1. Mechanisms of Stereoselective Polymerizations
Università di Salerno
Italy
Modeling Lab for Nanostructures
And Catalysis
Luigi Cavallo

2. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

3. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

4. Milano, Italy, 53 years and 4 days ago
Polypropylene made
Nobel prize to Karl Ziegler and Giulio Natta in 1963
“Nature synthesizes many stereoregular polymers, for example cellulose and rubber. This ability has been so far thought to be a monopoly of Nature operating with biocatalysts known as enzymes. But now Prof. Natta has broken this monopoly… The scientific and technical consequences of your discovery are immense and cannot even now be fully estimated.”
Presentation Speech, Stockholm, December

5. Milano, Italy, 53 years and 4 days ago
Polypropylene made
Nobel prize to Karl Ziegler and Giulio Natta in 1963
“Nature synthesizes many stereoregular polymers, for example cellulose and rubber. This ability has been so far thought to be a monopoly of Nature operating with biocatalysts known as enzymes. But now Prof. Natta has broken this monopoly… The scientific and technical consequences of your discovery are immense and cannot even now be fully estimated.”
Presentation Speech, Stockholm, December

6. Consequences of the discovery
About 100*106 tons/year of PE & PP in 2005
1 m3 blocks would wrap the equator 2.5 times

7. The Catalysts 1954 1962 1985 1988 2000 2001 TiCl3/AlR3 VCl4/AlR3
Brintzinger, Fischer, Mülhaupt, Rieger, Waymouth
Angew Chem Int Ed 1995, 34, 1143
Resconi Cavallo Fait Piemontesi
Chem Rev 2000, 100, 1253
Ewen
Scientific American May 1997
Coates
Chem Rev 2000, 100, 1223
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001
Ewen JACS 1984, 106, 6355
Kaminsky, Külper, Brintzinger, Wild
ACIE Engl. 1985, 24, 507.
Tshuva, Goldberg, Kol
JACS 2000, 122, 10706
Ewen, Jones, Razavi, Ferrara
JACS 1988, 110, 6255
Fujita, Kashiwa et al.
Macromol. Rapid Commun. 2001, 22, 1072

8. The Catalysts 1954 1962 1985 1988 2000 2001 TiCl3/AlR3 VCl4/AlR3
Brintzinger, Fischer, Mülhaupt, Rieger, Waymouth
Angew Chem Int Ed 1995, 34, 1143
Resconi Cavallo Fait Piemontesi
Chem Rev 2000, 100, 1253
Ewen
Scientific American May 1997
Coates
Chem Rev 2000, 100, 1223
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001

9. The Catalysts 1954 1962 1985 1988 2000 2001 TiCl3/AlR3 VCl4/AlR3
Brintzinger, Fischer, Mülhaupt, Rieger, Waymouth
Angew Chem Int Ed 1995, 34, 1143
Resconi Cavallo Fait Piemontesi
Chem Rev 2000, 100, 1253
Ewen
Scientific American May 1997
Coates
Chem Rev 2000, 100, 1223
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001

10. Mechanism of Chain Growth
+ CH2=CH2
Cossee, P. J. Catal. 1964, 3, 80

11. The Chain-Migratory Mechanism
Step (i+1)
Step (i)

12. The Three Polypropylenes
Same face
enchainment
Isotactic polypropylene (i-PP)
Opposite faces
enchainment n
Syndiotactic polypropylene (s-PP)
Random faces
enchainment
Atactic polypropylene (a-PP)

13. The Three Polypropylenes
Same face
enchainment
Isotactic polypropylene (i-PP)
Opposite faces
enchainment n
Syndiotactic polypropylene (s-PP)
Random faces
enchainment
Atactic polypropylene (a-PP)

14. Possible Stereomistakes
Enantiomorphic-site
sterocontrol
Chain-end
Sterocontrol
TiCl3/AlR3
Cp2TiCl2 at low T
VCl4/AlR3

15. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

16. The Catalysts 1954 1962 1985 1989 2000 2001 TiCl3/AlR3 VCl4/AlR3
Brintzinger, Fischer, Mülhaupt, Rieger, Waymouth
Angew Chem Int Ed 1995, 34, 1143
Resconi Cavallo Fait Piemontesi
Chem Rev 2000, 100, 1253
Ewen
Scientific American May 1997
Coates
Chem Rev 2000, 100, 1223
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1989
2000
2001
System with well defined chemistry!
Ewen JACS 1984, 106, 6355
Kaminsky, Külper, Brintzinger, Wild
ACIE Engl. 1985, 24, 507.

17. C2-symmetric systems (isospecific symmetry)
Mirror plane
(R)
(S)
(S)
(R)
C2-axis
C2-axis

18. C2-symmetric systems (isospecific symmetry)
(+)-Chain
(S)
(S)
(S)
(S)
(–)-Chain

19. C2-symmetric systems (isospecific symmetry)
(+)-chain
(–)-chain
monomer + – Mt P
Orientations of the growing chain
Messenger!
(+)-Chain
(S)
(S)
(S)
(S)
(–)-Chain

20. C2-symmetric systems (isospecific symmetry)
Favored !
(+)-Chain
(S)
(S)
(S)
(S)
(–)-Chain

21. C2-symmetric systems (isospecific symmetry)? re or si
(+)-Chain
(S)
(S)

22. C2-symmetric systems (isospecific symmetry)
(+)-Chain
(S) re
(S)

23. C2-symmetric systems (isospecific symmetry)
Favored ! si re
(+)-Chain
(+)-Chain
(S)
(S) si
(S)
(S)

24. The Chain-Migratory Mechanism
Step (i+1)
Step (i)

25. C2-symmetric systems (isospecific symmetry)
(+)-Chain
(S)
(S) si si
C2-axis
(S)
(S)
(+)-Chain

26. C2-symmetric systems (isospecific symmetry)
Homotopic coordination positions:
the same monomer enantioface is favored at each step
(i.e. an isotactic polymer is formed)
Cavallo, Corradini, Guerra, Vacatello
Polymer 1991, 32, 1329.
(+)-Chain
(S)
(S) si si
C2-axis
(S)
(S)
(+)-Chain

27. The Catalysts 1954 1962 1985 1988 2000 2001 Solved! TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001

28. The Catalysts 1954 1962 1985 1988 2000 2001 Solved! TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001

29. Other systems Mechanism of the chiral orientation of the growing chain
Heterogeneous
1954
Metallocene
1985
Post-Metallocene
2000
Mechanism of the chiral orientation of the growing chain
Corradini, Guerra, Cavallo Acc. Chem. Res. 2004, 37, 231

30. The Catalysts 1954 1962 1985 1988 2000 2001 Solved ? Solved! Solved!
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
2000
2001

31. The Catalysts 1954 1962 1985 1989 1988 2000 2001 Solved ? Solved!
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1989
1988
2000
2001
Ewen, Jones, Razavi, Ferrara
JACS 1988, 110, 6255

32. CS-symmetric systems (syndiospecific symmetry)
Mirror plane

33. CS-symmetric systems (syndiospecific symmetry)
Mirror plane
C2-axis

34. CS-symmetric systems (syndiospecific symmetry)
(+)-Chain si

35. CS-symmetric systems (syndiospecific symmetry)
(–)-Chain
(+)-Chain si re
Mirror plane

36. CS-symmetric systems (syndiospecific symmetry)
Enantiotopic coordination positions:
opposite monomer enantiofaces are favored in successive steps
(i.e. a syndiotactic polymer is formed)
(–)-Chain
(+)-Chain
Cavallo, Corradini, Guerra, Vacatello
Macromolecules 1991, 24, 1784. si re
Mirror plane

37. The Catalysts 1954 1962 1985 1989 1988 2000 2001 Solved? Solved!
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1989
1988
2000
2001

38. Chain Orientation as Messenger (1,2 propagation, site stereocontrol)
Configuration of the
catalytic site
Configuration of
monomer insertion
Flow of Information
Stereoregular
polymer

39. Chain Orientation as Messenger (1,2 propagation, site stereocontrol)
Configuration of the
catalytic site
(+)-chain
(–)-chain
Messenger!
monomer + –
Configuration of the chirally
oriented growing chain
Configuration of
monomer insertion
Flow of Information
Stereoregular
polymer

40. Experimental Validation of the Mechanism
If the chiral orientation of the chain is the key element, without a long chain propene insertion shouldn’t be enantioselective… P

41. Experimental Validation of the Mechanism
NMR study of propene insertion into the M-CH3 bond
Zambelli Locatelli Sacchi Tritto Macromolecules 1982, 15, 831.
CH3

42. Experimental Validation of the Mechanism
Enantioselectivity of propene insertion into M-13CH3
13CH3
(50%) +
13CH3
(50%)
Enantioselectivity of propene insertion into M-13CH2CH3
13CH2CH3
(10%) +
(90%)
13CH2CH3
The mechanism of the chiral orientation of the growing chain is confirmed

43. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

44. The Catalysts 1954 1962 1985 1988 1989 2000 2001 Solved? Solved!
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1988
1989
2000
2001
Fujita, Kashiwa et al.
Macromol. Rapid Commun. 2001, 22, 1072

45. Regiochemistry of Insertion
TiCl3/AlR3 1 1 2 2
Primary (1,2) Insertion 2 2 1 1
VCl4/AlR3
Secondary (2,1) Insertion

46. Stereorigid Catalysts
Heterogeneous
Ti-catalysts
The bridge confers stereorigidity
Interconversion
impossible
(R)
(S)
(R)
(S)

47. Stereoflexible Catalysts
Homogeneous
V-catalysts
Withouth a bridge stereoflexible complexes
Possible
Interconversion

48. Chain-Site-Monomer Interaction
re-chain/D-site/si-propene
(r-diad)
Steric
stress!
E in kcal/mol

49. Chain-Site-Monomer Interaction
re-chain/D-site/si-propene
(r-diad)
Steric
stress!
E = 3.8
re-chain/L-site/re-propene
(m-diad)
Steric
stress!
E in kcal/mol

50. Chain-Site-Monomer Interaction
re-chain/D-site/si-propene
(r-diad)
Steric
stress!
E = 3.8
re-chain/L-site/re-propene
(m-diad)
Steric
stress!
E = 1.9
re-chain/D-site/re-propene
(m-diad)
Steric
stress!
E in kcal/mol

51. Chain-Site-Monomer Interaction
re-chain/D-site/si-propene
(r-diad)
Steric
stress!
E = 3.8
re-chain/L-site/re-propene
(m-diad)
Steric
stress!
E = 1.9
re-chain/D-site/re-propene
(m-diad)
Steric
stress!
Favored!
re-chain/L-site/si-propene
(r-diad)
E in kcal/mol

52. A Possible Overall Picture
E in kcal/mol
si-propene
Ti-Pn
re-chain/L-site
Site
Isomerization
Ti-Pn+1
si-chain/L-site
Stereoerror
re-propene
DE‡ = 1.9
si-propene
Ti-Pn+2
re-chain/D-site
Site
Isomerization
Ti-Pn+1
si-chain/D-site
re-propene

53. Dissociative Mechanism on the basis of NMR-studies
Proposed Mechanism
Dissociative Mechanism on the basis of NMR-studies
Bickley & Serpone Inorg. Chem. 1979, 18, 2002
Bei, Dale, Swenson, Jordan OM 1997, 16, 3282
D-complex
L-complex
DG‡racemization = 10 ÷ 20 kcal/mol (Mt = Ti, Zr)

54. Monomer Assisted Dissociation
DFT calculations
Dissociation
Edissociation = 14.9 kcal/mol

55. Site Chirality as Messenger (1,2 propagation, site stereocontrol)
Configuration of the
growing chain
D-site
L-site
Messenger!
Configuration of the fluxional
octahedral active species
Configuration of
monomer insertion
Flow of Information
Stereoregular
polymer

56. re-chain/D-site/si-propene
Other systems
re-chain/L-site/si-propene
(r-diad)
re-chain/D-site/si-propene
(r-diad)
Mechanism of the chiral orientation of the growing chain
Milano Guerra Cavallo JACS. 2004, 37, 231
First proposed:
Corradini, Guerra, Pucciariello Macromolecules 1985, 13,42

57. The Catalysts 1954 1962 1985 1989 1988 2000 2001 Solved? Solved!
TiCl3/AlR3
VCl4/AlR3
1954
1962
1985
1989
1988
2000
2001

58. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

59. Enantioselectivity of Regiomstakes
C2-symmetric metallocene P
Favored re P si
Regiomstakes are
enantioselective
Guerra Cavallo Moscardi Vacatello Corradini
J. Am. Chem. Soc. 1994, 116, 2988.
CS-symmetric metallocene P re P
Favored si

60. Enantioselectivity in 1,2 vs 2,1 insertion
C2-symmetric metallocene
Opposite enantiofaces are favored in propagation and regiomistakes
The same enantioface is favored in propagation and regiomistakes
Guerra Cavallo Corradini Longo Resconi
J. Am. Chem. Soc. 1997, 119, 4394. P si P re
CS-symmetric metallocene P si P si

61. Selectivity in 2-butene/ethene Copolymerization
C2-symmetric metallocene P si P re P
cis =
CS-symmetric metallocene P si P si P
trans =

62. Ethene/2-butene Copolymerization Tests
C2-symmetric metallocene P
cis
cis-butene is selectively copolymerized
trans-butene is selectively copolymerized
Guerra Longo Corradini Cavallo
J. Am. Chem. Soc. 1999, 121, 8651.
CS-symmetric metallocene P
trans

63. Regiochemistry in Octahedral Systems

64. Octahedral-systems : Ligand Effect
Primary
Insertion
Slightly favored Strongly favored
Secondary
Insertion
DE‡Regio
kcal/mol
0.3
3.6

65. Octahedral-systems : Chain Effect
DE‡Regio
kcal/mol
Steric stress!
3.6
1.4
0.3
i-Bu
i-Pr
Growing Chain
-2.0
A secondary chain pushes insertion towards another secondary insertion
i-Bu
i-Pr
Growing Chain

66. Origin of Different Regiochemistry
Phenoxy-imine
Phenoxy-amine
Talarico Busico Cavallo JACS 2003, 125, 7172.

67. Origin of Different RegiochemistryMe
weak
antibonding
interaction
strong
Growing
Chain
Alkene
Phenoxy-imine
Phenoxy-amine
Talarico Busico Cavallo JACS 2003, 125, 7172.

68. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion Pairs
Final Remarks

69. Ion-Pairs Metallocene/Borane H2Si(Cp)2ZrMe+/MeB(C6F5)3-
Energetic and structure of ion-pairs fundamental to understand
activity, copolymerizations, “microstructure”
Static methods (i.e. classical QM calculations) not particularly suited
Metallocene/Borane
H2Si(Cp)2ZrMe+/MeB(C6F5)3-
Metallocene/Borate
H2Si(Cp)2ZrMe+/B(C6F5)4-
Excellent NMR study on Metallocenium Ion-Pairs Zuccaccia, Stahl, Macchioni, Chen, Roberts, Marks J. Am. Chem. Soc. 2004, 126, 1448

70. Dynamics of Ion-Pairs Classical Molecular Dynamics Simulations
(i.e. no Quantum Mechanics)
System simulated
1 Metallocenium ion-pair swollen
in roughly 1100 benzene molecules
Conditions : P = 1 atm, T = 25 °C
Sampling time : 5 ns
(can be longer)
Correa and Cavallo
J. Am. Chem. Soc. 2006, 128, 10952

71. Performance of the Model
The Metallocene/Borane
Ion-pair
Excellent agreement with several structural properties
Correa and Cavallo
JACS 2006, 128, 10952

72. Insight into the Metallocene/Borate Ion-Pair
F2 F3
(ps)
The unclear NMR data are due to a continous fluctuation between different geometries (as found in our MD simulations)
Correa and Cavallo JACS 2006, 128, 10952

76. Dynamic Behavior of the Metallocene/Borate Ion-pair
Future Applications of Classical Molecular Dynamics of the Catalyst/Counterion Pair :
Dynamic Behavior of the Metallocene/Borate Ion-pair
(Forming and breaking of M…F interactions)
Moving to other metallocenes and to non-metallocenes
Polymer chain extended to 10, 100, 1000 monomeric units
Key to explain activity and copolymerizations ?
Counterion displacement by a coordinating monomer

77. Outline
Introduction
Examples of Site Stereocontrol
Examples of Chain-End Stereocontrol
About Regiomistakes
Ion-Pairs
Final Remarks

78. Understanding the Mechanics… a previous teaching
Flying machine
Codex B, f.74 (1485)
Leonardo da Vinci
( )
Self-portrait
Aerial screw
Codex B, f.83 (1489)

79. Stereospecific Olefins Polymerization aka The best understood organometallic reaction
Experimentalists
Karl Ziegler
Giulio Natta
John Ewen
Tobin Marks
Maurice Brookhart
Jim Stevens
Bob Waymouth
Richard Jordan
Hans-Herbert Brintzinger
Walter Kaminsky
Gerhard Fink
Norio Kashiwa
Tominaga Keii
Kazuo Soga
Terunori Fujita
Adolfo Zambelli
Umberto Giannini
Luigi Resconi
Vincenzo Busico
Moshe Kol
Theoreticians
Paolo Corradini
Gaetano Guerra
Tom Ziegler
Tom Woo
Keiji Morokuma
Giuliano Lanza
All these people synergically contributed to
understand the mechanisms of this reaction
Absolutely not a comprehensive list!

80. Final Slide Why to understand ?
It is key for the rational design of new catalysts
It allows to develop new catalysts faster
It is an intellectual pleasure
Computational chemistry
It is a powerful tool for the rationalization and prediction of chemical behavior
The New Lab
Strong interaction between theoreticians and experimentalists

81. Acknowledgments The Crew
Dr. Computers U of Salerno Dr. G. Milano U of Salerno
Dr. A. Correa U of Salerno Dr. C. Costabile U of Salerno
Dr. G. Talarico U of Napoli Dr. L.Caporaso U of Salerno
Dr. G. Moscardi Basell Polyolefins Dr. H. Jacobsen U of Tulane
Dr. J. M. Ducéré U of Salerno Dr. J. Budria U of Eindhoven
Financial
Basell Polyolefins U of Salerno
MURST PRIN-2004 project MURST FISR project
Cineca Grant SuperCalcolo INSTM Italia

82. dōmo arigatō