1. Biorenewable Polymers 1: The Stereoselective Polymerisation of Lactide
4I-11 Case studies in Inorganic Chemistry
Imperial College
London
Lecture 7
Biorenewable Polymers 1:
The Stereoselective Polymerisation of Lactide
Dr. Ed Marshall
Rm: M220, Mezzanine Floor, RCS 1
& WebCT
4I-11 - Lectures 7 - Slide 1

2. Learning objectives
Imperial College
London
Over the next 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. 4I

3. polylactic acid, PLA lactide oligomers
Polylactide or Poly(lactic acid) - PLA (
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London
The first mainstream polymer to be made from renewable resources.
PLA is: biodegradable, biocompatible and bioresorbable
enzymatic
degradation
fermentation
corn
starch
lactic acid
step-growth
condensation
(-H2O)
ring-opening
polymerisation *
heat * *
(chain growth) *
polylactic acid, PLA
lactide
oligomers
These 2 lectures focus on this step 4I

4. tin(II) bis(2-ethylhexanoate)
Initiators
Imperial College
London
Typical initiators for lactide polymerisation are metal-alkoxides, e.g. Al(OiPr)3:
Acyl-oxygen bond breaks
Industrially, the initiator used is a tin(II) carboxylate - in the presence of alcohol, this is believed to form tin(II) alkoxides, and these are the actual initiating species:
tin(II) bis(2-ethylhexanoate)
"SnOct2"
true initiator 4I

5. Coordinative-insertion Mechanism other lactones open in a similar way
Mechanism of propagation
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London
Initiation involves nucleophilic attack of the alkoxide at the lactide carbonyl.
This leaves the monomer heterocycle intact. In order to open the ring, the monomer rolls around to place the acyl oxygen nearer the metal centre.
NB: Every step is reversible.
Coordinative-insertion Mechanism
other lactones open in a similar way 4I

6. Lactide - three different stereoisomers
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London
(S,S)-lactide
"L-lactide"
(R,R)-lactide
"D-lactide"
(S,R)-lactide
"meso-lactide"
50:50 mix = rac-lactide
Since L-lactic acid is the naturally occurring form, (S,S)-lactide is much cheaper than (R,R)-lactide. Rac-lactide is even cheaper (the industrial enzymatic conversion of starch into lactic acid is aspecific). Meso-lactide is not commercially available and must be separated from the (R,R) and (S,S) monomers by a steam distillation.
Most commonly studied: L-lactide and rac-lactide 4I

7. PLA - stereoregular microstructures (tacticities)
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London
isotactic
-(SSSSSSSS)-
"poly(L-lactide)"
S,S
isotactic
-(RRRRRRRR)-
"poly(D-lactide)"
R,R
heterotactic
-(SSRRSSRR)-
rac
syndiotactic
-(SRSRSRSR)-
meso 4I

8. Degradation time (months)
PLA - physical properties depend on tacticity
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London
Polymer
Tm (°C)
Tg (°C)
Modulus (GPa)
Degradation time (months)
isotactic PLA
170 60
2.7
>24
syndiotactic PLA
153 45
n/a
heterotactic PLA
amorphous 49
atactic PLA 55
1.9
There is one other important form of PLA known as an isotactic stereocomplex:
isotactic
poly(L-lactide)
mix and
co-crystallise
Tm > 235 °C
isotactic
poly(D-lactide) 4I

9. vacant coordination site and may then react with X
Single-site catalysts
Imperial College
London Ln X M
e.g. Cp2ZrMe+ for the
polymerisation of ethene
sterically bulky
ancillary ligand(s)
substrate approaches
vacant coordination site
and may then react with X
PLA stereochemistry potentially controlled by the sterics / chirality of Ln 4I

10. First report of stereoregular polymerisation of rac-lactide
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London
Spassky
rac-LA
isotactic bias
Pm = 0.68
60 °C
Stereoselectivity presumably arises from a chain-end control mechanism:
(S,S)-LA
k(S,S) / k(R,R) = 2.8
[Al](OMe)
[Al]-(S,S)-OMe
(R,R)-LA
k(R,R) / k(S,S) = 2.8
[Al](OMe)
[Al]-(R,R)-OMe
Macromolecular Chemistry and Physics 1997, 198, 4I

11. Subsequent modifications to salen Al initiators
Imperial College
London
Numerous salen ligands have been investigated (24 examples are reported in a recent paper), but the most notable one is:
Nomura
rac-LA
highly isotactic
Pm = 0.92
60 °C
Tm = 192 °C
But does this catalyst produce a PLA stereocomplex?
J. Am. Chem. Soc. 2002, 124, WebCT Nomura2002.pdf
Proc. Nat. Acad. Sci. 2006, 103, WebCT Gibson2006.pdf 4I

12. -RR---------------SS-
Enantiomorphic site control with chiral salen Al initiators?
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London
Spassky
rac-LA
k(R,R) / k(S,S) = 20
60 °C
enantiopure initiator
The polymer produced is a tapered stereoblock copolymer:
increasing R content
-RRRRRRRRRRR-
-RR SS-
-SSSSSSSSSSSS-
increasing S content
Tm = 185 °C
Macromolecular Chemistry and Physics 1996, 197, 2627 4I

13. Dispelling the stereocomplex myth
Imperial College
London
Smith & Baker / Coates
rac-LA
isotactic PLA
Tm = 191 °C
60 °C
Smith and Baker proposed (i) (correctly) that each initiator enantiomer consumes just one monomer enantiomer and (ii) (incorrectly) that the chains then form a stereocomplex.
racemic initiator
However, subsequent studies by Coates showed that the racemic initiator actually gives short chains of -RRRR- and -SSSS- but these then exchange between different metal centres.
The PLA product is not a stereocomplex -
it is a stereoblocky copolymer:
-(RR…RR)-(SS…SS)-(RR…RR)-(SS…SS)-
Elevated Tm values arise from cocrystallisation of short isotactic domains
J. Am. Chem. Soc. 2000, 122, WebCT Baker&Smith2000.pdf
J. Polym. Sci. Polym. Chem. 2000, 38, WebCT Coates2000.pdf 4I

14. Formation of isotactic PLA from chiral salen Al initiators
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(S)-selective
ligand
(S)-selective
ligand
(R)-selective
ligand
(R)-selective
ligand 4I

15.  meso-LA selectively cleaved at acyl bond adjacent to (R)-methyl
First report of syndiotactic PLA
Imperial College
London
Coates
Preferentially consumes
(R,R)-LA versus (S,S)-LA
enantiopure initiator
 meso-LA selectively cleaved at acyl bond adjacent to (R)-methyl
J. Am. Chem. Soc. 2002, 124, WebCT Coates2002.pdf 4I

16. ligand-assisted chain end stereocontrol
Lecture 7 Conclusions
Imperial College
London
1. Salen-supported Al-based initiators nearly always give highly isotactic PLA (from the racemic monomer). The highest isotacticities are usually observed with chiral salen ligands, although the Nomura initiator is actually achiral.
ligand-assisted chain end stereocontrol
2. The isotactic product is actually a stereoblock, not a stereocomplex. Tm values are therefore higher than for isotactic poly(L-lactide), but lower than for the stereocomplex.
3. Syndiotactic PLA may be prepared from meso-lactide using a chiral salen ligand (with a 2,2'-diaminobinaphthyl backbone). 4I