Insight into Pericyclic Reactions and Reaction Mechanisms

1. Dr. A. G. NikaljeDept. Of. Pharmaceutical Chemistry Pericyclic reactions

2. Pericyclic reactions • Electrocyclisation • Sigmatropic • Cycloadditions • Cheletropic reactions… • Frontier orbitals • Correlation diagrams (MOs, States) • Aromaticity of the Transition State

3. Pericyclic reactions A pericyclic reaction is a reaction wherein the transition state of the molecule has a cyclic geometry, and the reaction progresses in a concerted fashion.

4. Electrocyclic reactionring closure of conjugated systems An electrocyclic reaction is a pericyclic reaction where the net result is one p bond being converted into one s bond. electrocyclic reactions are photoinduced or thermal p p p s p p TS

5. Woodward- Hoffmann rulesand symmetry conservation • Concern pericyclic reactions. • Tell about the mechanism passing through the lowest activation barrier • Does not tell anything about the thermodynamic (reaction or reverse reaction) • Based on symmetry conservation

6. Why Woodward- Hoffmann rules are important? • Allows synthesis of compounds with determined asymmetric carbons. • First example of useful application of theory • Simplify sophisticated systems • Sample the main methods of analysis using theory • Prevails over alternative explanations such as steric effects.

7. Woodward- Hoffmann rules Roald Hoffmann 1937 American, Nobel 1981 Robert Burns Woodward 1917-1979 American, Nobel 1965

8. Roald Hoffmann 1937 American, Nobel 1981

9. Conservation of Orbital Symmetry H C Longuet-Higgins E W Abrahamson Hugh ChristopherLonguet-Higgins 1923-2004

10. What symmetry is preserved? A mirror A C2 axis W-H rules say that which symmetry element has to be preserved.

11. Up to now, implicitly we have only considered the mirror symmetry

12. Electrocyclic reactionThe orientation of CH3 depends on the symmetry conservation: when the mirror symmetry is preserved (here called disrotatory mode: rotation in opposite senses) we obtain the following reactions with asymmetric carbons disrotatory (2Z,4Z,6Z)-octatriene disrotatory The conrotation would give the opposite correspondance; the knowledge of the mechanism allows you to make the compound with the desired configuration.

13. It is the mechanism for photochemical process The conservation of the C2 axis (here called conrotatory mode- rotation in the same sense) is not observed by thermal cyclization

14. Electrocyclic reactionring closure of conjugated systems An electrocyclic reaction is a pericyclic reaction where the net result is one p bond being converted into one s bond. Electrocyclic reactions are photoinduced or thermal

15. Sigmatropic reaction Sigmatropic reaction is a pericyclic reaction wherein the net result is one s bond changed to another s bond. 1 1’ 3 2’ [2,3] [3,3]

16. Sigmatropic reaction Sigmatropic reaction is a pericyclic reaction wherein the net result is one s bond changed to another s bond.

17. Cope Rearrangementsigmatropic [3,3] Cope Rearrangement Oxy-Cope Rearrangement 1 1 Arthur Cope1902-1958 1’ 3 1’ 3 3’ 3’

18. Claisen rearrangementsigmatropic [3,3] Rainer Ludwig Claisen (1851-1930) German 1 1 1’ 1’ 3 3 3’ 3’

19. cycloaddition A cycloaddition is a reaction, in which two π bonds are lost and two σ bonds are gained. The resulting reaction is a cyclization reaction.

20. cycloaddition This generates chiral compounds. Steric hindrance does not systematically explain.

21. Cheletropic reaction A Cheletropic reaction is a pericyclic reaction where the net result is the conversion of a pi bond and a lone pair into a pair of sigma bonds; with both new sigma bonds adding into the same atom. .

22. Transition State Aromaticity (Dewar and Zimmermann) Does not explicit MOs (does not require any calculation) Based only on the signs of the overlaps and on the count of the electrons involved.

23. Huckel annulene The reaction goes through a ring

24. Huckel annulene The reaction preserving a mirror symmetry goes through a ring

25. Hückel annulene By convention all the AOs are oriented in the same direction (+ above the plane – below): The overlaps are positive: S>0 S>0 S>0 + + + + + S>0 + S>0 S>0 Reversing the sign of one AO still makes an even number of positive overlaps: This defines Hückel annulene For real unsaturated compound, this is always the existing situation + + + + - + S<0 S<0 +

26. Aromaticity according to Dewar Michael J. S. Dewar (Michael James Steuart Dewar) English born in Ahmednagar, India in 1918 The Dewar-Chatt-Duncanson model is a model in organometallic chemistry which explains the type of chemical bonding between an alkene and a metal (p-complex) in certain organometallic compounds. The model is named after Michael J. S. Dewar, Joseph Chatt and L. A. Duncanson .

27. Radical chain + C radical atomcomparing the chain with the ring: Aromaticity First order term. S A E = 0 E = 0 E = 0 E = 0 0 for the ring 2/√(N-1) for the chain 4/√(N-1) for the ring 2/√(N-1) for the chain

28. Radical chain + C radical atomcomparing the chain with the ring: Aromaticity Aromaticity accordingto Dewar S A When the SOMO is antisymmetric The ring is less stable than the chain The polyene is ANTIAROMATIC N-1 is odd N = 4n When the SOMO is symmetric The ring is more stable than the chain The polyene is AROMATIC N-1 is even N = 4n +2 The SOMO is once upon twice S (n=2n-1) or A (2n+1)

29. Hückel-type annulene Aromatic 4n+2 electrons; antiaromatic 4n electrons

30. August Ferdinand Möbius German 1780-1868 was a descendant of Martin Luther by way of his mother. http://www.youtube.com/watch?v=JX3VmDgiFnY

31. Moebius rings: Aromaticity S>0 S<0 A One negative overlap. … … A A p orbital binding through opposite lobes S A E = 0 E = 0 E = 0 E = 0 4/√(N-1) for the ring 2/√(N-1) for the chain 0for the ring 2/√(N-1) for the chain

32. Möbius annulenearomaticity rules are reversed 2b Aromatic 4n electrons; antiaromatic 4n+2 electrons

33. Aromatic systems have the largest HOMO-LUMO gap(the most stable ground state and the least stable first excited state) Antiaromatic systems have half filled degeneratenon bonding levels (the smallest gap; the most stable first excited state and the least stable ground state ) 2b

34. Aromaticity rules for are the opposite for thermal and photochemical reaction D hn

35. Electrocylic

36. Electrocyclic C2 axis of symmetry Mirror symmetry

37. Sigmatropic Mirror symmetry C2 axis of symmetry

38. Sigmatropic

39. Cycloadditions Suprafacial and antarafacial attack Suprafacial attack Antarafacial attack

40. Bond formation Supra Antara Supra Supra

41. Cycloaddition Supra-Supra Hückel Supra-Antara Möbius Antara-Antara Hückel Mirror symmetry Mirror symmetry C2 axis of symmetry unlikely

42. Transition State Aromaticity (Dewar and Zimmermann) Does not explicit MOs Based only on the sign of the overlaps And on the electron count

43. For a thermal reaction (ground state)4n (4) electrons one S<O 4n+2 (6) electrons all the S>O For a photochemical reaction (excited state)4n (4) electrons all the S>O 4n+2 (6) electrons one S<O

44. Bimolecular reactions: Favorable interaction in Frontier Orbitals. - this determines the conservationof a symmetry operation (axis or plane)Unimolecular reactions: Symmetry conservation of the HOMO - the HOMO accommodates the most mobile electrons- its amplitude is generally large at the reaction sites

45. Electrocyclic: symmetry conservation of the HOMO The HOMO is U symmetric for C2 (antisymmetric for s)

46. The “conservation of the HOMO” requires calculating the HOMO The “TS aromaticity” does not: it only look at the sing of overlaps and the # of electrons involved.

47. Symmetry alternates for MOs in a linear polyene HOMO symmetry switches according to N G: three nodes U: two nodes G: one node U: no node For a mirror symmetry U=S an G=A, for a C2 symmetry U=S and G=A

48. Photochemical reaction6-eConrotatory

49. ElectrocyclicMolecules with symmetric HOMOs give disrotatory ring-closure products. Ring Closure With Symmetric HOMO ground state 4n+2 electrons D excited state 4n electrons hn Molecules with symmetric HOMOs have the top lobe of one orbital in the same phase as the top lobe of the other orbital.

50. ElectrocyclicMolecules with antisymmetric HOMOs give conrotatory ring-closure products. Ring Closure With antiSymmetric HOMO ground state 4n electrons D excited state 4n+2 electrons hn Molecules with antisymmetric HOMOs have the top lobe of one orbital in the same phase as the bottom lobe of the other orbital.