2. 1 Chapter 7 Ring closure (and ring opening) 7.1Intramolecular cyclization by electrophile- nucleophile 7.2Cycloadditon 7.3Electrocyclic ring closure 7.4Ring opening

3. 2 7.1Intramolecular cyclization by electrophile- nucleophile 7.1.1Introduction (alkylation, acylation and condensation etc.)

4. 3 7.1.2 Facility of intramolecular ring closure: Baldwin’s rules Ring size345678910 Relative21.75.4*10 3 1.5*10 6 1.7*10 4 97.31.001.123.35 Rate Ring size111213141516 18 23 Relative8.5110.632.241.945.152.051.2 60.4 Rate Relative rate constants at 50  C (with 8-membered ring = 1) for the reaction: (where n = ring size, see also Chem. Lett. 1994, (4), 677-680)

5. 4

6. 5 Reacting bond is exocyclic to the forming ring Reacting atom is tetrahedral

7. 6 Mode of Nucleophilic Attack

8. 7 Baldwin Rules Exocyclic bonds Endocyclic bonds spsp 2 sp 3 Ring size(dig)(trig)(tet)(dig)(trig)(tet)* 3 disfavfavfavfavdisfav # 4 disfav favfavfavdisfav # 5favfavfavfavdisfav # disfav 6favfavfavfavfav disfav 7favfavfavfavfav *somewhat rare #for exceptions see JACS 1985, 107, 1778; TL 1985, 26, 4455; TL 1986, 27, 2223. Rules for certain closings of 3- to 7-membered rings See also for A. Padwa, An unusual example of a 6-Endo-dig addition to an unactivated carbon-carbon triple bonds, J. Org. Chem. 1995, 60, 5595-5603.

9. 8 Examples of Application  

10. 9

11. 10 Examples of Application

12. 11 7.1.3 Michael addition in ring-closure processes Robinson annulation Michael addition followed by intramolecular condensation, is referred to as Robinson annulation.

13. 12 7.1.1Cyclization leading to aromatic and heteroaromatic rings 7.1.4.1 carbocyclic

14. 13 7.1.4.2 heterocyclic rings Monocyclic compound

15. 14

16. 15 Benzo-fused compounds

17. 16

18. 17 7.2Cycloaddition (pericyclic reaction)  Via a cyclic transition state  In a concert manner: cleavage of old bonds and formation of new bonds at the same time  Neither electrophile-nucleophile interactions nor radical pathway  Reaction condition: heating or irradiation without catalysts usually  With high stereoselectivity

19. 18 7.2.1The Diels-Alder reaction  [4+2]-cycloaddition : Reaction between 4π-electron system (the diene) and a 2π-electron system (the monoene or dienophile)  syn addition for both diene and dienophile HOMO HOMO: Highest Occupied Molecular Orbital LUMO LUMO: Lowest Unoccupied Molecular Orbital

20. 19  Endo rule (Alder)

21. 20  The regioselectivity

22. 21  Examples of Application in organic synthesis

23. 22 7.2.2 1,3-Dipolar cycloaddition 7.2.3 Addition of carbenes and nitrenes to alkenes