  used to investigate polymerisation mechanisms and
  to shed light onto the causes of
  stereoselectivity.

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b-Diketiminate ligands
diketimine canonicals
Deprotonation results in a monoanionic bidentate
ligand - known as NacNac or BDI.
e.g.
(BDI)MgiPr
Ar 2,6-diisopropylphenyl
Dalton Trans. 2003, 3088 - WebCT Gibson2003.pdf
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First report of heterotactic PLA
Coates
rac-LA
(S)
(R)
(S)
(R)
CH2Cl2 25 C
Heterotactic PLA

• 100 equiv rac-LA consumed in 20 mins
• Highly stereoselective - Pr 0.90 (0.94 at 0 C)

R iPr, Pr 0.90 R nPr, Pr 0.76 R Et, Pr
0.79
steric bulk of iPr groups is essential for
stereocontrol
J. Am. Chem. Soc. 2001, 123, 3229 - WebCT
Coates2001.pdf
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The Mg analogue
Under the same conditions - i.e. CH2Cl2, 25 C
- (BDI)Mg(m-OiPr)2 gives atactic PLA
But the Mg initiator is heteroselective in
coordinating solvents
Chisholm
rac-LA
Heterotactic PLA, Pr 0.90
THF 25 C
Inorg. Chem. 2002, 41, 2785 - WebCT
Chishiolm2002.pdf
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However, magnesium BDI initiators can be
heteroselective
NMR studies reveal that in THF, the
Mg-propagating species is mononuclear, but in
CH2Cl2 it is dimeric. The Zn analogue is
monomeric even in CH2Cl2
Propagating Mg species in THF
Propagating Zn species in CH2Cl2
Heterotactic PLA formed when the propagating
species are mononuclear
J. Am. Chem. Soc. 2005, 127, 6048 - WebCT
Rzepa2005.pdf
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Computational studies

• Goals of this project
• to understand the mechanism of ring-opening
  better.
• to explain why the Mg and Zn initiators give
  heterotactic PLA.
• to explain why reduction in the N-aryl ortho
  substituents (e.g. from iPr to Et) leads to a
  loss in stereoselectivity.

• Method employed
• Reaction coordinate mapped out for the insertion
  of two LA units (LA1 and LA2) using
  (BDI)Mg(OMe)(THF) as the initiator.
• Free energies of competing transition states
  (i.e. R,R or S,S-lactide insertion) calculated.
• All calculations performed at a very high level
  B3-LYP 6-311G(3d) - many of the calculated
  geometries took 7 - 10 days to converge.

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The Reaction Coordinate - calculated for LA1
(R,R) LA2 (S,S)
Two transition states, TS1 and TS2
TS2 is higher in energy than TS1
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Revised mechanism
TS1 Formation of new M-O bond and cleavage of
M-OR bond
TS2 Formation of new M-O bond and cleavage of
heterocycle
Both transition states involve bond breaking /
forming
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Computing the origin of stereocontrol
Although initially calculated for LA1
R,R-lactide and LA2 S,S-lactide, we have to
consider several other possible
assemblies. Total number of assembly modes LA1
R,R or S,S LA2 R,R or S,S LA2 may
approach either face of the ring-opened LA1
8 possibilities
However, the 8 possible assembly modes exist as 4
enantiomeric pairs
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e.g. Consider the approach of S,S-LA2 to R,R-LA1
S
R
R
S
S
R
S
R
mirror image
8 possible assembly modes 4 enantiomeric
pairs ? only 4 calculations required
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Curtis-Hammett Principle
Since every stage of the ring-opening mechanism
is reversible, the product distribution (i.e.
whether R,R or S,S lactide is inserted) depends
only on the competing geometries for the
rate-determining step.
Calculated transition state free energies (kcal
mol-1)
lowest barrier for heterotactic PLA
In every case TS2 is rate-determining
Therefore, the reason for heterotactic
stereocontrol must lie within the four competing
geometries for TS2 - RR,RR - SS,SS - RR,SS - and
SS,RR.
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Competing TS2 geometries - the origin of
stereocontrol
RR,SS 18.9 kcalmol-1
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Competing TS2 geometries - the origin of
stereocontrol
RR,SS 18.9 kcalmol-1 RR,RR 20.2 kcalmol-1
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Competing TS2 geometries - the origin of
stereocontrol
SS,RR 18.9 kcal mol-1 RR,RR 20.2 kcal
mol-1 SS,SS 25.4 kcal mol-1
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Competing TS2 geometries - the origin of
stereocontrol
SS,RR 18.9 kcal mol-1 RR,RR 20.2 kcal
mol-1 SS,SS 25.4 kcal mol-1 SS,RR 28.1 kcal
mol-1
Heterotactic PLA formed via LA1 R,R and LA2
S,S. Next R,R then inserts via the enantiomer of
the SS,RR transition state
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Summary of the origin of stereocontrol
Heterotactic PLA formed via LA1 R,R and LA2
S,S. R,R-LA3 then inserts via the enantiomer of
the SS,RR transition state
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Conclusions

• Heterotactic PLA may be prepared using
  b-diketiminate Zn and Mg alkoxides, but the Mg
  initiators must be used in THF.
• The propagating species responsible for
  heterotactic PLA formation is mononuclear.
• Computational analysis reveals that the rate
  determining step is TS2, i.e. the cleavage of the
  monomer heterocycle.
• Heterotactic PLA arises because of the
  minimisation of Me - Me steric clashes in the
  competing geometries of TS2.

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