Transcript Organic photochemistry and pericyclic reactions (CY50003) 3-0-0

Organic photochemistry and
pericyclic reactions (CY50003)
3-0-0
O
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-πmethane, oxa di-π- and aza di-π-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
Compound
E = h
Excited electronic states
(selective excitation)
Ground electronic state
Thermal
activation
photochemical
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
h
R*
R
h
R
P
1R*
P
I
ISC
3R*
3I
1I
P
Antibonding orbital (*, *)
E2
E2>E1
Atomic orbital
E
E1
Bonding orbital (, )
Relative energies of atomic and molecular orbitals
*
*
E
Anti bonding
non bonding (n)


Relative energies of ,  and n MOs
Bonding
Most common transition module
* (E2)
n*(E1)
E2>E3>E1
n-* (E3)
Absorption maxima for few molecules and functional groups
Molecule
Iodobutane
Ethylene
Ethyne
Acetone
Butadiene
Acrolein
Transition
n-*



n-
n-*
*

n-*
max (nm)
224
165
173
150
188
279
217
210
315
E (Kcal/mol)
127.7
173.3
165.3
190.7
152.1
102.5
131.8
136.2
90.8
Functional group
RCH = CHR
Alkyne
Ketones
Aldehydes
Carboxylic acids
165
193
173
188
279
290
<205
173.3
148.2
165.3
152.1
102.5
98.6
<137.5
Antibonding (SOMO)
E
Bonding
S0
S1
T1
S0
Excited states
S1
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)
T1
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
no radiative
IC
(S1)
10-8s
ISC
ISC (Spin inversion)
(T1)
10-3s-1s
h
RD
F
P
Deactivation
F
RD
radiative
(S0)
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
+
+
+
P
O
S2
*
100 Kcal/mole
S1
1012/s
1011/s
T2 (*)
n-*
74 Kcal/mole
T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s
S0
CHO
pyrene aldehyde
O
2-acetonaphthone
lowest triplet state is *
O
fluorenone
Energy transfer through photosensitization
h
1D
D
ISC
1D
3D
D + 3A
A + 3D
3A
D = Donor
A = Acceptor
1 = Singlet
3 = Triplet
Products
S1
ISC
S1
Energy transfer
T1
74 Kcal
.mole-1
T1
69 Kcal/mole
120 Kcal/mole
S0
60 Kcal/mole
S0
Benzophenone
Butadiene
h
Ph2CO
1[Ph CO]
2
ISC
3[Ph
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 (1P1)
Hg (1S0) + h
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
h
O*
~
n-*
carbonyl chromophore
O
2.9 D
1665 cm-1
O
C
Dipolar species
O*
O
CF3
2.1 D
1225 cm-1
O*
CF3
1696 cm-1
1326 cm-1
O
S2
*
100 Kcal/mole
S1
1012/s
1011/s
T2 (*)
n-*
74 Kcal/mole
T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s
S0
CHO
pyrene aldehyde
O
2-acetonaphthone
lowest triplet state is *
O
fluorenone
Triplet lifetime depends on the nature of lowest excited states
O
O
MeO
= 0.0064 s, 77oK
n-*
 = 0.45 s, 77oK
*
O
O
Me
 = 0.13 s, 77oK
n-* & *
F
 = 0.039 s, 77oK
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
3S*
3
*
h
triplet
donor
h
h
185 nm
h
sens
h
H
H
heat
Ph
Ph
h
Dimer
Max = 380 nm
= 9 s
Ph
4+2
Ph
Ph
[1, 3] H
H
Trapping of a trans cyclohexene
h
sens
h
sens
H
OR
OR
H
h
H
O2N
H
O2N
R = H, Me
N N
h
N N
heat
H
H
N
h
heat
N
*
Ph
N
H
OH
h or
h-sens
Ph
OH
Ph
NH
H
O
Ph
NH2
O
oxaaziridine
N
H
H
N
OH
h or
h-sens
H
H
HO
N
N
H
O
O
h or
+
N
O
+
CN
N
h-sens
h
h
O
N
CN
CN
H
H
N
R2
N
h
R2
R1
R1
H
H
N
N
N
R
H
h
N
N
N
H
R
R
N N
R
R = Me
R=
R=
h
N N
R
R
R = CHMe
R=
R=
h
N N
N N
N
N
N
h (405nm)
h(436nm)/heat
h (313nm)
-N2
C
C
h (313nm)
-N2
N
R
R
R
1,7-H
h
HO
HO
previtamin D
Ergosterol
HO
Vitamin D
R=
R=
Vitamin D3
Vitamin D2
R
R
h
HO
previtamin D
OH
tachysterol
Photochemical synthesis of
oxetans
Paternò-Büchi Reaction
O
O
+
Paterno and Chieffi (1909), Buchi in 1954 mechanistic analysis
NH2
N
N
O
EtO
CO2 H
O
ON
HO
N
OH
Thromboxane A2
OEt
Oxetanocine
Insecticidal activity
HN
OAc
O
O
O
O
H2N
Merrilactone A
O
Bradyoxetin
OH
O
O
NH2
O
OR
H
OBz OAc
Palitaxel
O
Reaction mechanism
CHO
h
ISC
[PhCHO] S1
[PhCHO] T1
(n-*)
Kisc aromatic >> Kisc aliphatic (>>1010/s)
responsible
O
O
C
C C
H
electrophile
+
O
C C
+
Biradical intermediate
nucleophile
O
O
Major
Minor
Intermediacy of biradical
O
h
O
+
+
1
1.6
O
tBu
+
O
tBu
O
h
1 atm O2
tBu
O
O
O
O
O
h, 11 atm O2
O
O
Ph
O
Ph
+
O
O
h
Ph
O
Ph
C C
Ph
O
lifetime = 1.6 ns
Ph
O
O
Substrate spectrum of Paterno-Buchi Reaction
Aromatic ketones and aldehydes
O
O
H
h
+
H
O
O
54%
R
X
+
h
O
O
Me
X
R = H, X = S, 46%
R = Ph, X = O, 27%
R = Ph, X = S, 76%
X
+
h
+
X
O
O
+
X
O
Me
X=O
8%
33%
0%
X=S
11%
10%
38%
[4+2]
Carboxylic acid derivatives and nitriles
O
O
OMe
H
h
O
+
H
H
Ph
33%
34%
O
O
+
Ph
OMe
O
Ph
h
Ph
O
OMe
O
O
[2+2]
O
OAc
H2 O
Ph
H
OMe
1,7 sigmatropic
O
MeO
Ph
C
O
Ph
OH
+
OMe CH .
2
Ph
O
O
O
OMe
1
H
7
O
OH
Ph
OMe
O
O
-MeOH
Ph
O
H
1, 3 Bz shift Ph
O
1,3 H shift
O
Ph
O
N
CN
h
+
N
66%
Ph
CN
O
h
+
O
CN
O
O
h
O
O
COMe
O
Me
O
h
CN
O
-55oC
O
O
CN
R
R = Ph, endo/exo = 5.3:1
Oxetane formation: addition to heterocycles
h
+
O* T1
X
C
X
O* T1
X
O
X
C C
O
X
O
+.
Ph
O
Ph
Ph
+
h
N
Ph
C
C N
O
N
N
more stable
OH
Ph
Ph
Ph H
N
N
N
Ph
O
N
H
O
and
N
Ph C C
Ph
N
Ph
Ph
+
CO2Me *T1
O
h
O
CO2Me
O
O
Ph
Ph
Methyl coumarilate
R1 R3
R1
O
h
+
R
S
R4
R3
R2
R1
Se
R
R1 = R2 = H, R = Me
R = R2 = H, R1 = Me
R1 = H, R = R2 = Me
Ph
R4
R
S
O
R2
h
Ph
Ph
R2
Se
O
R
R3
+
R
R1 Ph
O
+
R2
R1 R4
S
O
R2
Ph
Ph
Ph
Si
Me Me
O
+
Ph
h, 436 nm
Ph
O
Ph
MeCN
Ph
Si Ph Ph
Me Me
Ph
18%
+
N
COR
Ph
Ph
h
Ph
N
COR
O
COMe
COMe
O
h
N
Ph
O
Si Ph
Me Me
51%
Ph
O
Ph
+
N
O
Ph
Ph
Ph
Enones and Ynones
O
O
O
+
+
42%
O
47%
O
O
Low T
+
Me
3% oxetane
+
CCl 3
Me
CCl 3
O
O
O
F
F
F
+
Me
+
Me
10%
O
O
O
Cl
Cl
Cl
+
Me
9 0%
+
Me
90%
10%
O
+
h
O
O
+
14%
O
+
86
O
h
+
O
O
O
C C
..
Alkenes substituted with electron donor
OAc
O
h
O
OAc
OAc
OAc
OTMS
OTMS
O
OEt
EtO
O
ZnCl2
+
O
O
O
O
h
EtO 2C
O
CO 2Et
O
O
+
H
h
O
O
H
O
SiMe3
O
h
Ph
Ph
+
O
+
Ph
SiMe3
O
Ph
Ph
Ph
SiMe3
24
Ph
O
h
O
OTMS
O
+
Ph
+
Ph
1
Ph
Ph OTMS
94
O
Ph
H
Ph
+
H
SMe
OTMS
Ph
6
O
h
O
Ph
SMe
+
Ph
Ph H
100
Ph H
0
SMe
Miscelleneous Paterno-Buchi Reaction
O
h
O
COM
O
+
+
H
O
Ph
h
Ph
Ph
+
Ph
O
Ph
O
h
+
Ph
R
O
300oC
O
O
Ph C C
Ph
R
R
O
O
Ph
Ph C
R
R
C
CHO
OAc
h
O
+
O
O
O
OAc
O
O
O
HO
HO
CO2Me
Ph
The Paterno-Buchi reaction as a photochemical aldol equivalent
O
h/70%
OEt
OEt
O
+
+
3
R'
OH
O
OH
O
O
+
OEt
:
OEt
H
7
OR
H2 O
H
R
H2O, RT
O
R'
O
R"MgX
R
OH
OH
R"
R
R'
h
O
O
R
R'
OAc
O
O
O
O
+
OAc
OAc
O
h
OAc
O
O
O
O
O
O
CHO
OH-/H2O
O
OH
H
CH2 OH
CH2 OH
NaBH4
H+
H
O
a
a
d
b'
O
R
b
c
R*
R
A
O
R
a'
enantiotopic faces a,a' and b,b'
non prostereogenic carbonyl
Parallel approach
B
b
diastereotopic faces a,b and c,d
prostereogenic carbonyl
Perpendicular approach
# Nucleophilic attack of carbonyl (half filled *)
towards the alkene empty *
#Nucleophilic attack of alkene toward carbonyl
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-.
O
Radical ion pair
R
O
C+.
R'
R
R
R'
R'
(nucleophilic)
C O
Exciplex
R
+
C OR
H C
C
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-.
O
Radical ion pair
R
O
C+.
R'
R
R
R'
R'
(electrophilic)
Exciplex
O C
R
R'
O C
+
# 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
R'
R
Parallel approach
perpendicular approach
n



A
D
* LUMO
D
LUMO
LUMO

 HOMO
*
A
D
HOMO
n
HOMO

A
D
n*
A
electron deficient alkene
A = electron acceptor
O
electronrich alkene
D = Donor
Fluorescence quenching of 2-norbornanone singlets by trans-DCE and cis-DEE
NC
EtO
OEt
O
O
CN
"edges"
(n-orbital attack)
5.1
"faces"
(-orbital attack)
1.2
O
OR
O
O
1.0
1.5
O
NC
OR
CN
Fast
Slow
OR
O
0.48
<0.03
O
O
NC
OR
CN
Slow
Slow
parallel approach
(-orbital attack)
perpendicular approach
(n-orbital attack)
Intermediacy of diradical explains certain facts
O
h
O
+
R CHO
O
endo:exo
Me
ethyl
isobutyl
phenyl
o-tolyl
mesityl
45:55
58:42
67:33
88:12
93:7
>98:2
R
+
benzene
R
O
H
H
R
H
O
Endo
H
Exo
R
H
O
ISC
endo
O
H
1A
H
X
H
X
3B
3A
Perpendicular approach
ISC
R
1B
exo
Enantiocontrol and diastereocontrol inPaterno-Buchi Reaction
O
Ph
O
O
+
CO2R*
H
H
h
O
+
Ph
O
Ph
O
H CO2R*
R*O2C
O
O
O
H
R* = (-) 8-phenyl menthyl; de>96%
R* = (-) menthyl; de 57%
O
Pri
Ph
O
O
O
O
Ph
O
one face of carbonyl blocked by the menthyl group
H
O
O
H
Ph
CO2R*
Me
O
OHC
O
O
NRO
O
O
N
H
N
H
h
O
O
O
NRO
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
H
O
N
H
O
O
NHO
O
O
NRO
O
NRO
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
h
O
O
O
h
O
Me2CO
O
O
O
h
O
O
H
O
Ph
Ph
h
O
O
Ph
O
Silica gel
O
O
O
O
O
h
O
O
Pd
h
Me
heat
O
azulene
O
OH
LAH
h
O
H
H
H
OH
h
HI
O
AcO
O
AcO
AcO
intermediate for 1 -hydroxy-vitamin D3
O
O
h
h
LAH
CHO
O
OH
R
O
MeOH
h
CHO
O
R
OH
O
OMOM
H3
h
C6H6
OMe
O
OMOM
OMOM
O
O
R
O
O
O
O+
H
O
O
H
OH
O
H
OH
O
H H
h
Ph
OH
.01N HCl
Me
H
+
O
O
O
Ph
THF
O
O
Me
H2, 5% Rh/Al2O3
Science, 1985, 227, 857
JACS, 1984, 106, 7200
ibid, 1984, 106, 4186
Ph
O
h
+
O
wet celite
Me
Ph
OH
O
Me
H
H
O
OH
H H
O
O
OH
O
H
H
H
Fruit fly attractant
R
O
O
R = Me, Ph, CO2nBu
H
H+
O
R
R
OH
OH+
O
Carboxydroxylation strategy by reductive cleavage of oxetanes
R4
R4
R3
h
+
R2
R3
R CHO
R4
R2
R1
R1
Ph
O TMS
R
R
H2
O
Ph
R
OX
R3
R2
R1
CHRY
H2
O
Ph
XY
O
HO
O
O
Ph
OH
O TMS
Ph
OH
R
OH
Total synthesis of (+)-Preussin
HO
Ph
N
HO
O
O
+
Ph
H
Ph
N
Ph
PG
N
N
PG
PG
Carbohydroxylation strategy fo N-containing unsaturated heterocycles
H
PhCHO/h
R
N
CO2Me
Ph
MeCN
H
HO
H2, Pd(OH)2/C
O
R
N
Ph
N
LAH/THF
Me
CO2Me
endo
H2, Pd(OH)2/C
PhCHO/h
N
CO 2Me
MeCN
HO
O
LAH/THF
Ph
N
17% CO 2Me
Chem.Eur.J, 2000, 6, 3838-48
Ph
N
R
MeO2C N
3
4
R
H1
H
N
H2
H
R
2
MeO2C N
H1
R
H2
CO2 Me
A 1,3 Strain
Pseudoaxial orientation of R
Ph
H
H
O
Ph
Si
R
MeO2C N
H
H2
Re
R
Favored
H1
O
MeO2C N
H1
H
H2
Possible explanation for the facial diastereoselectivity
h
+
PB
COMe
O
O
Et3Al
LDBB
AlEt3
O
C
1-e reduction of C-O bond
+
O
AlEt3
HO
Angularly fused triquinane
JOC, 1998, 63, 5302
TL, 1995, 38, 6851
Chiral enamides and diastereoselective PB reaction
O
N
Ph
N
O
Ph
N
Me
Ph
O
H
N
O
O
O
O
PhCHO/h
+
Ph
O
Ph
Me
N
Ph
Ph
N
Ac2O, TEA
H
O
Ph
MeCHO
H2N
O
H
H
NAc
Ph
Ph
2
1
H
H
Ph
N
Ph
NAc
Me
O
GS conformations of parent enamides
H
Me
Ph
N
H
O
Chiral enamides and diastereoselective PB reaction
O
N
O
O
N
Ph
Ph
O
O
HN
O
O
MeCH(OEt)2
N
O
PhCHO/ h
O
CSA
Ph
Ph
O
+
Ph
Ph
O
N
Ph
Ph
O
N
O
O
H2, Pd/C
Ph
OH
N
O
Ph
O
Li, NH3
Ph
OH
NH2
Ring opening of cis-aminooxetanes obtained by PB photocycloaddition
O
Ph
N
H
OH
LAH/ THF
O
Ph
H
NHMe
OH
Ph
O
R1
Ph
R1
TFA
O
TFA
OH
NBnBoc
NBn
O
Ph
NBnBoc
R1
Ph
R1
O
O
H
H+
O
R1
Ph
NBn
O
OtBu
O
R1
Ph
OH
Ph
+
NBn
R1
NBn
O +
C
OtBu
O
NBn
O
-tBu+
OH
Ph
R1
NBn
O
O
OtBu
Inversion occurs at this center
Tet.Lett, 1997, 38, 3707-10
CHO
Ph
h
+
TFA
O
O
TsCl/py
NMeBoc
Ph
OTs
NMe
NMeBoc
O
OH
LAH/THF
Ph
NMe2
Ph
OTs
O
NMe
OH
O
NaBH4, KOH/EtOH, water
Ph
NHMe
1
1
1
2
6
3
2
ortho
5
4
4
+
para
1
3
meta
Possible modes of addition in the arene-alkene photocycloaddition reactions
6
meta cycloaddition
(3C + 2C)
C
1
C 2
C
C
prefulvene
6
+
C* 
-
6
*
2
3
C
1
5
4
C
2
3
+
Exciplex
para cycloaddition
C* C*
C C
(4C + 2C)
(2C + 2C)
ortho cycloaddition
Mechanistic proposal for the arene-alkene photocycloaddition reaction
CN
CN
h
CN
+
+
2
5
C C
C C
O
O
O
O
z
z
z
O z
O
O
O
z = OMe
z = CONH2, CN, Me
C
C
R
R
-a
b
R
a
+
C
c
R
R
R
-b
R
-ac
C C
R
C
C
R
Possible mode of cleavage of the cyclophotoadduct
R
R
H
h
+
H
R
endo exciplex
R
O
h
+
O
O
secondary orbital intercation is not favored
due to presence of non bonded "O" electron
O
exo adduct
O
O
O
+
O
O
O
O
h
+
O
endo
exo
5
1


*


O
11
1
6
4
5
3
7
3
6
1
C
2
7
2
10
C
h
8
5
4
Favored
3
8
1
6
11
C
2
2
10
C
1
4
7
5
Disfavored
6
5
Isocomene
Br
3
Li, CuI
Li
+
+
Br
O
O
Tetrahedron, 1981, 37, 4445
Li, NH3
4
h
vs.
OMe
OMe
OMe
exo
endo
OMe
H
OMe
favored
disfavored
O
+
Br
Li, Et2O
Li, NH3
OMe
OMe
Allylic stereocontrol: for the synthesis of silphiperfolene
h
Me
Me
Me
vs
Me
H
H
Me
Me
Me
H
disfavored
favored
h, CH3CHO
O
H
H
O
Me
HO
OH
Me
H
Me
PhNO2SeCN
Bu3P
H2 O 2
Li, NH3(l)
H
Me
H
Silphiperfolene
Me
Tet. Lett, 1985, 26, 5987
7
6 5 11
11
10
4
5
h
3
OAc
1
8
4
9
1
3
2
OAc
9
2
Modhephene
H
H
CO 2H
H
hirsutene
-cedrene
retigeranic acid
O
H
O
HO 2C
O
O
O
H
O
O
OH
3-oxosilphinene
coriolin
isoiridomyrmecin
HO
O
O
rudmollin
OH
JACS, 103, 688, 1981
Tet.Lett, 23, 3983, 1982
ibid, 31, 2517, 1990
ibid, 24, 4543, 1983
ibid, 24, 5325, 1983
ibid, 31, 5429, 1990
ibid, 27, 1986, 1857.
subergorgic acid
+
O
C*
Li, Et2O
C*
NH3
Br
C
C
Li, NH3
Silphene
h
h
+
LAH
C
OAc
Me
MeI
Me
Me
Me2CuLi, THF
-780C
O
O
MnO2
C
OAc
LDA,
OAc
OR
(Me2N)2POCl
Me
+
OR
Me
H2, PtO2
Me
O3, MeOH
O NaBH3CN
OR
NaBH4
Me
O
Me
OMe
O
O
Me
Iso iridomyrmecin
CHO
O3, DMS
NH3+
OH
+
CO 2CHO
CHO
O
Br
Zn(BH4)2
TsCl, PCC
O
NBS, AIBN
O
O Ts
O
H2, Pt
KOH
O Ts
O
O
O
O
O
LDA, DMPU
h
I
O
Li, MeNH2
KHMDS
(Me2N)2POCl
O
Me 2N P O
O
O
P
NMe 2
Li, EtNH2
NMe 2
NMe 2
Laurenene
O
OH
C
h
h
C
OHC
C*
C*
HCONH2
+
CO2 H
H2NOC
H2NOC
4+2
HO2C
R2NOC
R2NOC
Retigeranic acid
O
(Ph3P)3RhCl, H2
Br2, AcOH
KOH
Ph3P+CH3Br-,
nBuLi
(-)-Carvone
CO2 H
Li, Et2O
Br
PCC
h, 3C + 2C
EGC/CSA
CHO
O
O
OH
C
(PhCO)2O, h
C
O
CH3CN
O
O
K, 18-C-6
NC
O
O
O
OH
O
Cl
LICA, THF
mCPBA
O
O
O
O
SOCl2
O
O
HO
NaClO2
O
HO2C
O
Subergorgic acid
O
Seven membered ring synthesis based on arene-olefin cycloaddition
OMe
H
h, 3C+ 2C
OH
OMe
H
Hg(OAc)2
OTBS
O
OH
THF, H2O
OTBS
NaBH4
MnO2,H2
(PhCO)2O
OTBS
H
H
H
OR
OR
MsCl, Pyr
OH
O
KHMDS, allyl-I
LAH, Heat
OTBS
OTBS
OTBS
OBn
OTBS
H
OTBS
H
H
O
O
OBn
CO2 H
O
OBn
O
O
H
O
HO
OH
Rudmollin
O
Tet. Lett, 1986, 27, 1857
HO
OH
O
OAc
OAc
OAc
OMe
OTBS
OMe
h
OTBS
C
OMe
OTBS
C
PhSeCl
OAc
OMe
C*
OTBS
OAc
OAc
C*
H
H
OTBS
OTBS
Cl
OTBS
O
O
Cl
O
KOH
O
H
O
H
OH
HO
OH
OTBS
OTBS
O
H
OTBS
OMe
H
OAcOTBS
OMe
OH
OH
Grayanotoxin
Disfavored
Favored
OAc
COX
R
COX
ClOC
R
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
OMe
X
Si-face of olefin in exo-adduct
(Re-face in endo-adduct)
OMe
Introduction
of PD tether
C
OMe
.
X
X
O
*
*
X
Re-face of olefin in exo-adduct
(Si-face in endo-adduct)
O
6-substituted
O
O
O
OH
O Et
O
O
Hg(OAc)2
OH
HO
+
OH
OMe
O
OH
O
O
7-substituted
O
Rn
O
Rn
O
O
2R
O
O
O
O
O
+
+
2S
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
C
O
C
Abolished stereochemistry at C-4
O
C
O
C
Re-face
Re-face
O
MeO
OMe
MgBr
CuCN
Cy-hex-2-enone
MeLi, allyl-I
L-selectride
MeO
MeO
9-BBN
H
DMP
OH
OTBS
OTBS
O
OMe
MeO
MeO
MeO
MeO
OTBS
OH
OTBS
OTBS
endo (favored)
exo ( disfavored)
OH
HO
O
HO
H
OH
aphidicolin
H
stemodinone
OH
Norish Type I Processes of Ketones
Basic Concepts
O
O
h
C
+
R
C
O
O
O
3 X 107
2 X 106
O
O
2 X 108
1 X 108
O
2 X 107
O
1 X 107
O
O
OMe
7 X 105
not measured
>109
# 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

 C
C
n

O
.
O
K
3.3 x 107/s
O*
O
O
4.7 x 10 8/s
1.8 X 10 9/S
O*
O*
<
<
Rate of  cleavage increasing ring strain
Intermediate trapping experiment
O
O
O
C
h
Me
C
NO
NO
acyl-alkyl diradical
O
O
O
O
h
C
-780C
C
C
C
O
H
Me
O
O
h
C
Ph
C
H
C Me
Ph
Me
C H
Ph
disproportionation
retention
O
H
Me
Ph
racemization
O
H
H
H
Ph
H
O
O
C
h
O
C
C
O
O
C
O
h
C
C
O
C
C
O
O
O
recombination
(CH2)n
(CH2)n
h
decarbonylation
C
C
(CH2)n
O
C
C
(CH2)n
(CH 2)n-1CH 3
+
(CH 2)n-1CH 3
O
disproportionation
(CH2)n
H
enal
(CH 2)n-1
O
O
ring expansion
ROH
OR
n
ketene
C
OR
O
ROH
O
(CH2)n
oxacarbene
(CH2)n
n
C
C O
O
C
O
C
O
h
C
O
C
ring opening
C
C
-cleavage
cyclization
O
O
ring opening and cyclization
O
h
O
O
C
(CH 2)n
(CH 2)n
(CH 2)n
OR
ROH
O
(CH 2)n
O
O
h
O
C
H
C
OMe
C
MeOH
O
O
O
h
O
O
O
O
O C
O
O
EtOH
O
O
O Et
O
O
O
O*
O*
h
C
C
C
C
+
CO
S1 (n-*)
Ring expansion
O
Oxa carbene
..
ROH
O
OR
cycloelimination
+
O
O
O
h
O
O
O
..
O
O
OH
R1
h
R1
O
R2
CN
R1
.. HO
H
O
O
R2
CN
CN
R2
H
Ph
E
Ph
Si
O
Ph
h
Ph
Si
O ..
Ph
Ph
Si
E
O
E
E
O
h
O
MeOH
h
ROH
O
O
h
h
ROH
tBuOH
S
S
h
MeOH
Cl
Cl
Zn
+
Me
O
Cl
COCl
O TBS
O TBS
O
Zn/Cu
Me
+
NH4Cl
O TBS
O TBS
3
O
h/ MeOH
OMe
O
TMSCN
1
O
CN
O TBS
1
1
BH3:SMe2
BH3:SMe2
O
N+Me 3 I-
O
MeI
HO
CN
+
O TBS
O TBS
Me
O
O
NH 2
O TBS
NH 2
O TBS
Muscarine
O
N+Me 3 IHO
Tet.Lett, 1988, 29, 159
allo-muscarine
NaOH
O2, h
Cl
Cl
O
O
O
Rose bengal
H2, Pd-C
OH
+
TBSCl
NaOAC/EtOH
O
O
OTBS
MeO2C
h
OTBS
OiPr
O
LAH
PTSA
iPrOH
MeO2C
OTBS
SiMe3
O
OR
O
OMe
OR
LiAlH(OtBu)3
OMe
OsO4, NaIO4
OR
O
OMe
O
BF3:OEt2
TBS-Cl
OTBS
O
OTBS
O
OMe
OH
OTBS
NaH, MeI
F-
PhCOCl
H2
OTBS
BzO
O
OMe
OMe
J. Org. Chem. 1987, 52, 2335
OBz
Pederol dibenzoate
OH
OH
O
h
O
O
O
C
O
OH
OH
O
h
R
R
OH
R'
Wittig
R
HO
OH
R' =
R=
CO 2H
OH
O
OH
O
h
C
OH
O
C
H
O
+
H
R
OTHP
R=
R
O
O
O
O
H
MeCO3H
H
H
H
O
Me
O TBS
O
DIBAL-H
H
CO 2-
Ph 3P+
Bu
O TBS
O TBS
CO 2H
OP
H
+
Me
Bu
CH2N2
HF, MeCN
PCC
H2, Pt/C
Bu
Me
h, MeOH
Bu
O
O TBS
OH
OP
CO2 Me
OP
CO2 Me
OP
H
Me
H
Bu
OH
O
H
H2 O2
O TBS
O TBS
Me2CuLi
H
Bu
Bu
O
LDA, PhSeCl
Me
C
O
C Bu
(CH 2)6CO 2Me
(CH2)6CO 2Me
..
O
Bu
MeO
O
Bu
Thromboxane analogue
• Norish type II photoelimination of ketones:
Cleavage of 1,4-biradicals formed by γhydrogen abstraction
O
R'
R
1O*
h
R'
R
1O*
R'
OH
1K
H
a
OH
R'
R'
R
R
R
n
1O*
1K
d
O
R'
R
R'
R
1O*
3K
d
3O*
Kisc
R'
R
R'
R
3O*
3K
H
OH
O
R'
OH
R'
R
R
R
n
OH
O
R
R
R'
R'
R
R'
R'
T1 (n, *)
S1 (n-*)
H
O
H
C
C
O
C
C
Ph
O
O
racemic
Ph
H
Ph
Ph
optically active
OH
O
Ph
Ph
# Yang cyclization
# cleavage
# hydrgen reversal
H
Solvent effect
X
Ph
Solvent
C
H
C
R
O
Ph
C
solvent
C
R'
R
Ph
OH
racemization
R'
O
H
R
R'
O
R
+
R'
O
# racemization is suppressed in H-bonding solvent
such as t-BuOH
valerophenone
# With H-bonding solvent conformational change of bi-radical
occurs hence influence the decay process.
O
n-*
OMe
O*
2X107
O
O
107
108
O
OMe
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
HO
Ph
h
Ph
O
h
PhCHO
Ph
Ph
O
105/s
Ph
O
h
h
O
H O*
KH = 1.7 x
Ph
105/s
Ph
108/s
K  cleavage = 2.5 x 107/s
+
O*
CHO
HO
Ph
C
+
C
O
O
H
H
H
1.3 x 108
6 X 108
O
7 X 109
Ph
KH
# 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
.
OH
H
O
HO
R
R
1,4 diradicals as intermediates in -hydrogen abstraction
+
O
H
R2
h
R1
R
ISC
C
OH
R
C
R2
R1
R
Spin center shift
R
X
X
O
H
h
Ph
Ph
OMs
O
C
R2
R1
R1
X = OAc, OTs, OMs, ONO2
O
C
O
-HX
O
R2
O
H
h
Ph
Ph
OTs
Photoenolization
R
R
H-Transfer
O
H
OH
O
spin-inversion
R
CO2Me
OH
R
CH3
R
R
OH
CO2Me
CO2Me
CO2Me
CO2Me
+
CO2Me
H
R
R
R
Ph
Ph
Ph
O*
O
OH
H
H
R'OD
H
D
R
R
R
Ph
Ph
Ph
OH
OD
O
h
O
OH
C
Ph
Ph
.
OH
HO
Ph
Me
.
C
Me
Ph
OH
O
Ph
Ph
OH
Synthetic applications
OAc
OAc
OAc
O
O
h
O
O
OAc
OAc
OAc
O
O
CHO
h
O
O
O
N
N
h
O
O
O
O
O
OH
O
h
(-)Ephidrine
Norish II, Cleavage
Enantioselective
H-transfer
CO2 Et
O
CO2 Et
O
h
4+2
OH
O
O
O
O
O
O
O
Photoenolization
MeO
OMe
MeO
OMe
OMe
OMe
O
O
O
CO2 Et
OH
O
MeO
OMe
OMe
Podophyllotoxin derivative
Norish type II process involving 1,6 and greater H transfer reactions
O
OH
OH
1, 7 H abstraction
C
1, 5 H abstraction
C
T1
C
C
h
O
OH
OH
S1
Photocyclization of cyclodecanones
Ph
Ph
Ph
O
O
h
Ph
n
Ph
C
O
nC
Ph
OH
O
n = 0, 1
photocyclization of -[o-(benzoyl) phenyl ] acetophenone
OH
n
O
O
O
h
OH
H
O
O
O
H
C
O
C
C
C
n
photocyclization of o-methylphenyl 1,3-diketone
R
O
O
R
R
OH
C C Ph
h
Ph
OH
Ph
photocyclization of o-benzyl substituted ketones
O
OHOR
OR
HO
h
O
OO
O
O
O
OR
Long distance H abstraction
O
X
X
Ph
O
O
O
h
O
h
O
OH
1, 9 H
Ph
O
X 1, 5 H
O
X
C
C
O
O
O
X
X
Ph
O
H
O
O
C
C
O
Ph
H
X = H or D
Me
n
Me
O
O
Ph
O
(CH2)x
(CH2)y
O
h
HO
Ph
n = 12-18
Remote oxidation of unactivated methylene groups
O
O
R
R
h
OH
R = H, Me
O
O
Ph
Ph
h
O
OH
O
O
Photochemical synthesis of tetrahydropyran-3-ols and benzopyranols
h
n=1
O
O
(CH2)n
(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
Ph
h
Ph
Ph
Ph
Ph
O
Tol
Ph
h
Ph
O
Ph
Tol
Ph
Ph
h
Ph
C
Ph
h
Ph
Ph
Ph
Ph
Ph
Ph
..
Ph
Ph
Ph
C
Ph
Ph
Ph
Ph
Ph
The basic reaction mechanism; singlet mechanism
Ph
R2
R2
h
R2
C
C
R1
Ph
Ph
h
R1
Ph
R1
R1
R2
Ph
Ph
R2
R1
..
R1
R2
Ph
The triplet rearrangement
a
Ph
Ph
h
Ph
Ph
sens
Ph
C
Ph
C
.
C
Ph
b
Ph
Ph
Ph
Ph
Ph
a
Tol
Ph
Tol
h
Ph
C
Tol
C
.
C
Ph
a
Tol
b
Ph
Me
b
Me
Tol
Ph
The triplet rearrangement of 3-phenyl regioisomer
a
Ph
Ph
h
Tol
Me
sens
Tol
C
Ph
C
.
C
Me
Tol
b
Me
b
Ph
Tol
a
Ph
Tol
Me
The triplet rearrangement of 3-methyl regioisomer
a
Me
Me
h
Tol
Ph
sens
Tol
C
Me
C
.
C
Ph
Tol
b
Ph
b
Ph
Me
Tol
a
Me
Tol
Ph
Proof of cyclobutenylcarbinyl diradical as an intermediate
a
Ph
N
Tol
N
Ph
h
C
.
-N2
b
a
Tol
b
Ph
Tol
Ph
Tol
The acylcyclopropene triplet rearrangement
O
Tol
O
Tol
h
Ph
Ph
Ph
Ph
Ph
a
b
Tol
O
Tol
Ph
Ph
b
.
C
sens
Ph
O
Tol
a
Ph
O
Me
Ph
The Di- Methane Rearrangement
C
h
C
C
C
h
C
Ph
C
C
Ph
C
h
Barrelene
Semibullvalene
Chem.Rev; 1996, 96, 3065-3112
Reaction regioselectivity
C
C
Ph
C
A
A
Ph
B
C
B
Ph
C
Ph
Ph
Ph
h
Ph
Ph
Ph
Ph
C
Ph
Ph
Major
Minor
# Stabilty of benzyhydryl biradical
# More available electron density for ring opening
C
Ph
C
Ph
Ph
Ph
C
C
Ph
Ph
X
C
C
Ph
Ph
C
Ph
Ph
Ph
C
Ph
Ph
Ph
Electronic factor on regiochemical outcome
h
Ph
Ph
CN
direct
+
NC
Ph
h
Ph
Ph
OMe
direct
Ph
Ph
+
Ph
NC
Ph
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
OMe
MeO
OMe
Multiplicity control of regioselectivity
Ph
C
Ph
Ph
s
s
Ph
Ph
Ph
Ph
Ph
t
t
Ph
C
CO2Me
C CO2Me
C
C
CO2Me
Ph
CO2Me
Ph
C
Ph
Ph
Ph
CO2Me
Ph
Ph
Ph
CO2Me
Ph
Ph
CO2Me
Ph
Ph
CO2Me
Ph
Ph
Ph
CO2Me
CO2Me
MeO2C
S1
S1
E
2K
2K
T1
T1
Large K vs. small K control of excited state selectivity
CO2Me
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
PhPh
Ph
Ph
Ph
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
h
NC
NC
Major
JACS, 1977, 99, 3723-33
The Oxa-di--methane rearrangement
Ph
H
Ph
Ph
Ph
O
Ph
h
H
Ph
Ph
O
OPDM
Ph
H
C
O
O
O
C
C
O
C
X
O
O
OAc
OAc
OAc
h, Direct
+
O
O
O
O
CD3
O
CD3
CD3
h
Ph
O
Chrysene/sens.
O
Ph
O
racemization
Retention of Configuration
h
O
Chrysene Sens.
O
h
O
Chrysene Sens.
O
Inversion of conviguration
H
CH2 CO2 H
O
h
CH2 CO2 H
acetone snes.
O
O
But
H
tBu
H
h
Direct
O
tBu O
O
tBu
H
H
tBuH
tBu
O
O
R1
R2
Me
R2
h
acetone snes.
R3
R3
R1
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
D
O
O
Me
O
O
Me
Ph
O
Me
O
Me
O
Me
O
Me
Me
O
O
OH
Me
Me
Ph
O
Ph
O
OEt
Me
Me
O
O
O
Me
Ph
Ph
Ph
O
Ph
O
Me
O
Ph
O
Ph
Unreactive towards OPDM
Ph
O
O
Ph
O
Ph
Ph
Ph
O
Ph
O
Ph
Ph
O
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
O
n
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
CO2Me
O
CO2Me
O
O
O
O
+
O
The OPDM rearrangement of Bridged cyclic -unsaturated ketones
R2
R
O
h, sens
R1
O
R1 = Me, R2 = H
R1 = H, R2 = Me
R1 = R2 = H
O
O
h, sens
h, sens
O
O
Synthetic application of OPDM rearrangement
OMEM
Me
H
OMEM
O
O
h/ sens
OMEM
O
O
H
(-)-Silphiperfol-6-en-5-one
7 steps
H
h
MeO2C
CO2Me
CO2Me
O
MeO2C
Sens
O
H
O
OH
Cedrol
Tetrahedron, 1981, 37, 4401-10
O
CO 2Me
CO 2Me
CO 2Me
CO 2Me
CO 2Me
O
O
O
H
OH
H
H
O
O
CO 2Me
H
CO 2Me
COMe
H
CO 2Me
COMe
OAc
H
NC
Cl
O
+
h/ sens
O
(racemic)-modhephene
OPiv
OPiv
OPiv
Li/NH3
Ac2O, DMAP/TEA
h/sens
O
OPiv
H
O
MeO
OAc
O
OHC
Swern
O
O
O
H
H
H
O
O
MeO
O
O
O
CO2Me
OTf
CO2Me
H
H
Pentalenolactone P methylester
JACS, 1992, 114,7387-95
H
O
OH
O
OH
OP
HO
+
HO
O
h
acetone
H
O
OP
(-) Hirsutene
PT (1), 2002, 2439
H
HO
OH
O
OH
h
(Me3Sn)2
sens
O
3-OH-Peristylane
R
R
h
O
MeO
Acetone/iPrOH
O
O
H
- Me
R
R
R
O
O H
R = CH2CH2OMe
O
H Donor
OH
C
C
O H
O H
O
b
O
O
O
h
O
a
O
O
O
OH
O
O
O
O
OH
OH
(-) Coriolin
O
O
Competition between all-carbon DPM and OPDM rearrangement
b
a
O
O
h
h
O
a = benzo vinyl
b = keto vinyl
O
O
O
DPM
vinyl-vinyl > keto-vinyl > benzo-vinyl
MeO2C
MeO2C
MeO2C
CO2Me
MeO2C
O
O
O
O
H
DPM
O
MeO2C
ODPM
O
O
ODPM
H
O
Not observed
O
O
O
R
O
X
DPM
O
X
R
O
Benzo-vinyl > keto vinyl
O
.
O
O
C
C
R
Stable biradical
O
X
O
R
X
O
The OPDM rearrangement of -unsaturated aldehydes
OAc
H
O
h
H
+
+
Direct or sens
O
O
O
CHO
O
OH
H
h, sens
Ph
Ph
O
Ph
CHO
Ph
h, sens
H
Ph
H
O
H
Ph
H
CHO
CHO
CHO
h, sens
CHO
CHO
h, sens
CHO
H
CHO
h, sens
n
Ph
Ph
n = 1, 90%
n = 2, 25%
n = 3, 25%
Direct
CHO
Ph
h
CHO
Ph
Sens
CHO
+
Ph
Ph
CHO
CHO
CHO
O
O
h
CHO
O
R = H, Bioallethrin
R = vinyl, pyrethrin
R
The Aza-di--methane (ADPM) Rearrangement
h, sens
N
Ph
Ph
Ph
H3O+
Ph
Ph
Ph
Ph
N
O
Ph
*T1
Ph
N
Ph
h, sens
R
Ph
Ph
N
Ph
R
C
N
Ph
R
X
C
Ph
Ph
Ph
N
C
N
N R
Ph
R
Ph
Ph
R
Ph
N
Ph
R
Ph
-.
Ph
Ph
Ph
R
Ph
Ph
C
Ph
N
R
Ph
N
Ar
N
+. R
Ph
Ph
Ph
Ar = Ph
Ar = 4-OMe
Ar = 4 Cl
Ar = 3 Me
Ar = 4 CN
SET
N
N
R
N
Ph
Ar = Ph
Ar = 4 Me
Ar = 4 Cl
Ar = 3 F
Ar = 4 CF3
Ar
N
Ph
Ph
OH
Ph
N
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
IP of the oxime can be raised by incorporating Ac group
OAc
N
N
OAc
N
N
OAc
N
OAc
OAc
N OAc
N
N
OAc
OAc
H
N
n
n = 1, 2, 3
OAc
n
N OAc
OAc
Photorearrangement of cyclohexenones
O
O
2
2
h
3
5
R
5
R
3
R
4
4
R
Type A
OAc
OAc
h/ tBuOH
O
O
O
Ph
h
O
Ph
Ph
Ph
H
Ph
O
+
Ph
O
h
Type B
Me
O
Me
O
+
Me
Mechanism and stereochemistry of Type A rearrangement
R1
R1
R2
R2
O
H
H
O
R1
O
R2
H
H
O
R1
H
H
R1
R2
O
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
O
h
R
R
R
O
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
O
OAc
Mechanism and stereochemistry of Type B rearrangement:
Aryl and vinyl migration
O
O
O
hdirect
H
Ph
h-sens
Ph
Ph
H
Ph
H
Major (endo)
+
H
Ph
Ph
Minor (exo)
O
Ph
Ph
C
Ph
H
O
O
Me
h
H
O
Ph
Me
H
Ph
H
X
Me
H
H
Me
C
Ph
O
O
Ph
Me
Me
Ph
O
R
R
R
R
h
Ph
Ph
Ph
Ph
R
R
R
C
R
C
Ph
Ph
C
+
Ph
C
+
Photochemical cycloaddition reaction
(enone olefin cycloaddition)
O
O
+
h
ISC
1(enone)*
3(enone)*
alkene
3(enone-alkene)*
Exciplex
h
biradical
enone
cycloadduct
Chem.Rev; 1988,88, 1453-73
O
O
W
X
O
ISC
Y
z
W
z
Y
X
n
n
n
hn
Exciplex
O
O
O
n
+
n
n
Reversion
O
ISC
O
O
+
n
n
n
O
H
h
C
CHO
closure
C
fission
CHO
abstraction
O
O
furopelargone
CHO
Regiochemistry of enone cycloaddition
O
CN
O Et
O
O
CN
O Et
O Et
O Et 
O
head to tail
O -

O
O Et
h

reversal of polarity
-
N
CN

O
CN
head to head
OAc
O
O
OMe
OAc
+
O
O
98%
OMe
O
O
O
OAc
O
96%
O
nBu
+
nBu
nBu
O
O
nBu OAc
only
CO 2 Et
O Et
O Et
O Et
O Et
82.5
O
O
O Et
CO 2 Et
+
EtO
81
O
CO 2 Et
17.5
O
SiMe 3
SiMe 3
SiMe 3
+
1
1
O
O
O
O
O
O
O
+
OAc
OAc
95
OAc
O
5
O
19
X
X=O
head to tail
O
O
O
O
O
O
CO2Et
CO 2Et
+
EtO
OEt
OEt
RT
-40OC
82.5
94
O
17.5
6
O
O
CO2Et
CO 2Et
head to head
+
EtO
CO2Et
OEt
O
83.5
91.5
16.5
8.5
O
O
CO2Et
CO 2Et
+
OEt
OEt
OEt
OEt
CO2Et
OEt
RT
-40OC
OEt
OEt
OEt
OEt
RT
-40OC
EtO
CO2Et
OEt
O
OEt
OEt
71
100
29
0
O
O
O
OAc
h
O
OAc
h
OAc
K+
O
O
O
Aqueous phase
O
K+
O
O
O
nHex
nBu
nBu
O
O
O
nBu
O
nBu
nBu
nHex
nBu
nBu
cyclohexane 51: 49
micelle
78: 22
Micelle core
nBu
nHex nHex
cyclohexane 53: 47
micelle
88 : 12
Stereochemistry of enone cycloaddition
O
O
O
Y
O
Y
+
+
Y
X
Y
X
1. ring fusion stereochemistry
2. stereochemistry of a wrt b or vice versa
3. Remote substituents effect (X and Z)
O
+
or
or
O
always cis ring fusion
O
Y
Y
+
O
O
Y
can be cis or trans
cis is favored
O
or
always cis ring fusion
O
b
X
O
O
a
X
1. ring junction stereochemistry
2. exo or endo (Y)
3. cis or trans with respect to each other (y)
4. effect of remote substituents X
O
z
Y
H
Y
Y
Y
Y
R
always cis fused ring junction
+
R
rigid cyclohexenones
(presnce of heteroatoms,
fused ring)
z
O
H
always cis
H
O
O
H
always cis
H
O
H
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
C
h
C
h
C
C
Intramolecular enone cycloadditions
O
O
OMe
HH : HT = 0 : 100
h
OMe
O
O
HH : HT = 26 : 74
h
O
O
HH : HT = 70 : 30
O
O*
d-
d+
h
O
O
R
d-
O
d+
HH : HT = 87 : 13
Me
h
O
O
O
C
h
OMe
OMe HH : HT = 100 : 0
C
R
enone cycloadditions in organic synthesis
h
H
MeOH
O
O
OMe
H
H
O
hirsutene
O
O
Ph3P=CH2
h
TsOH
isocumene
O
+
H H
O
H H
H+
MeLi
h
OH
OH
H
H
-caryophyllene alcohol
O
O
vinyl chloride, h
CO protect
O
TsOH
Na/ NH3, H+
Cargill rearrangement
modhephene
O
O
O
H
+
h
H
H
+
H
H
H
MgBr
O
O
H
H
KH
H
HO
H
18-C-6
H
thermal ring opening
O
O
O
O
Tet. Lett, 1981, 22, 4651
periplanone B
O
O
N
O
N
O
N
h
O
O
O
O
H
H
+
MeO 2C
MeO 2C
MeO 2C
OH
MeOH/H+
H
H
(-) Grandisol
CN
HO
JACS, 1986, 108, 306-307
SnMe 3
+
OP
OAc
OP
O
OP
O
-allyl Stille cross coupling
OP
Intramolecular 2+2
photocycloaddition
h
OP
OP
O
elimination
X
OP
O
Fragmentation
OP
enolate trapping
OP
O
O
CHO
OH
OP
AcO
Guanacastepenes
Guanacastepene A
JACS, 2006, 128, 7025-35
O
O
NOR
H
O
O
CO 2Me
CN
H
N
N
H
H
O
H
O
Dendrobine
O
O
TBHP, SeO2
h
NCS, DCM
O
Cl
O
H
Cl
O
H
LTMP, MeI
Li, NH3
Me
H
H
H
O OEt
O P OEt
LDA, ClPO(OEt)2
Me
Li, NH3
H
Acoradiene
HCA, 1983, 66, 522
H
O
H
H
MVK, Pyrrolidine
h
(CH2)n
(CH2)n
(CH2)n
O
O
n = 1, 2
[6,6,5,4] Fenestrane
O
h
O
CO2Et
NaH, HCO2Et
O
h
O
TSN3, TEA
CO2Me
N2
[5,5,4,4] Fenestrane ester
Tet. Lett, 1982, 23, 711
SiMe3
CO2Me
CO2Me
h
O
O
O
CO2Et
LAH, Swern
CO2Et
Li, NH3
O
Ph3P=CHCO2Et
O
H2, Pd/C
O
Laurenene
JACS, 1987, 109, 6199
De Mayo Reaction
O
+
h
O
OH
OH
O
O
O
h
O TBDPS
O TBDPS
O
O TBDPS
TiCl3
O
aq. HF
O
Azulene intermediate
R1
MeO 2C
CHO
h
R1
CO 2Me
H
OH
R2
R2
OH
methyl diformylacetate
R1
CHO
+
R2
CO 2Me
O
OH
tetrahydrocoumalate
OH
H
H
HO
h
+
OAc
OAc
OAc
OHC
CO2Me
OHC
O
HO
H
O
MeO
CO2Me
loganin aglucone acetate
HO
+
OHC
OH
H
H
CO2MeMeO
O
h
O
HO
OHC
MeO
H
O
O
O
OMe
OMe
CO2Me
O
O
O
CO2Me
Sarracenin
O
O
O
HO
O
h
OH
O
cis fused
OAc
O
O
O
acid or base
O
base
trans fused
h
OAc
O
O
O
Cl
+
OAc
Cl
H
h
OAc
O
Cl
Cl
O
Cl
base
Cl
O
HO
O
O
CO 2Me
h
+
OAc Cl
O
CO 2Me
Cl
CO 2Me
HO
OH
CO 2Me
MeO 2C
O
O
O
CO 2Me
OAc
OAc
h
+
OAc
O
O
O
O
O
O
H
H
O
-himachalene
O
O
O
O
OAc
O
O
OAc
OAc
h
OAc
O
O
O
OH
O
O
OH
OAc
base
h
OAc
+
CO
MeO
Pb(OAc)4
O
O
O
O
h
O
O
O
+
O
O
HO
CO 2Me
HO
CO 2Me
CO 2Me
O
O
O
OHC
OAc
base
h
+
OHC
CO 2Me
methyl isomarasmate
O
HO
CO
O
Pb(OAc)4
CO 2Me
acorenone
Non symmetrical -diketones
O
OH
O
Ph
O
OH
Ph
O
Ph
major
O
OH
O
OH
O
CO 2Me
OHC
CH3
OH
O
CO 2Me
OH
CHO
OMe
O
O
CO 2Me
OHC
HO
O
CH3
CH3
O
OH
O
CHO
CO 2Me
OH
OHC
CO 2Me
OH
O
CHO
CHO
O
HO
O
N
h
+
O
O
O
O
CHO
O
h
NC
+
HO
OH
O
h
O
O
O
DIBAL-H
O
+
CHO
O
O
CHO
OH
h
+
X
OBn
O
OAc
OBn
OBn
OAc
OAc
h
+
O
O
O
O
O
O
OH
OBn
OAc
CHO
OH
genipic acid
OMe
CO 2Me
O
O
O
NMe
CHO
N
NMe O
+
h
N
CO 2Me
CO2Me
OH
O
CO 2Me
X
h
OH
OH
OH
h
CHO
+
O
O
O
O
valerane
isovalerane
OH
O
+
h
CHO
O
O
1,3 -dicarbonyl compounds (intramolecular De-Mayo reaction)
O
O
O
(CH2)n
X
(CH2)n
(CH2)n
OR
OR
X = O, NR
O
O
O
O
OR
(CH2)n
(CH2)n
Different templates
O
OH
O
O
O
H
HO2 C
O
h, MeCN
DCC
+
O
O
OTBS
OTBS
O
O
O H
O
O
OH
H
H
O
MeO
O
O
H
OBn
H
MeO
H
OBn
H
Stoechospermol
H
OBn
Tet.Lett, 1985, 26, 3035
H
OTBS
O
OH
O
O
h
O
O
O
O
O
H
O
O
OH
O
H
CO2Me
O
O
O
O
O
O
O
O
O
O
O
H
H
CO2Me
CO2Me
Methyl ester of Pentalenolactone G
O
O
O
O
O
JOC, 1988, 53, 227
Intramolecular De-Mayo reaction
O
O
Ph
N
COCl
O
O
O
O
h
+
O
OCO2 Ph
OHO
O
JACS, 1978, 100, 2583.
Longifolene
O
O
HO
h
OMs
OAc
OAc
OAc
-bulnesene
O
O
O
O
HO
Me3CuLi2
TBS-Cl, h/Pyrex
Me
O
HF, THF, H2O
OTBS
OTBS
O
Me
Ph3P=CH2
RhCl3, 3H2O
BF3:OEt2
Me
Me
Me
Me
Me
Pentalene
Me
O
O
OAc
Ac2O
+
O
OAc
O
h
O
O
O
O
+
O
OAc
OAc
O
O
OTs
O
O
L-selectride
KTB
HO
Ts-Cl
HO
Dioxolenones as -keto ester equivalents
O
O
h, acetone
O
CO 2Me
PTSA/MeOH
O
O
O
O
(CH2)n
O
(CH2)n
(CH2)n
O
O
O
O
h
O
PTSA, MeOH
CHO
OTBS
O
DIBAL-H
OTBS
OTBS
OTBS O
Trans
H
cis:trans = 4:1
O
H
O
OTBS
O
O
Cis
O
O
O
O
O
H
CO2Me
O
PTSA/MeOH
h
O
H
O
H
O
H
Smallest known inside-outside bicycloalkane
O
O
O
Ac2O, TFA
LDA, MeOPhOCOCN
O
OMe
Acetone
O
O
h
O
KOH, MeOH
O
O
O
O
O
CO2 H
Ingenane skeleton
MeO2 C
MeO2 C
O
HN
h, MeCN
O
HN
O
O
O
O
O
O
O
O
NaBH4
CO2Me
HN
MeO2 C
HN
HN
NaH
O
O
OH
Perhydrohistrionicotoxin
O
O
OH
O
O
O
O
h
+
O
O
HO
O
O
RuO4
O
O
KOH/H2O
O
O
synthesis of Taxane sceleton (Chem. Lett, 1985, 323)
O
CO2H
O
O
O
H
H
h
O
O
O
O
O
nPr
OTMS
H
TMSOTf
O
nPr
nPr
HCl, H2O
O
O
O
O
MeLi
O
O
h
OH
HO
HO
grandisol
O
O
O
O
OH
HO 2C
h
fragrantol
O
O
O
OH
h
O
HO 2C
OH
O
O
O
O
OAc
OAc
h
+
+
OAc
O
OAc
OAc
O
O
O
O
+
OAc
78
22
OAc
OSiMe 3
O
OAc
O
MeMgI
O
O
CO 2Me
H O HO
HO
CHO
OH
n
O
lineatin
O
CO2R
O
O
CO2R
CO2R
H
H
+
h
O
OH
OH
O P OEt
OH
OH
OEt
H
H
epijunenol
O
O
O
h
heat
+
MeO
OH
H+
+
C
OMe
OMe
OMe
OMe
OMe
OMe
O
OHC
CO
OMe
O
CHO
helminthosporal
sativine
Copper (I) catalyzed intra and intermolecular photocycloaddition of alkenes
h
M
+
S
M-S
M
+
P
MLCT
*
4s (-acceptor)
3d (-donor)
LMCT

copper orbitals
molecular
orbitals
olefin orbitals
Schematic energy level diagram for copper (I)-olefin coordination
+
Cu
Cu
.
Cu
+
+
h, LMCT
+
+
Cu+
Cu+
-
+
-
h, MLCT
.
Cu++
.
.
-
Cu+
+
Cu
Cu+
CuOTf, h
trans fused
CuOTf, h
+
trans fused
h
CuOTf
CuOTf
trans fused
1,3 H shift
+
- Cu+
C
+
C
Cu
Cu
CuOTf, h
O
O
CuOTf, h
HO
HO
CuOTf, h
O
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
OMe
HO
OMe
HO
OH
OHC
CHO
O
HO
H
Robustadial A; H = 
Robustadial B; H = 
JACS, 1986, 108, 1311.
Photoreduction: Addition to a C-H bond
O
O
Meo
O
O
# Photochemical reduction of carbonyl compounds is a useful
complimentary method to the numerous thermal methods
OH
h
Ph
O
Ph
+
Ph2CHOH
C
Ph
Ph
HO
Ph
Ph
OH
Ph
Ph
Me
CH2.
Ph
O
Ph
OH
h
+
Ph
C
Ph
HO
Ph
+
Ph
OH
Ph
+
Ph
Ph
Ph
O
Ph
OH
h
+
CH3OH
Ph
C
+
Ph
HO
.CH2OH
Ph
H
Ph
OH
Ph
Ph
HO
Ph
OH
+
CH2OH
PH
Ph
H
Ph
OH
H
O
Ph
CH2OH
OH
h
Ph
O
Ph
+
Me 2CHOH
Ph
C
Ph
OH
+
Me
C
Me
Ph
O
Ph
HO
Ph
OH
Ph
OH
Ph
Ph
C
Ph
+
O
Ph
Ph
O
Ph
+
N
Ph
h
Ph
C O
N
+
OH
Ph
Ph
Ph
HO
C
Ph
Ph
Ph
OH
Ph
Ph
Ph
+
N
coupling
disproportionation
h
2
O
OH OH
OH
C OH
+
OH
OH
H -transfer
O
# which pathway is preferred depends on the radical pair
# nature of H donor and the conditions used for irradiation
+
OH
Photoreduction of the carbonyl * state via hydrogen abstraction
Kr M -1s-1
O
OH
OH
C
2 x 106
O
OH
OH
C
Ph
1 X 103
Ph
O
OH
OH
C
O
1.6 X 106
OH
OH
Me
C
1.6 X 105
Me
O
OH
OH
Me
C
Me
Me
Me
3.2 X 104
X
H
H
X
In plane approach
Perpendicular approach
* LUMO
* LUMO
*
n
HOMO
HOMO

H
H
C.
O.
First excited state (n*)
X
H
H
O
In plane approach
C.
O.
O
H
* LUMO
H .X
X
E2
*
n
E1
HOMO

H
C.
O.
First excited state (*)
Intramolecular photoreduction
R
O
O
O
Ph
OH
h
Ph
OR
OH
Ph
h
O
Ph
h
OH
O
Ph
O
O
Ph
h
O
O
O
Ph OH
Ph
Ph
h
O
O
Ph
H OH
Ph
O
h

Ph
Ph
Ph
O
C
Ph
OH
Ph
OH
OH
O
h
NMe 2
Ph
Ph
OH
NMe 2
+
H
H
Ph
NMe 2

 O
Ph
NMe 2
C
Ph
O
NMe 2
C
C
CO2Me
CO2Me
O
N
h
HO
N
Ph
Ph
z
Ph
CO 2Me
z
HO
+
Ph
Ph
Ph
N
z
Ph
Photoreduction of carbonyl (n*) state via electron and charge transfer
Ar2C=O*(T1)
+
Ar2C.-O-
RCH2NR'2
back electron transfer
Ar2C=O
+
RCH2N.+R'2
Kh
Proton transfer
RCH2NR'2
Ar2C.OH
+
RC.HNR'2
Disproportionation/
back H transfer
Ar
Ar
Ar
NR' 2
OH
R
+
Ar
Ar
Ar
OH
OH


n
n
n


H
O
N
O
H
H
n*

H
O
N
H
+
H
Competition between H-abstraction and charge transfer
O
O
O
N
XAN(n*)
O
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
HN
O
NH2
R'
260 nm (*)
N
PYRIMIDINES
270 nm (*)
N
O
R
N
R
Ura
Urd
UMP
R'=H
R'=H
R'=H
R=H
R = ribose
R = ribose phosphate
Thy
Thd
TMP
R ' = Me
R ' = Me
R ' = Me
R=H
R = deoxyribose
R = deoxyribose phosphate
Cyt
Cyd
CMP
R=H
R = ribose
R = ribose phosphate
O
NH2
N
N
N
N
N
HN
PURINES
H2 N
N
N
R
R
Ade
Ado
AMP
R=H
R = ribose
R = ribose phosphate
Gua
Guo
GMP
R=H
R = ribose
R = ribose phosphate
O
NH2
H
HN
N
O
NH
N
H
N
H
heat
O
NH
N
H
O
O
O
O
O
O
N
H
O
O
HO
O
H
O
HO
O P O
O P O
OH
O
OH
O
h
NH2
O
O
OH
NH
N
N
h
O
O
HO
O P O
O
OH
O P O
O
O
N
O
O
O
HO
N
N
O
O
N
O
O
N
O
O
N
O H
N
N
N
NH2
NH2
O
O
OH
HO
O P O
O
Possible photoreaction at dipyrimidine sequences (CT); cyclobutane and oxetane formation
OH
N
NH
N
h
O
N
O
N
OH
N
HO
HO
O
HO
N
N
O
h
O
OH
N
O
O P O
O
HO
O
O
N
O
O
OH
HN
N
heat
N
O
O
O P O
O
OH
O
N
O
O
O
O
OH
OH
N
N
O P O
OH
NH2
N
H
O
O
NH2
O
O
O P O
OH
O
N
NH
OH
O
O
O P O
O
H
heat
O
H
O
O
H
HN
NH
O
O
HO
O
H
H
O
N
O
O
NH2
NH2
N
N
O
O
O
OH
HO
O
O P O
O
OH
O
O
NH2
HN
O
HN
N
N
N
N
N
h
O
HO
O
N
N
N
O P O
O
O P O
N
NH2
O
O
O
N
O
NH2
N
N
O
HO
HO
OH
NH2
N
OH
O
O
N
N
O
O P O
N
N
N
N
O
O
NH2
N
O
h
N
N
O
O P O
O
NH2
N
N
O
N
N
OH
OH
Cycloadditions involving adenine; Cyclobutane and azetidine dimer formation
O
h
N
O
O
O
N
EtOH
N
O
H
H
OH
N
+
O
N
N
OH
O
O
h
H N
O
Thy
N
H
O
H N
O
NH
N
H
H
N
H H
O
O
HN
O
O
HN
HO
O
O
N
Lysine
OH
CO 2H
h
H 2N
O
HN
N
H
heat
O
O
N
NH2
+
NH
HO
O
HO
CO 2H
NH2
OH
HO
radical and nucleophilic photochemical addition reaction of thymidine derivatives
Structures of the major photoproducts induced by UVR
X
O
X
HN
H
N
O
N
O
N
HN
O
Cyclobutyl pyrimidine dimer
N
NH2
N
N
OH
N
N
H
N
N
Adenine-thymine heterodimer
O
O
N
O
O
N
O
O
H
HN
Me
N
OH
H
H
N
OH
H
Cytosine photohydrate
Dewar pyrimidinone
O
NH
NH2
H
OH
HN
O
Me
N
OH
H
Thymine phohydrates
DNA repair: photochemistry
O
R3
R1 R1
O
O
N
N
O
N
R2
H H
R3
R3
O
O
R2
N
R2
Cis-syn
O
H H
R3
R3
N
N
O
N
R1 R1
R1 R1
N
O
N
O
O
O
N
R2
R3
N
H H
R3
O
O
R2
O
N
N
N
R2
H H
R3
O
trans-anti
Cis-anti
trans-syn
R1 R1
N
N
R2
R2
structures of the pyrimidine dimers and abbreviations
O
OH
N
N
H
c-s[TT]; c-s[DMTD]
Cl
Cl
Cl
Cl
O
c-s[DMTD]; t-s[DMTD]; c-a[DMTD]
c-s[DMTD]; c-s[DMUD]
OH
(CHOH)3
N
N
N
N
NH
N
O
c-s[TT]
O
O
N
N
NH
O
c-s[TT]
Dimer splitting sensitizers
O
NH
O
c-s[TT]
Dimer splitting by covalently linked sensitizers
O
O
N
O
O
h
N
N
O
O
R
N
O
+
N
R
N
O
N
N
OMe
MeO
R=
N
H
N
H
N
H
H
OMe
O
N
N
O
O
NH
X
HN
+
O
NH
N
H
O
N
H
Complex
O
h
X = N, CH
1 flavin----------Thymine
3
O
N
N
X
flavin----------Thymine dimer
O
O
NH
C
dimer
+
HN
O
O
NH
N
N
H
O
electron transfer
radical pair
O
O
O
1 e from
HN
O
+
N
2
HN
flavin
O
NH
HN
O
Possible mechanism for flavin as sensitizers for dimer photomonomerization
NH
H2
C
O
O
N
O
N
N
N
O
O
HO2 C
N
H
HO
N
N
O
NH
O
Intramolecularly photosensitized dimer splitting by a deazaflavin (irr = 436 nm)
Dimer Splitting by noncovalently bound chromophores
COR1
CO
N
N
CO N
O
O
N
R2
R2
H N
H N
N
CO
NCOR1
NH
N
ON
NH
O
Bu
Bu
CO
MeO
R1 =
N
H
N
H
Photo reactivating enzyme (PRE) or photolyase (EC : 4.1.99.3)
5
O
5
Me
NH
HO
N
CH2
N
1
3
O
CHOH
O
Me
NH
Reduction
HO
e-
N
N
1
3
+
Dimer splitting
O
8-OH-5-deaza-isoalloxazine H2
CHOH
CHOH
OH
O P OR
O
8-hydroxy-5-deaza-isoalloxazine
NH2
N
O
N
OHOH
N
N
Scenedesmus acutus (green alga)
Bioluminescence
Fireflies
Artistic rendering of bioluminescent Antarctic krill
HO
S
S
N
N
Oxyluciferin
Firefly luciferin
OH
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
11-cis retinal
Rhodopsin
CHO
NH+
P
H+
NH+
N
P
P
Metarhodopsin II
Bathorhodopsin (contains all trans retinal)
H3O+
CHO
all trans retinal
Opsin
retinal isomerase
11-cis retinal
CHO
Nature's Fluorophore (GFP)
O
Tyr-66
HO
Gly-67
N
H
HN
HO
O
N
O
O
HN
HO
O
HO
NH
OH
NH
Ser-65
-H2O
O
O
N
HO
H
N
+
HO
O
O2
NH
N
HO
N
HO
Fluorophore (absorb = 397nm, emit = 509 nm)
Aequorea victoria (Pacific jellyfish)
O
NH
Photochemical aromatic
substitution reaction
Electron rich
SE is more common than SN reaction
# Majority of SE reaction is of SEAr 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
L
Nu-
hn
EWG
EWG
Nu
Nu
- L-
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=
+
18
OH-
HPo4=
H2O
NO2
NO2
NHCH3
OPO3=
h
+
MeNH2
+
HPo4=
+
MeOH
H2O
NO2
NO2
O
OMe
h
+
NO2
+
h
OHH2O
NO2
OH
OMe
heat
OMe
NO2
OMe
OHH2O/THF
OMe
NO2
OH
h
NO2
X
NO2
X
h, NO2-
h, NO2-
MeOH
NH2
MeOH
NH2
X = Cl, Br, I
NO2
NMe2
NMe2
SO2 X
Nu
h/Nu-
NH2
NH2
X = NH2, Me, CF3
Nu = CN-, NO2-, SCN-, MeO-
Cl
SO3Na
h/Na2SO3
R
R
R = NH2, NMe2, OH
OMe
OMe
OMe
CN
h, CN-
+
MeOH
CN
OMe
OMe
OMe
h,
CN
CN-
tBUOH
OMe
OMe
h, CNMeOH
OMe
CN
CN
NO2
h, CNMeCN/H2O
NO2
h, CNCN
tBuOH/H2O
CN
h, CNtBuOH/H2O
CN
h, CNtBuOH/H2O
Alternate mechanism SN(ET)Ar
L
L
L
h
Nu-
EWG
L
Nu
-L-
EWG
-.
EWG
EWG
Nu
Nu.
EWG
NHhex
OMe
SN(ET)Ar*
OMe
OMe
+
NO2
n-HexNH2
OMe
NHhex
SN2Ar
NO2
NO2
NO2
n-HexNH2
O2N
NHhex
MeO
GlyEt
SN(ET)Ar*
SN2Ar
OMe
NH2CH2CO2Et
SR+N1Ar* mechanism
L
L
L
-e-
h
.+
EDG
L
EDG
EDG
Nu
Nu
Nu
-L-
.
Nu-
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, CNtBuOH/H2O
CN
CN
OMe
OMe
h, CNtBuOH/H2O
NO 2
OMe
h, NaOMe
MeOH
OMe
OMe
OMe
h,
N
OCN-
O
NH2
H2O
H2O, O2
NO2
NO2
NO2
OMe
OMe
OH
h, OHMeCN/H2O
OMe
NO2
NO2
OMe
O2N
OMe
OMe
h, OHMeCN/H2O
O2N
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
+
O2, h/redn
(+)-Limonene
HO
HO
MeOH/RB
31%
+
+
11%
25%
21%
General effects controlling the regioselectivity of allylic oxidations of C-C double bond
1O
2
O
X
X
O Y
Y
Cis effect
CH3 (<2)
CH3 (7)
(53) H3C
CO2R
(<2) H3C
Geminal effect
CH3 (>98)
tBu
(34) H3C
(>98) H3C
CH3 (40)
(<2) H3C
Large group effect
CH3 (66)
(17) H3C
OMe
SOR
CH3 (>98)
tBu
CH3 (83)
Acyclic substrates
Me
Acetone/ R.B
Pri
Ph
R.T/ O2/ h
D H
Me
OOH
OOH
Pri
Ph
+
Me
Pri
D
H
Me
OOH
Me
Me
OSiRMe2
NC
CCl4, TPP
Me
OSiRMe2
H CN
h, O2
Ph
+
Me
OOH
OSiRMe2
H CN
 -unsaturated carbonyl compounds
CO2 Me
CO2 Me
CHCl3/TPP
0oC/ O2/ h
E
Z
CO2 Me
OOH
OOH
+
dr = 90:10
dr = 65:35
Cycloalkenes with excocyclic C-C double bond
MeOH, RB/ RT
O2/ h
OH
OH
+
OH
Na2SO3
35
O
H
OMe
CO2 H
12
+
23
O
H
O
H
MeOH/ RB
OOH
MeO
-78oC/ O2/ h
OMe
H
H
CO 2H
OMe
H
DCM/ MB
RT/ O2/ h
HCO2H/ DCM
H
O
H
O
O
H
OOH
H
O
H
OMe
H
CO 2H
CO 2H
O
qinghaosu
CCl4/ TPP
OSiMe3
OOSiMe3
O2/ h
Ph3P
OSiMe3
O
O
H
HO
O2/ h
OOH
R'
R
HO
R' = H, R = OH
R', R ; = O
O
EtOH/MB/O2/h
+
OOH
H
O
H
OOH
Major
Photooxygenation of 1,3-dienes
1O
2
1O
O
2
O
O
Ph
2
Ph
Ph
O
O
Ph
Ph
O
1O
2
+
O
Ph
Ph
O
O
O
O
O
Ph
Ph
O
O
Ph
Ph
1O
+
O
Ph
O
1O
2
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
O
O
n
X
X
1O
2
O
O
X = CH2, (CH2)2, CH=CH
1O
O
2
O
O
O
1O
Ph
2
O
O
Ph
O
O
O
O
O
O
1O
2
heat
+
O
O
O
O
O
O
Ph3P
MeOH
O
H H
OMe
O
H
S
S
1O
2
S
O
O
O
HN=NH
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
(CH2)n
n=1
n=2
n=3
n=4
n=5
1O
2
O
MeOH/DCM
RB
(CH2)n
+
ene products
O
16
20
22
50
67
84
80
78
50
33
1O
2
O
O
1O
2
OOH
Me
H
H
H
Me
H
1O
2
OMe
O
OMe
O
OMe
OMe
1O
OMe
2
O
OMe
+
OMe
O
CHO
OMe
OMe
OMe
OMe
O
O
O
1O
O
2
O
MeOH
+
OOH
+
O
+
OOH
1O
OOH
2
+
OOH
-Myrcene
O
1O
2
O
-Myrcene
OtBu
OtBu
OtBu
1O
OMe
2
O
O
OMe
+
OMe
Ar
O
O
h/O2
O
O
H
+
Ar
Ar
Cl
H
N
H
OH
Ar
N
epibatidine
OH
OTBS
OH
OTBS
OH
1O
OTBS
2
O O
h
OTBS
OH
OH
MeO
OH
HO
OH
OH
Pinitol
O
OH
O
OH
O
OH
OH
OH
b
c
a
O
+
O
O
O
O
d
O
e
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
h
O
R S OR'
R S OR'
R
.SO2OR
SO2.OR
O
O
H abstraction from
solvent
R OH
R H
proposed mechanism for photochemical reaction of sulfonates
O
O
OTs
RSO2O
O
OR
O
R = Ts
OTs
O
O
HO
O
O
O
O
O
O
O
OHOTs
OTs
O
O
OTs
O
O
O
O
h/MeOH
CHPh
OMe
O
CHPh
O
OMe
O
O
O
OTs
O
O
CHPh
X
OMe
O
h/MeOH
O
OTs
OTs
OH
h
O
No deprotection observed
O
O
O
O
O
h/ (Me2N)3PO
O
OSO2CF3
O
H2 O
H
O
H O
NO
NO 2
CH2OR
h
CHO
ROH
+
n-
O
NO
+
OH
OR
N OH
CH.OR
H
O
O
+
N O H
OR
+
N OH
H
CHOR
Acinitro intermediate
proposed mechanism for the photochemical cleavage of o-nitrobenzyloxy compounds
O
OH O
O2N
HO
O2N
Me
OH
O
OH
O
OHOH
OBn
OH
NO2
O O
OH
NO2
O O
OBn
BnO
HO
OH
R
OBn
R
R = H, OMe
HO
O
B
OR O
NO2
MeO
R
O-Nitrobenzyl group known as Caged group
NH2
NO 2
O
O
O
O
P O
P O
P O
O
O
O
N
O
N
N
NO 2
NH2
OH OH
Caged ATP
O
HO
H
CO 2-
O
O
N
Caged glutamic acid, neurotransmitter
NH2
CO 2- CO 2
N
CO 2- CO 2N
Ca+2
O
N
NO 2
O
O
O
P
O
NO 2
Photocaged Ca2+
Photolysis release Ca2+
N
O
O
Caged cAMP
OH
N
N
O
O
X
HN
O
NO2
X
N
H
O
h
365nm
X
HN
HO
N
H
O
X
X = H, Tyrosine
X = D, [D2] Tyrosine
Photodeprotection of o-nitrobenzyl adducts to yield natural amino acids
radical quencher
h
RO.
RO NO2
.NO2
R OH
photochemical removal of nitrate group
ONO2
O
O
O
O
R1
O
O
O
O
R2 O
O
R 1 = H; R2 = ONO2, 100%
R1 = ONO2; R2 = H, 92 %
O
H
OH
NO2
h/ MeOH
O
O
O
OH
NO
TFA
O
O
NO2
OMe
AcO
NO2 O
O
OMe
AcO
O
OMe
CH2OH
O
O O
O O
NO2
NO2
O
O
O
O2N
O
OMe
OAc
O
NO2
O
OMe
O
O
O
OAc
NO2
O
OMe
OAc
O
O
O
O
NO 2
O
OH
NO
O
C
O
+
N OH
O
OH
NO
O
O
O
O
O
+
N
O
OH
OH+
N
O
Proposed mechanism for the photochemical rearrangement of
o-nitrobenzylidine acetals to o-nitroso benzoates
o-nitrobenzyloxycarbonyl (NBOC)
NO2
O
N OH
N
H
O
OH
OR
O
OR
C O
OR
O
O
O
O
NO
NO
OR
O
OH
+
CO2
+
ROH
CHO
O
2-(o-nitrophenyl)-ethoxycarbonyl [NPEOC]
O
NO2
N
O
O
OR
OH
O
NO2
O
OR
+
CO2
+
ROH
1. light absorption and
intersystem crossing
S
O
O
Covalent linkage
2. Energy
transfer
3. H- Transfer
NH
O
O
O
NO2
N
O
4. -elimination and fragmentation
O
OH
S
O
O
NH
HO
+
CO2
+
O
N
NO2
OH
Intramolecular sensitized photocleavage of a protecting group of NPPOC type
O
S
S
O
O
OR
O
O
NO2
OR
O
NPPOC Protecting group
O
NO2
OR
O
NO2
O
S
S
OR
O
O
O
OR
O
NO2
O
O
NO2
OR
O
S
S
O
NO2
O
O
O
O
OR
O
NO2
O
Overview of different covalent linker attached with NPPOC group
Angew. Chem. Int. Ed. Engl, 2006, 45, 2975-78
MeNPOC [(-methyl-2-nitropiperonyl)-oxy] carbonyl
NO2
NO2
O
O
O
OH
O
COCl2, THF
O
O
O
O
NO2
O
NO2
HO
O
O
+
O
O
B
Cl
O
Pyridine
O
O
OH
O
NO2
HO
O
O
B
O
O
OH
O
O
O
O
NO2
O
O
B
O
h
O
O
O
B
+
O
O P OMe
O
O
+
O
O
O P OMe
O
CN
CN
JACS, 1997, 119, 5081
CO2
Cl
OH
O
R
O
h
O Ar
R
C
Ar
O
COR
Photo fries rearrangement
S-H
ArOH
+
RCO2H
or
RH
+
CO
Proposed mechanism for the photochemical cleavage and rearrangement of aryloxy esters
O oNB
O oNB
OCOR
R1
R = Ph, Me, CCl3, CPh3, 9-Fluorenyl
OCOR2
O
HO 2C
NH2
OtBu
NH
O
N
H
CO2Et
photochemical deprotection of ketones protected as
ketals of 1-(o-nitrobenzyl)-1,2-ethane diol
OH
OH
NO 2
O
O
+
R1
O
O
R1
+
R2
N
NO 2
O
NO
O
+
R1
O
OH
R2
OH
O
OH
O
R2
O
h
R2
R1
NO
R1
O
R2
O
OH+
N
O
R1
R2
Photochemical deprotection of carboxylic acids and amides
protected as o-nitrobenzyl ester and amide derivatives
NO2
NO2
R1
R2
O
R2
O
O2 N
O
O
R1 = H, R2 = Ph
R1 = ph = R2
R1 = Ph, R2 = (CH2)14 Me
R1 = Ph, R2 = Bn
R2 = Ph, Bn, CH2-naphthyl, -Boc Ala, Boc-Phe
O
N
H
(P)
NO2
H
N
R
O
R = Boc-Gly
R = Boc-Val
R = protected decapeptide
Carboxylic acid
OCOR'
h/ C6H6
R'CO2H
+
R"
O
R
O
R
R
R = OMe, R " = H
OAc
OAc
C
OMe
O
OMe
H
O
OAc
OAc
MeO
C
MeO
OMe
O
O
O
H
MeO
O
O
+
SOCOR
NO2
S
+
O
S
R
N O
+
h
NO 2
+
O
NO2
RCO 2-
NO 2
NO 2
C6H6
S
NO2
+
RCO 2H
NO 2
proposed mechanism for the photochemical cleavage of
dinitro phenylthio derivatives of carboxylic acids
O
H
SH
O
R1
S
O
R2
N
R3
h
O
R1.
S
O
S
O
R2
N
-SO2
R2
H N
R3
R3
R2
N
R3
SH
R2
SO 2.
N
R3
Proposed mechanism for photochemical reaction of sulphonamides
O
O P O
O
OH
h/MeOH
+
O P O
O
O
NO2
NO2
photochemical deprotection of phenol phosphates
H2N
N
O2N
N
O
O
O P OH
O P O
OBn
O
O
N
O2N
O O
O2N
NO2
N
S
S
S
RCOCl/ NaH
S
S
N
H
S
R
N
N
O
O
h/ R'OH
S
+
OR'
R
O
S
N
H
Photolysis of N-acyl-2-thionothiazolidines
S
h
S
H
N
O R'
R
S
R
C SH
N
C
O R'
O
R
R'
R2OH
R
Photochemical activation in N-Acyl-2-thionothiazolidine
OR2
R'
O
R
h
S
S
O
H
H
O
S
S
R3
R2
R1
h
R1
R3
R2
Photolytic dethioacetalization
Remote functionalization by Nitrites: The Barton Reaction
H
ONO
O
+
OH
N N
+
O
H
h
OH
+
heat
HO
H
O
N
+
H
NO
C
ON
OH
O
+
OH
NO
six membered cyclic TS for  hydrogen abstraction
H
ONO
C
HO
NO
HO
O
C
+
NO.
+
HO
NO.
O
O
OAc
HO
NOCl/ Pyr
H
H
H
H
H
h, PhMe
H
O
O
O
H
O
OAc
O
H
NO
H
H atom abstraction
H
H
O
OAc
C
OH
H
H
O
OH
O
ON
OAc
OH
O
N
OAc
OH
H
H
O
OAc
O N O
H
H
tautomerization
H
H
HNO2
O
OH O
O
H
Aldosterone 21-acetate
H
O
H
OAc
OH
O N O
NOCl
h, n-hexane, RT
Pyr, 0oC
iPrOH, reflux
OH
OH
N
OH
O
OH
H
Grandisol
Magnus et.al, 1976, JACS, 98, 4594
OH
OH
O
OH
OAc
OAc
OAc
OH
-cleavage
Norrish type-I
OH
OAc
O
O
OHC
OAc
OH
ONO
H
H
O
h
H
H
H
O
H
O
O
O
NOH
H
H
H
O
H
C
H
O
H
HO
N
O
ONO
h
O
H
X
benzene
N
OH
R
R
(CH2 )n
ONO
h
R
(CH2 )n
R
CS2
O
NO
ONO
O
h
H
H
benzene
H
+
H
O
O
H
H
H
C
H
H
OH
OH
N OH
C
H
H
H
H
.NO
Barton-McCombie reaction [R1R2CHOH to R1R2CH2]
H
H
R2
R1
R2
R1
OH
OH
2,4,6-Cl3C6H2OC(S)Cl, Pyr
[X = 2,4,6-Cl3C6H2O]
C6F5OC(S)Cl, Pyr
[X = C6F5O]
R2
R1
S
H
H
R2
R1
OH
X
O
Im2CS, THF
X=
N
N
PhOC(S)Cl, Pyr
[X = PhO]
H
R2
R1
OH
H
NaH, CS2, MeI
[X = SMe]
R2
R1
OH
S
H
R2
R1
X
O
nBu3SnH, h
.Sn-nBu3
S
H
S
H
R2
R1
R2
R1
O
O
S
H
R2
R1
X
O
C
Sn-nBu3
X
X
.Sn-nBu3
+
R1
R2
H
R1
nBu3SnH
H
R2
C
S
+
H
O
Sn-nBu3
X
Barton's thiohydroxamate ester chemistry: synthesis of alkyl pyridyl sulfides
O
+
Cl
R
N-Hydroxypyridine-2-thione sodium salt
N
O-Na+
S
DMF or POCl3
O
R
O
N
.R
+
+
N
S
thiohydroxamate ester
SR
h
O
O
R
O
N
R
O
N
C
S
S
.R
R
CO2
R-Cl
R-Br
R-I
CCl4
BrCCl3
CHI3
R
N
R-SPh
RSePh
PhSeSePh
PhS-SPh
O
S
nBu3SnH
R-H
O2
R-OH
Barton's Thiohydroxamate ester chemistry: Use of neutral molecule radical traps
O
O
S
N
S
h
O
O
O
S
N
O
N
S
C
S
S
-CO2
C
5-exo-trig
C
C
+
N
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
R3
N
H
3O
h, TPP
CO 2H
R4
R3
O
2
1O
2
R4
R3
N
COO-
CO 2H
N
OOH
R1
R1
R1
R2
R2
R2
O
O
OH
R1
R2
J. Am. Chem. Soc, 2004, 126, 8914
Angew. Chem. Intl. Ed. Eng. 2004, 43, 6532
OOH
R1
R2
h
SK
SK
A* B
A B
SK*
SK*
A+B
PET
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
CO2H CO H
2
CO2H
O
H
NN
O
Kemp's triacid
N
O
O
H
Ph
H
O
O
H
NN
O
N
X
R
OMe
OMe
h
N
H
R
OMe
O
H
H
O
O
R
endo
R
R = CH2CH2CH2OH
R = CH2OAc
R = OAc
R = Ph
R = CO2Me
R
OMe
OMe
H
H
O
O
exo
OMe
N
H
O
O
H
NO
H
N
O
NN
O
JACS, 2000, 112, 11525
O
O
H
h
H
O
N
H
N
H
93% ee
O
O
h
O
N
H
O
> 90% ee
H
N
H
O
OMe
O
H
N
H
O
NO
H
N
N
JACS, 2002, 124, 7982
N
O
O
PET
N+.
N
N
O
O
Ph
N
H
NH
O
h
C Ph
ISC
O
NH
H
H
O
O
O
O
N N
N N
O
-H+
N
N
O
N
C
Ph
NH
O
NH
H
N
H
O
O
70% ee
Nature, 2005, 436, 1139
N N
OH
C Ph
O
H
O
O
N N
O
Facial differentiation or complexation is key to enantiocontrol
O
OR
HN
OR
O
O
O
NH
N
NH
NH
Me
HN
O
O
CDCl3
O
N
R
Me
R
NH
O
R=
COPh
h
OR
O
O
O
NH
NH
HN
N
O
19% ee
O
R
NH
J.Org. Chem, 2003, 68, 15
O
Me