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

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

Facility of intramolecular ring closure: Baldwin’s rules Ring size Relative * * * Rate Ring size Relative 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), )

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

6 Mode of Nucleophilic Attack

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, 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,

8 Examples of Application  

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10 Examples of Application

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

Cyclization leading to aromatic and heteroaromatic rings carbocyclic

heterocyclic rings Monocyclic compound

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15 Benzo-fused compounds

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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

The 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

19  Endo rule (Alder)

20  The regioselectivity

21  Examples of Application in organic synthesis

,3-Dipolar cycloaddition Addition of carbenes and nitrenes to alkenes