Chapter 10 Pericyclic Reactions （周环反应）

Chapter 10 Pericyclic Reactions（周环反应）

Pericyclic Reactions• Continuous concerted reorganisation of electrons

• 5 major categories:– Electrocyclic ring opening/closure– Cycloaddition/cycloreversion reactions– Cheletropic reactions (e.g. carbene addition)

– Group transfer reactions (e.g. H2 transfer)

– Sigmatropic rearrangements

Sigmatropic Rearrangements

• Migration of a -bond across a conjugated -system

• [m,n] shift when the -bond migrates across m atoms of one system and n of another

R R

R R

[1,3]-shift1

2

3 1

2

3

1

2

3

1'2'

3'

1

2

3

1'2'

3'

[3,3]-shift

1' 1'

Conjugated π Systems

nonbonding

4

3

3

2

2

1

1 Bonding

Antibonding

2 p-orbitals 3 p-orbitals 4 p-orbitals

Suprafacial/Antarafacial• Suprafacial migration: Group moves across same face

• Antarafacial migration: Group moves from one face to the other

R'R

R R'

R R'

R'R

R'R

R R'

R'

R

R

R'

R'

RR

R'

R R'R'R

FMO Analysis• [1,3] Sigmatropic Rearrangements: H migration

R R'

H

R R'

H

R R'

H+

R R'

H

R R'H

Suprafacial migration Antarafacial migration

FORBIDDEN ORBITALLY ALLOWED BUTH CANNOT BRIDGE DISTANCE

2 allyl anion HOMO

1s proton LUMO

FMO Analysis• [1,3] Sigmatropic Rearrangements: C migration

R R'

CH3

R R'

CH3

R R'

CH3

+

R R'

C HH

H

R R'

C

H

HH

Suprafacial migrationRetention at carbon

Suprafacial migrationInversion at carbon

FORBIDDEN

2 allyl anion HOMO

ALLOWED

2p Carbon LUMO

FMO Analysis• [1,5] Sigmatropic Rearrangements

R R'

X

R R'

X

R R'

X+

H

C

C

3 pentadienyl anion HOMO

1s proton LUMO

Suprafacial migrationALLOWED

3 pentadienyl anion HOMO

2p carbon LUMO

Suprafacial migrationRetention at Carbon

ALLOWED

Antarafacial migrationInversion at Carbon

ALLOWED

Antarafacial migrationFORBIDDEN

Dewar-Zimmerman• Dewar-Zimmerman model:

– Choose a set of 2p atomic orbitals and arbitrarily assign phase– Connect the orbitals in the starting material– Allow reaction to proceed according to postulated geometry and

connect reacting lobes.– Count number of phase inversions: Odd = Möbius, Even = Hückel– Assign transition state as aromatic or antiaromatic based on

number of electrons:

– Aromatic = Thermally allowed (Photochemically forbidden)– Antiaromatic = Thermally forbidden (Photochemically allowed)

System Aromatic Antiaromatic

Hückel 4n + 2 4n

Möbius 4n 4n + 2

Dewar-Zimmerman• [1,3]-H shift

• [1,5]-H shift

R R'

H

R R'

H

H H

Suprafacial:Two Phase InversionsHückel TopologyFour electronsFORBIDDEN

H

R R'

H

R R'

H H

Suprafacial:Zero Phase InversionsHückel TopologySix electronsTHERMALLY ALLOWED

Antarafacial:Three Phase InversionsMöbius TopologyFour electronsALLOWED

Woodward-Hoffman• A ground-state pericyclic change is symmetry-allowed

when the total number of (4q+2)s and (4r)a components is odd.

• [1,5]-H shift – suprafacial

• [1,5]-H shift – antarafacial

H HH 4s

2s

No. (4q+2)s = 1No. (4r)a = 0Total = 1ALLOWED

No. (4q+2)s = 1No. (4r)a = 1Total = 2FORBIDDEN

H

H

H 4a

2s

Woodward-Hoffman• [1,7]-H shift – antarafacial

• [3,3] rearrangement

Chair Boat

RR

HH H

2s

6a


R

2s

2s

2s

R

2s

2s

2s



[1,2] Sigmatropic Rearrangements• [1,2]-C shift to cation: Wagner-Meerwein Rearrangement

• [1,2]-C shift to anion: Wittig Rearrangement

R RC

1 olefin radical cation

2p Carbon radical

Suprafacial migration: ALLOWED

R RC

2 olefin radical anion

2p Carbon radical

Suprafacial migration: FORBIDDENMust be stepwise

OR BuLi O

R

Li

OHH

+

[2,3] Sigmatropic Rearrangements

R'R

XY

R R'

YX X Y

R R'

X, Y = C, N, O, S, Se, P

* *

• FMO Analysis

X Y

2 allyl radical

2 vinyl radicalSuprafacial migration

ALLOWED


O

Ph

LiO PhO

Ph

Li+

BuLi [2,3]

• X=O, Y=C Wittig Rearrangement1

• X=S, Y=C Sulfonium Ylide Rearrangement2

1. Baldwin, JACS 1971, 93, 3556

2. Lythgoe, Chem. Comm. 1972, 757

S+

S

S SS

+

SLi

+

BuLi [2,3]


R

N+

CN

R

CN

Me2N

R

N+

CN

Li+

BuLi [2,3]

• X=N, Y=C Ammonium Ylide Rearrangement3 (Stevens)

• X=C, Y=C All-carbon Rearrangement4

3. Buchi, J. Am. Chem. Soc. 1974, 96, 7573

4. Smith, J. Org. Chem. 1977, 42, 3165

O

N2O

O

H

O

OR

Cu(I)

-N2

ROH[2,3]


R

N+

EtEt O OH

R

ON

Et

Et

R

[2,3] Zn/HOAc

• X=N, Y=O Meisenheimer Rearrangement5

• X=S, Y=O Sulfoxide Rearrangement6

5. Tanabe, Tet. Lett. 1975, 3005

6. Evans, Accts. Chem. Res. 1974, 7, 147

S+

OPh

OS

Ph

OH[2,3]

(MeO)3PMeOH

BuLiPhSCl


Se+

NPh

Ph

NHTs

PhN

Se

Ph

Ph

[2,3]

Ts

Ts

MeOH

• X=Se, Y=N Related Rearrangement7

• X=S, Y=N Related Rearrangement8

7. Hopkins, Tet. Lett. 1984, 25, 15

8. Dolle, Tet. Lett. 1989, 30, 4723

SPh

TsO

[2,3]NaN(Cl)Ts

S+

TsO

NPh

TsO

NPhS

N

TsTs

Ts(MeO)3PMeOH


R'R

XY

X

Y R'

H

R

H

Y

X H

R

R'

H

R'R

YX

R'

R YX

• Olefin Selectivity from starting olefin– 1,2-Disubstitution(E)

– R and R’ prefer to sit in pseudo-equatorial positions9

9. Nakai, Tet. Lett. 1981, 22, 69

O

CO2HOH CO2H

(E) selectivity: 75%2 LDA


R

XY

R'

X

Y H

R'

R

H

Y

X H

R

H

R'

R'R

YX

R'

R YX

• Olefin Selectivity from starting olefin– 1,2-Disubstitution(Z)

– Generally, higher levels of 1,3 induction seen with Z olefins10

10. Still, J. Am. Chem. Soc. 1978, 100, 1927

R

OBu3Sn

ROH Only E isomer

obtained

BuLi


R

XY

R'

X

Y R'

H

R

H

Y

X H

R

R'

H

R'R

YX

R'

R YX

• Olefin Selectivity from starting olefin– (E)-Trisubstituted

– E transition state still generally preferred but R-Me interaction may cause significant destabilisation10

n-Bu

OBu3Sn n-BuOH

>96% Z isomerBuLi


R

XY

R'

X

Y H

R'

R

H

Y

X H

R

H

R'

R'R

YX

R'

R YX

• Olefin Selectivity from starting olefin– (Z)-Trisubstituted

– Again, generally higher levels of 1,3 induction seen with Z olefins due to highly destabilising R-R’ interaction


R

XY

R'

X

Y H

H

R

R'

Y

X R'

R

H

H

R

YX

R'

R YX

R'

R > R'

• Olefin Selectivity from allylic position

– May expect selectivity dependent on size difference of R vs. R’11

11. Rautenstrauch, Helv. Chim. Acta 1971, 54, 739

S RR

SLi

BuLi (E):(Z) = 3:2


N

O

O

CH2OR

ROCH2

N

OH

O

CH2OR

ROCH2

BuLi

N

O

O

CH2OR

ROCH2

Li

96% de

• Chiral Auxiliaries12

– Via:

12. Katsuki, Tet. Lett. 1986, 27, 4577

O

MO

N CH2ORROCH2


OO

O

SnBu3

BuLi OO

OH

OO

OH

ratio 79:6

• Internal Relay of Stereochemistry13

– Via: (Felkin-Ahn)

13. Bruckner, Angew. Chem. Int. Ed. 1988, 27, 278

OO

OH

CH


t-Bu XY t-Bu

YX

t-Bu

YX

• Steric Effects

– Pseudo-equatorial attack generally favoured14

14. Evans, J. Am. Chem. Soc. 1972, 94, 3672

t-BuSPh

CO2Et

t-Bu S+

CO2Et

PhN2Cu(I)

selectivity 91:9


S S

CO2Et

S+

CO2Et

Cu(I)

N2CHCO2Et

[2,3]

• Ring Expansion15

• Ring Contraction16

15. Vedejs, Accts. Chem. Res. 1984, 17, 358

16. Stevenson, Tet. Lett. 1990, 31, 4351

N

N+

O

Ph

N+

O

Ph

N

O

Ph

N

O

Ph

Br

O

Ph

"

MeO

MeOH

"

[3,3] Sigmatropic Rearrangements• FMO Analysis

• Dewar-Zimmerman

2 allyl radical

Chair geometryALLOWED

Boat geometryALLOWED

X

Y Y

X

Y

X

Zero Phase InversionsHückel TopologySix electronsTHERMALLY ALLOWED


• Cope Rearrangement: Boat vs. Chair Transition State17

17. Doering, Roth, Tetrahedron 1962, 18, 67

trans-trans trans-cis cis-cis

X

Y Y

X

Y

X

X XO O

X, Y = C, O, N, etc

Cope Claisen

[3,3] Sigmatropic Rearrangements• Cope Rearrangement: Boat vs. Chair Transition State

H

Me

H

Me

Me

MeH

H

H

Me H

Me

HMe

H

Me

Me

HMe

H

HMe HMe

Me

HH

Me

H

Me Me

H

Me

HH

Me

HMe MeH

trans-trans

cis-cis

trans-cis

trans-cis

trans-trans

90%

10%

<1%

99.7%

0.3%

[3,3] Sigmatropic Rearrangements• Cope Rearrangement: Use of ring strain18

– Relief of ring strain upon rearrangement

• Oxy-Cope Rearrangement19

– Tautomerism shifts equilibrium to right

18. Brown, Chem. Comm. 1973, 319

19. Marvell, Tet. Lett. 1970, 509

H

H

5-20°C

OH

H

OH O

220°C keq ~ 105

[3,3] Sigmatropic Rearrangements• Oxy-Cope Rearrangement

– Significant rate acceleration for anionic Oxy-Cope.20

– Counter-ion also important

20. Golob, J. Am. Chem. Soc. 1975, 97, 4765

OH OH O

O O 1010 < k2 < 1017

k1

k1

k2

MeO

OX

OX

OMe

H

H

66°C

THF

OX Half-life T/°C

OH

OLi

ONa

OK

(66 yrs)

No rxn

1.2 hrs

1.4 min

66

OK

O- K+

11 hrs

4.4 min10

[3,3] Sigmatropic Rearrangements• Claisen Rearrangement

– Thermodynamic driving force: (C-O) -bond and (C-C) -bond formation

– X=Heteroatom leads to higher exothermicity and reaction rate

O

X

O

X

X = C, H, O, N

O

H

O

OR

O

H

O

OR~20 kcal/mol

~30

~30 kcal/mol

~20

[3,3] Sigmatropic Rearrangements• Synthesis of allyl vinyl ethers21,22

21. Watanabe, Conlon, J. Am. Chem. Soc. 1957, 79, 2828

22. Evans, Grubbs, J. Am. Chem. Soc. 1980, 102, 3272

OH

OEtO

AcOHg

OEt

O

O

O

Ph OPhCp2Ti

ClAlMe2

Hg(OAc)2

[3,3] Sigmatropic Rearrangements• Endocyclic Olefins23

• Exocyclic Olefins24

– Overlap equally good from either face

23. Ireland, J. Org. Chem. 1983, 48, 1829

24. House, J. Org. Chem. 1975, 40, 86

t-Bu

O

Et

t-Bu

Et

O

O

t-Bu

144°C

diastereoselection >87:13

Via Chair intermediate:

t-Bu

O

OEtt-Bu

O

OEt

t-Bu

O

EtO

ratio 52:48

[3,3] Sigmatropic Rearrangements• Olefin Selectivity

– R group prefers to sit in pseudo-equatorial position25

25. Faulkner, J. Am. Chem. Soc. 1973, 95, 553

O

H

Me

O

CHO

CHO

Me

H

O

R'

R

O

R'

R

CHO

R

CHOR'

(E) (Z)

110°C

R R’ (E):(Z)

Me Et 90:10

Me i-Pr 93:7

Et Et 90:10

[3,3] Sigmatropic Rearrangements• Olefin Selectivity

– Extra substituents lead to

enhanced diastereoselection25

Larger X => better

selectivity

Et

O

Me

XEt

Me

O

X

Et X

O

Me

Et

H

MeO

X

H

Et

Me

OX

X (E):(Z)

H 90:10

Me >99:1

MeO >99:1

Me2N >98:2

[3,3] Sigmatropic Rearrangements• Claisen Variants: Johnson Orthoester Claisen26

• Claisen Variants: Eschenmoser Claisen27

26. Johnson, Faulkner, Peterson, J. Am. Chem. Soc. 1970, 92, 741

27. Eschenmoser, Helv. Chim. Acta 1964, 47, 2425

O

OEt

O

OEtEtO

O

OEtOH

H+

MeC(OEt)3

O

NEt2

O

NEt2MeO

O

NEt2OH

NEt2

MeO

MeO

Xylene150°C

[3,3] Sigmatropic Rearrangements• Claisen Variants: Ireland Enolate Claisen28

– Substituted enolates afford an additional stereocentre29

28. Ireland, J. Am. Chem. Soc. 1976, 98, 2868

29. Ireland, J. Org. Chem. 1991, 56, 650

O

O

O

OTMS

O

OH

LDA

TMSCl

R'

O

R

OTBS

R'

O

R

OTBS

R

H

R'O

OTBSH

O

R

OTBS

R'

R

H

R'O

OTBS

H

O

R

OTBS

R'

[3,3] Sigmatropic Rearrangements• Lewis Acid catalysed Claisen rearrangement

– Presence of Lewis Acid can influence rearrangement30

30. Yamamoto, J. Am. Chem. Soc. 1990, 112, 316

O+LA

O+LA

O OLA

LA

R O XR

O

X

O

X

R O

X

R

LA

R

O

X

LA

LewisAcid

[3,3] Sigmatropic Rearrangements• Chiral Lewis Acid promoted Claisen rearrangement31

• Enantioselective Claisen Rearrangements32

31. Yamamoto, J. Am. Chem. Soc. 1990, 112, 7791 32. Corey, J. Am. Chem. Soc. 1991, 113, 4026

O

OO

OBL2

O

OH

O

OBL2

O

OH

>97% ee

96% ee

L2BBri-Pr2NEt

DCM

-20°C

-20°CL2BBrEt3N

PhMe

O SiMe3

Ph

O SiMe3

Ph(R)-1

1.1 - 2 eq

DCM, -20°C

88% eeO

O

Al Me

Si(t-Bu)Ph2

Si(t-Bu)Ph2

(R)-1

NB

N

Br

ArO2S SO2Ar

Ph Ph

L2BBr

[m,n] Sigmatropic Rearrangements• [4,5] shift

– [2,3] possible but [4,5] favoured. [2,5] and [3,4] forbidden

• [3,4] shift

Ph NMe2

NMe2PhPh NMe2

MeONa [4,5]

OMeO OH

OMe

OHMeO

Key Retrons• C=C + X: 1-6

• C=C + X: 1-5

• C=C + X: 1-4

RR'

X

R

R'XH

XH

R'

R

R R'

X

R

X

R'

RR'

XH

R

X

R'R'

HX R'

Cope rearrangement

Retro-ene reaction

Claisen rearrangement

[2,3] rearrangementWittig X=O

Ene reaction

Chapter 10 Pericyclic Reactions （周环反应）

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