Organic photochemistry and

pericyclic reactions (CY50003)

3-0-0

Sunlight (h) O
One Year

Carvone Carvonecamphor
 Course content
Principles of photochemical reactions; Excited states and
their properties; experimental set up for photochemical
reactions(1); Several useful photochemical reactions and
their applications in organic synthesis (isomerization,
Patterno-Buchi reaction (1), Norrish type I and II
reaction(1), Photoreduction, Rearrangements: di--
methane, oxa di-- and aza di--methane
rearrangements(2), Photocycloaddition (2), Photochemical
aromatic substitution reaction (1), Reactions with singlet
oxygen (1), Photochemical methods for protection and
deprotection(2). Photochemistry of biological systems
(photosensitized reactions of DNA/RNA, DNA damage and
repair-1).
 Books
CRC Handbook of Photochemistry and
Photobiology. Eds by. William M. Horspool
and Pill-Soon Song. 1994. CRC Press.
ISBN: 0-8493-8634-9
Synthetic organic photochemistry. Eds by.
William M. Horspool, Plenum press. 1984.
ISBN: 0-306-41449-X
 Organic E = h
Compound Excited electronic states
(selective excitation)

Ground electronic state

Thermal photochemical
activation reactions

Photo products
Thermally activated state
(change in vibrational, rotational and
transtational energy levels which is governed
by Boltzman distribution law)

# two pathways are entirely different hence the reaction outcome

Formation of new chemical entity

 Questions need to be asked during the analysis of photochemical reaction

1. What are the products of the photo reaction

2. what are the electronic characters of the reactive state

3. what are the spin characters of the reactive state

4. what intermediates are involved in the reaction

5. what orbitals are involved and how do they react

6. what are the various chemical and physical processes and

what are their rates with which a reaction of interest competes

h
R P
h
R R* I P

h ISC
1R*
R 3R* 3I 1I P
 Antibonding orbital (*, *)
E2 E2>E1

E Atomic orbital
E1
Bonding orbital (, )

Relative energies of atomic and molecular orbitals

*
Anti bonding
*
E
non bonding (n)

Bonding

Relative energies of , and n MOs

 Most common transition module

n*(E1) * (E2)

E2>E3>E1

n-* (E3)

Absorption maxima for few molecules and functional groups

Molecule Transition max (nm) E (Kcal/mol)

Iodobutane n-* 224 127.7

Ethylene 165 173.3
Ethyne 173 165.3
Acetone 150 190.7
n- 188 152.1
n-* 279 102.5
Butadiene * 217 131.8
Acrolein 210 136.2
n-* 315 90.8

Functional group

RCH = CHR 165 173.3

193 148.2
Alkyne 173 165.3
Ketones 188 152.1
279 102.5
Aldehydes 290 98.6
Carboxylic acids <205 <137.5
 Antibonding (SOMO)

Bonding
S0 S1 T1
S0 S1 T1
Excited states
X

S0 : Ground state (spin paired, Pauli exclusion principle)

S1: Excited singlet state
T1: Excited triplet state (spin inversion)

# T1 is more stable than S1 ( parallel spin, lesser inter-electronic repulsion)

LIGHT ABSORPTION AND FATE OF EXCITATION ENERGY:
Franck-Condon Principle

Ground state (E0) and two excited states (E1, E2) of a

molecule (vibrational and rotational levels are not shown).
 Modes of Dissipation of Energy (Jablonski diagram)

(S2)
10-11s IC no radiative
(S1) ISC
(T1) ISC (Spin inversion)
10-8s
10-3s-1s Deactivation
F F
h RD P RD
radiative

(S0) P
IC
S2 : The higher vibrational level of the excited singlet state S 1
IC: Internal conversion; RD: Radiative deactivation
F: Fluorescence (spin consevation); ISC: Inter system crossing
P: Phosphorescence (Spin inversion).

S1
+

T1
+ +
photosensitization
 O

S2
*
100 Kcal/mole 1012/s

1011/s
S1
T2 (*)
n-*
74 Kcal/mole T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s

S0

CHO O O

2-acetonaphthone fluorenone
pyrene aldehyde

lowest triplet state is *

 Energy transfer through photosensitization
h
D 1D
ISC D = Donor
1D 3D A = Acceptor
1 = Singlet
A + 3D D + 3A 3 = Triplet
3A Products

S1

S1 ISC
Energy transfer
T1
T1
74 Kcal
.mole-1 69 Kcal/mole
120 Kcal/mole 60 Kcal/mole

S0 S0
Benzophenone Butadiene

h ISC 3[Ph
Ph2CO 1[Ph
2CO] 2CO]

3
Dimeric products + Ph2CO
 Criteria of an ideal sensitizer
It must be excited by the irradiation to be
used, small singlet triplet splitting. High
ISC yield.
It must be present in sufficient
concentration to absorb more strongly than
the other reactants under the condition.
It must be able to transfer energy to the
desired reactant, low chemical reactivity in
Triplet state.
 Experimental set up for
photochemical reactions
Synthetic organic chemist (high intensity
light source, easy to handle, various
Flask size, specially designed systems)

Physical chemist or physical-organic

Chemist (mechanistic study)
 Basic equipments for photochemical reactions

Mercury vapor lamps (200-750 nm, 599 kj/mol-159 kj/mol)

1. Low pressure or resonance lamps (0.005-0.1 torr, operates at RT)

Emission at 253.7 and 184.9 nm

Hg (3P1) Hg (1S0) + h

Hg (1P1) Hg (1S0) + h

2. Medium pressure lamp (1-10 atm, and relatively high T)

Requires little time to warm up, more of direct irradiation lamp

3. High pressure lamp (200 atm and very high T)

Ideal lamp characteristic : Need of spectral overlap between the lamp and the absorption
spectrum of the compound to be irradiated.
 Lamps in conjugation with filters

Problems
# A greater degree of selectivity is required if irradiation into one of
the absorption bands of the molecule is required.
# Or if the product of the irradiation is sensitive to a wavelength different
from the one used to excite the starting molecule.

Solution
# Monochromatic source of light (Lamp and a diffraction grating)
# In conjugation with filters (solution or glass)
 Short and Long cutoff filter solutions

Wavelength of cutoff (nm) Chemical composition

Below 250 Na2WO4

Below 305 SnCl2 in HCl (0.1 M)

Below 330 2M Na3VO4

Below 355 BiCl3 in HCl

Below 400 KH phthalate + KNO2 (in glycol at

pH = 11)
Below 460 0.1 M K2CrO4 (NH4OH-NH4Cl at
pH = 10)
Above 360 1 M NiSO4 + 1M CuSO4 (in 5%
H2SO4)
Above 450 CoSO4 + CuSO4
Immersion Well Reactors
Components
# Lamps
# Immersion wells
# Reaction flasks
# Standard flasks
# Gas inlet flasks
# Flow-through flasks
# Larger capacity standard
flasks
Non-Rotating Annular
Photochemical Reactor

# Large Quartz immersion well.

# 400 watt medium pressure mercury lamp.
# Reactor base and carousel assembly
(non rotating), including support rod
and immersion well adjustable clamp.
# set of sample tube support rings for
eight 25mm sample tubes
# Only the inner or the outer tubes may be
irradiated effectively at one time
# UV Screen:- consisting of three black coated
consisting of three black coated aluminum
sections. A light tight lid, a removable front
and back section, that are joined by means
of a light tight seal
Semi-Micro Reactor
The semi-micro is a low cost, easy-to-use device for irradiating a standard
1 cm cuvette (or small tube) with either 254nm or 350nm radiation for any
preset time between 1 and 70 minutes. This reactor is ideal for preliminary
studies of small volumes of solution.
 # The multilamp reactors consist of a base, lid,
six or three lamp modules. Each module
contains two lamps.
# The base is hexagonal and provided with a
centrally located fan
# A number of modules up to six or three may
be operated.
# Switches are provided to control the fan and
lamp modules.
# Supports from the lid hold samples inside
the reactors. Magnetic strips are used to
eliminate light leaks between the lamp
modules.

Multilamp Reactors: Six and Three Modules

Complete photochemical reactor comprising:

* Multilamp reactor base with cooling fan

and
control switches
* Three twin lamp modules
* Six lamps of customers choice
* Magnetic light sealing strips

One set of attachments for supporting the

reaction flask comprising :
* Reaction flask support base
* Flask support rod holder
* Support rod hinged lid
 Purity of solvent and gases

Dilution (suppression of side reaction e.g.,

polymerization and dimerization.)
Spectral transmission of solvent ( solvents
devoid of low-lying excited states are best)
Purity of solvent (Oxygen free, impurities
free)
 Transmission characteristics of various solvents

Solvent 10% Transmission (nm) 100% Transmission (nm)

Acetone 329 366
Acetonitrile 190 313
Benzene 280 366
Carbon Tetrachloride 265 313
Cyclohexane 205 254
Diethyl ether 215 313
Dimethyl sulfoxide 262 366
Ethanol 205 313
Hexane 195 254
Propan-2-ol 205 313
Tetrahydrofuran 233 366

Measured for a 1cm path length of pure solvent

 Electronic configuration of Reactive states

O O* O
h
~ C
n-*
carbonyl chromophore
Dipolar species

O O* O O*

CF3 CF3
2.9 D 2.1 D 1696 cm-1 1326 cm-1
1665 cm-1 1225 cm-1
 O

S2
*
100 Kcal/mole 1012/s

1011/s
S1
T2 (*)
n-*
74 Kcal/mole T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s

S0

CHO O O

2-acetonaphthone fluorenone
pyrene aldehyde

lowest triplet state is *

Triplet lifetime depends on the nature of lowest excited states

O O

MeO
= 0.0064 s, 77oK = 0.45 s, 77oK
n-* *

O O

Me F

= 0.13 s, 77oK = 0.039 s, 77oK

n-* & * n-* & *

# Electron donating substituents such as Me and -OMe stabilize * state

# Electron withdrawing substituents such as CF3 and CN stabilize n-* state
 Cis-Trans isomerization of alkenes

A D A E

B E B D

3 *
3S*
 h

triplet
donor

h
 h

185 nm

sens

h heat
H

H
 Ph Ph
h
Dimer

Max = 380 nm
= 9 s

Ph
Ph Ph
4+2 [1, 3] H

Trapping of a trans cyclohexene

 h
sens

h
sens
 H OR OR H

H h H

O2N O2N
R = H, Me

h N N
N N
heat

H
H h N
N
heat
 *
Ph
N
H OH

Ph
h or NH Ph NH2
h-sens H O
O
oxaaziridine
Ph OH
N
H

H
N
OH
h or
h-sens
H O
N
H

H
N
HO
O
+ h or O CN
N +
N
CN
h-sens

h
h

O
N
CN
 H
H R2 N
N h

R1 R2
R1

H
H N R H
N
h N
N R
N
N H
 R h
N N N N
R R R

R = Me R = CHMe

R= R=

R= R=
 h
N N
N N

N N
N N

h (405nm)

h(436nm)/heat

h (313nm)
-N2 h (313nm)
-N2

C C
 R
R
R

h 1,7-H

HO
HO
previtamin D
Ergosterol
HO
Vitamin D

R= R=

Vitamin D2 Vitamin D3

R
h

HO

previtamin D OH
tachysterol
Photochemical synthesis of
oxetans
Patern-Bchi Reaction
 O
O
+

Paterno and Chieffi (1909), Buchi in 1954 mechanistic analysis

NH2
N
O N
CO2 H
EtO O HO O N N

OH
Thromboxane A2
OEt Oxetanocine

Insecticidal activity

OAc O
HN O O OH
O O
O OR
NH2 O
O
H2N H
Merrilactone A OBz OAc
O
Bradyoxetin Palitaxel
 Reaction mechanism

CHO
h ISC
[PhCHO] S1 [PhCHO] T1
(n-*)

Kisc aromatic >> Kisc aliphatic (>>1010/s)

responsible

O O
O
C C C
C C
H + +

Biradical intermediate
electrophile nucleophile

O
O

Major Minor
 Intermediacy of biradical

O h
O O
+ +

1 1.6

O
O tBu
tBu h
+
1 atm O2
tBu
O O
O
O O
h, 11 atm O2

O
O O O
h O
Ph Ph + Ph
O
Ph C C
O O Ph
Ph
lifetime = 1.6 ns
 Substrate spectrum of Paterno-Buchi Reaction

Aromatic ketones and aldehydes

O
O
H h
+ H
O
O
54%

h
+ R = H, X = S, 46%
X R X
R = Ph, X = O, 27%
O R = Ph, X = S, 76%
O

h
+ + [4+2]
X Me + X X

O O O
Me

X=O 8% 33% 0%

X=S 11% 10% 38%

 Carboxylic acid derivatives and nitriles

O O H
O
OMe h
+ Ph
H

H 33% 34%

O
O Ph O O O OAc
h [2+2]
+ O Ph H2 O
Ph OMe OMe Ph
O H OMe

1,7 sigmatropic
O
MeO
Ph O
OH
+ O
C Ph OMe
Ph OMe CH . O O H
2 1
7

O O
OH H
-MeOH O 1, 3 Bz shift Ph 1,3 H shift Ph
Ph O
OMe
Ph O O O
 N
CN
h
+

N
66%
Ph

CN O h
+
O
CN
O O
h O
O COMe
O Me

O O
h O
CN O CN
R
-55oC R = Ph, endo/exo = 5.3:1
 Oxetane formation: addition to heterocycles

h
+
O* T1 O* T1
X X

C C C
O O
O X X
X
+.

Ph
O h O N
N Ph C C N
+ O
and Ph C C
Ph Ph N
N N Ph

more stable
OH
Ph Ph H
Ph N N
Ph

N O
N
H
 CO2Me
Ph Ph h O
O
CO2Me *T1 +
O Ph
O
Ph

Methyl coumarilate

R1 R3 R1 R4
R1
O h R4 R3
+ +
R3 R4 O O
R S R2 R S R S
R2 R2

R1 R1 Ph
O h Ph
+
R2 Se R Ph Ph O
R2 Se
R
R1 = R2 = H, R = Me
R = R2 = H, R1 = Me
R1 = H, R = R2 = Me
 Ph
O h, 436 nm O
+ Ph
Ph Si Ph
Ph + O
Ph Ph Ph Si
Me Me MeCN Ph Ph Ph Si Ph
Me Me Me Me

18% 51%

Ph
O Ph
h
+ O
N Ph Ph N
COR COR

COMe
COMe
O N
N h O
Ph Ph Ph
Ph
 Enones and Ynones

O O O

+ +

42% 47%
O O
O
Low T
+ + 3% oxetane

Me CCl3 Me CCl3

O O O
F F F
+ +
Me Me
10% 9 0%

O O O
Cl Cl Cl
+ +
Me Me
90% 10%
O h O
O
+ +

14% 86

O h O
+ O
+

O O
C C
..
 Alkenes substituted with electron donor

OAc
O h OAc
O
OAc OAc
OTMS OTMS

O
EtO OEt ZnCl2 O
O
+ O O h
O O EtO2C O
CO2Et

H
O O h
O
+
O
H
 SiMe3
O h O
O
+ Ph
+ Ph
Ph Ph SiMe3
Ph Ph
SiMe3
24 1

h O O
O
+ Ph
OTMS
Ph
Ph Ph
+
OTMS Ph OTMS Ph

94 6

h O O SMe
O H
+
Ph SMe + Ph
Ph Ph Ph H Ph H
H SMe
100 0
 Miscelleneous Paterno-Buchi Reaction

O COM O
O h
+ +
H

O Ph Ph
h Ph Ph
+
Ph Ph O 300oC O

O h
+ O
O
Ph R Ph C C Ph
R
R

O O
Ph C Ph

R R
C
CHO
OAc
O h
+ O
O OAc O

O
O
O CO2 Me

HO

HO
 The Paterno-Buchi reaction as a photochemical aldol equivalent

O OEt h/70% OEt H2O, RT OH O

O O O
+ + OEt
+ OEt
H
3 : 7

OH O OR OH OH
R' H2 O O R'
R H R R"MgX R R"
R'

O
O
R
R'
OAc CHO
O O OH-/H2O
h O O H OH
OAc OAc
O + H CH2OH
O OAc O O
CH2OH

O NaBH4
O
H+ O
O O
 a a

b' d

O R O
R
b c
R R*

A B
a' b
enantiotopic faces a,a' and b,b' diastereotopic faces a,b and c,d

non prostereogenic carbonyl prostereogenic carbonyl

Parallel approach Perpendicular approach

# Nucleophilic attack of carbonyl (half filled *) #Nucleophilic attack of alkene toward carbonyl
towards the alkene empty * half filled n orbital

# Electron defficient alkenes favored this approach # Electron rich alkenes favored this approach

# Carbon-oxygen 1,4 biradical

 Regioselectivity a closer look (Perpendicular approach)

O-.

R Radical ion pair

O O
C+.
R'
R
R
R'
R'
Exciplex C O C OR
(nucleophilic) +
C H C R'
R
R' H

# nucleophilic attack of the filled -orbitalof the olefin to the excited carbonyl oxygen (n-orbital) to form an exciplex

# the attack results either in full or partial electorn transfer to generate a radical ion pair

# the ion pair or exciplex combines to form a C-O bond resulting a diradical intermediate

# the diradical if triplet lives long and undergoes other reactions before ISC

# finally the singlet diradical closes to yield the oxetane

 Regioselectivity a closer look (parallel approach)

O-.

R Radical ion pair

O O
C+.
R'
R
R
R'
R'
Exciplex
(electrophilic) R'
O C O C
R R
+
R'

# nucleophilic attack of the carbonyl by its half filled * to alkene *

# the attack results either in full or partial electorn transfer to generate a radical ion pair

# the ion pair or exciplex combines to form a C-C bond resulting a diradical intermediate

# the diradical if triplet lives long and undergoes other reactions before ISC

# finally the singlet diradical closes to yield the oxetane

 Parallel approach perpendicular approach

A
D

* LUMO
D

LUMO
HOMO
LUMO * D
A
HOMO
n
HOMO
A
D

n* electronrich alkene
D = Donor
O
A
electron deficient alkene
A = electron acceptor
Fluorescence quenching of 2-norbornanone singlets by trans-DCE and cis-DEE

NC EtO OEt
O O
CN
"edges" "faces"
(n-orbital attack) (-orbital attack)
1.2
5.1

OR
O O O NC
1.0 1.5
OR
CN
Fast Slow

OR
O NC
O O
0.48 <0.03 OR
CN
Slow
Slow

parallel approach perpendicular approach

(-orbital attack) (n-orbital attack)
 Intermediacy of diradical explains certain facts

O O
h R H H R
+ R CHO
+
O benzene
O H
O H
Endo Exo
R endo:exo

Me 45:55
ethyl 58:42
isobutyl 67:33
phenyl 88:12
o-tolyl 93:7
mesityl >98:2

R
H

O O
ISC ISC
endo 1A H R 1B exo
H H
X X
3A 3B

Perpendicular approach
 Enantiocontrol and diastereocontrol inPaterno-Buchi Reaction

H H
O h
O O O
O O Ph
+ O Ph + O
Ph CO2R* O
H CO2R* R*O2C H

R* = (-) 8-phenyl menthyl; de>96%

R* = (-) menthyl; de 57%

O
Pri
O O
Ph
O O
Ph Me
O

one face of carbonyl blocked by the menthyl group

H
O
Ph
O
H CO2R*
OHC O O

O N O N
H H

O NR O h
O
O NR O NR O
O + O
O

O N
H

R = H acetonitrile 1:1
benzene 83:17
toluene 95:5
R = Me, benzene 1:1
O
O
H
H
N O
N O H
H NR O
O
O NHO O
O
 Intramolecular oxetane formation

O OH
O R
h
R R
R +
O R R Me
R = H, Me

O O
h
H +
O

O
h

O
O
O
O O
O h O h
Me2CO O
O

O O
h O

H
 O Ph Ph O
Ph O

h Silica gel O
O O O O

O O
h Pd
h

Me heat
O
O
azulene

O OH
h LAH
O

H H
H

OH
h HI
O
AcO AcO AcO
O
intermediate for 1 -hydroxy-vitamin D3
 O O
h

h LAH

CHO
O OH

R
O OMe R
h MeOH O
O O
O O R O OH
O

OMOM OMOM OMOM

H3 O+
h
CHO H
C6H6 OH
O O O OH
O H H
 O H H
h .01N HCl OH
Ph
H Me
+ O Ph
THF
O O O
O Me
H2, 5% Rh/Al2O3
Science, 1985, 227, 857
H H OH
JACS, 1984, 106, 7200
ibid, 1984, 106, 4186 Ph wet celite Me
Ph
O OH
O
O Me

H H
O
h O O O OH
+ H
H H
Fruit fly attractant

R
H
R H+ R
OH
O OH+
O O O
R = Me, Ph, CO2nBu
Carboxydroxylation strategy by reductive cleavage of oxetanes

R4 R4
R3 R4
h XY OX
R3 O R3
+ R CHO
R2 R2
R2 R1 R CHRY
R1 R1

O H2

OTMS Ph OH Ph OH
Ph R OTMS R OH
R

H2 HO
O

Ph O O
Ph
 Total synthesis of (+)-Preussin

HO

Ph
N
HO
O O
+ Ph
Ph H N Ph N N
PG PG PG

Carbohydroxylation strategy fo N-containing unsaturated heterocycles

H HO
O H2, Pd(OH)2/C
PhCHO/h
R Ph
N Ph R R
MeCN N LAH/THF N
CO2 Me H
CO2 Me Me
endo

H2, Pd(OH)2/C
HO
PhCHO/h O
LAH/THF Ph
N MeCN Ph N N

CO2 Me 17% CO2 Me

Chem.Eur.J, 2000, 6, 3838-48

 R 4 3 H
H1 H1
MeO2C N N
R 2 MeO2C N
H R
H2 H2
CO2 Me
A 1,3 Strain
Pseudoaxial orientation of R

Ph
H
H O
Ph O
Si
R R Re
Favored
H1 H1
MeO2C N MeO2C N
H H
H2 H2

Possible explanation for the facial diastereoselectivity

 + h

PB
COMe
O O

Et3Al

LDBB

O C 1-e reduction of C-O bond

+
AlEt3 O
AlEt3

HO

Angularly fused triquinane

JOC, 1998, 63, 5302

TL, 1995, 38, 6851
 Chiral enamides and diastereoselective PB reaction

O O

N Ph N O N O

O Ph Ph

MeCHO PhCHO/h O O
N Ph +
H2N Ph
Ac2O, TEA Ph NAc Ph NAc
O
Ph Ph

2 1

H H H H
H Me Me
Ph H Ph
Ph
N Ph
Me N H N N H
Me
O O O
O

GS conformations of parent enamides

 Chiral enamides and diastereoselective PB reaction

O O

N O N O

Ph Ph

O O

MeCH(OEt)2 PhCHO/ h O
HN O N O O +
CSA O
Ph Ph Ph N O Ph N
Ph Ph
O O

H2, Pd/C

Ph OH Ph OH
Li, NH3
N O NH2
Ph
O
 Ring opening of cis-aminooxetanes obtained by PB photocycloaddition

O LAH/ THF OH
O

Ph N H Ph
H
NHMe

OH
R1
Ph Ph
O TFA R1 O TFA OH
R1 O NBn NBnBoc O NBn
Ph Ph R1
NBnBoc
O O

H OH OH
+ Ph Ph
O H+ O -tBu+
R1 R1
R1 R1 O + NBn O NBn
Ph Ph NBn C
NBn
OtBu O
O OtBu O OtBu

Inversion occurs at this center

Tet.Lett, 1997, 38, 3707-10
 CHO
Ph OTs
h O TFA
+
NMeBoc TsCl/py O NMe
Ph NMeBoc
O

OH
LAH/THF
Ph
NMe2
Ph OTs

O NMe
OH
O NaBH4, KOH/EtOH, water
Ph
NHMe
 1 1
1
6 2

3
2 5
4 4
ortho
+ para

meta

Possible modes of addition in the arene-alkene photocycloaddition reactions

 6
meta cycloaddition C C
(3C + 2C) 1
C 2 C

prefulvene 6
C*
+

*
6 - 2
3
C 5 1

4 2
C 3
+ Exciplex

para cycloaddition
C* C*

C C
(2C + 2C)

(4C + 2C) ortho cycloaddition

Mechanistic proposal for the arene-alkene photocycloaddition reaction

 CN CN
CN h
+ +
2
5

C C C C

O O
O O

z
O z z
O O
O
z = OMe
z = CONH2, CN, Me
 C
C
R

-a

b
R
a c C C
+
R
R -b R

R
R

-ac

C C
R

R
C

Possible mode of cleavage of the cyclophotoadduct

R
H R
h H
+ R

endo exciplex
 O h
+ secondary orbital intercation is not favored
O
O due to presence of non bonded "O" electron
O

exo adduct

O
O O
O O
h O
+ O +
O

endo exo
5 1

*


 11

C 10 2
8 h 1
2 C 3
7 1 7
3
6 5 4
6 4
5
Favored

3
8 11
2 C
1 10 2
C 1
4 3
6
5 7
Disfavored 6 5 4

Isocomene

Br Li, CuI Li
+ +
Li, NH3
Br
O O

Tetrahedron, 1981, 37, 4445

 vs. h

OMe
OMe OMe
exo
endo

H OMe
OMe

favored
disfavored

O Li, Et2O
+
Br Li, NH3
OMe OMe
 Allylic stereocontrol: for the synthesis of silphiperfolene

Me Me
h
Me vs Me
H
Me H
Me
H Me

disfavored favored

h, CH3CHO

H H
O O H
HO
Me OH Me Me

PhNO2SeCN
Bu3P
H2 O2

Li, NH3(l)
H

Me H

Silphiperfolene Me

Tet. Lett, 1985, 26, 5987

 6 5 11 11
7 5 4
10 h
1
3
8 4 OAc
1 9
2 3 2
OAc 9
Modhephene

H H

H CO2 H
hirsutene
-cedrene retigeranic acid
O

O H HO2 C
O
O
O
O O H
OH
3-oxosilphinene subergorgic acid
isoiridomyrmecin coriolin

HO JACS, 103, 688, 1981

OH
O Tet.Lett, 23, 3983, 1982
ibid, 31, 2517, 1990
O ibid, 24, 4543, 1983
ibid, 24, 5325, 1983
ibid, 31, 5429, 1990
rudmollin ibid, 27, 1986, 1857.
 O Li, Et2O C*
h
+
NH3 C*
Br

Li, NH3

Silphene
 h C LAH
+ OAc OAc
O
OAc C MnO2

Me Me Me Me
LDA, -780C Me2CuLi, THF

MeI
O
(Me2N)2POCl
OR + OR
Me

H2, PtO2

Me
O3, MeOH O NaBH3CN
OR
NaBH4 O
Me Me
OMe

O
Me
Iso iridomyrmecin
 CHO

NH3+ O3, DMS OH

+
CO2-
CHO CHO

Br O O
Zn(BH4)2
TsCl, PCC O NBS, AIBN H2, Pt
O KOH

OTs
OTs
O O
O O O O O OH
LDA, DMPU
h

O
Li, MeNH2 O P NMe2 Li, EtNH2
O
NMe2
KHMDS Me2N P O
(Me2N)2POCl NMe2
Laurenene
 h C
h
C
HCONH2

OHC +
C*
H2 NOC H2 NOC CO2 H
C*

4+2
HO2 C R2 NOC
R2 NOC

Retigeranic acid
(Ph3P)3RhCl, H2
Br2, AcOH
O KOH

CO2 H
Ph3P+CH3Br-,
nBuLi

(-)-Carvone
 Li, Et2O PCC
h, 3C + 2C
Br CHO EGC/CSA
O
OH O

C (PhCO)2O, h
K, 18-C-6
C NC O
O O CH3CN
O
O O

OH
O Cl
mCPBA LICA, THF SOCl2
O O O

O O O
O

HO
NaClO2 HO2 C

O O

Subergorgic acid
 Seven membered ring synthesis based on arene-olefin cycloaddition

OMe OMe
H H
h, 3C+ 2C Hg(OAc)2
OH O
OTBS
OH
THF, H2O
OTBS OTBS

NaBH4
MnO2,H2 H H
H
(PhCO)2O OR MsCl, Pyr
OR
O OH
KHMDS, allyl-I LAH, Heat
OTBS OTBS OTBS
OBn
OTBS OTBS

H
H H

O O
O
OBn CO2 H O HO
OBn O O
OH

O
HO
OH O
Tet. Lett, 1986, 27, 1857
Rudmollin
 OAc OAc
OMe OAc OMe
OTBS OMe OTBS
h
OTBS
C C

OAc PhSeCl
OMe
OTBS C*
OAc OAc
C* H
H

OTBS OTBS
OTBS Cl
O O
O Cl

KOH

O
O H
H OH OTBS H
HO
OH H OMe OAcOTBS OMe OAc
OTBS
OTBS OH
OH
O Grayanotoxin

Disfavored Favored
 COX
COX R R ClOC
h R
R R
R

X = OMe, R = Me

O
O
COCHN2
R
R
R
R

Fenestrane derivative

Tetrahedron, 1985, 41, 5697

 OMe
OMe
C OMe

+ .
X
X
X
X OMe
Si-face of olefin in exo-adduct
(Re-face in endo-adduct)

Introduction OMe
of PD tether C
OMe
.
X

X
X OMe
Re-face of olefin in exo-adduct
* *
O O (Si-face in endo-adduct)
6-substituted 7-substituted

O O
O OH OEt O O

Hg(OAc)2

OH
HO OH O O
O OH
+
 O Rn Rn O

O O O O
O
O
2R + + 2S

O O O O
O O
O O

Rn Rn
Si- face attack to the olefin Re- face attack to the olefin

Stereochemistry at 2- position is important

Abolished stereochemistry at C-2

O O
C C Abolished stereochemistry at C-4 O
O O C
C C
O
C
Re-face Re-face
 MeO MeO MeO

OMe CuCN
9-BBN

MgBr Cy-hex-2-enone DMP H

MeLi, allyl-I
L-selectride OH OTBS O OTBS

MeO OMe
MeO MeO

MeO
OTBS
OH OTBS OH
OTBS
endo (favored)
exo ( disfavored)

OH
HO

HO
H H
OH
aphidicolin stemodinone
 Norish Type I Processes of Ketones
Basic Concepts

O O
h C
+ C
R
 O O O

2 X 106 3 X 107 1 X 108

O O
O

2 X 107
2 X 108 1 X 107

O O
O

OMe
7 X 105 >109
not measured

# Norish type I reaction is much faster for n-* compared to * excited states

# n-* reactivity is due to the weakening of the -bond by overlap of this bond with the half
vaccant n-orbital of oxygen.

# This overlap is not possible for * excited states

# Electron releasing group at para position lead to stabilization of * excited states hence decrease in reactivity
 R
R

R1
R1 .

C C

C C

O C C
 O O O

K 3.3 x 107/s 4.7 x 108/s 1.8 X 109/S

O* O*
O*

< <

Rate of cleavage increasing ring strain

 Intermediate trapping experiment

O O O
Me
C NO
h C NO

acyl-alkyl diradical

O O
O O
h C
-780C C C
C
O O
h O
H
C Me
Me C H
C H
C Me
Ph Ph
Ph

retention disproportionation

O
H O
Me
Ph H H
H
racemization
Ph H
O O O O
C C
h C C

O O O O
C C
h C C
 O O
recombination

(CH2)n (CH2)n

h
decarbonylation
C C (CH2 )n-1 CH3
(CH2)n (CH2)n
+
O (CH2 )n-1 CH3
C
C O
disproportionation
(CH2)n H
enal
(CH2 )n-1

O O
ring expansion ROH
OR
n
n

ketene

C OR
O
ROH O
(CH2)n
(CH2)n
oxacarbene
 C
O C O
C C

O O O C
h
C ring opening C
C
-cleavage

cyclization

O O
ring opening and cyclization
 O h O O
C
(CH2)n (CH2)n (CH2)n

ROH OR O

(CH2)n

O O O
h C H
C

OMe
C MeOH
O O

O OEt
O C O
O h O EtOH O

O O O O
O O
 O O* O*
h C C
+ CO
C C
S1 (n-*)

Ring expansion

Oxa carbene
O
.. cycloelimination

ROH + O

O OR
 O
O
O
h
O
.. O
O

O
OH R1 O R1 H
h O
.. HO O
R1 CN R2 R2
CN CN
R2
H

E Ph Ph
Ph Ph Ph Ph
Si O Si
h Si E O E
O ..

E
 O h O h

MeOH
ROH

O O h
h
ROH
tBuOH

S h

S
MeOH
 Me O Me Me
Cl Cl Zn O Zn/Cu O
+ Cl +
OTBS COCl
NH4Cl
OTBS OTBS OTBS

3 1

O OMe O CN O CN
TMSCN
h/ MeOH +

OTBS OTBS OTBS

1 1

BH3:SMe2 BH3:SMe2

O O
N+Me3 I- MeI O
NH2 NH2

HO OTBS OTBS

Muscarine
O
N+Me3 I-

HO
Tet.Lett, 1988, 29, 159 allo-muscarine
 NaOH O2, h O O H2, Pd-C
OH
+
Cl Rose bengal O
Cl TBSCl

NaOAC/EtOH

O OTBS O h MeO2C O OiPr LAH

OTBS

iPrOH PTSA
MeO2C
OTBS

SiMe3
O OR
O O OR
OMe OMe OsO4, NaIO4 O
OMe

BF3:OEt2 O
OTBS TBS-Cl OTBS
OTBS
OR
O PhCOCl
LiAlH(OtBu)3 OMe NaH, MeI F-
OH H2

OTBS
BzO
O
OMe
OMe

OBz
J. Org. Chem. 1987, 52, 2335
Pederol dibenzoate
 OH OH O
h
O O O
C

O
OH
OH
h O
Wittig R'

R R
HO R
OH OH

R' = CO2H
R=
OH

OH OH
O O C O O
h
C
H
+ H
R
OTHP R
R=
 O O
O
O O
MeCO3H LDA, PhSeCl Me2CuLi
H H H H H
Bu H2 O2
Bu Bu
OTBS OTBS OTBS

O OH

O O
DIBAL-H
H Me H Me +
CO2- Ph3 P+
Bu Bu
OTBS OTBS

OP CO2 H CH2N2 OP CO2Me

h, MeOH
H Me H Me
HF, MeCN
Bu PCC Bu
H2, Pt/C
OTBS O

CO2Me OP OH
OP
H Me
(CH2)6 CO2Me (CH2)6 CO2Me
C Bu ..
C MeO O Bu
O Bu
O
Thromboxane analogue
 Norish type II photoelimination of ketones:
Cleavage of 1,4-biradicals formed by -
hydrogen abstraction
 O 1 O*
h
R' R'
R R

R'
1 O* 1K OH a OH R'
H
R'
R R R
n

1 O*
1K
d O
R'
R R'
R

1 O*
3K
Kisc 3 O* d O
R' R' R'
R R R

R'
3 O* OH R'
3K
H OH
R'
R R R
n

OH
R'
O R
R'
R
 S1 (n-*) T1 (n, *)

H H H
O C O O
C
C C racemic
Ph Ph Ph
H
O

Ph
optically active O OH
Ph
Ph

# Yang cyclization

# cleavage

# hydrgen reversal
 Solvent effect

Ph Solvent Ph Ph
C H C
solvent OH racemization
O O
H
C C
R' R R'
R R R'

O
R
+
R'

O
# racemization is suppressed in H-bonding solvent
such as t-BuOH

# With H-bonding solvent conformational change of bi-radical

valerophenone occurs hence influence the decay process.
n-* O
OMe
O* 2X107

O
O

107 108

OMe O O
O
1X105

O* MeO
*
 Conformational effects

O O
h
+

trans-4-tert butyl-2,2-di-n-propyl cyclohexanone

h

no -further reaction

O Ph HO
Ph
h

h
Ph PhCHO

O
 O Ph
105/s
Ph

h h

O
H O*
Ph 105/s K cleavage = 2.5 x 107/s C C
Ph
KH = 1.7 x 108/s
+
O*

CHO
HO
Ph
+
 H
O
H
O

H
O Ph
7 X 109 KH
1.3 x 108 6 X 108

# Restriction of conformational freedom plays important role

#The mobility of parcipating molecules (carbonyl compound and hydrogen donor) is severely restricted at the TS
during intermolecular hydrogen abstraction process.

# the more freezing in bond rotation is higher the rate of H abstraction

 OH OH
OH
R R
R
.

H OH
HO
O
R

R +

1,4 diradicals as intermediates in -hydrogen abstraction

 H R2 R2 O
OH C R2
O h -HX O C
C R R2
R R1 ISC R R1 Spin center shift R C R1
X X
R1

X = OAc, OTs, OMs, ONO2

O
H h
O Ph

Ph
OMs

H O
O h
Ph
Ph
OTs
 Photoenolization

R R R

H-Transfer OH O
O
H spin-inversion CH3

R
R CO2 Me R OH
CO2 Me CO2 Me
OH
+
CO2 Me CO2 Me
CO2 Me
 H H

R R R
Ph Ph Ph

O O* OH

H H D

R'OD R R
R
Ph Ph Ph

OH OD O
 Me
.
h

O OH
C

Ph Ph

Me
.

OH
C Ph
HO
Ph
OH

O Ph
OH
Ph
 Synthetic applications

OAc OAc
OAc
O
O h O
O
OAc OAc
OAc
O
O

CHO

O O
O

N
N h

O O

O O
 O OH O
h (-)Ephidrine

Norish II, Cleavage Enantioselective

H-transfer

O O
O O
O CO2 Et
O CO2 Et
h 4+2
OH
O O
O
Photoenolization

MeO OMe
MeO OMe
OMe
OMe

O O
O

CO2 Et
O OH

MeO OMe
OMe

Podophyllotoxin derivative
 Norish type II process involving 1,6 and greater H transfer reactions

OH O OH
1, 7 H abstraction
C 1, 5 H abstraction C
T1
C C

OH
OH
S1

Photocyclization of cyclodecanones

Ph Ph
Ph Ph
C
O O
OH
O h Ph n
Ph nC
n OH
O

n = 0, 1
photocyclization of -[o-(benzoyl) phenyl ] acetophenone
 O O O

h
OH

H H
O O O O
C C

C C
n

photocyclization of o-methylphenyl 1,3-diketone

R R R
OH Ph
C C Ph
O h OH

O Ph

photocyclization of o-benzyl substituted ketones

O HO
OHOR
OR
h
O
OO O O O
OR
 Long distance H abstraction

X X O
Ph O O
h
O
OH
O 1, 9 H
O O Ph

h X 1, 5 H

X O X O
X
C Ph Ph
O C O C
O C O
O H O H

X = H or D

Me
n
Me (CH 2)x (CH 2)y
O O O
h
HO
Ph O O
Ph
n = 12-18

Remote oxidation of unactivated methylene groups

 O R
R OH
h R = H, Me

O O

Ph Ph
h OH

O
O O

Photochemical synthesis of tetrahydropyran-3-ols and benzopyranols

 h

n=1
O
(CH2)n O
(CH2)n
O
O

O
HO

h
n=2

O
O
(CH2)n
(CH2)n
O
O

HO
HO

Remote oxidation and photocyclization of steroids

 The -cyclopropane rearrangement

Ph
h
Ph

Ph Ph
Ph Ph

O
Tol
h O
Ph

Ph Ph
Tol Ph
Ph Ph C
h Ph
C
Ph Ph Ph Ph
Ph Ph

Ph Ph
h Ph
..
Ph Ph
Ph Ph Ph Ph

The basic reaction mechanism; singlet mechanism

R2 R2
R2 C
h
C
Ph R1 Ph R1
Ph R1

R2 R2
h R1
..
Ph R1
Ph R1 R2 Ph
 The triplet rearrangement

a
Ph Ph
C Ph C
h
. b Ph
sens C
Ph Ph Ph Ph
Ph Ph
Ph Ph

a
Tol Tol
h C Tol C Tol
a
. b
C
Ph Ph
Ph Me Ph

b Me

Tol Ph
 The triplet rearrangement of 3-phenyl regioisomer

a
Ph Ph
C Ph C
h Ph
. a
b
sens C
Tol Me Tol Me
Tol Me
Tol Me

Ph Tol
 The triplet rearrangement of 3-methyl regioisomer

a
Me Me
C Me C
h Me
. a
b
sens C
Tol Ph Tol Ph
Tol Ph
Tol Ph

Ph

Me Tol
 Proof of cyclobutenylcarbinyl diradical as an intermediate

a
Ph Ph C
h
N . b
-N2
Tol N a
Tol

b Ph

Tol

Ph Tol
 The acylcyclopropene triplet rearrangement

O a
Tol O O
Tol Tol
h b
C .
sens
Ph Ph Ph Ph Ph Ph

b a

Tol O Me

O Ph
Ph Ph

Tol Ph
 The Di- Methane Rearrangement

C
h

C C C

h C
Ph Ph
C C C

Barrelene Semibullvalene

Chem.Rev; 1996, 96, 3065-3112

 Reaction regioselectivity

C
C A A B B
Ph
C
Ph C Ph C C
Ph
Ph Ph
h

Ph
Ph

Ph
Ph
Ph Ph
Major
Minor
# Stabilty of benzyhydryl biradical

# More available electron density for ring opening

 C
Ph C Ph C
Ph C Ph
Ph Ph

C C
Ph Ph
C
Ph C Ph
Ph
Ph

Ph

Ph
 Electronic factor on regiochemical outcome

h
+ NC
Ph direct NC
Ph CN
Ph Ph Ph Ph

h
Ph + Ph
Ph OMe direct
Ph Ph Ph
OMe MeO

# there is a strong tendency for electron donors to appear on the residual - bond of the photoproduct

# and for electron withdrawing groups to be found on the product three membered ring
 Reaction regioselectivity

CN
CN
Ph
Ph
Ph

Ph

CN
CN

OMe Ph
Ph
Ph Ph

MeO OMe
OMe
 Multiplicity control of regioselectivity

Ph Ph
Ph Ph Ph
C Ph s s t t C
Ph CO2Me
C CO2Me C C Ph C
Ph CO2Me
Ph CO2Me Ph CO2Me Ph CO2Me

Ph Ph
Ph Ph Ph Ph
Ph
CO2Me Ph
CO2Me Ph CO2Me
Ph MeO2C CO2Me
CO2Me
Ph Ph

S1

S1
2K
E 2K

T1 T1
Large K vs. small K control of excited state selectivity
 Effect of excited state multiplicity on reaction outcome

h, Direct Ph
Ph

Ph
Ph

Free rotor effect

h, sens Ph
Ph

h, sens

2,3-naphthobarrelene

# di--methane triplets which have double bonds not incorporated in a ring structure or not inhibitited from free rotation
in some other manner are commonly unreactive.

# In contrast cyclic di-enes tend to be perfectly reactive as triplets, and this can be ascribed to their inability to undergo
free rotation in the excited state.

# If rate of radiationless conversion of the triplet reactant is slower than the rate of reaction, despite in the presence of free
rotor group, triplet reactivity in an acyclic system was observed. Generally in this case free rotation is inhibited by effects
such as steric hindrance, so that the triplet may be reactive.
 h, sens Ph
Ph Ph Ph
PhPh
Ph Ph

# The original generalization is that cyclic molecules are more likely to react successfully from the triplet
excited state via sensitization while acyclic molecule tend to perform better as singlets (obviously in the
case of triplet reactivity absence or presence of free rotor is important).

h, sens

h, Direct

# For many cyclic molecules, direct irradiation with formation of the singlet excited state does not lead to a
successful di-p-methane rearrangement. This behaviour arises not because the singlet excited state is incapable
of a di-p-methane rearrangement but rather because many cyclic systems have potentially available facile alternative
pericyclic process which competes all too successfully.
 h

MeO
h
MeO

MeO Minor Major

h
NC

NC
JACS, 1977, 99, 3723-33
 The Oxa-di--methane rearrangement

Ph H H
Ph
Ph Ph
h
Ph
Ph O O
OPDM Ph H
Ph

O C
O
O C
O

C
X O

O
 OAc OAc
OAc

h, Direct
+
O O
O O O
CD3 CD3 O
CD3

h
Ph
O Chrysene/sens.
Ph O
racemization
 Retention of Configuration

Chrysene Sens.
O O

Chrysene Sens.
O O
 Inversion of conviguration

H
CH2 CO2 H
CH2 CO2 H h

O acetone snes.

O
O tBu O
H
But h
tBu tBu
H Direct H H
O tBuH
tBu

O
O R2
R1
Me h
R3
R2
acetone snes. R1
R3
Mechanism I
 The OPDM rearrangement of acyclic -unsaturated ketones
Key structural features favoring OPDM

# Conjugation of the alkene moiety with phenyl, vinyl or oxo groups (efficient triplet energy transfer,
biradical stabilization)
# disubstitution or alternatively, monosubstitution by bulky groups at the central carbon

O O O
D Me O O

Ph Me
O
Me O O O O
Me Me Me Me

O
OH OEt
Me Ph Me Me O
O O O
Me Ph O

Me
O Me
Ph Ph
O
Ph O
O O Ph Ph
Ph Ph

Unreactive towards OPDM

 O O O
Ph Ph Ph

Ph Ph

O O
Ph Ph O
Ph

Ph
O
O O
Ph
O
O

# The cental methylene carbon is di-substituted or having bulky mono substitution

# Conjugation with vinyl, phenyl or carbonyl groups
The OPDM Rearrangement of cycloalkenyl -unsaturated ketones

O
h

n O n

n = 1, 2 n = 1, 2

X
O
n

n = 1, 2, 3
O
h

O
 The OPDM rearrangement s of monocyclic and
condensed polycyclic -unsaturated ketones

O
O

O
O O
O

O O
O O
 O CO2 Me
O CO2 Me

O O

+
O
The OPDM rearrangement of Bridged cyclic -unsaturated ketones

R
O
R2
h, sens

R1 O

R1 = Me, R2 = H
R1 = H, R2 = Me
R1 = R2 = H

O h, sens
O

O O
h, sens
 Synthetic application of OPDM rearrangement

OMEM

Me H
OMEM

O
O

h/ sens

O OMEM

7 steps H
H

(-)-Silphiperfol-6-en-5-one
 CO 2Me
h CO2Me
MeO2C
O
Sens
MeO2C O H

O O
OH

Cedrol

Tetrahedron, 1981, 37, 4401-10

CO2Me CO2Me
CO2Me CO2Me CO2Me
CO2Me
O O
O
H OH
H H H

O O
CO2Me
CO2Me
COMe
COMe

OAc
H
H
 O
NC Cl
+

h/ sens

(racemic)-modhephene
 OPiv
OPiv OPiv
Li/NH3
h/sens Ac2O, DMAP/TEA
O
OPiv
O H

OAc MeO
O
OHC

Swern
O O O

H H H

O MeO
O O O
O

CO2Me OTf
CO2Me
H H
H
Pentalenolactone P methylester

JACS, 1992, 114,7387-95

 OH O
O OH OP
HO
+

HO
O

h
acetone

H
O

OP H

(-) Hirsutene

PT (1), 2002, 2439

 HO O OH
OH h (Me3Sn)2

sens
O
3-OH-Peristylane

R R
h
O R = CH2CH2OMe
Acetone/iPrOH
MeO O
O H
- Me

R R R

H Donor
O O OH
C C
O H O H O H
 O
b
O O
O
h
O O
O
a

O O
OH O
O

O
OH
OH

(-) Coriolin

O
Competition between all-carbon DPM and OPDM rearrangement

b
a

O O
h h

O O

a = benzo vinyl
b = keto vinyl
 O

O
DPM

vinyl-vinyl > keto-vinyl > benzo-vinyl

MeO2C
CO2Me
MeO2C MeO2C
O O
O
MeO2C O
H MeO2C H O
O
DPM
ODPM Not observed

O
O
ODPM
 O O
O
O DPM X

R X O
R
O

Benzo-vinyl > keto vinyl

O O

. C O
C
O

R X R X

Stable biradical O O
 The OPDM rearrangement of -unsaturated aldehydes

OAc
H
O
H h

Direct or sens
+ +
O O O
O CHO
OH

h, sens
H
Ph
Ph O CHO
Ph Ph

h, sens
H H
Ph
Ph O CHO
H H
 CHO
CHO
h, sens

CHO
CHO
h, sens

CHO CHO
H
h, sens
n
Ph Ph

n = 1, 90%
n = 2, 25%
n = 3, 25%
 Direct
CHO
Ph
h

Ph CHO

Sens
CHO +
Ph
Ph

CHO

CHO

CHO
O
O
h CHO O

R
R = H, Bioallethrin
R = vinyl, pyrethrin
 The Aza-di--methane (ADPM) Rearrangement

h, sens Ph H3O+ Ph

Ph N
Ph Ph Ph Ph
N O
Ph

*T1

h, sens Ph
N C N
Ph Ph R N
Ph Ph R Ph R

Ph N
Ph C N R R
Ph
N Ph
R Ph Ph
 N
Ph Ph R N
Ph Ph Ar

Ar = Ph
Ar = 4-OMe
Ar = 4 Cl
SET Ar = 3 Me
Ar = 4 CN
-.
N
N Ph
Ph R Ph +. R
Ph

N Ar
Ph Ph

Ar = Ph
Ph Ar = 4 Me
Ph R Ar = 4 Cl
C N Ph Ar = 3 F
N Ar = 4 CF3
Ph R
 N N
Ph Ph OH Ph Ph OMe

SET from "N" lone pair to the alkene moiety is restricted due to low IP of oxime and oxime ether

h, acetophenone sens
Ph
N
Ph OAc Ph
Ph N
OAc

IP of the oxime can be raised by incorporating Ac group

 N
OAc

N
OAc
N N
OAc OAc

N
OAc
N OAc

OAc
N N
OAc

H
N n
n OAc N OAc

n = 1, 2, 3
 Photorearrangement of cyclohexenones

O O
2 h 2
5 3
5 3
R R
R R
4 4 Type A
OAc

OAc

h/ tBuOH

O
O

O
Ph H
h Ph
O O
+
Ph Ph Ph Ph

h O O
Type B +
Me Me
Me
 Mechanism and stereochemistry of Type A rearrangement

R1 R1
R2 R2

O
H H
O

R1
O
R2

H H
O
H
R1 H R1 O
R2 R2

O
5

2
3
R1
R2
4
 Inversion occurs at C-4

Me
Me

O
O

O O O
hn

+
Me nPr Me nPr
nPr Me
Inversion occurs at C-4

# Cleavage of the bond between C4 and C5 of the enone is concerted with dformation of bond
between C3 and C5 and C2-C4.

# In a formal sense the reaction occurs with inversion at C4 and retention at C5

# In a fuse ketone the rearrangement occurs on only one face of the enonebcause of steric constraints
(i.e, the necessary of cis-fusion of the cyclopropaneto both five and six membered ring), hence yielding one product.
 R R
O
O
h

R R No reaction

R = Me
R=H

O
Twisted ( around C=C bond) relaxed excited triplet state of ketone
 Competiting reactions

O O O O
h
+
C +
C

AcOH

OAc
 Mechanism and stereochemistry of Type B rearrangement:
Aryl and vinyl migration

O O O

hdirect H H
+
h-sens Ph H

Ph Ph H Ph
Ph Ph
Major (endo) Minor (exo)

Ph
C
Ph H
Ph
 O O
Me
h
H O
Ph
Me Ph H Me

Ph
H O
X

Me

H
H O Ph
Me C O
Me
Ph
 R R R R

Ph
Ph Ph
Ph

R
R
R C
R C

+
C

Ph Ph Ph
+
C
 Photochemical cycloaddition reaction
(enone olefin cycloaddition)

O O

h
+

ISC
alkene
1(enone)* 3(enone)* 3(enone-alkene)*

Exciplex

biradical
enone

cycloadduct

Chem.Rev; 1988,88, 1453-73

O O
W X
ISC O
z Y W z
n n
n Y X
hn Exciplex

O O
n
+

n n

Reversion
ISC

O
O O

+
n
n n
O

H h
C closure
CHO

C CHO
fission

abstraction

O CHO

furopelargone
 Regiochemistry of enone cycloaddition

O CN O OEt O
CN

OEt

OEt OEt
O
-
head to tail
O - O

OEt
h

- CN N O
CN
head to head
reversal of polarity
 OAc
O O
OMe OAc
+
O O
OMe
98% 96%
O O O O O
OAc nBu
+
nBu
nBu nBu OAc
only 81 19
O O O
CO2 Et OEt
CO2 Et
OEt
+
OEt
EtO OEt
OEt CO2 Et
82.5 17.5

O O O
SiMe3 SiMe3
SiMe3
+
1 1

O O O
O O O
O
+
OAc OAc OAc
O O
95 5
 X

X=O
head to tail
O
O
O

O O O
OEt
CO2Et CO2Et
OEt
+ OEt
EtO OEt
OEt CO2Et
RT 82.5 17.5
O -40OC 94 6
O O O
OEt
CO2Et CO2Et
head to head OEt
+ OEt
EtO OEt
OEt CO2Et
RT 83.5 16.5
-40OC 91.5 8.5
O O O
OEt
CO2Et CO2Et
OEt
+ OEt
EtO OEt
OEt CO2Et
RT 71 29
-40OC 100 0
 O O O
OAc

O
OAc

h OAc

K+ Aqueous phase O
O
K+
O O O
O O

nHex nHex

nBu nBu

O
O
O nBu
O

nBu Micelle core

nBu nHex nHex

nBu nBu cyclohexane 53: 47

nBu
micelle 88 : 12
cyclohexane 51: 49
micelle 78: 22
 Stereochemistry of enone cycloaddition

O O O O
Y Y
+ + z
a b z
Y Y
X X X X

1. ring junction stereochemistry 1. ring fusion stereochemistry

2. exo or endo (Y) 2. stereochemistry of a wrt b or vice versa
3. cis or trans with respect to each other (y) 3. Remote substituents effect (X and Z)
4. effect of remote substituents X

O O O O
O

+ or or or

always cis ring fusion O

O O always cis ring fusion

Y Y
+ O O
H
Y Y Y
Y
+
can be cis or trans
cis is favored R Y Y
R
rigid cyclohexenones always cis fused ring junction
(presnce of heteroatoms,
fused ring)
 O
H

always cis

H
O
O
H

always cis

O
H

O
H

H
Regiochemistry of the intramolecular [2+2] photocycloaddition of 1,4; 1,5 and 1,6 dienes
"Rule of FIVE"

h C

C
h

C
 Intramolecular enone cycloadditions

O O
OMe
HH : HT = 0 : 100

OMe h

O O

HH : HT = 26 : 74
h

O O

O*
HH : HT = 70 : 30
O h d+ d-
O

O d- R
O d+

HH : HT = 87 : 13
h Me

O
O O
R
C
C
OMe HH : HT = 100 : 0
h

OMe
 enone cycloadditions in organic synthesis

h H
MeOH H

O O
O H
OMe
hirsutene

O O

h Ph3P=CH2
TsOH

isocumene

O O
H H H H OH
h MeLi H+
+ OH

H H

-caryophyllene alcohol

O O
vinyl chloride, h O
CO protect TsOH
Na/ NH3, H+
Cargill rearrangement
modhephene
O O O
H h H
+ H
+
H
H H

MgBr

O
O
HO
H KH
H

H H 18-C-6 H

thermal ring opening

O
O O

O periplanone B

Tet. Lett, 1981, 22, 4651

 O O O
N N
h N
O O O

O O
H H

+
MeO2C MeO2C
MeO2C
OH

MeOH/H+

H H

(-) Grandisol

CN HO
JACS, 1986, 108, 306-307
 O OP
O OP

SnMe3 -allyl Stille cross coupling OP

OAc OP
+

Intramolecular 2+2
photocycloaddition h

OP OP
O O
X OP Fragmentation
elimination OP

enolate trapping

OP O CHO
O OH
OP
AcO
Guanacastepenes

Guanacastepene A
JACS, 2006, 128, 7025-35
 O O
NOR
H

H
N N
O
CO2Me CN H
H
O

H
O
Dendrobine
 O
O
TBHP, SeO2
h
NCS, DCM Cl

O O O
H H H
Cl Me
Li, NH3 LTMP, MeI

H H H

O OEt

O P OEt
Me
LDA, ClPO(OEt)2 Li, NH3
H

Acoradiene

HCA, 1983, 66, 522

 O
H H
MVK, Pyrrolidine
(CH2 )n h
(CH2 )n
(CH2 )n
O O
n = 1, 2

[6,6,5,4] Fenestrane

h
CO2Et O O

NaH, HCO2Et
h

TSN3, TEA O
CO2 Me
N2
[5,5,4,4] Fenestrane ester
Tet. Lett, 1982, 23, 711
 SiMe3

CO2 Me

CO2 Me
h
O
O
O

CO2Et
LAH, Swern CO2Et
Li, NH3

O
Ph3P=CHCO2Et H2, Pd/C O

Laurenene

JACS, 1987, 109, 6199

 De Mayo Reaction

O h
O
+
OH O
OH

O
h
OTBDPS OTBDPS OTBDPS
O TiCl3
O

aq. HF

Azulene intermediate

CO2Me
MeO2 C CHO CO2Me
R1 h R1 R1
CHO
+
O
R2 H OH R2 R2
OH
OH
methyl diformylacetate
tetrahydrocoumalate
 OH
H
HO H h HO O
+ OAc OAc OAc
OHC
OHC CO2 Me
MeO H
CO2 Me
O
loganin aglucone acetate
H OH
HO H h
+ O HO O
O O
OHC
OHC CO2 MeMeO OMe
H OMe
MeO O CO2 Me

O O
O

CO2 Me

Sarracenin
 O
O O HO O

h
OH

cis fused

O acid or base
OAc O O
O
base
trans fused
h
OAc
O

O O O O
H
Cl Cl Cl
h base
+

Cl Cl Cl
OAc OAc
O HO
 O O O
CO2Me CO2Me
h
+
Cl HO
OAc Cl CO2Me
CO2Me OH
MeO2 C CO2Me

O
O OAc
O OAc
h
+
OAc
O O
O O OH
O
O
H

H -himachalene
O O

OAc
O O OAc
O O OAc

h
O O O
OAc
 O O OH
OAc
OAc h base
+ CO
MeO

Pb(OAc)4

O
O O
O h O
O
O +
O O
CO2Me
HO CO2Me HO CO2Me

O
O O
OHC
OAc h base
+
OHC
CO2Me

HO O
methyl isomarasmate
CO Pb(OAc)4 O
CO2Me

acorenone
 Non symmetrical -diketones

O OH O O OH O

Ph Ph Ph
major

O OH O O OH O

CH3 CH3 CH3

O OH OH O
O O
CO2Me CO2Me
CO2Me

OH
OHC CHO
OHC CHO OHC

HO OMe CO2Me CO2Me

O OH
O OH
CHO CHO
O HO
O N
h
+
O O O

O CHO NC
O
h
+
OH HO

O O
O
O h DIBAL-H
O
+
O CHO
O

CHO
h X
+
OH
OBn OBn OBn
OAc OAc
OAc O
h O O
+
O
O
O O

OH OBn
OAc
CHO
OH
genipic acid
OMe
CO2 Me
O

O
O
NMe CHO
N
NMe O h
N O
CO2 Me
CO2 Me CO2 Me
+ X
OH h OH
 OH h OH
CHO
+
O O O

valerane isovalerane

OH
h CHO
O +
O
O
 1,3 -dicarbonyl compounds (intramolecular De-Mayo reaction)

O O O
(CH2)n
(CH2)n
(CH2)n
X OR OR

X = O, NR

O O

O (CH2)n OR
(CH2)n

Different templates
 O
OH O O O
H
HO2C h, MeCN
DCC
O
O + O
OTBS
O OTBS O O H
OTBS

O O OH
H
H
O
O
MeO
H MeO
OBn H
OBn

O
H H

Stoechospermol
H H
OBn

Tet.Lett, 1985, 26, 3035

 O OH
O

O h

O O O
O O

O O OH
O H H O
CO 2 Me O

O O O
O O O

O
H
O
H
O CO 2 Me Methyl ester of Pentalenolactone G
CO 2 Me
O
O
O O
O JOC, 1988, 53, 227
 Intramolecular De-Mayo reaction

O
O
Ph
COCl N
O O
h
+
O O

O
OCO 2 Ph
OH-
O

Longifolene JACS, 1978, 100, 2583.

O
O
h HO OMs

OAc
OAc OAc O

-bulnesene

O
 O HO
O TBS-Cl, h/Pyrex Me3CuLi2

OTBS
O OTBS

O Me
HF, THF, H2O Ph3P=CH2 Me BF3:OEt2

Me
RhCl3, 3H2O
Me

Me

Me Me
Me

Pentalene
 O O OAc
Ac2O
+
O OAc O

O
O O
O

+
O
OAc OAc
O

OTs
O O O
L-selectride
KTB

Ts-Cl
HO
HO
 Dioxolenones as -keto ester equivalents
O
O
O
h, acetone O PTSA/MeOH CO2 Me
O
O (CH2)n
(CH2)n
O (CH2)n

O O
O
O O PTSA, MeOH OTBS CHO
h
O O
DIBAL-H
OTBS
OTBS cis:trans = 4:1

OTBS O O H O O
Trans Cis
H O O
OTBS
 O O O O
h PTSA/MeOH
O O

H CO 2 Me H

O O

H H

Smallest known inside-outside bicycloalkane

 O
O O
LDA, MeOPhOCOCN Ac2O, TFA
O OMe
Acetone

O
O h O KOH, MeOH
O

O
O

O O

CO 2H
Ingenane skeleton
 MeO 2C MeO 2C
O
HN HN
O h, MeCN O

O O
O
O O O O

NaBH4
CO 2Me MeO 2C
HN HN
HN
O
NaH
O O
OH O OH O
O
Perhydrohistrionicotoxin
O O

h
+
O O

HO

O
O O

RuO4 KOH/H2O
O
O

O CO2H
O

synthesis of Taxane sceleton (Chem. Lett, 1985, 323)

O O O
H H
h

O O O
O
O OTMS
H nPr
nPr nPr HCl, H2O
TMSOTf

O O O
 O O
MeLi HO OH
O O

h HO

grandisol

O O O
O
OH

h HO2C

fragrantol
O O O OH

O
OH

O
HO2C
 O O O
OAc
OAc h
+ +
OAc

O
OAc O O O
OAc O
+
OAc
78
22

OSiMe3
OAc
O MeMgI O
HO
O O CHO
OAc CO2 Me HO H O OH
n

O
lineatin
O
 CO2R
O O CO2R
CO2R

+
h
H H

O
OH O P OEt
OH OH OH
OEt

H
H
epijunenol

O O O
OH
+
h H+ C
heat
+ OMe
MeO OMe
OMe OMe
OMe

OMe OHC O

CO
OMe CHO
O sativine
helminthosporal
 Copper (I) catalyzed intra and intermolecular photocycloaddition of alkenes

h
M + S M-S M + P

MLCT

*
4s (-acceptor)

3d (-donor)
LMCT

molecular olefin orbitals

copper orbitals
orbitals

Schematic energy level diagram for copper (I)-olefin coordination

 +
Cu
Cu
. + Cu

h, LMCT

+ +

Cu+ + Cu+
Cu+ -
-

h, MLCT

.
Cu++
Cu+ +
. . Cu
-
CuOTf, h

trans fused

CuOTf, h
+

trans fused

h
CuOTf

CuOTf
trans fused

+
1,3 H shift C - Cu+
+
C
Cu Cu
 CuOTf, h
O O

CuOTf, h
HO HO

O CuOTf, h O The observed selectivity is assumed to arise from

a preferential formation of the less sterically crowded
copper (I)-diene complex, leading to exo pdt.
H H
exo pdt

O
NaIO4/RuO4

O O
 Cu+
OH Cu+
OH

HO HO
H H

H H
exo
endo (favored)

HO Cu+
HO
H
Cu+

HO HO

endo exo (favored)

 OH OH

CuOTf, h

-panasinsene -panasinsene

HO HO
CuOTf, h

H
CuOTf, h
HO HO
HO

grandisol
HO HO
CuOTf, h
MeO OMe MeO OMe
CuOTf, h

HO HO
OMe OMe

OH
OHC CHO

HO O
Robustadial A; H =
Robustadial B; H =
H JACS, 1986, 108, 1311.
Photoreduction: Addition to a C-H bond

O
O

Meo

# Photochemical reduction of carbonyl compounds is a useful

complimentary method to the numerous thermal methods
 OH Ph
Ph h HO
O + Ph2CHOH C Ph
Ph Ph Ph Ph OH
Ph

Me CH2.
Ph Ph
OH HO
h
O + C + Ph
Ph Ph Ph
Ph OH + Ph
Ph
Ph

Ph
Ph h OH HO H OH
O + CH3OH C + .CH2OH
Ph
Ph
+
Ph Ph OH CH2OH
Ph PH
Ph

Ph
HO H
Ph OH
H

O
Ph CH2OH
 OH OH
Ph h
O + Me2CHOH C + C
Ph Ph Ph Me Me

Ph
O
Ph

Ph
HO OH
Ph
Ph OH Ph
C
Ph
+ O
Ph

Ph Ph OH Ph
+
Ph Ph h N
O + N
C O C + N
Ph Ph Ph
Ph

Ph
HO
Ph
Ph OH
Ph
 OH OH
coupling

h disproportionation OH
O 2 C OH + OH

OH

H -transfer
O +
OH

# which pathway is preferred depends on the radical pair

# nature of H donor and the conditions used for irradiation

 Photoreduction of the carbonyl * state via hydrogen abstraction
Kr M -1s-1
O OH
OH
C
2 x 106

O
OH
OH
C
1 X 103

Ph
Ph

O OH
OH
C
1.6 X 106

O OH
OH
C 1.6 X 105

Me Me

O OH
OH
C 3.2 X 104

Me Me
Me Me
 X

H
X
In plane approach
Perpendicular approach

* LUMO * LUMO

n
HOMO
HOMO

H
H
C. O.

First excited state (n*)

 X

H
H

In plane approach

O. C. O

H
X
H .X * LUMO

E2

n E1
HOMO

H
C. O.

First excited state (*)

 Intramolecular photoreduction

R O
O O OH
h Ph
Ph

OR

OH
Ph
h

Ph
h OH
O
Ph

O
O h
Ph O
O
O
Ph OH
Ph H OH
Ph Ph
O h

O Ph
O
 h

Ph
C Ph
Ph O Ph Ph OH Ph OH

O OH OH H
NMe2
h
Ph NMe2 Ph H + Ph NMe2

O NMe2
O NMe2
C
Ph C C
Ph

CO2 Me
CO2 Me
N z
O CO2 Me HO
h HO N z
Ph N
+ Ph
Ph Ph
Ph z Ph
 Photoreduction of carbonyl (n*) state via electron and charge transfer

Ar2 C=O*(T1 ) + RCH2 NR'2 Ar2C.-O- RCH2N.+R'2

back electron transfer

Kh
Proton transfer

Ar2 C=O + RCH2 NR'2 Ar2 C.OH + RC.HNR'2

Disproportionation/
back H transfer

Ar Ar
NR'2 Ar
Ar + Ar
OH OH Ar
R OH


n n n

N O
O
H H
n*

H
+
O N
H H
 Competition between H-abstraction and charge transfer

O O

O N O
XAN(n*) AZAX(*)

Quencher

Tol m-Xyl Mes Dur

# the rate constants for photoreduction by CT are higher than those expected for
H abstraction
# The quantum yields are solvent-polarity dependent
# Direct spectroscopin evidence proved it
Deuterium isotope effects quenching constants (H abstaction or ekectron transfer)

Kq

COMe CH3 1 X 105

H-abstraction

COMe CD3 0.2 X 105

COCF3 CH3 7.5 X 106

Electron
transfer

COCF3 CD3 7.5 X 106

 DNA photochemistry

O
NH 2
R'
HN
260 nm (*) N
PYRIMIDINES 270 nm (*)
O N
O N
R
R
Ura R'=H R=H
Urd R'=H R = ribose Cyt R=H
UMP R'=H R = ribose phosphate Cyd R = ribose
CMP R = ribose phosphate

Thy R ' = Me R=H

Thd R ' = Me R = deoxyribose
TMP R ' = Me R = deoxyribose phosphate

O
NH 2
N
N HN
N PURINES
H 2N N N
N N
R
R

Ade R=H Gua R=H

Ado R = ribose Guo R = ribose
AMP R = ribose phosphate GMP R = ribose phosphate
 O
NH 2 O
O H
H HN
N NH
NH heat
O N
O N H N O
H N O H
H
O
O O
O O
O
HO O P O
HO O P O OH
OH O
O

h
NH 2 NH 2 NH 2
O OH
N N O H N
NH N O N O
h O N O N
O N
N O N N

O O O
O O
O O O
O
OH OH
HO HO O P O HO O P O
O P O
OH
O O O

Possible photoreaction at dipyrimidine sequences (CT); cyclobutane and oxetane formation

 NH 2 O
NH 2 O H O
O H
N H HN H
N NH NH
NH OH heat OH
h O N O N
O N H N O H N O
N O
O O
O O O
O O O
O
HO HO O P O
HO O P O
O P O OH OH
OH O O
O

NH 2 NH 2
O
OH OH
OH
N N
N O N O HN
N O
h heat
O N O N
N N O N
N
O O
O O O
O O
O O
OH OH
HO HO O P O OH
O P O HO O P O
O O
O
 O O
NH 2 NH 2
HN N
N HN
N
O N N
N h O N N
N
N
O O OH
O
O O O
HO O P O HO
OH O P O
O O

NH 2 N
NH 2
N N NH 2
N N
N O
N N N NH 2
N N h
N
O N N
O
O O P O
O N
O N
HO O P O O
OH
O

OH

Cycloadditions involving adenine; Cyclobutane and azetidine dimer formation

 O O O

h OH
N N H N
H +
EtOH
O N O N O N
OH

O O O
H N h H N NH
Thy H
O N O N N O
H H
H H
O

O HN
O
HN O N CO2H
O h CO2H HN
HO N heat NH2
O +
Lysine H2N N O NH
H O
HO NH2
O
OH HO
OH
HO

radical and nucleophilic photochemical addition reaction of thymidine derivatives

 Structures of the major photoproducts induced by UVR

X O
X NH2
HN HN OH H
H
N N H
O N N O
O N OH
O N H O N
N H
Cytosine photohydrate
Cyclobutyl pyrimidine dimer Dewar pyrimidinone

O
NH2 O O
N H OH
NH
HN Me HN Me
N
N N O OH OH
O N O N
N H H
Adenine-thymine heterodimer Thymine phohydrates
 DNA repair: photochemistry

O O O O O R2 O R2
R3 R1 R1 R1 R1 R1 R1 R1 R1
R3 R3 R3 R3 N O R3 N O
N N N N N N
N N
O N N O O N N O O N R3 O N R3
H H H H H H H H
R2 R2 R2 R2 R2 O R2 O

Cis-syn trans-syn Cis-anti trans-anti

structures of the pyrimidine dimers and abbreviations

O
N OH
Cl Cl

N Cl Cl
H
O
c-s[TT]; c-s[DMTD] c-s[DMTD]; c-s[DMUD] c-s[DMTD]; t-s[DMTD]; c-a[DMTD]

OH
(CHOH)3
N N O N N O
N N O
NH NH
N NH
O O
O
c-s[TT] c-s[TT]
c-s[TT]

Dimer splitting sensitizers

 Dimer splitting by covalently linked sensitizers

O
O R O O
N h R
N N
N +
O N O N O N
O N

OMe

MeO
R=
N N
H H N H
H OMe
 O O
N N O
HN NH Complex
NH
+
X O N N O
H H
O h
X = N, CH

1 flavin----------Thymine dimer

3 flavin----------Thymine dimer
O O
N N O
HN NH
C NH
+
X O N N O electron transfer
H
O
radical pair

O O
O
1 e from
HN HN
HN 2
+
flavin O NH
O N O NH

Possible mechanism for flavin as sensitizers for dimer photomonomerization

 H2
C

O O

N N

O N N O
O
HO2 C
N
H
HO N N O

NH

Intramolecularly photosensitized dimer splitting by a deazaflavin (irr = 436 nm)

 Dimer Splitting by noncovalently bound chromophores

COR1
N CO

N O
CO N O
N H N
R2
R2 N H N N
NH ON Bu
NH O Bu
CO
NCOR1
CO

MeO
R1 =
N N
H H
 Photo reactivating enzyme (PRE) or photolyase (EC : 4.1.99.3)

O 5 O
5
Me Me 3
3 Reduction NH
NH
+ Dimer splitting
HO N N O HO N N O
e- 1
CH2 1
CHOH 8-OH-5-deaza-isoalloxazine H2
CHOH
CHOH
OH
O P OR
O
8-hydroxy-5-deaza-isoalloxazine

NH2 Scenedesmus acutus (green alga)

N
N
N N
O

OHOH
 Bioluminescence

Fireflies

Artistic rendering of bioluminescent Antarctic krill

HO S S

N N
OH
Oxyluciferin
Firefly luciferin
Image of bioluminescent red tide event of 2005 at a beach in Carlsbad California showing brilliantly glowing crashing waves
containing billions of Lingulodinium polyedrum dinoflagellates
 Chemistry of vision

Cys-NH2
h

Opsin

CHO Rhodopsin
11-cis retinal NH+
P
H+

NH+ N
P P

Metarhodopsin II
Bathorhodopsin (contains all trans retinal)

H 3 O+ retinal isomerase
CHO

all trans retinal CHO

Opsin 11-cis retinal
 Nature's Fluorophore (GFP)

Tyr-66 O Gly-67 O

N N
H
HN O HN O
HO HO O HO HO OH

NH NH
Ser-65

-H2O

O
O
N
+ O2 N
N O
HO H N O
HO
NH
HO NH
HO

Fluorophore (absorb = 397nm, emit = 509 nm)

Aequorea victoria (Pacific jellyfish)

Photochemical aromatic
substitution reaction
 Electron rich

SE is more common than SN reaction

# Majority of SE reaction is of S EAr type

# Arenium ion or -complex is the intermediate

# SE1 mechanism follows (leaving group departs before electrophile arrives)

SNAr type reaction

# Meisenheimer complex

# Electron withdrawing group favored the reaction

# SN2 mechanism follows

 Mechanism of SN2Ar* reaction

ex
L L Nu
L Nu
hn Nu- - L-
-
EWG EWG EWG
EWG

L : Leaving group; EWG : Electron withdrawing group; Nu: nucleophile

# Fomation of exciplex (usually triplet state)

# Formation of -type complex

# the rate determining step is addition of nucleophile to the leaving group bearing carbon atom
 18-
O
OPO3=
OH-
h + HPo4=
+ 18
H2O
NO2
NO2

NHCH3
OPO3= h
MeNH2 + HPo4=
+
H2O
NO2
NO2

O
OMe
h + MeOH
+ OH-
H2O
NO2
NO2
 OH
OMe
heat

OMe NO2
OMe OH-

H2O/THF OMe
OH
NO2 h

NO2

X NO2 X NO2
h, NO2-
h, NO2-
MeOH
MeOH
NH2 NH2 NMe2 NMe2

X = Cl, Br, I
SO2X Nu

h/Nu-

NH2 NH2

X = NH2, Me, CF3

Nu = CN-, NO2-, SCN-, MeO-

Cl SO3 Na

h/Na2SO3

R R
R = NH2, NMe2, OH
OMe OMe OMe

h, CN- CN

MeOH
+

CN
OMe
OMe CN
OMe h, CN-
tBUOH

OMe OMe

h, CN-
MeOH

OMe CN
NO2 CN

h, CN-
MeCN/H2O

h, CN-
NO2 CN
tBuOH/H2O

CN

h, CN-
tBuOH/H2O
CN

h, CN-
tBuOH/H2O
 Alternate mechanism SN(ET)Ar

L L L

h Nu- Nu.
-.
EWG EWG EWG

L Nu Nu

-L-
-
EWG EWG
 NHhex
OMe
SN(ET)Ar*
OMe
OMe
NO2
+ n-HexNH2
OMe
NHhex
NO2 SN2Ar

NO2

n-HexNH2
NO2 O2 N NHhex
SN(ET)Ar*

SN2Ar
MeO GlyEt
OMe
NH2CH2CO2 Et
 SR+N1Ar* mechanism

L L L

h -e- Nu-
.+

EDG EDG EDG

L Nu Nu Nu
-L- ArL
. .+

EDG EDG EDG

L : Leaving group; EDG : Electron donating group; Nu: nucleophile: ArL: ground-state substrate
 Synthetic applications

CN

h, KCN

Bu4N+CN-/ MeCN

OMe OMe

h, CN-

tBuOH/H2O
CN

CN
OMe h, CN- OMe

tBuOH/H2O

NO2
OMe

h, NaOMe

MeOH
OMe OMe OMe
N O H2O NH2
h, OCN-

H2O, O2

NO2 NO2 NO2

OMe h, OH- OH

OMe MeCN/H2O OMe

NO2 NO2

OMe h, OH- OMe

O2 N OMe MeCN/H2O O2 N OH
Photochemical reactions with singlet Oxygen

1O
2
 O2 h
1O
2 ?
The fate of singlet oxygen

# deactivated by chemical acceptor

# physical quenching is possible by solvent and sensitizer

# 2+2, 4+2 cycloaddition and ene reaction are the probable reactions

# Nonpolar solvents (halogenated or fluorinated hydrocarbons) suppress electron transfer

reaction hence increase the lifetime of singlet Oxygen

# Weak electron acceptors TPP, metaloporphyrins, with low triplet energies should used as
sensitizers. RB is possible (in polar solvents) in some cases, use of MB should be avoided.

# Regio and stereoselectivity for certain transformation should be determined directly at the peroxide stage.
In many cases further transformation (reduction, rearrangement and cleavage) clearly
change the regio as well as stereochemistry of the products.
 HO OH
MeOH/RB HO HO

O2, h/redn
+ + +

25% 21%
31% 11%
(+)-Limonene
General effects controlling the regioselectivity of allylic oxidations of C-C double bond

1O
2
X O X
Y O Y

Cis effect
CH3 (7) CH3 (<2)

(53) H3C CH3 (40) (>98) H3C OMe

CO2R Geminal effect SOR

(<2) H3C CH3 (>98) (<2) H3C CH3 (>98)

tBu Large group effect tBu

(34) H3C CH3 (66) (17) H3C CH3 (83)

 Acyclic substrates

Me Me OOH
Acetone/ R.B
OOH + Me
Pri Ph Ph Ph
R.T/ O2/ h Pri Pri
D H D H

Me
OOH
Me OSiRMe2
Me
CCl4, TPP NC
Me OSiRMe2
h, O2
+
H CN
Me OOH

OSiRMe2
H CN
 -unsaturated carbonyl compounds

CO2Me
CO2Me
CO2Me

OOH
CHCl3/TPP OOH

+
0oC/ O2/ h

E dr = 90:10
Z dr = 65:35
 Cycloalkenes with excocyclic C-C double bond

MeOH, RB/ RT
O2/ h OH OH

+ +
Na2SO3 OH

35 12 23

O
H

OMe
CO2H
O
H O
H
MeOH/ RB

OOH
-78oC/ O2/ h MeO
OMe H
CO2 H OMe
H CO2 H
H

DCM/ MB
RT/ O2/ h HCO2H/ DCM

H
O
H
O

O
OOH H
H
O H
OMe
CO2 H
O
H

qinghaosu
 CCl4/ TPP Ph3P
OOSiMe3 OSiMe3
O2/ h
OSiMe3 O O

H
HO
O2/ h OOH

R'

R
HO
R' = H, R = OH
R', R ; = O O O

EtOH/MB/O2/h
+
OOH OOH
H
H
Major
 Photooxygenation of 1,3-dienes

1O
2 1O
O 2
O O
O + O
O

Ph Ph
Ph
Ph 1O Ph Ph
2
O O
+ O
O Ph
Ph
Ph
Ph Ph
Ph

1O
O 2 O O
1O
O 2 O O
O O O
O O O
 H
H'

H' H

H H'

H
H'

tBu
1O
2

tBu O O

62%

1O
2

O O
23%
 (CH2)n
1O
2
n
O
O

X
1O
2 O
X
O

X = CH2, (CH2)2, CH=CH

 1O
2 O
O O
O

1O
2
Ph O Ph
O
O
O
 O O
O

+
1O
O O O
2 heat O
O
O O
Ph3P
MeOH

O O
H H
OMe
O
H

S S
1O
2 HN=NH
O O
S O O
Chemoselectivity in photooxygenations of 1,3 dienes

3 factors controlling the reactivity

# the amount of s-cis conformer in the equlibrium necessary for 4+2

# the relative reactivity difference of the C-C double bonds

# the appropriate alignment of allylic H for ene reaction

1O (CH2)n
2
(CH2)n O + ene products
MeOH/DCM
O
RB

n=1 16 84
n=2 20 80
n=3 22 78
n=4 50 50
n=5 67 33
 1O
2

O
O

1O
2

OOH

H H
H Me

Me H
 1O
2
OMe
OMe O
O

OMe OMe

1O
2 OMe
O +
OMe OMe
O
OMe CHO
OMe

OMe
OMe
O
O
 O
O
1O
2 O
+ + +
O OOH
MeOH
OOH

1O OOH
2
+
-Myrcene OOH

O
1O O
2

-Myrcene
OtBu
OtBu OtBu
1O
2
O
+ OMe
OMe O

OMe
 O O
Ar O O
h/O2
H + Ar

Ar H

H Cl OH
N
Ar
N

epibatidine OH
OH OTBS 1O
OTBS
2
O O
OH OTBS h OTBS

OH
OH
MeO OH
O

HO OH
OH
OH

Pinitol
 O
OH O
OH
OH
OH
b
a c
O
+ O O d
O O

e O

g f
O
O
HO O
O

a, b, c; Reduction
d, e; Thermolysis
f; Deoxygenation
g; Acid/base Catalyzed reactions
Photo removable protecting
groups
 O O
h
R S OR' R S OR' R .SO 2OR SO 2.OR
O O

H abstraction from
solvent
R OH

R H

proposed mechanism for photochemical reaction of sulfonates

O
O
O
OR
OTs RSO 2O OTs R = Ts O
O

O O O Ts
HO O O
O O O
O
O
OTs O
OHO Ts
O
 O O
O h/MeOH O
CHPh OMe CHPh OMe
O O
O OTs O

O
O
CHPh OMe
X O
h/MeOH O OH

OTs OTs

h
No deprotection observed

O O

O O
O O
h/ (Me2N)3PO
H
O H2O O
OSO2 CF3 O H O
 NO
NO2 CHO
h
CH2OR
ROH +

n-

O NO
+
N OH OH
OR
CH.OR H

O +
N O H
O OR
+
N OH H

CHOR

Acinitro intermediate

proposed mechanism for the photochemical cleavage of o-nitrobenzyloxy compounds

 O O2N OH O O 2N
HO Me
OH O O
OH OHOH

OBn
OH
NO 2
NO 2 O O
O O
OBn
OH
BnO
HO
OBn R
OH R MeO
R
R = H, OMe

HO B
O
NO2

OR O
 O-Nitrobenzyl group known as Caged group

NH2
N
NO2 O O O N
O P O P O P O N O O CO2-
O N
O O O NO2
HO O
H
NH2
OH OH

Caged ATP Caged glutamic acid, neurotransmitter

NH2
CO2- CO - CO2- CO2- N
2
N
N N NO2 O O N
Ca+2 O N
P
O O O
NO2 O
OH

Photocaged Ca2+ Caged cAMP

Photolysis release Ca2+
 O O
X h X
N N
H H
HN HN O
O O 365nm HO
X X
NO2
X = H, Tyrosine
X = D, [D2] Tyrosine

Photodeprotection of o-nitrobenzyl adducts to yield natural amino acids

 radical quencher
h
RO NO2 RO. .NO2 R OH

photochemical removal of nitrate group

ONO2
O
O O O
O
O
R1
O O
R2 O O
R 1 = H; R2 = ONO2, 100%

R1 = ONO2; R2 = H, 92 %

O H NO2 OH OH
O O
h/ MeOH NO TFA NO2
O
O O
 OMe
AcO O OMe
AcO O OMe
NO2 O
CH2OH
O
O O
O O
NO2
NO 2
O O
O
O
O 2N OMe
O
OAc NO 2

O OMe
O

O
O
NO 2
OAc
O OMe
OAc
 O
O
O OH
O

NO
NO2

O O
C O O
OH
+
N OH NO
O

O
O O
O
OH OH+
+
N N
O O

Proposed mechanism for the photochemical rearrangement of

o-nitrobenzylidine acetals to o-nitroso benzoates
 o-nitrobenzyloxycarbonyl (NBOC)

O O
NO2 N OH N
OH
OR O OR
O OR C O

O H O O

NO
NO
O OR CO2 ROH
+ +
OH O CHO

2-(o-nitrophenyl)-ethoxycarbonyl [NPEOC]
O
NO2 N
O OH O NO2
+ CO2 + ROH
O OR O OR
 1. light absorption and
intersystem crossing

Covalent linkage O
O
2. Energy 3. H- Transfer
NH
transfer
O O
N O 4. -elimination and fragmentation
O
O
NO2

OH

O
O
NH
HO
N O
O
+ CO2
+
NO2
OH

Intramolecular sensitized photocleavage of a protecting group of NPPOC type

 S S
O OR

O
NO2
O O
O OR
NPPOC Protecting group O OR
O
NO2 O
NO2

O O OR

O OR O O
NO2
O
NO2
O OR

S S O O
NO2

O O

Overview of different covalent linker attached with NPPOC group

O OR

O
Angew. Chem. Int. Ed. Engl, 2006, 45, 2975-78
NO2
 MeNPOC [(-methyl-2-nitropiperonyl)-oxy] carbonyl

NO2 NO2 NO2 O

O O OH COCl2, THF O Cl

O O O O
O O O O

NO2 O
NO2 O
B O O B
HO O O
O Cl Pyridine
+ O
O O
OH OH
O

HO B
NO2 O O

O O B h O
O
+ O + CO2
O O O P OMe
O O
O O
O P OMe
O CN

CN JACS, 1997, 119, 5081

 OH
O h O
R O Ar C Ar O COR Photo fries rearrangement
R

S-H

ArOH + RCO2H

or

RH + CO

Proposed mechanism for the photochemical cleavage and rearrangement of aryloxy esters

O oNB
OCOR O oNB
R1 OCOR2

R = Ph, Me, CCl3, CPh3, 9-Fluorenyl O

HO2C
N CO2Et
NH2 H
OtBu NH

O
 photochemical deprotection of ketones protected as
ketals of 1-(o-nitrobenzyl)-1,2-ethane diol

OH O R1
O R1
O R2
R2 h O
OH O
+ R1 R2 + OH
NO2 N
NO2
O

OH O R1 O R1
O R2 R2
O O
O OH OH+
+ R1 R2
NO N
NO
O
 Photochemical deprotection of carboxylic acids and amides
protected as o-nitrobenzyl ester and amide derivatives

NO2
NO2

O R2
O R2
O2 N O
R1 O

R1 = H, R2 = Ph
R1 = ph = R2
R1 = Ph, R2 = (CH2)14 Me R2 = Ph, Bn, CH2-naphthyl, -Boc Ala, Boc-Phe
R1 = Ph, R2 = Bn

NO2
O
H
N R
N
H O

(P)
R = Boc-Gly
R = Boc-Val
R = protected decapeptide
 Carboxylic acid

OCOR' h/ C6H6
+ R'CO2H
R" O
O R
R
R
R = OMe, R " = H

OAc

OAc
O
C OMe
H
O
OMe

OAc
OAc OMe MeO
MeO
C O O
O H

MeO

O
 O
O +
+ S
SOCOR S R
+ NO2
NO2 h N O
O + RCO2-

NO2 NO2 NO2

C6H6

S
NO2
+ RCO2H

NO2

proposed mechanism for the photochemical cleavage of

dinitro phenylthio derivatives of carboxylic acids
 O R2 R2
-SO2
H S N H N
R3 R3
SH O

O O R2
R2 h
R 1. S N
R1 S N
R3 O R3 SH
O
R2
SO2. N
R3

Proposed mechanism for photochemical reaction of sulphonamides

 O O
OH
O P O h/MeOH
+ O P O
O O
NO2
NO2

photochemical deprotection of phenol phosphates

H2 N
N
O2 N N
O O
N
O P OH O P O N
O
OBn O
O2 N
O O
O2 N NO2
 S RCOCl/ NaH S S
S S S
R
N N N
H O
O R

h/ R'OH O S
+ S
R OR'
N
H
Photolysis of N-acyl-2-thionothiazolidines

S S
h R
S C SH O
N H N R R'
C
R R2OH
O R' O R'

R
Photochemical activation in N-Acyl-2-thionothiazolidine OR2
R'
O
 h

S
O
S H H

O
S S
R3 R1 h R3 R1

R2 R2

Photolytic dethioacetalization
 Remote functionalization by Nitrites: The Barton Reaction

H H H
ONO h O C O
+ NO + NO

O
+ + OH N H ON
N N HO OH OH
OH
O +

heat
six membered cyclic TS for hydrogen abstraction

H
ONO O

C
C
+ NO.
+ NO.
HO HO

NO
HO
 O O
OAc OAc
HO O N O
NOCl/ Pyr H
H h, PhMe

H H H H

O O

O O
H OAc
C OAc
O OH
NO
H H
H atom abstraction
H H H H
O O
O OH
ON O
OAc N OAc
OH OH
H H
tautomerization
H H H H
HNO2
O O
OH O
O OAc

H
Aldosterone 21-acetate
H H
O
 OH NOCl O N O
h, n-hexane, RT
Pyr, 0oC iPrOH, reflux

OH
N OH

OH O OH

H
Grandisol

Magnus et.al, 1976, JACS, 98, 4594

 OH OH

O
OH
OH

OAc OAc OAc OAc

OH O O

-cleavage OHC

Norrish type-I OAc OH

 ONO
O

H h H
H H
H H
O
O

O
O
NOH C
H
H
H H
H H
O
O
HO
N
ONO O
h
O X
H
benzene
N

OH

(CH2 )n (CH2 )n
R R
ONO h
R O

R CS2
NO
ONO O

h
H H + .NO
benzene
H H

O O
H

H C H
H
H

OH OH
N OH
C
H H
H H
 Barton-McCombie reaction [R1R2CHOH to R1R2CH2]

H
H R2
R1 OH
R2
R1 OH
2,4,6-Cl3C6H2OC(S)Cl, Pyr
C6F5OC(S)Cl, Pyr [X = 2,4,6-Cl3C6H2O]
[X = C6F5O]

H H S NaH, CS2, MeI H

R2 R2 R2
OH R1 O X R1 OH
R1 [X = SMe]
Im2CS, THF

N PhOC(S)Cl, Pyr
X= N [X = PhO]

H
R2
R1 OH
 H S
R2
R1 O X

nBu3SnH, h

.Sn-nBu3

H S H S Sn-nBu3
R2 R2 C
R1 O X O X
H S R1
R2
R1 O X

H nBu3SnH R1 S Sn-nBu3
+ R1
.Sn-nBu3
C +
R2 H R2 H O X
Barton's thiohydroxamate ester chemistry: synthesis of alkyl pyridyl sulfides

+ N
N-Hydroxypyridine-2-thione sodium salt
R Cl
O-Na+
S

DMF or POCl3

O
N .R + + CO2
R O N
S
SR
thiohydroxamate ester

O O
N N
R O R O C
S S R

.R
 R-Cl

R-Br
R-I
CCl4

BrCCl3 CHI3

R N R-SPh
RSePh PhS-SPh
PhSeSePh
O S

nBu3SnH O2

R-H R-OH

Barton's Thiohydroxamate ester chemistry: Use of neutral molecule radical traps

 O
S
N
O
S

O
O S
S N
N O C
O
S
S

-CO2
C

5-exo-trig C
+ N
C S
S
 Organocatalytic enantioselective photoreactions (OCEP)

K
A

A-K
A K AB
B
h (S)
B B*

The photochemical excitation and the enantioselective key step are decoupled

# Reactants A & B do not react with each other (or if they do so very slowly in GS or ES)

# One of the reactants B is, through sensitization (S), converted into excited state B*

# While A forms a complex A-K with the chiral catalyst (not necessarliy covalent)

# The complex A-K now reacts with B* because of its changed electronic properties to give B-A-K

# Complex B-A-K dissociates into product A-B, releases K and the cycle continues.
 R4 3O
2
R3 h, TPP
N CO2H R4
H R4 1O R3
R3
2 N COO-
O N CO2H OOH
R1
R1 R1 R2
R2 R2

O O
OH OOH
R1 R1
R2 R2

J. Am. Chem. Soc, 2004, 126, 8914

Angew. Chem. Intl. Ed. Eng. 2004, 43, 6532
 h SK
SK
A* B A B
SK*

PET
SK*
A+B A B

#The central role is played by a chiral complexing reagent SK

# Which at the same time acts as a sensitizer and transfers th energy to the substrate

# After the excitation of SK, a complex with A and B is formed, in which the excitation energy is transferred

# the enantioselective key step then occurs, and SK is released again

# The important points of this approach are high facial differentiation in the complex SK-AB and the
exclusion of intermolecular sensitization
 H
O NN O
CO2H CO H
2
CO2H

Kemp's triacid
O N O X
H
Ph H

O N
H
O NN O
 OMe R R

OMe OMe
h
H H
N O
H O O
R
endo
R
R
R = CH2CH2CH2OH
OMe
R = CH2OAc OMe
R = OAc H
H
R = Ph O
R = CO2Me O
exo

OMe

N O
H H H
O NO N O NN O

JACS, 2000, 112, 11525

O
O
H
h
H 93% ee
N O
H N O
H

h O
H > 90% ee

N O
H N O
H

OMe

N O
H
H H
N O
O NO N N
O

JACS, 2002, 124, 7982

 PET
N N N+.

O O
h C Ph
Ph
ISC
N O NH O NH O
H
H H
O N N O O N N O

-H+

N
N
O OH
N C
Ph C Ph
NH O NH O
H H
N O O O
H N N O N N O

70% ee

Nature, 2005, 436, 1139

Facial differentiation or complexation is key to enantiocontrol

O
OR
OR HN

O O O
O O
NH NH Me
NH HN Me O
CDCl3 N R
N R NH

R= COPh

OR

O O
O
NH NH Me
HN
O
N R
O NH

19% ee J.Org. Chem, 2003, 68, 15 O