Pericyclic Reactions (McM chapt 30)

Polar react. (nucleophiles and electrophiles) Nu E

Radical react. R R'

Pericyclic react. (concerted, cyclic TS#)

Electrocyclic react.
Cycloadditions (i.e. Diels Alder)
Sigmatropic rearrangement
Pericyclic react. (concerted, cyclic TS#)
Rearrangement of polyene
Electrocyclic react.
Termal (react. in ground state)
Cycloadditions (i.e. Diels Alder) or photochemical
Sigmatropic rearrangement (react of exited state)

ring strain
Electrocyclic react. - Stereospesific react.

Termal cond.:

H3C H H H
H H3C
CH3 CH3
E,Z Cis

H CH3
H3C CH3
H H
CH3 H

E,E Trans

Opposite stereochem. under photochem. cond.

Pericyclic react. are symmetry allowed react.

Woodward Hoffmann rules

Symmetry in reactants are preserved during pericyclic react.

Maximum bonding interactions by transferring electrons between
molecular orbitals of the same symmetry in reactant and products.

The lobes of the reactant MOs must be of the correct algebraic sign
for bonding to occur in the TS

Results can generally be predicted just by looking at Front Molecular Orbitals

(FMO; HOMO and LUMO) - Fukui
Symmetry allowed react.

Woodward Hoffmann rules

Symmetry in reactants are preserved during pericyclic react.

Results can generally be predicted just by looking at Front Molecular Orbitals

(FMO; HOMO and LUMO) - Fukui

Butadiene
(ground state)

LUMO: Lowest uoccupied MO

HOMO: Highest occupied MO

Molecular orbitals
1,3-butadiene
HOMO

LUMO -bond

HOMO -bond

Conrotatory
Both rotate same way

Stereospesific react.

H3C H H H
H H3C
CH3 CH3
E,Z Cis

S: Symmetric
A: Antisym.
H CH3
H3C CH3
H H
CH3 H

E,E Trans
Molecular orbitals HOMO
hexatriene
LUMO -bond LUMO -bond

Disrotatory HOMO -bond

Rotation opposite way

H3C CH3
CH3 CH3

E E
Cis

H3C CH3

H3C
CH3

E Z
Trans

Electrocyclic react. -Symmetry allowed

No. of electrons Reactions in the ground state

4n Conrotatory

4n + 2 Disrotatory
Photochemical electrocyclic react.

HOMO exitet state

(= LUMO ground state)

Disrotatory
Photochemical electrocyclic react. - opposite stereochemistry
HOMO exitet state
(= LUMO ground state)

Disrotatory

H3C H CH3 H
H H3C
H CH3
E,Z trans

CH3 CH3
H3C CH3
H H
H H

E,E cis

No. of electrons Reactions in the ground state Reactions in exited state

(termal) (Photochem.)
4n Conrotatory Disrotatory

4n + 2 Disrotatory Conrotatory
 h

HO conrot. ring-opening HO

previtamin D3 vitamin D3
7-dehydrocolestol
cyclohexadiene HO
 Applications in synthesis - Synthesis of occidentalol

J. Org. Chem. 1973, 38, 728

h termal cond.
+
CO2Me 6, con CO2Me 6,dis CO2Me CO2Me
O H H H

(+)-carvone MeLi MeLi

1. Base (epimerization)
2-MeLi
+

H OH H OH

H OH
7-epi-(-)-occidentalol (+) occidentalol

(-)-occidentalol
 Cycloadditions (i.e. Diels Alder)

[4+2] add. termal cond.

Suprafacial cycloadd.

[4+2]
LUMO - diene
HOMO - Diene

LUMO - dienophile HOMO - dienophile

[4+2]
A C
A C
B D Both interact. may lead to product
B D

In reality, the electron rich species reacts via its HOMO

Stereospecific react.
and the electron poor species via its LUMO.
 Suprafacial and antarafacial cycloadd.

Antarafacial cycloadd

Photochemical HOMO - Diene

Suprafacial cycloadd.

rotation of
h -systh
HOMO - Diene

Difficult!
LUMO - dienophile

LUMO - dienophile

DA-prod. DA-prod.
Normal electron demand DA - Electron poor dienophile (Michael accept.)

LUMO -alkene

LUMO -alkene

EWG

HOMO - LUMO gap

EWG
HOMO-alkene

HOMO-alkene

Ethene etc, very low react.

Michael accept.
Lower LUMO, largest coefficient on -carbon

C.f. conjugate addition, -carbon attacked by Nu

Nu EWG
endo - exo selectivity (Not in McM)

O
O O O Endo O
O Exo
O O
O O O
O

HOMO - Diene

Primary interact., bond formation HOMO - Diene

O
Secondary interact., extra TS# stabil.
O O

LUMO - dienophile
O O O
 Regioselectivity in Diels Alder (Not McM)

DA is ortho - para directing

+ +
COMe COMe COMe COMe

COMe COMe COMe COMe

+ +

Also alkynes, and arynes, can be dienophiles

Ox
+
EWG EWG
EWG
Reactivity of diene as nucleophile sec and allylic

Reactivity of alkene
H-X
H H
as electrophile

Nu

O
H
H

H sec / prim and allylic

prim, not allylic
sec, not allylic

HOMO diene largest LUMO -alkene

coeff.

EWG
Bond formation almost complete in TS
Interact between the largest HOMO and LUMO coeff
largest
(or between most nucleophilic C in diene,
coeff and most electrophilic C in alkene)

+
(-)
COMe COMe
(+) COMe

almost no bond formation

in TS
[2+2] Cycloadditions
Suprafacial cycloadd. Antarafacial cycloadd. (termal cond.) Suprafacial cycloadd. (photochem. cond.)

HOMO-alkene
HOMO - Diene HOMO-alkene
exited state
h
LUMO -alkene

LUMO -alkene LUMO -alkene

Geometrical constrains
Difficult to make small rings
by antrafacial cycloadd

No. of electrons Reactions in the ground state Reactions in exited state

(termal) (Photochem.)
4n Antarafacial Suprafacial

4n + 2 Suprafacial Antarafacial
 O O O O
H H
RN h RN NR
O N
NR
O N N O
Cancer
R N O RH HR
R
Photochemical + isomers
[2+2]

Psoralenes - Psoriasis

O
O
N N
O O N N
HN R NH2 HN R
O O NH2
N h N
O O O O O O
R' R'
 Carbenes McM chapt 7.6, lab ex. 7

Carbanion
H -H

sp3 B sp3

Carbocation
X -X

sp3 sp2

Carbene Neutral C
C
H - H-Cl Divalent
6 valence electrons - Highly reactive t1/2 < 1 s
sp3 sp2 Electron deficient /electrophilic properties
 singlet carbene triplet carbene

p-orbital

bonding non-bonding
sp2-orbitals sp2-orbital

2 half-filled p-orbitals
electrons with parallell spin
electron pair, opposite spin
cation / anion properties
diradical properties
Gives triplet signal in esr spektrum

Triplet normally somewhat more stable than singlet

Singlets more reactive

dihalocarbene
X Stabilizing overlap
in singlet state
 Carbenes and carbeniods in synthesis

Generation of carbenes

X Base X X
X X cf lab ex 7
X
X H X

Not in McM
h
H H or heat H
N N + N2
N N H
H H

Diazomethane
(toxic, explosive)

(From Hg-species)
 Carbene Cycloadditions
Singlet Carbene

Empty p-orb
LUMO of carbene
R R
R

C
R R
sp2 hybr orbital with lone pair
R
HOMO of carbene

Empty p-orb
LUMO of carbene
R R HOMO of carbene

C C

R R

HOMO alkene
LUMO alkene
 Carbenoids - Simmons Smith reaction
Insertion
CH2I2 + Zn(Cu) I-CH2-ZnI cf. Grignard
CH3X + Mg CH3-MgX
Zn-Cu alloy (Carbenioid)

Other methods

TS# ?
I-CH2-ZnI
ZnI I
H H H H
H2C

One-step - Concerted H H
Stereospesific
Enentioselective Simmons Smith
Allylic alcohols (Chiral auxilary or catalyst)

antifungal, nat. prod.

Other carbenoids
 Cycloadditions with 1,3-dipolar reagents
[4+2] cycloadd. Not in McM

O
O O
O O
O O
O

Ozone

Other ex of 1,3-dipoles
O O
R R R R
O O OH
Os H2O N N N
Os N
O O O
O OH N
N N N
OsO4
N N N N
azides

H R H R H R H
R
C C C C

N N N N

N N N N

diazoalkanes

Synthesis of heterocycles
 Sigmatropic Rearrangements
-bonded subst migrates accross a -electron systhem

[1,3] Rearrangement (H-shift)

5
1 1
H
H -bond to
H -bond to formed
H be broken 3 1 3
1 2
2

LUMO -bond

h
Suprafacial H
HOMO bond
H
Antarafacial

Too strained TS#

[1,5] Rearrangement (H-shift)

5 5
1 1 4
H 4 H
-bond to
be broken 1 3 1 3
2 2

LUMO -systhem butadiene

Suprafacial
H
H

HOMO bond

No. of electrons Reactions in the ground state Reactions in exited state

(termal) (Photochem.)
4n Antarafacial Suprafacial

4n + 2 Suprafacial Antarafacial
 h [1,7] sigmatropic
rearrangement

HO conrot. ring-opening HO HO

previtamin D3
7-dehydrocolestol
cyclohexadiene

vitamin D3
HO
 [3,3] Rearrangements; Claisen rearrang. etc.
Claisen rearrangement

Allyl-vinyl ether or O
Allyl aryl ether

1 2 1 2
3 3
O O -bond to
-bond to be formed
be broken 3 3
1 1
2 2

taut
O HO
O H

Cope rearrangement
2 1 2
1 3 3

R 1 R 1 3 Suprafacial
3
2 2 Disrotatory

6 electrons
Oxy-Cope rearrangement
(4n+2)
2 1 2 2
1 1
3 3 taut 3

HO 1 HO 1 3 O 1 3
3 2
2 2