Pericyclic reactions

Pericyclic reactions

1. 1 PERICYCLIC REACTION Prepared By : Mahendra G S M-Pharm, Pharmaceutical Chemistry JSSCP, MYSURU

2. FLOW OF PRESENTATION Introduction 1 Classification 2 Mechanism 3 Example 4 2

3. Introduction Pericyclic reactions are "Any concerted reaction in which bonds are formed or broken in a cyclic transitions state”. (electrons move around in a circle). i.e . there is a single transition state from start to finish, in contrast to a stepwise reaction . 3 . Angew . Chem. Int. Edit.   1969 , 8(5),343-348.

4. . Pericyclic reactivity can be understood in terms of frontier molecular orbital (FMO) theory and the outcome of reactions can be predicted using the Woodward-Hoffmann rules. . Pericyclic reactions require light or heat and are completely stereospecfic ; that is, a single stereoisomer of the reactant forms a single stereoisomer of the product. Properties of pericyclic reactions : (a) Little, if any, solvent effect (b) No nucleophiles or electrophiles involved. (c ) Not generally catalysed by Lewis acids. (d) Highly stereospecific . (e) Often photochemically promoted. 4

5. Classification: 1. Cycloaddition reaction . 2. Electrocyclic ring closing and ring opening reaction 3. Sigmatropic Rearrangements 4. Cheletropic 5. Group Transfer

6. Cycloaddition reaction A  cycloaddition  is a pericyclic chemical reaction, in which "two or more unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction. Designated as [A+B]. A and B refers to number of atoms containing π-electrons Three important classes of cycloaddition reactions ( i ) Diels-Alder reaction (iii) [2+2] Cycloaddition (ii) [1,3]-Dipolar cycloaddition 6

7. Diels-Alder Reaction Reaction between a conjugated diene and dienophile . Highly effective method for the formation of cyclohexene ring Discovered by Professor Otto Diels and his student Kurt Alder in 1928 and received Nobel prize in 1950 7  J. Am. Chem. Soc.;  2005 ; 127(43) pp 15002 - 15003; hv

8. This is because the electron- withdrawing group reduces the LUMO energy and improves the overlap with the orbitals in the diene . 8

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10. FMO Theory Cycloaddition can be explained using frontier molecular orbital (FMO) theory. Frontier Molecular Orbital Theory was developed in the 1960s by Kenichi Fukui who recognised that chemical reactivity can often be explained in terms of interacting Highest Occupied MOs (HOMOs), Lowest Unoccupied MOs (LUMOs) The alkene ( dienophile ) component has two electrons is a "single" π-bond. FMO theory, here, identifies the HOMO and LUMO components of this system: 10 The Journal of Chemical Physics   20  (4): 722.

11. 11 Likewise, the diene which has four electrons in is conjugated π-system can have its HOMO and LUMO identified within FMO theory: The Journal of Chemical Physics   20  (4): 722.

12. If we examine the phases at the ends ( terminis ) of the diene and dieneophile we find that the LUMO/HOMO interactions are phase matched: 12 In the FMO diagrams above, the sizes or coefficients, are all the same size, but usually they are of different sizes. The rule is that the coefficients match as well: small with small and large with large. Thus, the regioselectivity of the cycloaddition can be explained

13. [2+2] Cycloaddition reaction The  [2+2] photocycloaddition  is a cycloaddition-type reaction – it generally entails the formation of new molecules by the reaction of two unsaturated molecules via two atoms from each molecules (hence "[2 + 2]"). 13   Polym. Int.   58  (7): 720

14. 1,3 dipolar cycloaddition reaction These are 3 atom 4 electron diene which react with dienophile and form 5-member ring This is called 1,3 dipole and this cycloaddition reaction called as 1,3 dipolar cycloaddition reaction Mechanism 14 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 867

15. Molecular rearrangements in which a σ-bonded atom or group, flanked by one or more π-electron systems, shifts to a new location with a corresponding reorganization of the π-bonds are called sigmatropic reactions. The total number of σ-bonds and π-bonds remain unchanged.  Diffenent type of sigmatropic rearrangement reaction are- Sigmatropic Rearrangements (3,3)-sigmatropic rearrangement (2,3)-sigmatropic rearrangement (1,5)-sigmatropic rearrangement 15

16. Claisen rearrangement or (3,3)-sigmatropic rearrangement This is a example of (3,3)-sigmatropic rearrangement This is one-step mechanism without ionic intermediate or any charge Similar like a Cycloaddition reaction 16 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 35, p 897

17. Electrocyclic Reactions An electrocyclic reaction is a reversible reaction that involves ring closure of a conjugated polyene to a cycloalkene , or ring opening of a cycloalkene to a conjugated polyene . For example, ring closure of 1,3,5-hexatriene forms 1,3-cyclohexadiene, a product with one more ! bond and one fewer " bond than the reactant. Ring opening of cyclobutene forms 1,3-butadiene, a product with one fewer ! bond and one more " bond than the reactant. 17

18. EXAMPLE OF PERICYCLIC REACTION 18

19. Synthesis of citral 19 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 897-930

20. Fischer indole synthesis 20 J.J. Li, Name Reactions, 4th ed, p 245

21. Pericyclic Reactions in Biological Systems 21 J. Am. Chem. Soc . ;  2005 ; 127(43) pp 15002 - 15003;

22.   Oxidation of 3-alcohol to carbonyl compund 22 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 897-930

23. Synthesis of substituted alcohol 23 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 897-930

24. Diels-Alder reactions: Alkaloid synthesis: 24 J. Org. Chem. ,  2013 ,  78  (19), pp 9738–9747

25. Synthesis of intermediate of estrone 25 J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 897-930

26. Diels-Alder reactions for the synthesis of carbohydrate J. Clayden , N. Greeves , S. Warren, P. Wothers , Oxford, chapter 34, p 897-930

27. Thank you 27