30. Orbitals and Organic Chemistry: Pericyclic Reactions

1. 30. Orbitals and Organic Chemistry: Pericyclic Reactions Based on McMurry’s Organic Chemistry, 7th edition

2. Pericyclic Reactions – What Are They? • Involves several simultaneous bond-making breaking process with a cyclic transition state involving delocalized electrons • The combination of steps is called a concerted process where intermediates are skipped Why this chapter? • To gain a better understanding of pericyclic reactions • Understanding biological pathways where these reactions do occur

3. 30.1 Molecular Orbitals and Pericyclic Reactions of Conjugated  Systems • A conjugated diene or polyene has alternating double and single bonds • Bonding MOs are lower in energy than the isolated p atomic orbitals and have the fewest nodes • Antibonding MOs are higher in energy • See Figure 30.1 for a diagram

4. 1,3,5-Hexatriene • Three double bonds and six  MOs • Only bonding orbitals, 1, 2, and 3, are filled in the ground state • On irradiation with ultraviolet light an electron is promoted from 3 to the lowest-energy unfilled orbital (4*) • This is the first (lowest energy) excited state • See the diagram in Figure 30.2

5. Molecular Orbitals and Pericyclic Reactions • If the symmetries of both reactant and product orbitals match the reaction is said to be symmetry allowed under the Woodward-HoffmannRules (these relate the electronic configuration of reactants to the type of pericyclic reaction and its stereochemical imperatives) • If the symmetries of reactant and product orbitals do not correlate, the reaction is symmetry-disallowed and there are no low energy concerted paths • Fukui’s approach: we need to consider only the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), called the frontier orbitals

6. 30.2 Electrocyclic Reactions • These are pericyclic processes that involve the cyclization of a conjugated polyene • One  bond is broken, the other  bonds change position, a new σ bond is formed, and a cyclic compound results • Gives specific stereoisomeric outcomes related to the stereochemistry and orbitals of the reactants

7. Electrocyclic Interconversions with Octatriene

8. Electrocyclic Interconversions with Dimethylcyclobutene

9. The Signs on the Outermost Lobes Must Match to Interact • The lobes of like sign can be either on the same side or on opposite sides of the molecule. • For a bond to form, the outermost  lobes must rotate so that favorable bonding interaction is achieved

10. Disrotatory Orbital Rotation • If two lobes of like sign are on the same side of the molecule, the two orbitals must rotate in opposite directions—one clockwise, and one counterclockwise • Woodward called this a disrotatory (dis-roh-tate’-or-ee) opening or closure

11. Conrotatory Orbital Rotation • If lobes of like sign are on opposite sides of the molecule: both orbitals must rotate in the same direction, clockwise or counterclockwise • Woodward called this motion conrotatory (con-roh-tate’-or-ee)

12. 30.3 Stereochemistry of Thermal Electrocyclic Reactions • Determined by the symmetry of the polyene HOMO • The ground-state electronic configuration is used to identify the HOMO • (Photochemical reactions go through the excited-state electronic configuration )

13. Ring Closure of Conjugated Trienes • Involves lobes of like sign on the same side of the molecule and disrotatory ring closure

14. Contrast: Electrocyclic Opening to a Diene • Conjugated dienes and conjugated trienes react with opposite stereochemistry • Different symmetries of the diene and triene HOMOs • Dienes open and close by a conrotatory path • Trienes open and close by a disrotatory path

15. 30.4 Photochemical Electrocyclic Reactions • Irradiation of a polyene excites one electron from HOMO to LUMO • This causes the old LUMO to become the new HOMO, with changed symmetry • This changes the reaction stereochemistry (symmetries of thermal and photochemical electrocylic reactions are always opposite)

16. Rules for Electrocyclic Reactions

17. 30.5 Cycloaddition Reactions • Two unsaturated molecules add to one another, yielding a cyclic product • The Diels–Alder cycloaddition reaction is a pericyclic process that takes place between a diene (four  electrons) and a dienophile (two  electrons) to yield a cyclohexene product Stereospecific with respect to substituents

18. Rules for Cylcoadditions - Suprafacial Cycloadditions • The terminal  lobes of the two reactants must have the correct symmetry for bonding to occur • Suprafacial cycloadditions take place when a bonding interaction occurs between lobes on the same face of one reactant and lobes on the same face of the other reactant

19. Rules for Cylcoadditions - Antarafacial Cycloadditions • These take place when a bonding interaction occurs between lobes on the same face of one reactant and lobes on opposite faces of the other reactant (not possible unless a large ring is formed)

20. 30.6 Stereochemistry of Cycloadditions • HOMO of one reactant combines with LUMO of other • Possible in thermal [4 +2] cycloaddition

21. [2+2] Cylcoadditions • Only the excited-state HOMO of one alkene and the LUMO can combine by a suprafacial pathway in the combination of two alkenes

22. Formation of Four-Membered Rings • Photochemical [2 + 2] cycloaddition reaction occurs smoothly

23. 30.7 Sigmatropic Rearrangements • A s -bonded substituent atom or group migrates across a  electron system from one position to another • A s bond is broken in the reactant, the  bonds move, and a new s bond is formed in the product

24. Sigmatropic Notation • Numbers in brackets refer to the two groups connected by the  bond and designate the positions in those groups to which migration occurs • In a [1,5] sigmatropic rearrangement of a diene migration occurs to position 1 of the H group (the only possibility) and to position 5 of the pentadienyl group • In a [3,3] Claisen rearrangement migration occurs to position 3 of the allyl group and also to position 3 of the vinylic ether

25. Sigmatropic Stereospecificity: Suprafacial and Antarafacial • Migration of a group across the same face of the  system is a suprafacial rearrangement • Migration of a group from one face of the  system to the other face is called an antarafacial rearrangement

26. Stereochemical Rules of Sigmatropic Rearrangements

27. 30.8 Some Examples of Sigmatropic Rearrangements • A [1,5] sigmatropic rearrangement involves three electron pairs (two  bonds and one s bond) • Orbital-symmetry rules predict a suprafacial reaction • 5-methylcyclopentadiene rapidly rearranges at room temperature

28. Another Example of a Sigmatropic Rearrangement • Heating 5,5,5-trideuterio-(1,3Z)-pentadiene causes scrambling of deuterium between positions 1 and 5

29. Orbital Picture of a Suprafacial [1,5]-H Shift

30. Cope and Claisen Rearrangements are Sigmatropic • Cope rearrangement of 1,5-hexadiene • Claisen rearrangement of an allyl aryl ether

31. Suprafacial [3,3] Cope and Claisen Rearrangements • Both involve reorganization of an odd number of electron pairs (two  bonds and one s bond) • Both react by suprafacial pathways

32. 30.9 A Summary of Rules for Pericyclic Reactions