Imperial CollegeLondon

Lecture 8

Biorenewable Polymers 2:The Stereoselective Polymerisation of Lactide

Dr. Ed Marshall

Rm: M220, Mezzanine Floor, RCS 1

e.marshall@imperial.ac.uk

www.ch.ic.ac.uk/marshall/4I11.html

4I-11 - Lecture 8 - Slide 1

4I-11 Case studies in Inorganic Chemistry

Every step is reversible.

Coordinative-insertion Mechanism

Imperial CollegeLondonRecap of Lecture 7: Mechanism of propagation

4I-11 - 8 - 2

Imperial CollegeLondonLast lecture

4I-11 - 8 - 3

(salen)Al(OR) and derivatives convertrac-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

Imperial CollegeLondonRemaining 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 -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-11 - 8 - 4

Imperial CollegeLondon-Diketiminate ligands

diketimine canonicals:

Deprotonation results in a monoanionic bidentate ligand - known as NacNac or BDI.

e.g.

Ar = 2,6-diisopropylphenyl[(BDI)MgiPr]

4I-11 - 8 - 5Dalton Trans. 2003, 3088 - WebCT Gibson2003.pdf

R = iPr, Pr = 0.90R = nPr, Pr = 0.76R = Et, Pr = 0.79

Imperial CollegeLondonFirst report of heterotactic PLA

Coates

rac-LA

CH2Cl225 °C

(S)(S)

(R)(R)

Heterotactic PLA

• 100 equiv rac-LA consumed in 20 mins

• Highly stereoselective - Pr = 0.90 (0.94 at 0 °C)

steric bulk of iPr groups is essential for stereocontrol

4I-11 - 8 - 6J. Am. Chem. Soc. 2001, 123, 3229 - WebCT Coates2001.pdf

Under the same conditions- i.e. CH2Cl2, 25 °C -

[(BDI)Mg(-OiPr)2] gives atactic PLA

Imperial CollegeLondonThe Mg analogue

rac-LA

THF25 °C

Heterotactic PLA, Pr = 0.90

Chisholm

But the Mg initiator is heteroselective in coordinating solvents:

4I-11 - 8 - 7Inorg. Chem. 2002, 41, 2785 - WebCT Chishiolm2002.pdf

Imperial CollegeLondonHowever, 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:

Heterotactic PLA formed when the propagating species are mononuclear

Propagating Mg species in THF

Propagating Zn species in CH2Cl2

4I-11 - 8 - 8J. Am. Chem. Soc. 2005, 127, 6048 - WebCT Rzepa2005.pdf

Imperial CollegeLondonComputational 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:(i) Reaction coordinate mapped out for the insertion of two LA units (LA1 and LA2) using (BDI)Mg(OMe)(THF) as the initiator.

(ii) 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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Imperial CollegeLondonThe Reaction Coordinate - calculated for LA1 = (R,R) & LA2 = (S,S)

Two transition states, TS1 and TS2

TS2 is higher in energy than TS14I-11 - 8 - 10

Imperial CollegeLondonRevised mechanism

TS1:Formation of new M-O bondand cleavage of M-OR bond

TS2:Formation of new M-O bondand cleavage of heterocycle

Both transition states involve bond breaking / forming

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Imperial CollegeLondonComputing 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:

Mg

LA1

LA2

Mg

Mg

Mg

Mg

Mg

MgMg

mirror plane

SS

RR

RR

SS

SS

R

RR

SS

S

R

S

S

SS

RR

R

S

R

RR

RR

SS

mirror plane

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Imperial CollegeLondone.g. Consider the approach of S,S-LA2 to R,R-LA1

8 possible assembly modes = 4 enantiomeric pairs ∴ only 4 calculations required

S

S SS

RR R

R

mirror image

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Imperial CollegeLondonCurtis-Hammett Principle

Since every stage of the ring-opening mechanism is reversible, the productdistribution (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):

LA1 LA2 TS1 TS2

RR RR 13.5 20.2

SS SS 6.7 25.4

RR SS 10.5 18.9

SS RR 12.5 28.1

In every case TS2 is rate-determining

Therefore, the reason for heterotactic stereocontrol must lie within the fourcompeting geometries for TS2 - RR,RR - SS,SS - RR,SS - and SS,RR.

lowest barrier for heterotactic PLA

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Imperial CollegeLondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:18.9 kcalmol-1

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Imperial CollegeLondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:18.9 kcalmol-1

RR,RR:20.2 kcalmol-1

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Imperial CollegeLondonCompeting 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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Imperial CollegeLondonCompeting 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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Imperial CollegeLondonSummary of the origin of stereocontrol

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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

Imperial CollegeLondonConclusions

• Heterotactic PLA may be prepared using -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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