Pericyclic reactions

Transcription

1 Pericyclic reactions 1

2 TC Pericyclic reactions - Characteristics of pericyclic reactions - Important types of pericyclic reactions Electrocyclic reactions Cycloadditions/cycloreversions Sigmatropic rearrangements Group transfer reactions (ene reactions) Woodward-offmann rules Examples of electrocyclic reactions Examples of cycloadditions 2

3 verview Pericyclic reac-ons Concerted reac-ons to cleave and form some covalent bonds containing pi-electrons at the same -me via a transi-on state Eelectrocyclic reac-ons A A Δ A A R hν A A Cycloaddi-on reac-ons R R Δ Δ R R R Cheletropic Reac-ons S [4+1] S Sigmatropic reac-ons R [1,3]-shift 3 R 2 1 Group transfer reac-ons R + hydrogen transfer R + 3

4 verview Characteris-cs of pericyclic reac-ons Solvents and other reagents are unnecessary (in some cases) nly heat or photoirradia-on are required for ac-va-on of the reac-ons Concerted reac-ons (via no reac-on intermediates) Stereospecific reac-ons number of electrons involved affects on the reac-vity reac-on condi-ons (heat or light) affects on the reac-vity Bonds form and cleave simultaneously Typical pericyclic reac-ons in living organisms Me R Me R Me R Me hν conrotatory Me Δ [1,7] -shift provitamin previtamin vitamin D 2 : R = vitamin D 3 : R = 4

5 Examples of pericyclic reactions Electrocyclic reac-on Conjugated π bonds cause ring closing or ring opening. Δ or hν 4π electron system Δ or hν Number of electrons involved affects on the reac-vity. 6π electron system Conjugated π bonds use terminal two p orbitals to form a new σ bond to cause ring closure. A ring-opening reac-on is its reverse reac-on. A A Δ A A hν A A π bond 1 σ bond 1 Reac-on condi-ons (heat or light) affects stereochemistry of the products. thermally allowed reac-on photochemically allowed reac-on 5

6 Examples of pericyclic reactions Cycloaddi-on/Cycloreversion Two or more conjugated π molecules add to form new m σ bonds in a concerted manner to cause ring closure. π bonds m σ bonds m + hν [2+2] Paterno-Buchi reaction + Δ [4+2] Diels-Alder reaction Retro reac-on, cycloreversion, may proceed. Δ retro [4+2] 2 retro Diels-Alder reaction ozonolysis: 6

7 Summary six electron examples electrocyclic reaction cycloaddition sigmatropic rearrangement ene reaction bond changes in pericyclic reactions 7

8 Summary practice quiz: The following 2-step scheme proceeds via two pericyclic reactions. Show the structure of the intermediate. Also, answer which class of pericyclic reactions occur in each step.? 8

9 Review of M rbital interac-ons rbital interac-ons Most of pericyclic Most reac-ons of pericyclic proceed reac-ons stereospecifically. proceed stereospecifically. Explained by Woodward-offmann Explained by Woodward-offmann rules rules rbitals interact rbitals to form interact a bonding to form ab-bonding a bonding orbital. ab-bonding n orbital. σ (bonding) σ (bonding) σ (bonding) σ (bonding) π (bonding) π (bonding) π* (an-bonding) 9

10 Electrocyclic reactions stereochemistry Stereochemistry of electrocyclic reac-on conrotatory Δ or hν conrotatory = = disrotatory Two types of reac-on paths to form a σ bond depending on the the rota-onal direc-ons of terminal π bonds 10

11 Electrocyclic reactions stereochemistry disrotatory conrotatory conrotatory disrotatory 11

12 Electrocyclic reactions stereochemistry Stereochemistry of electrocyclic reac-on conrotatory disrotatory Two types of reac-on paths to form a σ bond depending on the the rota-onal direc-ons of terminal π bonds Empirically, under thermal condi-ons, butadienes (4π electron system 4q) go conrotory, and hexatrienes (6π electron system: 4q+2) go disrotatory. Reverse reac-on proceeds with rota-on in the same direc-on 12

13 Electrocyclic reactions stereochemistry Stereochemistry of electrocyclic reac-on 4q electron system (4q) 6 electron system (4q+2) Reac-ons under photochemical and photochemical condi-ons show opposite stereochemistry. What is signs of the wave func-on of each p orbital? 13

14 Electrocyclic reactions stereochemistry Molecular orbitals of conjugated π electron system an-bonding orbital A A S nonbonding orbital S A bonding orbital A S S A S In frontier molecular orbital theory, electrons in M primarily participate in reactions. 14

15 Electrocyclic reactions stereochemistry Stereochemistry of electrocyclic reac-on: heat Conrotatory Conrotatory: Thermally allowed Ψ 2 : M of diene Bonding interac-on in TS Disrotatory Disrotatotry: Thermally forbidden Ψ 2 : M of diene An-bonding interac-on in TS For hexatrienes (4q+2), disrotatory process is thermally allowed, and conrotatory process is thermally forbidden. 15

16 Electrocyclic reactions stereochemistry Stereochemistry of electrocyclic reac-on: light Change of sign of M by photoexcita-on Disrotatory Ψ 3 : M of diene acer photoexcita-on (original LUM) Bonding interac-on in TS Disrotatory: Photochemically allowed Conrotatory: Photochemically forbidden For hexatrienes, (4q+2), conrotatory process is photochemically allowed, and disrotatory process is photochemically forbidden. Fron-er Molecular rbital (FM) theory expains selec-vity Woodward-offmann rule 16

17 Woodward-offmann rule For electrocyclic reac-ons, thermal reac-ons are determined by M, photochemical reac-ons are determined by LUM. outcome of the Woodward-offmann rule π π 17

18 More examples of electrocyclic reactions Electrocyclic reac-on except 4π electron system Stereochemistry differs depending on number of π electrons. Retro reac-ons may proceed. general scheme practice quiz: Show chemical structures of the intermediates/products of the reactions below. Show the configuration of the bonds shown in blue in the scheme above. 8π system 273 K conrotatory 273 K 273 K 6π system 273 K disrotatory 273 K 273 K 8π system conrotatory 6π system disrotatory 6π electron system: selec-vity is different from that in 4π electron system (disrotatory is thermally allowed) 8π electron system: selec-vity is same as that in 4π electron system (conrotatory is thermally allowed) 18

19 More examples of electrocyclic reactions Photochemical electrocyclic reac-on Photochemical electrocyclic reac-on may give unstable compounds. Me Me hν Me tropone deriva-ve aroma-c disrotatory Nonaroma-c conrotatory aromatic nonaromatic aromatic 19

20 More examples of electrocyclic reactions Stereochemistry of electrocyclic reac-on Ph Ph cis hν disrotatory 4e hν conrotatory 6e R R Ph Ph Δ conrotatory 4e Δ disrotatory 6e Ph Ph trans Stereochemistry can be inverted by thermal or photochemical reac-ons. Me Me Δ conrotatory 4e Conrotatory process toward inside is unfavorable because of steric repulsion between two methyl groups in the TS. 20

21 Review of Diels-Alder reaction conformation of diene react rapidly react slowly does not react 21

22 Review of Diels-Alder reaction exothermic reaction - two σ bonds formed at the expense of two π bonds but the retro Diels-Alder reaction may facilely occur in some cases specially when one of products is aromatic or gas Good DA dienes Good DA dienophiles 22

23 Review of Diels-Alder reaction endo-type addition is preferred 23

24 Interactions of M in the Diels-Alder reactions DA reaction under thermal conditions - allowed normal electron-demanded Diels-Alder reaction inverse electron-demanded Diels-Alder reaction energy LUM M LUM Thermal condi-ons π 4 s + π2 s M of diene LUM of diene Cf. photochemical π 2 s M LUM LUM of ethylene M of ethylene LUM Signs of all fron-er molecular orbitals are bonding suprafacial suprafacial suprafacial suprafacial Phase inversion: 0 ückel system thermally allowed In [m + n] 24 cycloaddi-on, if all the π electron system proceed by suprafacial p

25 Interactions of M in the Diels-Alder reactions EDG in diene, EWG in dienophile - accelerated energy energy Me 25

26 Interactions of M in the Diels-Alder reactions EWG in diene, EDG in dienophile - inverse electron-demanded DA can occur energy energy LUM M Cl Cl Cl Cl Cl Cl 26

27 Interactions of M in the Diels-Alder reactions another example of inverse electron-demanded DA practice quiz: The reaction above is multistep reactions involving two pericyclic reaction steps. Provide the intermediates and explain how the product is produced. 27

28 Interactions of M in the Diels-Alder reactions DA reaction under photochemical conditions - prohibited [4 + 2] Cycloaddi-on: Diels-Alder reac-on energy LUM Fron-er LUM molecular orbital theory Thermal condi-ons π 4 s + π2 s Thermal condi-ons π 4 s + π2 s M M of diene M LUM of diene LUM of ethylene M (originally LUM) LUM M of of ethylene Cf. photochemical condi-ons Cf. phot π 2 s + π 2 s antibonding interaction LUM LUM Dewar-Zimmerman rule Fron-er molecular orbital theory energy LUM M Signs of all fron-er molecular Signs orbitals of all are fron-er bonding molecular orbitals are bonding [4 + 2] Cycloaddi-on: Diels-Alder reac-on [2+2] cycloaddition under photochemical conditions - allowed ([2+2] cycloaddition under thermal conditions - prohibited) Thermal condi-ons π 4 s + π2 s M of diene LUM LUM of diene [4 + 2] M Cf. photochemical condi-ons π 2 s + π2 sphase inversion: 0 ückel system M (excited) LUM thermally allowed bonding interactions Phase inversion ückel system thermally allow In [m + n] cycloaddi-on, if all In the [m π + electron n] LUM of ethylene M of ethylene LUM cycloaddi-on, system proceed if all the by π suprafacial electron system processes, proceed by su it is thermally allowed when it total is thermally π electrons allowed of (m+n) when are total (4q+2), π electrons and of (m+n) are (4q+2 Signs of all fron-er molecular it is photochemically orbitals are allowed bonding it when is photochemically total π electrons allowed of (m+n) when are total (4q). π electrons of (m+n) ar 28

29 C N Lewis SnCl4, AlCl3, ZnCl2 Regioselectivity of DA reaction TS TS 1, (2E,4Z) 2,4 (a) (b) Diels-Alder positions of EDG and EWG groups affect the regioselectivity 1 TS more nucleophilic c Diels Alder 1,3 Me Me Me 2-methoxybuta-1,3-diene 1 1,3 1,4!+ C N Me Me! Me Me CN CN C1 + C2!+ + (24.8) CN C C CN CN! 1 1,3 3,4 1-methoxybuta-1,3-diene major minor CN C N more electrophilic + + Me 1 1,3 2-methoxybuta-1,3-diene C N 1-methoxybuta-1,3-diene 1 1,3 Me +!+ Me Me +! CN CN Me!+ C N CN Me!!!+ CN Me 1,4 + Me 3,4 Me Me CN (24.7) (24.7) 1 1,3 1-methoxybuta-1,3-diene 3,4! CN CN C N CN C +!+ (24.8) Me Me Me 1 1,3 2-methoxybuta-1,3-diene 1,4 C1 C2 1,3 29 c Diels Alder

30 Practice quiz Predict the major product of the Diels-Alder reaction using the following combinations of a diene and a dienophile. CN C (a) + (b) + (c) + C 2 Et 30

31 Effect of Lewis acid in DA reaction Diels-Alder reac-on with Lewis acid + Lewis acid (LA): BF 3, AlCl 3, SnCl 4, TiCl K C 2 Cl 2 none AlCl 3 t 1/2 2,400 h t 1/2 <1 min Accelera-on by stabiliza-on of LUM LUM LUM LUM energy M M M LA 31

32 Effect of Lewis acid in DA reaction + C 2 Me 273 K C 2 Me + C 2 Me none 88% AlCl 3 96% 12% 4% Improvement of endo selec-vity Coordina-on to BF 3 + AlCl 3 AlCl 3 LUM LUM LUM Stabiliza-on of LUM and change of M coefficient by coordina-on to LA M M M 32

33 [2+2] cycloaddition [2+2] cycloaddition under photochemical conditions - allowed Cf. photochemical condi-ons LUM Thermal condi-ons π 4 it is photochemically when total π electrons of (m+n) are (4q). allowed s + π2 s total π electrons of when (m+n) thermally are is (4q+2), allowed and it LUM π M of diene 2 s + π 2 processes, suprafacial by proceed system electron π the all if cycloaddi-on, n] + [m In s M (excited) LUM energy Mthermally allowed [4 + 2] ückel system M [4 + 2] LUM Cycloaddi-on: of ethylene Diels-Alder reac-on LUM Fron-er molecular orbital theory binding interactions Signs of all fron-er molecular orbitals are bonding [2+2] cycloaddition under thermal conditions Cf. photochemical - prohibited condi-ons Thermal condi-ons π 4 s + π2 s Dewar-Zimmerman rule π M of diene LUM of diene 2 s + π2 s orbitals are bonding molecular fron-er all of Signs LUM LUM LUM LUM energy Phase inversion: 0 Phase inversion: 0 M of ethylene LUM of ethylene LUM ückel system M LUM of ethylene M of ethylene M M thermally allowed LUM Signs of all fron-er molecular orbitals are bonding diene M of diene of LUM In [m + n] cycloaddi-on, if all the π electron system proceed by suprafacial processes, 33 antibinding interaction π 2 s + π 2s Thermal condi-ons π s + π s

34 [2+2] cycloaddition in living organisms hλ 34

35 Practice quiz Explain whether the following reactions are thermally allowed or photochemically allowed. (a) + (b) + (c) + Ph N N N + C 2 Me Ph N N N NEt 2 NEt 2 C 2 Me 35