Imperial College

London4A3 Advanced Polymer Synthesis

Biorenewable Polymers 2:

The Heterotactic Polymerisation of rac-Lactide

4A3 - Slide 19

Imperial College

London

Every step is reversible

Coordinative-Insertion Mechanism

Recap of Lecture 1: Mechanism of propagation

4A3 - Slide 20

Imperial College

LondonLast lecture

(salen)Al(OR) and derivatives convert

rac-lactide into isotactic poly(lactide)

Product is a stereoblock copolymer, with short sequences of all R and

short sequences of all S stereocentres.

correct structure

incorrect structure

4A3 - Slide 21

Imperial College

LondonLearning outcomes

Over lectures 1 and 2 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.

4A3 - Slide 22

Imperial College

Londonb-Diketiminate ligands

Diketimine canonicals

Deprotonation results in a monoanionic bidentate ligand:

e.g.

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

Dalton Trans. 2003, 3088 - WebCT Gibson2003.pdf 4A3 - Slide 23

Imperial College

London

R = iPr, Pr = 0.90

R = nPr, Pr = 0.76

R = Et, Pr = 0.79

First 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

J. Am. Chem. Soc. 2001, 123, 3229 - WebCT Coates2001.pdf 4A3 - Slide 24

Imperial College

London

Under the same conditions (CH2Cl2, 25 °C)

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

The Mg analogue

rac-LA

THF

25 °C

Heterotactic PLA, Pr = 0.90

Chisholm

However, the Mg initiator is heteroselective in coordinating solvents:

Inorg. Chem. 2002, 41, 2785 - WebCT Chishiolm2002.pdf

Prof. Chisholm is lecturing on Thursday 18th

October at 12pm on lactide polymerisation

4A3 - Slide 25

Imperial College

LondonHowever, 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

4A3 - Slide 26

Imperial College

LondonComputational studies – J. Am. Chem. Soc. 2005, 127, 6048-6051

Goals of this research project:

• to understand the mechanism of ring-opening better.

• to explain why the Mg and Zn initiators give heterotactic PLA.

Method:

(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.

J. Am. Chem. Soc. 2005, 127, 6048 - WebCT Rzepa2005.pdf 4A3 - Slide 27

Imperial College

LondonThe Reaction Coordinate - calculated for LA1 = (R,R) & LA2 = (S,S)

Two transition states, TS1 and TS2

TS2 is higher in energy than TS1

4A3 - Slide 28

Imperial College

LondonRevised 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

4A3 - Slide 29

Imperial College

LondonComputing the origin of stereocontrol

We have to consider several possible ways in which the PLA may form:

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

LA2

LA2

LA1

4A3 - Slide 30

Imperial College

LondonBut the 8 assembly modes exist as 4 enantiomeric pairs

8 possible assembly modes = 4 enantiomeric pairs

∴ only 4 calculations required

S

S SS

R

R R

R

mirror image

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

4A3 - Slide 31

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

Imperial College

LondonOnly four sets of calculations required

4A3 - Slide 32

Imperial College

LondonCurtis-Hammett Principle

All stages of the ring-opening mechanism is reversible, so the cause of

stereoselectivity arises from the energetics of 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 in TS2

lowest barrier for

heterotactic PLA

4A3 - Slide 33

Imperial College

LondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:

18.9 kcalmol-1

4A3 - Slide 34

Imperial College

LondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:

18.9 kcalmol-1

RR,RR:

20.2 kcalmol-1

4A3 - Slide 35

Imperial College

LondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:

18.9 kcal mol-1

RR,RR:

20.2 kcal mol-1

SS,SS:

25.4 kcal mol-1

4A3 - Slide 36

Imperial College

LondonCompeting TS2 geometries - the origin of stereocontrol

RR,SS:

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

4A3 - Slide 37

Imperial College

LondonSummary 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

4A3 - Slide 38

Imperial College

LondonConclusions

• 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.

4A3 - Slide 39